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Regulatory programs to foster medical product development: user experience in the United States and Japan

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Regulatory programs to foster medical product development: user experience in the United States and Japan

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REGULATORY PROGRAMS TO FOSTER MEDICAL PRODUCT DEVELOPMENT:
USER EXPERIENCE IN THE UNITED STATES AND JAPAN

by

Nami Migita

A Dissertation Presented to the
FACULTY OF THE USC SCHOOL OF PHARMACY
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF REGULATORY SCIENCE

May 2022

Copyright 2022 Nami Migita

ii
Dedication

This work is dedicated to my father, Masao Migita, who has been my constant
source of inspiration. Thank you for believing in me and making me see this long
journey through to the end.

iii
Acknowledgments

This work would not have been possible without the support and encouragement
of many people.
First, I would like to express my deepest gratitude to my advisor and mentor, Dr.
Frances Richmond, for her tireless guidance and support with full encouragement and
enthusiasm. I have benefited greatly from her wealth of knowledge. Second, I would
like to thank my dissertation committee members – Dr. Daryl Davies, Dr. Susan Bain,
Dr. Benson Kuo, and Dr. Frances Richmond – for their valuable inputs and suggestions
throughout this work. Third, my heartfelt thanks to Dr. Eunjoo Pacifici for reviewing my
survey, Dr. Terry Church for reviewing my survey and references, and Megumi
Wakamatsu for helping me with English/Japanese translations. Then, I would like to
thank the DRSc 2014 Cohort, USC Regulatory Science program staff, my survey focus
group, and survey participants for all their invaluable inputs on my work. Finally, I
would like to give my special thanks to Dr. Koichi Masuyama (Tokyo University of
Pharmacy and Life Sciences) for sharing his knowledge about the MHLW, PMDA, and
PMDA’s consultation services and supporting my Japanese survey.

iv
Table of Contents
Dedication ........................................................................................................................... ii
Acknowledgments.............................................................................................................. iii
List of Tables .................................................................................................................... vii
List of Figures .................................................................................................................... ix
Abstract .............................................................................................................................. xi
Chapter 1. Overview ............................................................................................................1
1.1 Introduction .................................................................................................... 1
1.2 Governmental Initiatives to Support Medical Product Translation ............... 3
1.3 Statement of the Problem ............................................................................... 5
1.4 Purpose of the Study ...................................................................................... 5
1.5 Importance of the Study ................................................................................. 6
1.6 Limitation, Delimitations, Assumptions ........................................................ 7
1.7 Organization of Thesis ................................................................................... 8
1.8 Abbreviations ................................................................................................. 9
Chapter 2. Literature Review .............................................................................................12
2.1 Introduction .................................................................................................. 12
2.2 History and Evolution of Universities ......................................................... 12
2.2.1 The United States ............................................................................ 13
2.2.2 Japan ............................................................................................... 17
2.3 Governmental Policy Environment for Promoting Commercialization ....... 23
2.3.1 The United States ............................................................................ 24
2.3.2 Japan ............................................................................................... 28
2.4 Regulatory Agency's Support for Promoting SMEs in Medical Product
Business Sector ............................................................................................ 34
2.4.1 The United States ............................................................................ 34
2.4.1.1 NIH’s Support for Promoting SMEs ................................. 35
2.4.1.2 FDA’s Support for Promoting SMEs ................................ 38
2.4.2 Japan ............................................................................................... 43
2.4.2.1 PMDA’s Support for Promoting SMEs ............................. 52
2.4.2.2 AMED’s Support for Promoting SMEs ............................. 54
2.5 Status to Date ............................................................................................... 59
2.5.1 The United States ............................................................................ 59
2.5.2 Japan ............................................................................................... 70
2.6 Summary and Study Direction ..................................................................... 74
2.7 Defining and Assessing Customer Satisfaction ........................................... 75

v
Chapter 3. Methodology ....................................................................................................80
3.1 Introduction .................................................................................................. 80
3.2 Phase 1 – Development of Survey Instrument ............................................. 80
3.3 Phase 2 – Focus Group Analysis: Validation of the Survey Instrument ...... 81
3.4 Phase 3 – Dissemination of the Survey ........................................................ 82
3.5 Phase 4 – Analysis of Collected Data .......................................................... 82
Chapter 4. Results ..............................................................................................................84
4.1 Survey Participants ...................................................................................... 84
4.2 Demographic Profile of Respondents .......................................................... 85
4.3 U.S. Survey Results ..................................................................................... 94
4.3.1 Experiences with U.S. FDA’s Services to Support SMEs .............. 99
4.3.2 Feedback from Respondents who did not Use the FDA’s Services to
Support SMEs ............................................................................... 107
4.3.3 Respondents Unaware of the FDA’s Services to Support SMEs . 108
4.3.4 Respondent Experiences Regarding Personal Interactions with the
FDA .............................................................................................. 110
4.4 Japanese Survey Results ............................................................................ 113
4.4.1 Experience with Japanese PMDA’s Consultation Service to Support
SMEs ............................................................................................ 118
4.4.2 Feedback from Respondents who did not Use the PMDA’s
Consultation Services to Support SMEs and Academia ............... 127
4.4.3 Respondents’ Awareness of PMDA’s Web Contents................... 129
4.4.4 Respondents Unaware of the PMDA’s Website for “Academia” or
“Industry” ..................................................................................... 130
Chapter 5. Discussion ......................................................................................................132
5.1 Overview .................................................................................................... 132
5.2 Consideration of Study Methodology ........................................................ 132
5.2.1 Delimitations ................................................................................ 132
5.2.2 Limitations .................................................................................... 134
5.3 Insights of Results ...................................................................................... 139
5.3.1 Promotional Gap ........................................................................... 140
5.3.2 Understanding Gap ....................................................................... 142
5.3.3 Procedural Gap ............................................................................. 144
5.3.4 Behavioral Gap ............................................................................. 149
5.3.5 Perception Gap ............................................................................. 154
5.4 Conclusions and Recommendations for Future Direction ......................... 157
References ........................................................................................................................160
Appendix A: U.S. Survey Questionnaire .........................................................................175
Appendix B: Japanese Survey Questionnaire ..................................................................188

vi
Appendix C: U.S. Survey Results – Medical Devices .....................................................203
Appendix D: U.S. Survey Results – Pediatric Medical Devices .....................................223

vii
List of Tables
Table 1: Abbreviations ....................................................................................................9
Table 2: Timeline of Japanese Technology Transfer Policies ......................................22
Table 3: Major Similarities and Differences between SBIR and STTR Programs .......37
Table 4: Nature of CDER SBIA Outreach Services .....................................................42
Table 5: Category of PMDA Consultation Services concerning Clinical Trials and
NDA for a New Drug .................................................................................46
Table 6: History of the Establishment of AMED .........................................................51
Table 7: Differences between ACT-MS and ACT-M ...................................................58
Table 8: Summary of Performance for FYs 2002-2006 SBIR Phase II Awardees ......67
Table 9: Number of Consultation by Topic and Product Type .....................................70
Table 10: Number of RS General Consultations and RS Strategy Consultations ..........72
Table 11: Number of Products under the “Sakigake Designation System” by Year ......73
Table 12: Status of Verification Programs (as of January 2015) ....................................74
Table 13: Crosstabulation of Size of the Company with Job Functions Held ................92
Table 14: U.S. and Japanese Respondents’ Comments on “Other”, Figure 18 ..............93
Table 15: Crosstabulation of Awareness of the FDA’s Services by Product Type ........98
Table 16: Familiarity with Services Offered to Support SMEs ......................................99
Table 17: Crosstabulation of Awareness by Product Categories ....................................99
Table 18: Comments on Content of FDA’s Website ....................................................101
Table 19: Routes Used to Obtain Information ..............................................................102
Table 20: Actual Communication Route Vs. Preferred Route .....................................103
Table 21: Views Regarding FDA’s Enthusiasm about Supporting Respondents .........103
Table 22: Ability of FDA Services to Increase Confidence .........................................104
Table 23: Comments on the FDA’s Services for SMEs ...............................................104
Table 24: Positive/Negative Experience When Trying to Interact with the FDA ........106
Table 25: Reason(s) Not to Access the FDA’s Services for SMEs ..............................107
Table 26: Comments Regarding Additional FDA Support ...........................................107
Table 27: Interest in the FDA’s services for SMEs ......................................................108
Table 28: Comments Recommending Additional FDA Services to Assist
Commercialization ...................................................................................109
Table 29: Experience with Personal Interaction with the FDA ....................................110
Table 30: Satisfaction with Personal Interactions with the FDA ..................................111
Table 31: Positive/Negative Experience with Interactions with the FDA ....................111
Table 32: Comments on Personal Interaction with the FDA ........................................112
Table 33: Comments on Whether Personal Interactions with FDA Provides More
Personalized or Tailored Supports ...........................................................113
Table 34: Comments on “Other”, Figure 24 .................................................................114

viii
Table 35: Comments related to Figure 28 .....................................................................118
Table 36: Comments related to Figure 29 .....................................................................119
Table 37: Route Used to Obtain Information ...............................................................120
Table 38: Comments related to Table 37 ......................................................................120
Table 39: Actual versus Preferred Communication Route ...........................................121
Table 40: Perceptions of PMDA’s Enthusiasm for Supporting Respondents ..............122
Table 41: Effect of Consultation on Respondents’ Confidence ....................................122
Table 42: Comments on the PMDA’s Consultation Services for SMEs or Academia .123
Table 43: Positive/Negative Experience Interacting with PMDA ................................125
Table 44: Satisfaction/Dissatisfaction with the PMDA’s Consultation Service ...........127
Table 45: Reason(s) Not to Apply or Have the PMDA Consultation Service ..............127
Table 46: Reasons for Not Pursuing PMDA Consultation Services .............................128
Table 47: Comments on Potential Ways to Accelerate Commercialization .................128
Table 48: Comments on Satisfaction with the PMDA’s Web Contents .......................130
Table 49: Respondents’ Thoughts about the PMDA’s Web Contents Specific to
“Academia” or “Industry” ........................................................................131
Table 50: Comments related to Table 49 ......................................................................131
Table 51: Crosstabulation of Awareness of by the Size of the Company ....................141
Table 52: PMDA Regulatory Science Consultation Fees .............................................156

ix
List of Figures
Figure 1: PMDA’s Safety Triangle / Three-Pillar System .............................................44
Figure 2: Relationships underlying Regulatory Science General Consultation and
Regulatory Science Strategy Consultation (R&D) ....................................53
Figure 3: Consortium Structure Envisioned by AMED .................................................56
Figure 4: SBIR Grants, Phase I: Competing Application, Awards, and Success Rate ..59
Figure 5: SBIR Grants, Phase II: Competing Application, Awards, and Success Rate .60
Figure 6: Summary of Outcomes associated with “Stimulating Technological
Innovation” ................................................................................................62
Figure 7: Summary of Outcomes associated with “Using Small Business Concerns to
Meet Federal Research and Development Needs” .....................................63
Figure 8: Summary of Outcomes associated with “Commercializing Innovations” .....66
Figure 9: Satisfaction concerning Overall Consultation Work ......................................71
Figure 10: Service Gaps as Identified by the Hill Model .................................................77
Figure 11: Conceptual Model of Service Quality ............................................................78
Figure 12: Zone of Tolerance relevant to Service Perceptions ........................................79
Figure 13: Types of Organizations Represented by Participants .....................................86
Figure 14: Size of Company by Number of Employees ..................................................87
Figure 15: Types of Medical Products Developed by Respondent’s Organization .........88
Figure 16: Organizational Level of Respondents .............................................................89
Figure 17: Functional Roles of Respondents within the Company/Organization ............91
Figure 18: Development Stage when Planning a Regulatory Filing Strategy ..................93
Figure 19: Sources of Information on the FDA’s Services to Support SMEs. ................95
Figure 20: Was Information about the Support of SMEs on FDA’s Website Easy to
Find? ..........................................................................................................96
Figure 21: Did FDA Explain Clearly its Offered Services? .............................................96
Figure 22: Awareness of the Following Services Offered by the FDA ...........................97
Figure 23: Satisfaction or Dissatisfaction with the FDA’s Web Contents to Support
SMEs ........................................................................................................101
Figure 24: Source of Information on the PMDA’s Consultation Services to Support
SMEs. .......................................................................................................114
Figure 25: Was Information regarding PMDA’s Consultation Meetings Easy to Find?
..................................................................................................................115
Figure 26: Were PMDA Consultation Services Explained Clearly? .............................115
Figure 27: Does PMDA Appear to Understand the Needs of SMEs or Academia? ......116
Figure 28: Satisfaction or Dissatisfaction with the Contents of PMDA’s Consultation
Service for SMEs and Academia .............................................................117
Figure 29: PMDA Consultation Meetings Respondents Had ........................................119
Figure 30: Reaching the PMDA Staff When Necessary ................................................124

x
Figure 31: Satisfaction/Dissatisfaction with the PMDA Consultation Service ..............126
Figure 32: Satisfaction with PMDA’s Web Contents for Academia/Industry ...............130
Figure 33: RS Strategy Consultation Process Flow (Example) .....................................147
Figure 34: At the Bottom of the FDA’s Email (Example) .............................................150

xi
Abstract

Universities, research institutes, and small- and medium-sized enterprises (SMEs) play a
critical role in developing medical products but face significant hurdles. They may lack
clinical and regulatory strategies, personnel, and processes critical to product
commercialization. Governments have recognized these challenges and have attempted
to introduce programs to address some of those obstacles. However, little systematic
research has explored the views and experiences of academic groups and SMEs with
governmental programs specifically available for medical product development in the
United States and Japan. Using a novel survey constructed with reference to the “service
gap” theory, 62 U.S. participants provided insights into their experiences and satisfaction
with programs provided by the FDA’s Division of Industry and Consumer Education
(DICE) in the Center for Devices and Radiological Health (CDRH) or the Small Business
and Industry Assistance (SBIA) program in the Center for Drug Evaluation and Research
(CDER). Nearly half were unaware of these targeted services; however, among those
who used at least one of the services, most felt that FDA’s services gave them a sufficient
explanation regarding their services. About two-thirds were satisfied with those services.
Forty-three Japanese participants provided similar input related to PMDA’s “Regulatory
Science General Consultation” and “Regulatory Science Strategy Consultation (R&D)”.
Most were aware of these consultation services and felt that the PMDA gave sufficient
information about the process. However, their overall satisfaction rate of 55% was lower
than that of the U.S. respondents.

xii
Findings suggest that the targeted programs are valued by emerging enterprises but can
sometimes miss the mark in anticipating and responding to the needs of their
stakeholders. Gaps in satisfaction are most evident in procedures, which some
respondents often characterized as slow, bureaucratic, and unhelpful. Results suggest
that programs could be improved if regulators take account of the less mature state and
knowledge of newly formed companies and, using this lens, modify these programs
logistically if they are to produce more effective outcomes.

1
Chapter 1. Overview
1.1 Introduction
The medical product industry depends on a constant supply of novel products.
These products often come from innovations that originate in academia or small- and
medium-sized enterprises (SMEs). However, universities, research institutes, and SMEs
face significant hurdles in developing their products from promising “seed” research or
technologies. They are not always familiar with clinical and regulatory strategies or
processes foundational to product commercialization. They also lack the financial
resources to engage expensive regulatory and quality professionals who can educate and
guide their activities. They may not afford the costly equipment and services needed to
ensure that testing and production are carried out under regulatory rules.
Insufficient knowledge of regulatory systems, marginal financial assets, and poor
strategies for medical product development can sideline emerging businesses and result
in the loss of potentially valuable therapies. These can be problematic for the whole
medical product sector. Large pharmaceutical and medical device companies today
typically fill their pipelines with new technologies and potential products developed in
universities and SMEs, where they can be “de-risked” before acquisition by venture
capital-backed small firms (FDA, 2013). Further, SMEs play a significant role as part of
the vast economic fabric of society. According to the International Trade Administration
in the United States Department of Commerce, “more than 80% of medical device
companies in the United States consist of fewer than 50 employees, and many (notably
startup companies) have little to no sales revenue” (ITA, 2018). In Japan, SMEs account

2
for 99.7% of companies and employ more than 60% of all workers (SME Support Japan,
2017).
Governments are acutely aware of the challenges faced by these small but
essential operations. Industrialized countries such as the United States and Japan are
therefore considering ways to foster innovations in SMEs, universities, and research
institutes, where much of the innovation is believed to occur. Governmental support for
development may also provide an alternative, value-added activity to supplement
traditional sources of academic research whose traditional grants programs for research
are under pressure. For example, in 2018, the National Institutes of Health (NIH)
awarded only 18% of the 54,000 proposals that it considered (Piper, 2019). In Japan,
101,263 grants-in-aid for scientific research applications were submitted in 2016, and
only 26,676 (26.4%) were funded (JSPS, 2017).
In the past, scientific granting agencies have been reluctant to fund later-stage
research to support commercialization that they feel should be funded by private
businesses. At the same time, government funding bodies and taxpayers have tried to
encourage the translation of fundamental discoveries in pathophysiology, pharmacology,
and engineering into clinical tools for patient benefit. This translation is critical to
supporting the changing commercial strategies of the medical products industries. It has
become essential because larger medical product companies have recently announced
cuts in their internal research and development expenditures. Instead, they appear to be
looking to acquire promising “seed” research or technologies from universities, research
institutes, or SMEs to feed their product pipelines. However, both the large and small
organizations struggle with the mismatch between the extent to which the small research

3
enterprises can advance their technologies and the reluctance of larger companies to
adopt an immature candidate technology. The gap created by this mismatch has been
termed the “valley of death” (Hudson and Khazragui, 2013).
1.2 Governmental Initiatives to Support Medical Product Translation
Governmental agencies in industrialized countries, sensitized to the problems of
translating medical technologies, are considering ways to foster technology development
in universities and SMEs. These organizations face multiple challenges beyond the scope
of a single agency, or this dissertation, to address. However, one major area of concern
specific primarily to the medical products industry is the long and complex regulatory
path that must be taken to prove that the developing product is sufficiently safe and
effective to gain health authority approval.
In the United States, the Food and Drug Administration (FDA) has made
dedicated efforts to assist small businesses with certain identified barriers. It has
provided fee reductions and financial incentives for SMEs and has attempted to enhance
access and information to make the regulatory process more transparent. It has targeted
training programs for small business needs and has engaged with external groups to
facilitate partnerships and greater outreach to small companies. Notably, the FDA has
recently established novel regulatory approval pathways for highly innovative products.
It has also participated with various grant programs that can support academia and SMEs,
most notably the Small Business Innovation Research (SBIR)/Small Business
Technology Transfer (STTR) programs managed through NIH and the National Science
Foundation (NSF). However, recent research to assess the effectiveness of the SBIR and
STTR programs has suggested that some awardees continue to face barriers related to the

4
FDA regulatory process and appear to believe that NIH could assist awardees to work
more effectively with the FDA.
Likewise, Japanese agencies, including the Ministry of Health, Labour and
Welfare (MHLW) and Pharmaceuticals and Medical Devices Agency (PMDA), have
attempted to implement service and support programs for medical product development,
albeit smaller in scale to those in the United States. For example, in 2007, MHLW, in
collaboration with the Ministry of Education, Culture, Sports, Science, and Technology
(MEXT), established a 5-year strategy to address “drug/device lag”, a situation in which
the approval of products for the Japanese market took much longer than that for the
United States or Europe. Then, the Japan Agency for Medical Research and
Development (AMED), the Japanese version of NIH, was established in Japan in 2015.
In February 2018, the Medical Venture Total Support Project began. This project is a
matching service between medical ventures and subject matter experts/venture capitalists
via a portal site “MEDISO” (Medical Innovation Support Office) run by the MHLW. At
the same time, in 2011, the PMDA launched a scientific consultation service called the
“Pharmaceutical Affairs Consultation on Research and Development (R&D) Strategy.”
This consultation service, which offers guidance and advice to academic or SME
researchers, mainly focuses on guiding the transitional activities related to clinical trial
designs and strategies, especially for proof of concept to Phase IIa trials. By the end of
March 2018, PMDA conducted more than 1,700 free introductory consultations to
explain the procedures of the consultation system and the Japanese medical product
development process, more than 2,500 free pre-consultation to identify issues that might
require a face-to-face consultation, and 900 face-to-face consultations, for which the

5
applicant must pay and during which more substantive scientific and regulatory
discussions take place.
1.3 Statement of the Problem
Programs to assist academia and SMEs in dealing with regulatory impediments
have existed in both the United States and Japan for a decade. However, it is unclear
whether these programs have had the anticipated effect. Both programs have attempted
to assess whether program goals have been met by conducting their surveys to support
recipients. Typically, such assessments have been studied by asking recipients of grants
or other forms of support about their level of satisfaction with various aspects of the
services that they have received. However, much is still unknown about whether the
programs now in place have satisfied their broader audience – academia and SMEs – who
want to bring new medical products to market. Areas of challenge for these
organizations may exist even before securing their services, but this aspect of usefulness
and transparency has not been probed. For example, it may be interesting to find out
whether broader audiences, such as academic and SME researchers, who can be the
potential users of these services, know about these support programs. In addition, no
research to date has compared U.S. and Japanese governmental programs to foster
medical product development in academia and SMEs.
1.4 Purpose of the Study
The present study explores the views of SMEs and academia concerning
governmental support programs designed to foster new product development in the
medical products sector. Of particular interest are three governmental programs that

6
appear to be most influential in the United States and Japan. The programs are the FDA’s
resources provided by the Division of Industry and Consumer Education (DICE) in the
Center for Devices and Radiological Health (CDRH) for medical devices; the Small
Business and Industry Assistance (SBIA) program in the Center for Drug Evaluation and
Research (CDER) for drugs; and PMDA’s “Pharmaceutical Affairs Consultation on R&D
Strategy” consultation service. A goal of the study was to explore whether directions that
the United States or Japan regulatory agency has taken are adequate to foster medical
product development in academia or SMEs. A survey was developed to query the views
and experiences of two stakeholder groups in the United States and Japan, respectively.
It was structured by reference to a customer satisfaction model, using the framework
called the “service gap” theory described by Hill. It was disseminated to a sample of
past, current, and potential users of the targeted programs in the country in which they
worked.
1.5 Importance of the Study
Little systematic research has been conducted to explore the views of academia
and SMEs regarding the opportunities and challenges associated with governmental
programs that are specifically available for medical product development. The results of
this survey give us a better understanding of whether researchers in SMEs and academia
view these programs as a useful resource and whether steps that the United States and
Japanese governments have taken are adequate to foster medical product development in
their organizations. The programs established in the two countries are different in many
respects. The results may be used to identify aspects of the programs working well and
see if additional modifications should be taken in each country. In addition, regulators

7
can use this information to understand whether their directions to foster the medical
product development in SMEs and academia are on track and to identify best practices
for supporting SMEs and academia.
At the same time, results can be useful to those who work in SMEs or academic
organizations, who wish to understand how best to work with the regulators through these
programs. These understandings are important if they can help organizations develop
strategies that might improve their overall approach toward medical product development
and thus their success.
1.6 Limitation, Delimitations, Assumptions
Many research studies begin from a rich background of academic literature on
which they can build. Apart from a few studies conducted by funding agencies to assess
their effectiveness with grant recipients, little has yet been written about the views and
experiences of the broader community of investigators and SMEs who are potential users
of the regulatory services provided by the FDA and PMDA. Without such a background,
it was more challenging to build a survey on the foundation of previous work in the field.
I deliberately delimited this study by focusing on the satisfaction of academic and
SME researchers or companies that have participated, been participating, or will
participate in one of the FDA or PMDA’s programs to support them in medical product
development. Thus, the study did not examine other aspects of the same programs.
Further, the study explored the views of only one stakeholder, the current or potential
client of the services. It did not include the views of the service providers or other
potential stakeholders such as private funding groups who might also be working with
SMEs or academia. They face many challenges during product development, but this

8
study only focused on those hurdles associated with regulatory and clinical aspects of that
path.
The study was limited, to some extent, by the availability of relevant respondents
and their knowledge related to such governmental programs. I recognized the challenge
to identify appropriately qualified candidates for this survey but feel satisfied that the
numbers of respondents were sufficient to reach some measure of saturation. Previous
methodological literature had identified that customer satisfaction is a construct that is
difficult to measure, so using a model that explores different aspects of satisfaction
proved important to capture several indicators that gave insight into the construct. The
survey method proposed here spans two cultures, creating a concern that cultural
differences in approaches to survey participation might affect the comparability of the
results. However, it did not appear to limit the relative willingness of the participants to
answer what they might be considered as sensitive questions. Survey questions for the
United States and Japanese respondents also differed, in some respects, because the
programs offered to them are in different languages and different governmental
programs. Therefore, care was taken to align the questions to permit some comparison of
the respondents' views without introducing bias.
1.7 Organization of Thesis
The proposed study has been organized into five (5) chapters.
Chapter 1 provides an overview leading to the study questions, including
background information, problem statement, purpose, importance of the proposed study,
and limitation, delimitation, and assumption. Chapter 2 outlines the current state of
knowledge in this field by studying the available literature relating to the current support

9
services offered to academia or SMEs by the governments and regulatory agencies in the
United States and Japan. Chapter 2 also looks at the framework for evaluating questions
of interest. Chapter 3 defines the methods used in the proposed study in more detail.
Chapter 4 reviews the study results conducted through the issued survey instrument. And
chapter 5 contains a discussion of the study findings and conclusions.
1.8 Abbreviations
Table 1: Abbreviations
Abbreviation Description
AMED Japan Agency for Medical Research and Development
CDC Center for Disease Control and Prevention (U.S.)
CBER Center for Biologics Evaluation and Research (U.S.)
CDER Center for Drug Evaluation and Research (U.S.)
CDRH Center for Devices and Radiological Health (U.S.)
CSTP Council for Science and Technology Policy (Japan)
CTIP
The West Coast Consortium for Technology & Innovation
in Pediatrics
DICE Division of Industry and Consumer Education (U.S.)
DSMICA
Division of Small Manufacturers, International and
Consumer Assistance (U.S.)
DOD Department of Defense (U.S.)
FDA Food Drug Administration (U.S.)
FFRDCs Federally Funded Research and Development Centers (U.S.)
FSMA Food Safety Modernization Act (U.S.)
GDP Gross Domestic Product
GHQ General Headquarters of Allied Powers (Japan)
GOJ Government of Japan
HEW Department of Health, Education, and Welfare (U.S.)
HHS Department of Health and Human Services (U.S.)

10
Abbreviation Description
IP Intellectual Property
IPA Intellectual Property Agreement
IVD In Vitro Diagnostics
MHLW Ministry of Health, Labour and Welfare (Japan)
NIH National Institutes of Health (U.S.)
JAAME
Japan Association for the Advancement of Medical
Equipment
JSPS Japan Society for the Promotion of Science
MATTB
Manufacturers Assistance and Technical Training Branch
(U.S.)
MEDISO Medical Innovation Support Office (Japan)
METI Ministry of Economy, Trade, and Industry (Japan)
MEXT
Ministry of Education, Culture, Sport, Science and
Technology (Japan)
NDA New Drug Application
NIH National Institutes of Health (U.S.)
OCE Office of Communication and Education (U.S.)
OECD Organisation for Economic Co-operation and Development
OPSR
Organizations for Pharmaceuticals Safety and Research, also
known as KIKO (Japan)
OTAT Office of Tissues and Advanced Therapies (U.S.)
PASE Professional Affairs and Stakeholder Engagement (U.S.)
PhRMA Pharmaceutical Research and Manufacturers of America
PMDA
Pharmaceuticals and Medical Devices Agency in Japan
(Japan)
PMDEC
Pharmaceuticals and Medical Devices Evaluation Center
(Japan)
RFA Regulatory Flexibility Act (U.S.)
RFC Reconstruction Finance Corporation (U.S.)
RI Research Institute
SBA Small Business Administration (U.S.)
SBIA Small Business and Industry Assistance (U.S.)

11
Abbreviation Description
SBIR Small Business Innovation Research (U.S.)
SBRFEA Small Business Regulatory Enforcement Fairness Act (U.S.)
SME Small- and Medium-Sized Enterprise
SMEA Small and Medium Enterprise Agency (Japan)
STTR Small Business Technology Transfer (U.S.)
SWPC Smaller War Plants Corporation (U.S.)
TLO Technology Licensing Offices

12
Chapter 2. Literature Review
2.1 Introduction
Medical product innovation as a national strategic and economic imperative is a
relatively new area of focus for countries worldwide. In the past, the medical product
business was often considered “a world unto itself,” where the marketing and sales
strategies primarily determined the success or failure of products. However, in the last
few decades, a concern about the increasingly sophisticated nature of certain products,
including drugs and medical devices, has led innovation to be seen as an economic good
and a tool for economic growth. Further, governments have recognized the importance
of small- and medium-sized businesses, often spun out of universities, as an engine for
developing new, innovative products. In the literature review that follows, I trace the
evolution of universities from an “ivory tower” to an engine responsible for new startup
formation and industry innovation. I then examine government policies and supports to
foster that technology development. Of particular focus will be the role of the U.S. FDA
and the Japanese PMDA in facilitating the success of medical product development in
academia and small businesses.
2.2 History and Evolution of Universities
The evolution of universities in both the United States and Japan can be described
as having three epochs. In the first, universities were put into place to provide societies
with individuals who had specific essential skills needed to manage the protection and
governance of the societies through professions such as religion, medicine, and law. In
the second, the university became a source for research, particularly basic research that
would not be supported in the private sector. Universities attained respect as an “ivory

13
tower” where work would not, and should not, be sullied by subordination to commercial
pressures. In the third, universities became recognized as essential engines for
commercial growth. New approaches were considered to foster the transfer of new
knowledge that could drive health, public safety, and economic well-being by
transferring research products into marketable products.
2.2.1 The United States
Higher education is nearly as old as its original colonial government in British
North America (Geiger, 2015). Before the 1860s, early colonial institutions, such as
Harvard University, provided education mainly for those entering the ministry (Jaschik,
2014). The passage of the 1862 Morrill Land Grant Act, also known as the “Land Grand
Act,” was a milestone event that diversified the university system by creating land-grant
colleges to provide useful training and scientific research on agriculture, home
economics, and mechanical arts/engineering (Jaschik, 2014). The Act was also notable
because it was the first law created through a higher education partnership between
federal and state governments (Lieberman, 1988). Through this legislation, Morrill also
wanted to ensure that education would be accessible to all social classes. The educational
aim diverged from traditional classical studies and enabled more advanced research to
prepare the learners for the world they would encounter once they left the school
(Lightcap, 2004). It deviated from fundamental medical research typical for their British
and other European partners (Mowery et al., 2004). World War II then drove the
expansion of the more practical research envisaged by Morrill, fueled by the war by
increases in federal funding for research (Mowery et al., 2004). Throughout this time, the
federal government provided massive university-based science financing projects to

14
deliver military technology, and these projects strengthened relationships among the
federal government, universities, and industry. Universities came to rely on grants from
the federal government and industry to underwrite research activities (Lehrer and
Asakawa, 2004).
In the mid-1960s, science was much valued. About 5.5% of the federal budget
was directed at science and technology. However, as years passed, it became apparent
that scientific discoveries were failing to deliver on their promises to improve the public
good. Because the government held the intellectual property that came out of grant-
funded research, no meaningful incentives existed for universities and faculty to work
toward commercialization. Scientists pursuing such practical goals were often
stigmatized (Rose et al., 2015). Thus, in 1968, the Department of Health, Education, and
Welfare (HEW) introduced the first uniform Institutional Patent Agreement (IPA) to give
nonprofit institutions the first option to retain principal rights and administer inventions
made in the course of federally-funded research. It fueled the growth of university
patents during the 1970s and laid the later enactment of the Bayh-Dole Act of 1980.
However, these incentives were only modestly successful in assuring the subsequent
production of useful goods.
The Bayh-Dole Act of 1980 (94 Stat. 1980) marked a pivotal milestone to promote
the industrial implementation of university research by extending university privileges to
patent and licensing innovations from federally financed studies. Under the provisions of
the Act, non-profit institutions, including universities and small businesses, can hold the
intellectual property created under federally funded programs. If, however, the research
products are essential for national interest or if the university fails to negotiate and

15
disseminate the intellectual property in good faith, the government has march-in rights to
exercise the patents worldwide (Association of University Technology Managers, 2017).
Some believe that this Act was as significant for the United States’ innovation and
economic development as the Morrill Act (Etzkowitz et al., 2000).
The legislative and funding forces of the 1980s and 1990s made it increasingly
acceptable for academicians to pursue the activities needed to transform basic research
into successful innovation. Some universities and researchers began to develop spin-off
companies in the medical product sector. One such firm was Genentech, a company
founded in 1976 that employed the new gene-splicing methods to create biological
medicines, a move seen by many to mark the beginning of today's biotechnology industry
(Dabic, 2016). However, these new potential opportunities unmasked at least two
significant hurdles. First, universities began to realize that the process of translating early
discoveries into effective treatments for patients is time-consuming, costly, and often
unsuccessful (CureSearch, 2014). This challenge has often been characterized as a
“valley of death,” a place where good ideas struggle and then fail to gain market status
because the time and cost of animal and clinical testing are insurmountably high. Even
the largest universities typically did not have the funding or regulatory expertise to move
further down the translational path efficiently by themselves. They also lacked the
financial and legal expertise to bargain with the pharmaceutical industry on an equal
footing (Hudson and Khazragui, 2013).
Second and perhaps more important were the cultural changes required to
transition American universities to more entrepreneurial organizations (Faust, 2009).
Initially, the publication of research and graduates production were considered to be the

16
principal roles for an institution dedicated to the public good. One illustration of this
position is that, in 2008, medical researchers published 800,000 papers; however, only 21
new drugs were approved by the Food and Drug Administration in 2010. In the article
“Careers ’95: The Future of the Ph.D.” published in 1995, Holden discussed complaints
by corporate research teams that traditional Ph.D. training was ill-suited to meet their
needs for versatile individuals capable of transferring a research project quickly into
commerce (Holden, 1995). Even at that time, universities were struggling to understand
how to restructure themselves to take advantage of the new opportunities. Strategies that
were explored included, for example, disrupting traditional department barriers to make
way for more interdisciplinary work or forging new revenue-generating ties with
industry, government, and the public. However, today, universities appear to be caught
in a traditional model. Most funding opportunities are directed at the support of Ph.D.
students and postdoctoral fellows engaged in cutting-edge basic science in numbers far
exceeding society’s need for academic faculty. In contrast, few training opportunities
exist for students in areas related to translating ideas to products (Richmond and Church,
2019).
Nonetheless, the forces at play in today’s market-focused landscape favor the
development of an “entrepreneurial university.” Universities have vital roles as inventors
and transfer agents for knowledge and technology (Etzkowitz et al., 2000). This role is
well described by the “triple-helix” model of university-industry-government linkages in
the innovation processes that identify synergic interactions of academia with industry and
government. The triple helix model advances the view that innovation and economic
development would profit from a more significant role for the university. It recognizes

17
that hybridizing the capabilities of players from university, industry, and government
could create new organizational architectures that might foster the eventual
commercialization of new knowledge (Pinto et al., 2016). Thursby et al. captured the
challenges of this shift in a 2000 whitepaper:
Historically, commercial use of university research has been viewed in
terms of spillovers. Recently, there has been a dramatic increase in
technology transfer through licensing as universities attempt to
appropriate the returns from faculty research. This change has prompted
concerns regarding the source of this growth – specifically, whether it
suggested a change in the nature of university research (Thursby and
Thursby, 2002).
2.2.2 Japan
Like the United States, Japan made significant progress in modernizing education
and science throughout the latter half of the 19
th
century. The autocratic but enlightened
Emperor and government during the Meiji restoration of 1868 put in place the
educational, administrative, and technical infrastructure to protect Japan from
colonization by turning it into one of the world’s great powers (Duke, 2009). The
transformation provided an opportunity for Japan to restructure its political, social, and
economic institutions to facilitate industrialization. However, Japan’s industry was not
yet at a mass production stage and lacked technological expertise. To catch up with the
superior scientific and technological achievements of the West, it promulgated the
Fundamental Code of Education of 1872 that outlined an initial plan for a national
educational system (Kobayashi, 1980). In 1877, Tokyo’s Kaisei Gakko (a public school
of Western studies) and Tokyo Igakko (a national medical school) merged to form the
University of Tokyo (or Tokyo Imperial University at that time), the first modern
university in Japan, under an “Imperial University” system (Sorimachi, 2007). It
consisted of four faculties – the Faculties of Law, Science, Letters, and Medicine.

18
However, no graduate schools yet existed. For the first 50 years, the Ministry of
Education hired about 400 teachers from Western countries, who instructed the students
in their native languages until the turn of the century (Kobayashi, 1980). The Japanese
government had no formal system for promoting academic research until well into the
20
th
century. The absence of a previous research model on which to build, coupled with
high demands for technical expertise, retarded research development.
The second phase in Japanese higher education started with the promulgation of
the Imperial University Ordinance (Imperial Ordinance No 240. 1886), which established
a more contemporary scheme for the “Imperial University,” specifying that education
should serve the aims of the state. In 1890, Tokyo Imperial University was expanded to
include the Faculty of Agriculture. In 1897, Kyoto Imperial University was established
and modeled closely after Tokyo Imperial University. Thereafter, Tohoku Imperial
University was founded in 1907, and Kyushu Imperial University in 1910, with a
curricular emphasis on applied science and technology (Kobayashi, 1980). This period
of university reformation coincided with the first industrial revolution in Japan.
However, Japan’s industrial capabilities were still based on technologically less
sophisticated manufacturing operations typical for the textile and other light industries at
that time. Most of the required technologies were imported from the West, and the role
of the Imperial Universities in research and development was limited. Several private
institutions of higher education also existed but were relegated to “special schools.” For
example, Keio University, founded in 1868, and Doshisha University, founded in 1875,
were recognized only as universities until 1918 (Kobayashi, 1980).

19
During the third stage, Japan made significant progress in industry and higher
education. The Russo-Japanese War (1904-1905) precipitated the expansion of Japan’s
military strength; this was followed by an even more significant build-up for World War I
(1914-1918) when the usefulness of scientific research became more important
(Steinberg, 2008, Bala Subrahmanya, 2008). Consequently, the government in 1918
passed the University Act, which charged universities with a role in research as well as
education. Several new academic research institutes were founded to promote
development in fields of aerospace, metallurgy, seismology, and chemistry, but funding
for researchers remained scarce through the 1920s. In 1932, the Japan Society for the
Promotion of Science was established and became the primary source of academic
research funding (JSPS, 2015). However, this expansion was primarily directed at the
research to strengthen engineering and military-related technologies related to wartime
needs.
The fourth stage extends from the end of World War II to the present. When
Japan was defeated in World War II, the associated destruction brought industrial
production back to its level at the beginning of the century. Further, Japan’s pre-war
education scheme was being criticized for its undemocratic stratification and commitment
to army expansionism and ultra-nationalistic strategies. Consequently, a new
Constitution (May 4, 1947) and a Fundamental Law on Education (Mar. 31, 1947) came
into effect while still under American occupation. These redirected the educational focus
of post-war Japan. Significant reforms were also carried out in primary and secondary
education. Shortly thereafter, in 1949, the occupation authorities initiated a total reform
of the Japanese higher education system. All institutions of higher education were

20
transformed into four-year undergraduate colleges with or without graduate schools or
research institutes. However, this post-war research system had similar features to the
pre-war system, differing primarily in the fact that military research facilities were
closed, and the science policymaking process was democratized. In the immediate post-
war period, strategies to foster technology development continued to stress the adoption
of foreign technology, using a pre-war model of importation and adaptation (Collins and
Wakoh, 2000).
The devastation and confusion left by the war began to fade in the mid-1950s.
Japan’s military research facilities and factories were replaced by modernized facilities
using technologies from the United States corporations. Increased demands resulting
from the Korean War between 1950 and 1953 also fueled the reconstruction of the
Japanese economy (Sorimachi, 2007). Soon, Japan began to distinguish itself as a
civilian industrial nation – a “factory of the world.” By 1993, Japan’s per-capita GDP
had risen to the highest of all nations. However, Japanese university education did not
play a significant role in economic growth because it failed to encourage the type of U.S.-
style industrial-university corporations needed for “practical” research that might lead to
economic gain (Sorimachi, 2007).
By 2005, Japan began to lose its preeminence as the “factory of the world” to
developing countries, such as China. Japan’s per-capita GDP fell to the 14
th
in the world.
Politically, many structural reforms and deregulations were carried out to confront this
new reality. On the educational front, the new Fundamental Law on Education was
implemented on Dec. 22, 2006 (Act No. 120. 2006). It emphasized the importance of

21
“community spirit” and “inheritance of tradition.” Article 2 encourages the populace to
foster…
…a spirit of autonomy and independence by respecting the value of the
individual, as well as emphasizing the relationship between one’s career
and one’s everyday life and fostering the value of respect for hard work;
… fostering the value of respect for tradition and culture and love of the
country and regions that have nurtured us… (Act No. 120. 2006).
However, this was not enough to stem the tide. As the post-bubble economic
downturn entered its sixth year, the Japanese legislature in 1996 enacted a new Science
and Technology Basic Plan. It outlined an ambitious five-year strategy for improving the
Japanese infrastructure to support public R&D and linking its scientific research more
effectively to societal needs. Soon thereafter, the 1998 Law for Promoting University-
Industry Technology Transfer provided government funds to create technology licensing
offices (TLOs) at universities. The new policies set forth by the Council for Science and
Technology Policy (CSTP) made the system much more transparent, with the expectation
that greater transparency should increase private investment in academic research in
Japan.
At the turn of the 21
st
century, Japan’s 89 national universities and four university
collaborative research institutions underwent changes in operational status. Under a
proposal originally submitted in December 2001 by CSTP, Japan’s highest scientific
decision-making body, universities were given more independence and control over the
intellectual property (IP) rights of inventions created at their institutions (Act No. 112.
2003). This move, much like that in the United States, was spurred by the expectation
that universities would increase the number of companies that they could spin out, and
private investments from industry collaborations would become more common. In 2002,
Japanese corporations invested ¥155 billion ($1.4 billion) in foreign R&D, but only ¥51

22
billion ($484 million) in research conducted at Japanese universities (Kandachi, 2004).
This move was a critical change to cement the Japanese government’s efforts to prioritize
the commercialization of science and technology, as shown by the timeline mapped in
Table 2.
Table 2: Timeline of Japanese Technology Transfer Policies

Source: Japanese National Universities are Now “Incorporated” (Kandachi, 2004)
These new policies emphasizing a more productive relationship between
universities and industry must be appreciated from a broader historical perspective. For
much of their history, Japan’s universities had a political mandate to mobilize the
nation’s young people to achieve clearly articulated national goals – modernization in the
pre-war period, autonomy and victory in the Pacific War, and economic recovery in the
post-war era. Because researchers had been pressured previously to align their research
to the needs of the state, many resisted and became estranged from government and

23
industry. This gulf led many to believe that change would not be as rapid or pronounced
as in the United States after the passage of the Bayh-Dole Act (Collins and Wakoh, 2000).
Evolutionary change inevitably affected medical research and medical product
commercialization. The Pharmaceuticals and Medical Devices Agency (PMDA) stated
in their “Regulatory Science General Consultation and R&D Strategy Consultation”
brochure that the well-developed research capability in Japan was not yet matched by a
similarly matched capability in medical product development (PMDA, 2021d). They
acknowledged that the “valley of death” between basic research and product
commercialization would be difficult to cross without substantial funding and support.
Items to consider include establishment/maintenance of the clinical trial environment,
challenges in obtaining financial resources, and immaturity of scientific evaluation
methods to predict the safety and effectiveness of medical products in man based on the
results from basic research. This meant that researchers would have to learn how to
conduct their basic research studies to meet Japan’s regulatory requirements.
2.3 Governmental Policy Environment for Promoting Commercialization
Translating scientific findings from basic research to commercialized new
medical treatments is a demanding undertaking that is well recognized to depend on
multiple stakeholders. These include not only government, academic research institutes,
and industry but also diverse special interest entities, such as disease advocacy groups
and venture capitalists. These stakeholders often approach development activities with
different views and needs that can lead to gaps in communication and inefficiencies in the
development process itself. Governments have recognized that such challenges exist,

24
particularly for small- and medium-sized enterprises (SMEs), and have introduced
programs that can address some of those obstacles.
2.3.1 The United States
The national dedication to healthy commercial growth and competition can be
recognized in a sequence of laws adopted as early as 1890, during the new era of rapid
industrialization, urbanization, and financial concentration. These include the Sherman
Antitrust Act (26 Stat. 1890), the first federal act that outlawed monopolistic business
practices; the Clayton Act (38 Stat. 1914a) that defined unethical business practices, such
as price-fixing and monopolies, and upheld various rights of labor; the Federal Trade
Commission Act (38 Stat. 1914b) that outlawed unfair methods of competition and unfair
commercial acts or practices; and, the Robinson-Patman Act (49 Stat. 1936) that
protected small businesses from being expelled from the marketplace by uncompetitive
practices such as price discrimination, promotional allowances, and unfair advertising. A
detailed description of these acts is beyond the scope of this literature review but is
described in some detail elsewhere (FTC, 2019). However, experience gained during the
Great Depression and World War II helped Congress realize that these rules were not
enough to encourage the efforts of small businesses. Many felt that the role of the
government should go beyond legislation to establish fair trading practices and address
issues that impede the establishment and growth of small businesses. The free-market
economy was seen to provide a fertile “seedbed” for starting, growing, and supporting
small businesses, but marketing challenges often weighed disproportionately on smaller
firms. Thus, impediments to their development were not necessarily the result of illegal

25
anticompetitive conduct but instead challenges associated with developing and
commercializing novel products (Office of Advocacy, 2016).
In early efforts to address the issue, the government focused on market
imperfections associated with financial systems. In response to the financial unrest of the
Great Depression in the 1930s, the Reconstruction Finance Corporation (RFC), initially
created to loan money to all business, was permitted to lend money directly, or with the
involvement of private-sector lenders, to companies that could not acquire credit
elsewhere on reasonable terms. Shortly thereafter, the Small Business Act of 1942
established the Smaller War Plants Corporation (SWPC) to help small firms play
essential roles in the defense industry during World War II. The SWPC was a temporary
wartime agency whose activities ended in 1946 when its functions were transferred back
to the RFC and an Office of Small Business within the Department of Commerce (Office
of Advocacy, 2016).
Congress also passed the Small Business Mobilization Act of 1942, which
recognized that small businesses lacked the economies of scale necessary to compete
with big companies. It allowed a price differential to encourage smaller businesses to
operate in support of war efforts. In addition, the Armed Service Procurement Act of
1947 mandated that “… a fair proportion of total Federal purchases and contracts be
placed with small business concerns in both peacetime and wartime” (US Navy, 2019).
When the Korean War began, Congress created another wartime agency, the Small
Defense Plants Administration (SDPA), in 1950, whose functions were similar to those of
the SWPC. Congress also passed the Defense Production Act of 1950, which stated,
“Small business concerns shall be given the maximum practicable opportunity to

26
participate as contractors, and subcontractors at various tiers, in all programs to maintain
and strengthen the Nation’s industrial base and technology base undertaken pursuant to
this chapter” (OLRC, 1950).
By 1952, the RFC was no longer considered necessary; however, to maintain the
support of small businesses, President Eisenhower signed the Small Business Act of 1953.
The Small Business Act created the Small Business Administration (SBA) to centralize
programs and services to support smaller businesses (67 Stat. 1953) in a single agency.
However, a substantial unmet need was still evident. The fundamental interests of SMEs,
such as assuring the competitive strength of their businesses and acquiring more
opportunities for free market entry, were greatly influenced by the legislative, regulatory,
and administrative procedures of government in which they were rarely represented.
Small firms lacked the voice enjoyed by larger enterprises that could afford to position
their officials in Washington and participate in business organizations and trade
associations. This imbalance was addressed when President Nixon signed Executive
Order 11518, “providing for the increased representation of the interests of small
business concerns before departments and agencies of the United States Government”
(Executive Office of the President, 1970, Office of Advocacy, 2016). The executive
order stipulated that the SBA,
… as the spokesman for and advocate of the small business community,
shall advise and counsel small business concerns in their dealings with the
departments and agencies of the United States Government to the end that
the views of small business concerns will be fully heard, their rights fully
protected, and their valid interests fully advanced.
In 1974, the role of the SBA was further strengthened through Public Law 93-386
by assigning a special office, the Chief Counsel for Advocacy, dedicated to SBA’s

27
advocacy role. However, the activities, staffing, or administrative powers of the office
were not clarified until a second law, Public Law 94-305, was signed by President Ford
in 1976 to clarify and strengthen the roles of the Chief Counsel. The Chief Counsel
would be appointed by the President and confirmed by the United States Senate. As
described in the Act,
The Office of Advocacy will, if we are successful, be a key point of
effective spokesmanship and policy leverage for small business within the
executive branch of the Government…. There is surely challenge enough
here for anyone with an appetite for hard work and a zest for
entrepreneurship of ideas and program policy innovation. (Milton D.
Stewart, first Chief Counsel for Advocacy (1978 -1981))
Public Law 94-305 provided the basic legislative framework under which
advocacy operates today. The Office of Advocacy of the United States Small Business
Administration (SBA) serves as an independent voice for small businesses within the
federal government.
Maybe no other single law, except perhaps that giving Advocacy its basic charge
impacted on the office’s mission and activities than the Regulatory Flexibility Act (RFA)
promulgated shortly thereafter. Implemented in 1980, the RFA responded to
dissatisfaction that federal regulation often had disproportionate adverse effects for many
smaller businesses. The new law stipulated that government agencies must consider and
mitigate, where possible, the impacts of their regulatory actions on small businesses
(Office of Advocacy, 2016). Yet that law faced a significant hurdle with changing
longstanding regulatory cultures at some agencies; cooperation, therefore, could not be
secured without some means of judicial review or punishment. To rectify this situation,
the Small Business Regulatory Enforcement Fairness Act of 1996 (SBREFA) was signed
by President Clinton in 1996. It added a method for RFA judicial review and directed the

28
inclusion of small businesses in the rulemaking process. President Bush also recognized
the importance of Advocacy’s participation early in the regulatory process and the need
for improved RFA compliance among some agencies. His Executive Order 13272, titled
Proper Consideration of Small Entities in Agency Rulemaking, stipulated that:
Each agency shall establish procedures and policies to promote
compliance with the Regulatory Flexibility Act, as amended…. Agencies
shall thoroughly review draft rules to assess and take appropriate account
of the potential impact on small businesses, small governmental
jurisdictions, and small organizations (Executive Office of the President,
2002).
2.3.2 Japan
Japan has 3.5 million SMEs. They account for 99.7% of companies and employ
more than 60% of all workers (SME Support Japan, 2017), creating essential employment
opportunities.
Many SMEs became established in the chaotic economic environment that
followed World War II. However, they often faced more challenges than larger
enterprises due to poor management capabilities, insufficient access to key technologies,
and restricted funding sources. In 1947, the Act concerning Prohibition of Private
Monopoly and Maintenance of Fair Trade, the Japanese Antimonopoly Act, and the Law
for Elimination of Excessive Concentration of Economic Power were introduced to
encourage a more diverse economy accessible to SMEs (SME Agency, 2005). To this
end, the Small and Medium Enterprise Agency (SMEA) in Japan was founded in 1948 as
an extra-ministerial bureau of the Ministry of Commerce and Industry under the guidance
of the General Headquarters of Allied Powers (GHQ). The SMEA was modeled on the
RFC in the United States. Charged to retard economic centralization, the SMEA

29
organized programs for SMEs into four categories: management support, financial
support, fiscal support, and commerce and regional support (Nakagawa, 2012).
A year later, the Small- and Medium-Sized Enterprise Cooperatives Act of 1949
was introduced to address certain of the social and economic disadvantages of SMEs.
The Act recognized that SMEs had a low societal profile because they typically operated
on a small scale, often as subcontractors or suppliers of larger enterprises (SME Agency,
2005, Bala Subrahmanya, 2008). The purpose of this Act stipulated in Article 1 of the
Act was
… to provide for the organizations necessary for persons engaged in a
small- and medium-sized commercial business, industrial business, mining
business, transport business, service business or any other business and
other persons, such as workers, to engage in business in a cooperative
manner based on the spirit of mutual support, and to secure the
opportunity for these people to conduct fair economic activities, thereby
promoting their voluntary economic activities and achieving an
improvement in their economic status (Act No. 181. 1949).
The Act provided indirect/non-monetary support to SMEs or foundations that
enabled their members to create officially recognized cooperative organizations that
would improve the economic opportunities of the SMEs while still encouraging their
independence. Cooperatives proliferated; by 1963, 23,851 corporate cooperatives could
be identified (Yoshimura and Kato, 2007).
In 1953, the organization and roles of the Chamber of Commerce and Industry, an
incorporated body based on the Civil Code of that time, were strengthened by obtaining
legal status based on the Chamber of Commerce and Industry Law. A number of
additional post-war measures were introduced as well. They included essential tools to
support SMEs in such areas as access to financial resources (the establishment of the
National Life Finance Corporation in 1949 and the Japan Finance Corporation for Small

30
Business in 1953), taxation benefits (the Blue Returns System in 1949), and management
consulting and guidance services (the Management Consulting System and the
Consulting Desk for SMEs in 1948, and the Registration System of SMEs Consultant in
1952). Detailed descriptions of these support systems are beyond the scope of the
literature review here but are described in some detail elsewhere (SME Agency, 2005).
The Japanese government further increased its focus on SMEs as the country
grew rapidly throughout the 1960s. At that time, a pyramid structure of business was
evident in manufacturing sectors producing automobiles, machine tools, and textiles, with
SMEs on the bottom. The productivity and salaries of employees in SMEs were low
compared to larger enterprises (Economist Intelligence Unit, 2010, Yoshimura and Kato,
2007). The SME Basic Law, enacted in 1963, recognized an SME as a disadvantaged
group requiring additional support programs. The Small and Medium Enterprise Agency
explained the SME Basic Law as follows:
The SME Basic Law was designed to (a) eliminate SMEs disadvantages
derived from economical and social restrictions, (b) support their self-help
efforts, (c) improve their productivity and trading conditions to rectify the
dual-structured gap, and (d) serve to improve the social status of their
employees. … The SME Basic Law shows a basic idea of measures for
SMEs. And then specific measures are decided and implemented under the
SME Basic Law (SME Agency, 2005).
Many startup companies entered the commercial sphere during the high-growth
period of the 1970s, but numbers fell soon thereafter, suggesting that entrepreneurship
was stagnating. In the 1980s, more than 60% of SMEs in the manufacturing sector were
subcontractors that maintained their business by developing good relationships with
larger enterprises that gave them work. Subcontracting SMEs were then vulnerable when
the larger enterprises faced difficulties, as they did in the face of the oil crisis, economic
depression, and era of the weakening Japanese yen. Previously, SMEs were regarded as

31
vulnerable entities requiring special social policies to remedy the disadvantages that they
faced. However, the maturation of the economy, the diversification of consumer needs,
the IT revolution, and the progress of globalization were trends making clear that the
policies and tools of the 1960s were no longer appropriate in the 1990s (SME Agency,
2005). Therefore, in December 1999, GOJ restructured the SME Basic Law to expand
the range of SMEs eligible for support and enhance that support for startups and SMEs
engaged in innovation. To encourage the vigorous growth of independent SMEs, it
aimed: 1) to promote business innovation, new business startups, and other self-
sustaining enterprises; 2) to strengthen the management base of SMEs by enriching
business resources; and 3) to facilitate their ability to adapt to economic and social
changes by offering a safety net (Yasuda, 2009, SME Agency, 2005).
To promote business innovation and assist in fund-raising, new capital markets
(MOTHERS from November 1999 and Nasdaq Japan from June 2000) were created and
gave SMEs new funding opportunities. A credit guarantee system was introduced, and
the bond market was made accessible to SMEs. The government also allocated funding
that could support research conducted by SMEs, with a Japanese version of the SBIR
system that was established to offer consistent support up to the commercialization phase
of products. However, SMEs often lacked the resources to manage a business and
procure outside resources because of their small size, so other programs aimed to
supplement those scarce resources. First, the GOJ created support centers with “one-
stop” services to provide funds and infrastructure support in areas such as human
resource management, IT implementation, and technical assistance at national,
prefectural, and local levels. Emergency relief measures also were put into place to

32
protect SMEs in the face of unexpected events, such as a sudden change in the trade
structure (i.e., exchange rate), restrictions in the supply of raw materials, natural disaster
or the collapse of a large enterprise on which the SME depended. These new measures
include, but were not limited to, financial measures to provide disaster relief and
measures to avoid chain-reaction bankruptcies (SME Agency, 2005).
The new policies also aimed at increasing the number of partnerships and
cooperatives among SMEs in the same sector among SMEs across sectors and with
volunteer organizations. These relationships were thought to empower the SMEs to
create new technologies and widen access to needed resources through exchange
programs and alliances with industry, academia, and government. The substantial
revisions of the SME Basic Law thus attempted to transform SMEs into important
enterprises that could drive the economy, rather than impoverished entities requiring
protection. However, the financial resources to realize these objectives were still quite
limited (Yoshimura and Kato, 2007).
The collapse of the bubble economy and subsequent recession in the 1990s forced
some large Japanese enterprises to transfer their production overseas. Some SMEs also
considered similar measures; establishing operations in jurisdictions such as East Asia
became a crucial business strategy for many Japanese SMEs. To support such
diversification, many programs to support SMEs as they expanded their overseas
investment and trade were put into place by private training enterprises, financial
institutes, and government organizations such as the Japanese External Trade
Organization (JETRO) and the Organization for Small and Medium Enterprises and
Regional Innovations, Japan (SMRJ) (Yoshimura and Kato, 2007).

33
In 2002, new legislation, the Act for the Support of Small and Medium-sized
Enterprise Challenges (Act No. 110. 2002), was introduced to amend the Act for
Facilitating New Business Activities of Small and Medium-sized Enterprise of 1999 (Act
No. 18. 1999). It allowed a new kind of enterprise created with startup capital of only
one yen (¥1) rather than the minimum ten million yen (¥10 mil) required to start a
traditional company and provided loan guarantees and direct aid through state-affiliated
financial institutions.
By 2006, the Ministry of Economy, Trade, and Industry (METI) had implemented
various measures called out by new policies in five areas/pillars: 1) supporting
manufacturing SMEs in high-tech areas to expand manufacturing capacity in Japan; 2)
securing and developing human resources for SMEs; 3) supporting SMEs as they
addressed the challenges of new business development and reorganization; 4) facilitating
the financial security of SMEs; 5) revitalizing shopping districts and city centers.
Furthermore, the Act of Promotion of Business Activities by Small and Medium-sized
Enterprises Utilizing Regional Resource in 2007 (Act No. 39. 2007) attempted to develop
business demand for SMEs by utilizing resources, such as production technology,
agricultural/forestry/fishery products, and tourist resources, derived from local industries
as designated by prefectural governments to conduct new business activities. The
Japanese cluster policy initiative was guided centrally and was divided into “industry”
and “intellectual” cluster initiatives. METI promoted “regional industrial clusters”
through a program launched in 2001 involving 19 sites, 5,000 companies, and 200
universities. That program now supports academia-industry-government round tables,
information sharing, and workshops, as well as helping to coordinate cluster activities

34
and programs. Government investments in cluster policies are relatively modest to date,
so only a small percentage of Japan’s industrial enterprises are officially engaged as
participants. However, these initiatives may be significant if they create a new model
that can be replicated by local industrial cluster organizations across Japan (Shapira,
2008).
2.4 Regulatory Agency's Support for Promoting SMEs in Medical Product Business
Sector
Most of the initiatives described above were designed to support a range of
innovative organizations and activities that could be used by academic organizations and
SMEs developing medical products but were not exclusively designed for that group. To
understand the special initiatives designed to foster the development of innovation in the
medical products sector, it is essential to look more specifically at laws and regulations
that influence the development of medical therapies, typically administered through
government agencies that oversee those activities. These agencies include the National
Institutes for Health (NIH), the FDA in the United States, the Japan Agency for Medical
Research and Development (AMED), and the PMDA in Japan.
2.4.1 The United States
For more than one hundred years, United States laws have been in place to ensure
the safety of medical products, the most important of which was the Food, Drug, and
Cosmetic Act of 1938. This Act and its multiple subsequent amendments increased the
regulatory requirements and level of oversight under which medical product companies
could operate (FDA, 2011). They often served as a brake on innovative activities
because of the higher costs to meet new requirements. A review of this history is well

35
documented elsewhere (FDA, 2011, FDA, 2018e, FDA, 2019b). The specific issues of
importance to this dissertation relate to changes in the innovation climate for medical
products over the last 25 years. Two governmental bodies have been key to fostering the
environment for translational activities in the United States. These are the National
Institutes of Health (NIH) and the Food and Drug Administration (FDA).
2.4.1.1 NIH’s Support for Promoting SMEs
The NIH is the primary federal agency to promote biomedical research. Its
mission is to “seek fundamental knowledge about the nature and behavior of living
systems and to apply that knowledge to enhance health, lengthen life, and reduce illness
and disability.” The NIH invests approximately $39.2 billion annually in medical
research. More than 80% of that funding is used for almost 50,000 competitive grants to
over 300,000 researchers at more than 2,500 universities, medical schools, and other
research institutions in the United States and worldwide (NIH, 2017). The NIH also
administers two essential programs – the Small Business Innovation Research program
(SBIR) and the Small Business Technology Transfer program (STTR) – both critical for
supporting translational activities.
The United States Congress established the SBIR program in 1982 and the
STTR program in 1992 with a goal……to support scientific excellence and
technological innovation through the investment of Federal research funds
in critical American priorities to build a strong national economy… one
small business at a time (SBIR, 2016b).

Under these programs, eligible government agencies must set aside a portion of
their extramural budget for small domestic companies conducting innovative R&D
activities with strong commercial potential. Both programs fund projects in two to three
tranches, including 1) a Phase I grant, easier to obtain, that supports feasibility-related

36
experimental study or theoretical research/research and development (with awards
typically less than $150,000 total costs for six months for SBIR and one year for STTR);
2) a larger Phase II grant for continued research/research and development efforts (with
awards normally less than $1,000,000 total costs for two years); and, for some agencies, a
Phase III grant to support commercialization (SBA, 2017). The SBA serves as the
coordinating agency for the SBIR and STTR programs (NIH, 2016b).
SBIR – The SBIR program is a competitive awards-based program for small
companies to develop the commercial potential of their innovations. It has four specific
goals: 1) to stimulate technological innovation; 2) to meet Federal research and
development needs; 3) to foster and encourage participation in innovation and
entrepreneurship by women and socially or economically disadvantaged persons, and 4)
to increase private-sector commercialization of innovations derived from Federal R/R&D
funding. Eleven federal agencies with extramural R&D budgets of more than $100
million are now required to allocate 3.2% of those budgets to the programs (NIH,
2016b). In FY2017, these obligations amounted to approximately $2.6 billion, of which
approximately $2.0 billion (76%) were attributed to the Department of Defense (DoD)
(approximately $1.2 billion, 43%) and the Department of Health & Human Services
(HHS) (approximately $886 million, 33%) (SBA, 2017).
STTR – Modeled after the SBIR program, STTR was created by the Small
Business Technology Transfer Act of 1992 to bridge the gap between basic research and
commercialization (National Academies of Sciences Engineering and Medicine, 2015).
Like the SBIR program, it aims: 1) to stimulate technological innovation and 2) to
increase private sector commercialization of innovation derived from federal R&D.

37
However, it uniquely calls out the third goal, 3) to foster technology transfer through
cooperative R&D between small businesses and research institutes (Table 3). To this
end, the SME must partner formally with a research institution. Every year, federal
agencies with budgets exceeding $1billion in extramural R&D are required to reserve
0.45% of the extramural research budget for STTR awards to SMEs (SBIR, 2016a). In
FY2017, the total STTR obligations amounted to approximately $367 million, of which
approximately $287 billion (78%) were attributed to the DoD (approximately $161
million, 44%) and the HHS (approximately $127 million, 34%) (SBA, 2017).
Table 3: Major Similarities and Differences between SBIR and STTR
Programs
SBIR STTR
Phase 1 duration 6 months 12 months
Number of participating agencies 11 5
Phase 1 award size Up to $150,000 Up to $150,000
% of Agency’s extramural R&D budget [FY16] 3.00% 0.45%
IP allocation agreement required No Yes
Nonprofit RI or FFEDC participation required No Yes
PI employment Small business Small business or PI
Applicant Small business Small business
Source: SBIR/STTR: Course 1. Program Basics: Tutorial 3 (SBIR, 2019)

Other NIH Programs include 1) the NIH SBIR/STTR Niche Assessment Program,
open to all active HHS SBIR/STTR Phase I awardees, to provide industry analysis and
information so that SMEs can strategically position their innovations in the marketplace;
2) Corp™ at NIH, to provide scientists in life science and biotechnology with practical
entrepreneurial training; 3) the NIH SBIR/STTR Commercialization Accelerator Program
(CAP), to train Phase II awardees about gaining regulatory approval by the FDA and
reimbursement from Centers for Medicare & Medicaid Services and private insurance
(NIH, 2016a). NIH also funds a number of small projects. Included is an R25 research
grant “to support to develop or implement a program as it related to a category in one or

38
more of the areas of education, information, training, technical assistance, coordination,
or evaluation” (NIH, 2019a). One of the R25 grants titled NIH Bluepoint for
Neuroscience Research Education Program on Translational Devices funds courses to
give senior post-doctoral fellows, academic researchers, clinician-scientists, and small
business entrepreneurs a more systematic education regarding medical devices
development and translation.
2.4.1.2 FDA’s Support for Promoting SMEs
FDA is responsible for advancing the public health by helping to speed
innovations that make medical products more effective, safer, and more
affordable and by helping the public get the accurate, science-based
information they need to use medical products and foods to maintain
and improve their health (FDA, 2018a).

This three-part mission gives the FDA a mandate to foster innovation as it advises
on the management of investigational and market submissions for medical products. It
can nudge them to advocate for laws and regulations that create an innovation-friendly
environment. In 2012, President Obama reemphasized FDA’s role in “promoting
innovation to speed patient access to safe and effective products; increasing stakeholder
involvement in FDA processes; and enhancing the safety of the drug supply chain” by
signing the Food and Drug Administration Safety and Innovation Act (FDA, 2018c),
which drove an internal reorganization in ways that could adapt to the rapidly changing
science now typical for FDA-regulated industries.
Following Presidential Executive Order 13272 Proper Consideration of Small
Entities in Agency Rulemaking of August 13, 2002, the FDA also issued procedures and
policies to ensure that the rulemaking process considers the potential impact of its draft
rules on small businesses, small governmental jurisdictions, and small organizations

39
(FDA, 2016b, Executive Office of the President, 2002). It identified four barriers for
small businesses: 1) limited financial resources; 2) lack of understanding on how to
effectively engage with FDA staff or utilize available resources; 3) lack of experience in
product development (e.g., clinical trial design, scientific standards); and 4) lack of
experience with the regulatory application process. To address these issues, at least
within its sphere of control, the FDA has focused on helping SMEs to understand
regulatory review processes and requirements, supporting them by providing information
about FDA laws, and directing them to helpful resources such as guidance documents and
training materials (FDA, 2013).
In addition, the FDA has a few more tangible ways of assisting small businesses.
First, the FDA provides user fee discounts for qualified SMEs based on the Prescription
Drug User Fee Amendments, Biosimilar User Fee Act, Generic Drug User Fee
Amendments, and Medical Device User Fee Amendments. The small business
qualification criteria and type of discounts are not the same. For example, the
Prescription Drug User Fee Amendments VI allows the FDA to grant fee waivers for pre-
authorized SMEs that are submitting their first human drug application (21 USC 379h(d))
and provides an application fee exemption for orphan-drug applications (21 USC
379h(a)(1)(F)). Likewise, under the Biosimilar User Fee Act II (Title IV of the FDA
Reauthorization Act of 2017), the FDA waives the application fees for pre-authorized
SMEs submitting a first biosimilar product application if they do not have another
product that has been approved under a human drug application or a biosimilar.
Initially, no small business reduction or waiver was provided in the Generic Drug
User Fee Amendments I program; however, in the Generic Drug User Fee Amendments

40
II effective on October 1, 2017, the FDA has established “a tiered fee system to account
for the size of the business. Small Abbreviated New Drug Application (ANDA) holders
(with 1-5 approved ANDAs) will pay one-tenth of the large ANDA holder fee, medium
ANDA holders (with 6-19 approved ANDAs) will pay four-tenths of the large ANDA
holder fee, and large ANDA holders (with 20+ approved ANDAs) will pay the full
ANDA holder fee” (FDA, 2017c). Similarly, the Medical Device User Fee Amendments
also provide qualified and certified small businesses a substantial reduction in most of
their user fees when submitting applications for medical devices (FDA, 2018d).
The FDA has also participated in the SBIR Program as part of the HHS.
Researchers propose their research ideas to SBIR and STTR Omnibus grant solicitations
after speaking to an HHS SBIR/STTR program manager before applying relevant to the
FDA (NIH, 2019b). Additional incentives for medical product development that are not
designed exclusively for small businesses are also including but are not limited to 1) the
Orphan Products Grants Program in Office of Orphan Products Development, 2)
incentives of additional marketing exclusivity under the Best Pharmaceutical for Children
Act, and 3) a priority review of a drug under the Neglected Tropical Disease Priority
Review Program.
A potentially important initiative by the FDA has been establishing a dedicated
small business assistance arm or program in each of its medical product Centers and
regional offices.
These include the establishment of the Division of Industry and Consumer
Education (DICE, formerly known as DSMICA) in the Center for Devices
and Radiological Health (CDRH), CDER Small Business and Industry
Assistance (SBIA), Assistance Programs in the five FDA regional offices,
and the creation of small business assistance offices in each of the Centers
(FDA, 2016c).

41

The Division of Small Manufacturer, International, and Consumer Assistance
(DSMICA) was created by the CDRH, as required by the Medical Device Amendments
of 1976, to provide technical and regulatory assistance to the industry, particularly SMEs,
to help them comply with regulatory requirements for medical devices. On April 1,
2014, the FDA renamed the DSMICA to the acronym DICE with the following mission:

To educate our stakeholders with understandable and accessible science-
based regulatory information about medical devices and radiation-
emitting electronic products.

Our stakeholders include the medical device industry, consumers,
patients, healthcare providers, FDA colleagues, and other Federal, State,
and local government agencies.

To achieve our mission, we stay current on regulatory issues and new
scientific advances, anticipate our stakeholder needs and ensure that the
information we disseminate is accurate, timely, and appropriately targeted
for each audience (FDA, 2016a).

As part of its role, personnel at DICE answers questions by phone and email from
developers and consumers of medical devices and radiation-emitting electronic products.
They also develop educational resources related to the FDA regulations and policies for
the FDA website. For example, on the FDA website, DICE sets up the “Device Advice:
Comprehensive Regulatory Assistance” page as CDRH’s primary text-based resource to
explain many aspects of its laws, regulations, guidance, and policies related to medical
devices. CDRH Learn, also on the CDRH web page, serves as an educational site to
provide learning modules, including videos, audio recordings, and slide presentations,
about many topics related to medical devices and radiation-emitting products such as
product registrations and pre-market/post-market topics.

42
For the pharmaceutical products, Small Business and Industry Assistance (SBIA),
in the Center for Drug Evaluation and Review (CDER), likewise supports small
pharmaceutical businesses and industry to understand the regulatory aspects of human
drug products and clinical research (Table 4). The mission of the CDER SBIA program
is “to engage with small pharmaceutical business and industry by providing timely and
accurate information on human drug development and regulation” (FDA, 2021b). Its
website hosts links to various information and educational materials relating to FDA
laws, regulations, and guidance affecting SMEs (FDA, 2021b).
Table 4: Nature of CDER SBIA Outreach Services
Services Description
Direct Communication Services Respond to SMEs or industry inquiries via phone and email.
Webinars Offer webinars on various topics of interest to SMEs and industry
Conference and Workshops Host several conferences each year, including Regulatory Education
for Industry (REdI) conferences.
CDERLearn Offer web-based learning tutorials on the CDER Small Business and
Industry Education Series platform.
Small Bis Buzz Send email updates regularly to educate the industry on new
regulations, guidance, and meetings.
CDER Small Business
Chronicles
Publish the electronic newsletter every other month, highlighting
various regulatory issues.
Source: About CDER Small Business and Industry Assistance (SBIR) (FDA, 2021b)

For the biologics industry, the Center for Biologics Evaluation and Research
(CBER) established a Manufacturers Assistance and Technical Training Branch
(MATTB) to answer questions and provide information about CBER regulated products
for the industry and public (FDA, 2019c). This service is not targeted at SMEs; however,
the MATTB website provides similar information to the CDER SBIA website. The FDA
has also attempted to improve communication between the FDA and industry by
launching the “FDA Basic for Industry” in January 2011 to explain the regulatory process
in a more user-friendly format (FDA, 2017d). Furthermore, the FDA offices have
provided technical assistance to small enterprises, hosted exchange meetings to hear the

43
views and perspectives of small businesses, conducted educational workshops, developed
educational materials, and established an accessible and efficient channel through which
small businesses can obtain information from the FDA (FDA, 2016c).
2.4.2 Japan
In Japan, two organizations are responsible for approving and registering medical
products and thus have a special role in promoting innovation and commercialization
from universities and SMEs. The Ministry of Health, Labour, and Welfare (MHLW) is
responsible for creating policies and systems that guide the evaluation of the safety,
efficacy, and quality of medical products. It also formally approves the marketing
applications of medical products after being recommended for approval by an
independent administrative agency, the Pharmaceuticals and Medical Devices Agency
(PMDA). Under the Act on the Pharmaceuticals and Medical Devices Agency, the
PMDA was established in April 2004 as an independent administrative agency with non-
civil service status following the Reorganization and Rationalization Plan for Special
Public Corporations approved in a Cabinet meeting in 2001. The PMDA focuses on
three key service areas: 1) relief services for people suffering from adverse health effects;
2) product reviews of medical product approval based on the quality, efficacy, and safety
data submitted; and 3) safety measures by collecting and evaluating post-marketing data
and providing patients and healthcare professionals with reliable information. It provides
these three services in an integrated manner through a “safety triangle” system shown in
Figure 1 below (PMDA, 2019, Roberts and Stokes, 2015).

44
Figure 1: PMDA’s Safety Triangle / Three-Pillar System

Source: PMDA Profile of Services (PMDA, 2019)

As part of its activities, the PMDA reviews applications for market authorization
from companies developing medical products and then submits its report to the MHLW
for subsequent approval (Roberts and Stokes, 2015).
The Japanese regulatory system is rigorous. However, it was challenged by
“drug/device lag” for many years, a situation in which the approval of products for the
Japanese market took much longer than that for the United States or Europe. This lag
was believed to stem from two factors: delays in submitting marketing applications to the
Japanese agency (development lag) and slow reviews at the regulatory agency (review
lag). To address this issue, the MHLW and the Ministry of Education, Culture, Sports,
Science and Technology (MEXT) collaborated on a 5-Year Strategy for the Creation of
Innovative Pharmaceuticals and Medical Devices in April 2007. It called for: 1)
intensive investment of research funds; 2) development of venture businesses; 3)
development of an environment for clinical research/trials, including the facilitation of

45
clinical trials by developing a nationwide network; 4) cooperation with Asian countries;
5) acceleration and quality improvement of examinations; and 6) proper evaluation of
innovative products (Cabinet Office, 2009). PMDA also strengthened its review system
by tripling the number of reviewers by 2009 and enhancing its consultation system
(PMDA, 2019).
One of the newer initiatives arising from that initiative was the implementation of
consultations for those seeking PMDA’s guidance to ensure that their development or
regulatory strategies were appropriate and in line with PMDA’s expectations before
moving forward (Hosoda and Ishiji, 2015). First designed for pharmaceutical products,
the consultation menu was extended after 2007 to meet the various needs of companies
developing new medical devices and cellular or tissue-based products using state-of-the-
art technology. Furthermore, after 2009, the PMDA offered prior assessment
consultations, in which PMDA’s reviewers assess data related to the quality, efficacy,
and safety of a product in the pre-submission phase. This consultation process forms part
of the product/application review once the application is submitted (PMDA, 2019). The
PMDA also provides simpler consultation services to address logistical requests for
information, such as confirmation of application category, pre-consultation meetings to
determine key issues to base the broader consultation meetings, and general meetings to
orient the client to the regulatory system in general. Table 5 below shows PMDA’s
current consultation services menu for pharmaceutical products.

46
Table 5: Category of PMDA Consultation Services concerning Clinical Trials
and NDA for a New Drug
Category Brief Description Fee (JPY)
1. Consultation on
pharmaceutical
procedures
Consultation about the clinical trial procedures for a new
drug application (NDA). No data evaluation will be
included.
¥150,900
2. Consultation
before the start of
an expanded drug
trial
Consultation on extended clinical trial(s), based on safety
information obtained by the time of consultation, the
applicant determines there is no issue to ensure patient safety
and would like to discuss the following changes from the
original/prior clinical studies.
• Change on inclusion/exclusion criteria
• Testing items, frequencies of testing, testing duration,
etc.
¥261,500
3. Consultation on
bioequivalence
testing, etc. of
drugs
Consultation on cases that are not classified as Phase I-III
clinical trials or quality/safety consultations but require data
evaluation, such as determination of application
classification or evaluation of bioequivalence studies.
¥600,400
4. Drug safety
consultation
Consultation focused on non-clinical studies, including
pharmacokinetics, pharmacodynamics, toxicities, etc.
¥1,925,300
5. Drug quality
consultation
Consultation on quality, including standards/test methods,
stability, manufacturing process, etc.
¥1,596,500
6. Pre-Phase I study
consultation for
drugs
Consultation on the rationale for conducting the first trial
with human subjects and study design
¥4,578,500
*¥3,441,000
7. Pre-Phase IIa study
consultation for
drugs
Consultation specific to dose-finding study with a small
number of subjects based on the result of Phase I study
¥1,752,800
*¥1,320,200
8. Pre-Phase IIb study
consultation for
drugs
Consultation specific to study to be conducted after Phase I
study completion and before the clinically recommended
dosage is determined.
¥4,784,300
*¥3,592,900
9. End of Phase II
study consultation
for drugs
Consultation on the design of Phase III study after the
clinically recommended dosage is determined
¥9,497,400
*¥7,134,300
10. Pre-application
consultation
Consultation on contents of NDA when clinical studies end
or about to end
¥9,497,400
*¥7,130,100
11. Protocols of post-
marketing clinical
trials
Consultation on the protocols of post-marketing clinical
trials required for re-evaluation or re-examination ¥2,557,000
12. Completion of
post-marketing
clinical trials
1) Preparation of application materials, etc.
For the purpose of reevaluation and reexamination, when
preparing materials for application at the stage where clinical
trials and use-results surveys that have been conducted since
the time of approval as well as newly conducted clinical
trials and use-results surveys have been completed or are
about to be completed, cases concerning how to compile the
application materials and the sufficiency of the materials.
2) Review of approval conditions, etc.
In cases where the review of approval conditions, etc. is to
be promptly evaluated, and a report is to be prepared.
¥2,557,000

¥1,269,800

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Category Brief Description Fee (JPY)
13. Additional
consultation
• The second and subsequent consultations to be
conducted prior to the Pre-Phase II consultation after the
pre-Phase I
• The second and subsequent consultations after the pre-
Phase IIb consultation but before the end-of-Phase II
consultation
• The second or subsequent consultations before pre-NDA
consultation after completion of the end-of-Phase II
study consultation
• The second or subsequent consultations to be conducted
between pre-NDA consultation and submission of NDA
• The second and subsequent consultations to be
conducted after consultation on reevaluation/review the
clinical trial plan and before consultation post-
reevaluation/review clinical trial
• The second and subsequent consultations conducted
after the consultation of the post-reevaluation/review
clinical trial and before the completion of the
reevaluation/review
¥2,889,700
*¥2,171,200
14. Consultation for
the application plan
using the registry
data
When the applicant wishes to use the registry to evaluate the
efficacy and safety of a specific item in an application for
approval or reevaluation, the applicant should consult with
the registry about the appropriateness of using the registry in
accordance with the purpose of use and the sufficiency of the
evaluation items. It does not matter whether the registry has
been established or is being established
¥980,300
*For orphan drugs
Source: An Excerpt from PMDA Website (translated into English and partially modified) (PMDA, 2021e)
The PMDA also introduced three new consultation services on April 1, 2020: 1)
development pipeline meeting, to allow manufacturers to share information about their
product under development; 2) consultation for innovative pharmaceutical manufacturing
technologies, to discuss quality control/assurance strategies for new production
technologies; and 3) consultation for pharmaceutical database utilization, to obtain advice
for businesses mulling the use of databases for drug filing and re-examination requests to
assure quality and compliance (Pharma Japan, 2020a, Pharma Japan, 2020b).
By 2010, the PMDA was well into its rejuvenation program when the Japanese
Cabinet issued the “New Growth Strategy – Blueprint for Revitalizing Japan.” The New
Growth Strategy set forth strategies to regain a “strong economy” that might lift Japan

48
from its 20-year economic slump. It identified seven growth areas: 1) green innovation;
2) life innovation; 3) the Asian economy; 4) tourism and the regions; 5) science-and-
technology and IT-oriented nation strategy; 6) employment and human resources; and 7)
the financial sector. Two of its strategies are particularly relevant to this research. The
“life innovation” growth area set targets for 2020 “to foster industry growth to meet the
demand for medical nursing care, and other health-related services and create jobs;
roughly ¥50 trillion in new markets and 2.84 million new jobs” (Prime Minister of Japan
and His Cabinet, 2010). More specifically,
… we will promote research and development of highly safe, superior, and
innovative pharmaceuticals and medical and nursing care technologies
from Japan. We will advance unified approaches among industry,
government, and academia, foster drug development ventures, and
promote research, development, and application in a number of fields.
These include new drugs, regenerative medicine and other state-of-the-art
medical technologies, remote medical treatment systems making full use of
information and communications technologies, the use of manufacturing
technologies to improve personal mobility for the elderly, and medical and
nursing care robots. As prerequisites, we will work to resolve the drug and
device lag as an urgent issue, improve the clinical testing environment,
and expedite drug approval decisions (Prime Minister of Japan and His
Cabinet, 2010).
Regarding “science-and-technology and IT-oriented nation strategy,” the 2020
targets were also directed at the activities of universities and SMEs:
… Increase the number of universities and research institutions that lead
the world in respective fields. … Encourage utilization of intellectual
property possessed by small and medium-sized enterprises. … Increase
public- and private-sector investment in research and development to over
4% of GDP (Prime Minister of Japan and His Cabinet, 2010).
These new governmental initiatives appeared to recognize that universities and
SMEs are places where innovation might yield commercializable products. They were
being put into place when Japan’s national universities were also undergoing change to
promote collaborations and increase research competitiveness as a follow-up to MEXT’s

49
2001 radical reform plan for universities (Tsubouchi et al., 2008). That plan called for
three significant changes: the reorganization of national universities, the implementation
of improved business methods in national universities through a corporatization initiative,
and the introduction of competitive mechanisms in the university sector (Yamamoto,
2004). As a result, in 2004, national universities became “incorporated” and were given
control of the intellectual property rights for their university-based innovations
(Kandachi, 2004). Under the new “incorporated” model, researchers in national
universities were mandated to report all of their inventions to the university. The
university would then decide how to share license royalties among the inventor, the
department, and the university. Such transparency was viewed as a way to increase
private investment in academic research. However, the reform measures have had only
modest effects. Even though basic research in Japan has had substantial governmental
and public investment for seed discovery and the development of medicines and
biologics, amounting to ¥1.3 trillion in 2011, few medical products have been approved
and made widely available in clinical practice for patients (Urushihara and Kawakami,
2014). Nonetheless, the number of collaborations between academia and industry has
increased significantly. As of March 2018, 2,093 companies have been established from
Japanese universities, 659 (31.5%) of which were life, biotech, health care, and medical
equipment companies (Nikkei Asian Review, 2018).
In June 2013, additional initiatives under the “Japan Revitalization Strategy” and
“Healthcare and Medical Strategy” were adopted to encourage the commercial
development of novel medical products seen as key to medical excellence and expansion

50
of Japan’s share of the global market. During the meeting of the Headquarter for
Healthcare and Medical Strategy Promotion in 2013, Prime Minister Abe stated:
As an important pillar of the growth strategy, concrete advances must be
made in the development of leading-edge medical technologies, including
regenerative medicine, for the realization of a society of good health and
longevity. … R&D in the medical field does not become trapped in the
vertically segmented bureaucracy of ministries and agencies.
Today, I hope we can decide on the related budget requests for the next
fiscal year. The budget requests will be compiled by the Headquarters for
Healthcare and Medical Strategy Promotion as the control tower for the
first time. ... In order to fully execute the growth strategy aimed at
revitalizing the economy, I ask that ministers work in concert toward the
promotion of R&D in the medical field (Headquarters for Healthcare and
Medical Strategy Promotion, 2013).
The Act to Promote Healthcare and Medical Strategies was enacted in May 2014.
Subsequently, the Japan Agency for Medical Research and Development (AMED), the
Japanese version of NIH, was established in 2015 as defined by the sequential steps
shown in Table 6 (Prime Minister of Japan and His Cabinet, 2018).
By 2015, Japan had put AMED in place, but, unlike NIH, it lacked a dedicated
campus. In addition, its budget, approximately $1.2 billion in 2015, was just a fraction of
NIH’s $30 billion. Also, three separate ministries – MEXT, MHLW, and METI – have a
say in how much that money is spent (AMED, 2019a, Normile, 2015). In 2019, with a
budget still set at $1.2 billion, AMED supported 2,416 projects in 27 countries (AMED,
2019a).

51
Table 6: History of the Establishment of AMED
Date Event
February 2013 The Office of Health and Medical Strategy was established
“In order for Japan to realize the world's most advanced medical technologies
and services and achieve a longer healthy life expectancy, at the same time aim to
foster medical, pharmaceutical and medical devices as strategic industries and to
become a pillar of Japan's economic revitalization, On February 22, 2013, the
‘Office of Health and Medical Strategy’ was established in the Cabinet
Secretariat” (Prime Minister of Japan and His Cabinet, 2020).
June 2013

Cabinet approved the establishment of “control tower” function for medical R&D, in
line with “Japan Revitalization Strategy: Japan is Back” policy strategy
“To push forward the development of practical applications of Japan’s
outstanding innovative medical technologies, establish control tower function
(Japanese version of NIH) which will create arrangements to ensure integrated
research management, the linking of research and clinical practice, and high
quality clinical research and clinical trials that meet international standards.” In
addition, university reforms to strengthen industrial competitiveness and
academia-industry collaboration and innovation of SMEs were discussed in this
strategy (Prime Minister of Japan and His Cabinet, 2013).
February 2014 Cabinet approved bills for the Act on Promotion of Healthcare Policy and Act on the
Independent Administrative Agency of Japan Agency for Medical Research and
Development.
May 2014

Act on Promotion of Healthcare Policy and Act on the Independent Administrative
Agency of Japan Agency for Medical Research and Development were enacted.
July 2014 Cabinet approves Healthcare Policy.
“The Policy was formulated under Article 17 of the Act on Promotion of
Healthcare Policy in accordance with the basic principles prescribed in Article 2
based on the basic measures prescribed in Articles 10 to 16 (promoting R&D,
improving the R&D environment, ensuring fair and appropriate operation for
R&D, establishing a better examination system for putting R&D results into
practical application, promoting the creation and oversees development of new
industry activities, promotion of education, securing personnel, etc.)” (Prime
Minister of Japan and His Cabinet, 2014).
April 2015 The Japan Agency for Medical Research and Development (AMED) was established.
Source: Modified from “AMED Overview – History” (AMED, 2017a)
A further step by the MHLW, taken in April 2017, was to establish a Venture
Support Strategy Office to promote seamless advancement from product review to
reimbursement by obtaining Japanese National Health Insurance coverage through the
Economic Affairs Division, Health Policy Bureau of the MHLW. This office supports
business needs for venture capital-backed medical-product companies by helping to
match medical ventures and subject matter experts/venture capitalists called registered
“supporters” via a portal site “MEDISO” (Medical Innovation Support Office) run by the
MHLW. These supporters include but are not limited to experts in R&D,

52
regulatory/health economics, IP, business/finance, marketing, and domestic and
international law (MHLW, 2019c, MHLW, 2019a).
2.4.2.1 PMDA’s Support for Promoting SMEs
The broad range of consultation opportunities developed over the past 20 years
has been an important part of the strategy for industry support. They allow interactions
with PMDA to discuss developmental concerns such as non-clinical or animal studies,
clinical trial requirements, or manufacturing issues for drugs, medical devices, and
cellular and tissue-based products. The PMDA held 162 clinical trial consultations for
new drugs in FY2004. In FY2020, the number of clinical trial consultations for new
drugs increased to 755. The median period from submission to approval for a new drug
(a regular item) in FY2004 was 22.4 months (median), a review time shortened to 11.9
months by FY2020 (PMDA, 2020a).
However, the consultation meetings above were most useful for those who could
already understand the general regulatory process. Universities, research institutes, and
venture capital groups with promising “seed” research or technologies in Japan still often
appear to be unfamiliar with development strategies that lead to commercialization of the
medical products (Masuyama, 2013). Thus, PMDA launched a new consultation system,
the Pharmaceutical Affairs Consultation on Research and Development (R&D) Strategy,
in July 2011, directed primarily at the needs of universities, research institutes, and
venture companies that have discovered promising “seed-stage” technologies (PMDA,
2016). This system offers guidance and advice on the design of nonclinical and early-
stage clinical studies needed from the final stage of drug candidate selection to proof-of-
concept, Phase II trials (Miyata et al., 2014).

53
Furthermore, in April 2017, the Pharmaceutical Affairs Consultation on R&D
Strategy was separated into two types of consultations – the Regulatory Science General
Consultation and the Regulatory Science Strategy Consultation (R&D). Regulatory
Science General Consultations mainly target SMEs and academia but do not exclude
other organizations such as large enterprises. This type of consultation service is
available not only at PMDA’s headquarters in Tokyo but also at the Kansai Branch in
Osaka and the PMDA Operation Center for Consultation on R&D Strategy in Kobe so
that SMEs would be able to access the service easily (Kondo et al., 2019, PMDA, 2019).
Differences between Regulatory Science General Consultation and Regulatory Science
Strategy Consultation (R&D) are shown in Figure 2 below. Also, in April 2018, PMDA
initiated a program of Collaborative Consultation on Practical Application on Innovative
Products. This program encouraged information-sharing with the Medical Innovation
Support Office, Economic Affairs Division, Health Policy Bureau of MHLW to assure
continued support for products from development and approval to reimbursement through
National Health Insurance price listing (PMDA, 2019).
Figure 2: Relationships underlying Regulatory Science General Consultation
and Regulatory Science Strategy Consultation (R&D)

Source: PMDA Profile of Services (PMDA, 2019)

54
Based on the “Japan Revitalization Strategy (2014 Revision),” another key
strategy, the “Strategy of Sakigake (Front Runner in Japanese),” was introduced by
MHLW in June 2014, in a further effort to position Japan at the forefront of innovative
medical product development (MHLW, 2014). A new expedited program, called the
Sakigake Designation System, prioritizes PMDA consultations and reviews to innovative
medical products at an early stage of development when certain eligibility conditions are
met. Moreover, the program attempted to ensure that the applicants’ manufacturing
system would supply a newly approved product consistently to clinical settings. To
facilitate the logistics related to a designated product, a PMDA manager is appointed to
be a review partner, called a “concierge.” The concierge serves as a liaison between the
MHLW and PMDA and manages the progress of product review, aiming to ensure a
standard review period of 6 months (PMDA, 2019).
2.4.2.2 AMED’s Support for Promoting SMEs
AMED also plays a significant role in supporting medical product translation
through its Department of Industrial-Academic Collaboration. The department supports
R&D projects with two stated goals: 1) to maximize the benefits of industry-academia
collaborations by fostering commercialization of “high-quality medical technologies that
are both innovative and beneficial to patients”; and 2) to strengthen clinical research
collaboration by requiring researchers to establish a collaboration or framework that
advances a promising new product from the “discovery of principles” phase to the
“establishment of the proof of concept in human subjects” phase and further
“confirmation of clinical effectiveness, including the clinical trial” phase.

55
The Department seeks to optimize outcomes and comprehensively accelerate
practical applications (AMED, 2017b). Thus, certain eligibility conditions must be
satisfied to qualify for its support: 1) the project must go beyond an “exploratory
element” to qualify; 2) R&D outcomes must be established as a technological seed to
address medical/clinical needs; and 3) R&D output must be relevant to the diagnosis,
treatment, and prevention of diseases or disorders, or prognosis management.
One of the programs directly applicable to medical device development by SMEs
has been provided by the Division of Medical Device Research, Department of
Industrial-Academic Collaboration of AMED. This program, the “Development of
Medical Devices through Collaboration between Medicine and Industry,” aims to foster
the medical device sector and improve the quality of medical treatment by promoting the
new participation of SMEs, venture businesses, and other parties with skills relevant to
the medical device industry. It also promotes cooperation between industry and medical
institutions to use the manufacturing capabilities at which Japan excels to develop and
program medical devices. In FY2018, the budget for this project was ¥3.04 billion
(approximately $28.2 million) (AMED, 2019c). As with some of the other AMED
programs, beneficiaries must work in consortia consisting of SMEs, manufacturing and
marketing enterprises, and medical institutions. Consortia gain a number of
opportunities. The program helps to support the costs of developing medical devices and
testing them in clinical trials and provides opportunities to gain advice from professional
consultants on topics ranging from IP protection to market development. SMEs can also
gain support from the Small Business Innovation Research Program with such benefits as

56
low-interest loans and reduction or waiver of patent fees from the Japan Finance
Corporation (AMED, 2019c).
Three programs, in particular, are designed with medical device translation in
mind.
1) The Development/Commercialization Program (subsidized) – AMED solicits
proposals for the commercialization of medical devices, from which it selects projects.
The chosen consortium will then be assisted as it moves from creating a prototype to
conducting non-clinical and clinical trials and the preparations for commercialization.
AMED personnel will assist with regulatory activities, commercialization, IP, and
technical aspects, mainly through consultations. Figure 3 below shows the concept of the
consortium approach. (AMED, 2019c)
Figure 3: Consortium Structure Envisioned by AMED

A consortium must consist of a medical institution, a manufacturing SME, and a manufacturer and marketing
enterprise. The grant includes not only costs related to R&D but also costs of clinical trials, regulatory consultations,
etc. During development, face-to-face advice from subject matter experts is given on issues on regulatory matters, IP,
sales, etc., based on the development stages. Also, a program supervisor and a program officer are assigned to manage
the approved project.
Source: Development of Medical Devices through Collaboration between Medicine and industry (AMED, 2019c)

57

2) Networks for Supporting Development of Medical Devices (contracted) – To
encourage better management of device development in the future, AMED fosters
collaboration networks between the national government and local regions so that smaller
medical device manufacturers and startups can gain access to various support systems,
including regulatory assistance and IP, technology and marketing advice, in an
interconnected way. The program allows accompanying consultants or subject matter
experts from medical institutions, consultancies, sales industries, academic societies, and
financial institutions, as well as specialized (e.g., PMDA, JETRO, etc.) and regional
support institutions (e.g., municipalities, Chamber of Commerce and Industry, etc.), to
provide seamless support/advice according to development stages (AMED, 2019c).
3) Others – AMED also offers a more targeted program called the “Acceleration
Transformative Research for Medical Innovation” to enhance industrial-academic
collaboration (AMED, 2019c). This program supports industry-academia collaboratives
whose innovative R&D can create new medical products for its rapid aging society. As
in other programs, universities, businesses, and hospitals must collaborate to develop the
“technology seeds” derived from academia. It has two progressive schemes, the
Acceleration Transformative Research for Medical Innovation Set-up (ACT-MS) scheme
and the Acceleration Transformative Research for Medical Innovation (ACT-M) scheme.
The purpose of ACT-MS is to “achieve the breakthrough points for application to
healthcare regarding challenging technology seeds in early stages.” That of ACT-M is to
“solve issues for practical use (commercialization) concerning technology seeds that
completed the exploratory stage.” Table 7 illustrates the differences between ACT-MS

58
and ACT-M. In FY2018, the budget for this project was ¥1.3 billion (approximately
$12.0 million) (AMED, 2019b).
Table 7: Differences between ACT-MS and ACT-M
ACT-MS ACT-M
Purpose Achieve the breakthrough points for
application to healthcare with regard to
"challenging technology seeds in early
stages."
Solve issues for practical use
(commercialization) with regard to
"technology seeds that completed the
exploratory stage.”
Contents With regard to the technology seeds
owned by universities and other related
organizations, industrial-academic
collaboration clarifies issues so as to
determine the possible applications to
healthcare. Furthermore, universities
and other related organizations conduct
studies (brush-up research) to establish
techniques (methods) to solve issues.
With regard to the technology seeds that
businesses aim at practical use,
industrial-academic collaboration
carries out R&D to establish proof of
concept (POC) targeting humans
(“verification of
possibilities/reproducibility” and
“demonstration of practicality” to link
to clinical evaluation).
Form of proposal A "joint proposal" by the university and
other related organizations that own
technology seeds and businesses or
entrepreneurship that wish to utilize
them (hereinafter referred to as a "set-
up business")
A "joint proposal" in which an R&D
system enabling clinical use and
verification has been constructed by the
university or other related organization
that owns technology seeds and
businesses aiming at its practical use.
Form of contract A direct contract between each
participating institution (universities
and other related organizations only)
and AMED (1-year contract)
A direct contract between each
participating institution and AMED (1-
year contract)
Role of businesses Share common understandings with
universities and other related
organizations and clarify the
breakthrough points for technology
seeds, then draw up and implement
plans to put them to practical use and
commercialization (business models)
after achieving the goals.
After defining the roles of the
universities and related organizations,
conducts their R&D as well. Although
it is not a matching fund, specify and
present the R&D costs, personnel
expenses, etc., that are planned to be
paid by businesses.
R&D period Within 2 years in principle
(approx. 1 year and 6 months)
(FY2018 to FY2019)
Within 3 years in principle
(approx. 2 years and 6 months)
(FY2018 to FY2020)
R&D system Industry-academia collaborative R&D
team
The project leader (the representative of
the application) should be a researcher
at a university or other related
organization.
Industry-academia collaborative R&D
team
The project leader (the representative of
the application) may be either from a
university or other related organization
or business.
Who is eligible to
receive assistance
for R&D costs
Universities and other related
organizations only
Universities, other related
organizations, and businesses
Source: Acceleration Transformative Research for Medical Innovation (AMED, 2019b)

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2.5 Status to Date
2.5.1 The United States
In the United States, award numbers are often used to illustrate the uptake of its
translational programs. Figure 4 and Figure 5 below show NIH SBIR Award applications
and success rates from 1998 to 2019. However, other metrics are difficult to find.
Figure 4: SBIR Grants, Phase I: Competing Application, Awards, and Success
Rate

Note: FY 2009 and 2010 exclude awards made under the American Recovery and Reinvestment Act of
2009 (ARRA) and all ARRA solicited applications and awards.
Source: NIH Data Book Report ID: 115 (NIH, 2020)

60
Figure 5: SBIR Grants, Phase II: Competing Application, Awards, and Success
Rate

Note: FY 2009 and 2010 exclude awards made under the American Recovery and Reinvestment Act of
2009 (ARRA) and all ARRA solicited applications and awards.
Source: NIH Data Book Report ID: 116 (NIH, 2020)

In 2008, NIH conducted a survey to evaluate the NIH SBIR program, published
as a final report in January 2009. The survey was administered to all 918 qualifying
small entities that earned a Phase II NIH SBIR grant in FY2002-2006 and had a response
rate of 78% (719 respondents). The survey attempted to understand whether the
supported programs were aligned with the goals of the SBIR programs. However, the
survey focused particularly on three of the four program goals: to stimulate technological
innovation (Goal 1), to use small business concerns to meet Federal R&D needs (Goal 2),
and to increase the commercialization of innovations (Goal 4).
The survey results suggested that the SBIR program was broadly successful at
achieving its goals. Eighty-eight percent of awardees with ongoing projects expected
sales after they had completed their projects, about the same percentage as reported in a

61
2002 survey, in which 85% expected sales (NIH, 2003). Forty-one percent of
respondents indicated that their SBIR-funded product, process, or service was still in
development at the time of the survey. Another 20% identified that the SBIR-funded
product, process, or service was being commercialized, and 22% said the target
populations used it. Ten percent indicated that the development of the product, process,
or service was “on hold” pending additional funds or was inactive for some other reason.
Eight percent of the awardees reportedly had quit working on the project. (Numbers total
more than 100% due to rounding.)
Figure 6 shows that survey respondents surpassed the NIH SBIR performance
target for Goal 1 of the SBIR program. Goal 1 consists of two performance indices. The
first performance index is set out in Index 1.1 as “Regardless of sales, 40% or more of
NIH SBIR awardees develop products in support of the NIH mission.” Survey
respondents as a group were developing or commercializing 587 products, including 290
projects under development, 143 projects at the commercialization stage, and 154
projects ready for commercial use. For the second performance index set out in Index
1.2, “10 % of SBIR awardees received additional Phase I or Phase II awards related to the
core technology”, and 57% of the respondents had received additional awards.

62
Figure 6: Summary of Outcomes associated with “Stimulating Technological
Innovation”

Source: Extracted from National Survey to Evaluation the NIH SBIR Program (NIH, 2009)
Figure 7 displays outcomes related to Goal 2, “using small business concerns to
meet Federal R&D needs.” Its three performance indices included Index 2.1, “50% of
more of NIH SBIR awardees make contributions to knowledge in health promotion,
disease prevention, diagnosis, health care, and amelioration and cure of disease”, Index
2.2, “50% or more NIH SBIR awardees can obtain and to disseminate health-related
information”, and Index 2.3, “50% or more of NIH SBIR awardees express satisfaction
with the usefulness of the NIH SBIR program.” All three performance indices exceeded
far more than 50%, the NIH SBIR program benchmark.

63
Figure 7: Summary of Outcomes associated with “Using Small Business
Concerns to Meet Federal Research and Development Needs”

Source: Extracted from National Survey to Evaluation the NIH SBIR Program (NIH, 2009)
To measure performance on contributions to knowledge (Index 2.1), the survey
asked the awardees to choose which of the following 11 specific medical, societal, and
technological outcomes were associated with their funding projects: Treating disease or
disability; Improving research tools; Detecting disease or disability; Preventing disease
or disability; Diagnosing disease or disability; Reducing the cost of medical care;
Developing health information for the general public; Developing information for health
professionals; Fostering new research collaborations; Training research investigators;
Other outcomes. The most common outcomes were “reducing the cost of medical care”
(62%) and “treating disease or disability” (53%). In summary, 587 out of 719 awardees
(82%) indicated they were contributing to at least one of them (Measure 2.1.1).

64
Regarding Performance Index 2.2, two measures were set out. Measure 2.2.1
quantified awardees’ perception of the value of the outreach and knowledge services
offered by the NIH SBIR/STTR program. When asked if they knew that they could
communicate with NIH employees for more information regarding the program or
support with the application, review, award, and award management, 96% of awardees
answered in the affirmative. The second measure, Measure 2.2.2, quantified awardees
who anticipated or were disseminating SBIR-supported technology and information
among populations using and receiving health and healthcare resources. Eighty-two
percent of respondents (587 out of 719) answered positively.
Performance Index 2.3 defined the satisfaction of awardees with four selected
aspects (the quality of instructions for preparing applications, the review process, the
award process, and the post-award administration) of the SBIR program. Measure 2.3.1
gauged the extent of satisfaction with the NIH SBIR application, review, award, and post-
administration process. Between 88% and 90% were completely or mostly satisfied with
the quality of the instructions for preparing applications, the award process, and the post-
administration process. One aspect which generated a somewhat lower level of
satisfaction was the review process; however, 74% were still completely or mostly
satisfied; and only 4% were completely or mostly dissatisfied.
The survey findings of awardee outcomes related to Goal 4, “the
commercialization of innovations,” are illustrated in Figure 8. The Performance Index
4.1, “40% or more of NIH SBIR awardees commercialize new or improved products in a
health-related field,” had six performance measures: sales (33%), sales amount ($395.5
million), FDA approval (21%), licensing arrangements (26%), other evidence of

65
commercialization (e.g., various types of marketing activities, public stock offerings, and
giving trade or commercial names to the SBIR-funded product) (64%), and additional
funding (36%). Awardees were considered to have commercialized a new or improved
product if they had achieved at least one of the criteria. By these criteria, 76% of
respondents commercialized new or improved products in health-related fields. Most
respondents expected sales when the SBIR-supported projects entered the commercial
phase; awardees developing drugs, biologics, and diagnostics showed a significantly
lower expectation for sales (68-81%) than that of other types of products (85-94%).
Regarding Index 4.2, “40 percent of NIH SBIR awardees grow their companies,” 81% of
respondents indicated that the SBIR award had allowed them to recruit additional
workers. Sixteen percent perceived that the Phase II award had no influence on
recruiting, and 3% were unsure.

66
Figure 8: Summary of Outcomes associated with “Commercializing
Innovations”

Source: Extracted from National Survey to Evaluation the NIH SBIR Program (NIH, 2009)
Overall, as shown in Table 8, at least 82 percent of awardees responded that they:
“developed products consistent with NIH mission; contributed to knowledge in fields of
interested to NIH; demonstrated capability to get and disseminate health-related
information to target populations; expressed satisfaction with the usefulness of the NIH
SBIR program in terms of the application, award, and post-award administration
program; and, grew their companies” (NIH, 2009). However, this survey did not ask
awardees questions specific to the regulatory support they received or their satisfaction
with their interactions.

67
Table 8: Summary of Performance for FYs 2002-2006 SBIR Phase II
Awardees

Source: National Survey to Evaluate the NIH SBIR Program (NIH, 2009)
Also, HHS reviewed FY2011 data from four HHS Operational Divisions, NIH,
CDC, FDA, and Administration for Children and Families, that participated in the SBIR
program, to assess the degree to which the awardees were eligible and that the awards
satisfied the program guidelines and goals. HHS reported that it had provided SBIR
support of $360 million to almost 1,000 awardees in 2011 and had the largest average
SBIR award of any participating agency. Although all awardees self-certified that they
expected to fulfill SBIR eligibility criteria, HHS observed that 31% of the awardees had
doubtful or unverified eligibility for at least one criterion (Levinson, 2014).
More specifically to the FDA, CDER’s Small Business Assistance Program
responded to 3,351 emails and 6,026 phone calls in 2016 (FDA, 2017b) compared with
over 1,500 emails and 4,100 phone calls in 2012 (FDA, 2013). More recent information
on CDRH, CBER, and DICE cannot be found.

68
Despite the achievements described above, some have suggested that there is still
room for improvement. For example, many agencies manage their SBIR/STTR programs
with less focus on business imperatives than on subsidizing specific technologies that
meet particular R&D requirements or needs of agency subject-matter experts. This may
be a legitimate application of the SBIR/STTR programs. However, agencies may be seen
to favor a subset of the applicant pool as a consequence of prioritizing innovations over
businesses. As a result, firms that have already won multiple awards may become adept
at using contract research programs to support their research and may have little
motivation to commercialize it (Rozansky, 2019). Also, several respondents have
expressed frustration with the grant application process, such as the difficulties of fixing
minor problems with applications, especially when making the first submission. One of
the comments also captures concerns about the review process: “Often review panels do
not understand the FDA process and difficulties getting clearance or approval from the
FDA… Review panel members should be educated on the purpose of Phase IIBs before
the review panel, and proposal reviews take place” (National Academies of Sciences
Engineering and Medicine, 2015).
The time-consuming application processes can distract from other important
activities; many top researchers spend 50% of their time writing grants. In 2018, NIH
awarded only 18% of the 54,000 proposals it considered, so repeated applications are
often required to obtain support (Piper, 2019).
In the 2014 NIH SBIR/STTR programs survey, many survey respondents pointed
to challenges in dealing with the FDA to obtain approval for required clinical trials, and
the following solutions were proposed:

69
“Hiring and making available FDA consultants” (as is the case with the
National Heart, Lung, and Blood Institute)

“Better education for applicants starting at a relatively early stage
through NIH-sponsored webinars and workshops.”

“Improved training and better processes for study section panelists, where
there appears to be an information gap related to FDA requirements.”

“Strategic review by NIH and FDA of NIH vision for innovation and FDA
caution.”

“Advocacy for NIH projects at FDA” (National Academies of Sciences
Engineering and Medicine, 2015)
Companies with SBIR/STTR awards often face barriers concerning the FDA
regulatory process. These companies often do not have enough expertise in dealing with
the FDA or its complex regulatory approval process. Respondents appear to believe that
NIH could provide better support for awardees in dealing with the FDA, as reflected in
the following comments:
“Small businesses are often inadequately informed about the requirements
and process for obtaining FDA approval for products they envision.
Efforts by the NIH to 1) educate and encourage small businesses to
appropriately approach the FDA for regulatory approval and 2)
encourage the FDA to work with and facilitate the regulatory process for
medical devices arising from NIH-funded small business and academic
grants would be enormously helpful.”

“FDA process is very uncertain and heavily dependent on the particular
reviewers assigned to the application. Any help with respect to helping
small business to receive from the FDA more clear guidance with respect
to the Agency’s expectations regarding the supporting clinical data
needed would be a huge significance and help avoid small companies
going out of business due to uncertainty and long lead time associated
with the FDA process.” (National Academies of Sciences Engineering and
Medicine, 2015)
However, apart from these anecdotal comments, finding information about the
experience and concerns of users attempting to use these translational programs proved
difficult. In particular, the feedback comes mostly from those funded by the programs

70
and does not represent more broadly the views and experiences of those who might have
been unsuccessful or those who did not apply for different reasons. It might be argued
that surveys directed at successful applicants in any grants program might be biased in
favor of positive perceptions.
2.5.2 Japan
In Japan, the Medical Innovation Support Office (MEDISO) organized and
implemented by MHLW monitored the accomplishments of its Medical Venture Total
Support projects from Feb. 5, 2018 (when it was established) to Jun. 30, 2019.
Applicants for consultations totaled 217, divided between venture companies, 132 (61%),
academia, 37 (17%), and others, 48 (22%). Approximately 30% of the consultations
dealt with pharmaceuticals, 40% with medical devices, and 10% with regenerative
medical products. Table 9 shows the breakdown of consultations according to the topic
discussed. Of all the consultations (n=238), the largest number was consultations
regarding legal compliance (48%), followed by financing (32%).
Table 9: Number of Consultation by Topic and Product Type

Law and
Regulation
Marketing
Reimburse-
ment
Business
Planning
Financing
Business
Strategy
IP
Global
Expansion
Others
Drug 29 11 9 22 28 11 13 6 13
Medical
Devices
50 29 25 29 23 16 12 17 10
Regenerative
Products
16 3 4 6 12 6 4 2 4
Others 17 14 3 8 12 9 6 7 6
Total 112 57 41 65 75 42 35 32 33
(From Feb. 5, 2018, to Jun. 30, 2019)
Source: Breakdown of Consultation [in Japanese] (MHLW, 2019c)
MEDISO also measured the satisfaction of its participants with the consultations
(Figure 9). Most of the sixty-four respondents (29% of participants) who gave an opinion

71
regarding their satisfaction with the consultations were satisfied or somewhat satisfied
(86.3%) with the consulting services.
Figure 9: Satisfaction concerning Overall Consultation Work

(64 responses)
Source: Satisfaction Concerning Overall Consultation Work [in Japanese] (MHLW, 2019c)
As discussed above, the PMDA had also introduced Regulatory Science (RS)
General Consultations and RS Strategy Consultations services that target universities,
research institutes, and venture companies with promising “seeds” from July 2011. From
that point to FY2020, the numbers of consultations of different types are shown in
Table 10.

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Table 10: Number of RS General Consultations and RS Strategy Consultations
RS General Consultation/
Pre-consultation
Start-
FY2014
*1

FY2015 FY2016 FY2017 FY2018 FY2019 FY2020 Total
RS General Consultation
*2
(of which, conducted at
Kansai Branch)
*4

928
(83)
221
(56)
190
(63)
231
(57)
202
(62)
161
(53)
169
(61)
2,102
(435)
Pre-consultation
*3
(of which, conducted at
Kansai Branch)
*4

1,078
(83)
411
(60)
388
(52)
336
(61)
326
(52)
346
(53)
390
(55)
3,275
(416)
Special Zone Medical
Device Pre-Consultation
*4
(of which, conducted at
Kansai Branch)
*5

-
1
(0)
9
(1)
5
(1)
4
(1)
1
(0)
0
(0)
20
(3)

Full-Scale Consultation
Meeting
Start-
FY2014
*1

FY2015 FY2016 FY2017 FY2018 FY2019 FY2020 Total
RS Strategy
Consultation (R&D) for
Drugs
162 58 40 61 49 44 49 463
RS Strategy
Consultation (R&D) for
Medical Devices
65 16 20 24 26 25 17 193
RS Strategy
Consultation (R&D) for
Regenerative Medical
Products
*6

2 11 14 13 5 11 13 69
Consultation on Quality
and Safety of
Regenerative Medical
Products
*7

49
[96]
29
[55]
26
[64]
29
[71]
25
[54]
29
[53]
25
[55]
212
[448]
RS Strategy
Consultation (R&D) on
Pharmaceuticals
Development Plans,
etc.
*8

1 0 0 0 0 0 0 1
Total
276
[323]
114
[140]
100
[138]
127
[169]
105
[134]
109
[133]
104
[134]
938
[1,174]
*1 – RS Strategy Consultation (Former: Pharmaceutical Affairs Consultation on R&D Strategy) Services was implemented on July 1,
2011.
*2 – Until March 31, 2017, conducted as an individual interview as part of the Pharmaceutical Affairs Consultation on R&D Strategy.
*3 – Until March 31, 2017, conducted as part of the Pharmaceutical Affairs Consultation on R&D Strategy.
*4 – Implemented on October 1, 2013
*5 – Implemented on November 20, 2015.
*6 – Implemented on November 25, 2014. (Till then, conducted as RS Strategy Consultations for Drugs or Medical Devices.)
*7 – Included those accepted as RS Strategy Consultations for Drugs until November 24, 2014. Also, the figures in [brackets] are the
total numbers of cases (when individually accounted for) where consultations were conducted over multiple days to the extent
necessary to adequately confirm the quality and safety of the product before submitting a clinical trial plan for a regenerative medical
product.
*8 – Implemented on November 25, 2014. (Till then, held as RS Strategy Consultation (R&D) for Drugs.)
Source: PMDA Annual Report FY2018 [in Japanese] (PMDA, 2020a)
Also, the specialized Sakigake program had, by April 2019, reviewed 68 Sakigake
applications – 40 for drugs, 15 for medical devices/IVDs, and 13 regenerative medical

73
products – that were submitted for designation by November 2018. From these
submissions, five drugs, four medical devices/IVDs, and two regenerative medicine
products were selected for the Sakigake designation (MHLW, 2019b). Table 11 shows
the number of products under the “Sakigake Designation System” from the first round of
the Sakigake designation in 2015 to 2019. However, this review did not indicate the
level of satisfaction with the Sakigake program amongst its participants.
Table 11: Number of Products under the “Sakigake Designation System” by
Year
Designation Year

Product Type
First
Round
Second
Round
Third
Round
Fourth
Round
2015 2016 2017 2018 2019
Drug 5 - 5 6 5
Medical Device - 1 3 2 3
IVD - - 1 - 1
Regenerative Medical Product - 3 3 3 2
Total 5 4 12 11 11
Source: Information extracted from (PMDA, 2020c, MHLW, 2019b)
Additionally, a review of the AMED Industrial-Academic Collaboration Program
was published in March 2015. It detailed the five-year period from FY2010, during
which AMED received 920 proposals from consortiums aiming to commercialize
medical devices. It chose 107 projects from the proposals for support as they progressed
toward commercialization.
Table 12 shows the status of 107 selected projects as of January 2015. Between
FY2010 and FY2014, 19 projects out of 107 selected projects were successfully
commercialized. (MRI, 2015)

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Table 12: Status of Verification Programs (as of January 2015)
Year
No of
Selected
Project
Project Term Completed Project Term On-going
Total
Commer-
cialized
On-
going
Cessa-
tion
Total
Commer-
cialized
On-
going
2010 36 36 12 21 3 0
2011 12 12 3 9 0 0
2012 28 6 1 4 1 22 3 19
2013 13 0 13 13
2014 18 0 18 18
Total 107 54 16 34 4 53 3 50
Source: Table 2-5 of the AMED 5-year Summary Report [in Japanese], translated into English (MRI, 2015)
Table 12 shows the 54 projects in total that completed their established term.
Four had stopped, and the other 50 had either been commercialized or were still under
development. Of the 50 still viable projects, 12 (24%) were able to submit or were still
planning to submit their regulatory applications as originally scheduled. However, 33
(66.0%) responded that their regulatory filings were, or would be, filed later than they
had originally planned. Reasons for the delay were “change in manufacturing system or
product (e.g., product specifications, material change),” “review/change of sales system,”
“delay in conducting a clinical trial,” or “delay in answering inquiries from PMDA.” In
one project, the regulatory filing was accelerated. The reason for this was “a part of the
medical device under development could be used as a standalone device, which had a
medical need; therefore, it was commercialized” and “the submission category was
changed.” Among these 50 projects, 15 (30.0%) had PMDA consultations, and 9
(18.0%) used support from external regulatory consultants (MRI, 2015).
2.6 Summary and Study Direction
The literature discussed above traces the evolution of universities and SMEs. It
attempts to examine governmental policies to promote commercialization, with a focus
on regulatory support programs to help academia and SMEs succeed in the medical

75
products sector. Extensive literature search provided little additional evidence to reflect
the experience and views of stakeholders outside of those collected by the agencies
dispensing the support. Thus, it does not fully characterize the obstacles that might still
exist in using these systems by their end-users. This study provides more information on
this aspect of program effectiveness. Of most interest were the satisfaction of applicants
and potential users with the most targeted of these programs, including FDA’s resources
provided by the DICE within the CDRH for medical devices and by CDER SBIA
program for drugs, and PMDA’s Regulatory Science General Consultation and
Regulatory Science Strategy Consultation Services.
2.7 Defining and Assessing Customer Satisfaction
“Satisfaction is the consumer’s fulfillment response. It is a judgment that a
product or service feature, or the product or service itself, provided (or is providing) a
pleasurable level of consumption-related fulfillment, including levels of under- or
overfulfillment” (Oliver, 2014).
Studies that examine customer satisfaction often identify that satisfaction is a
perception for which specific evidence is not readily accessible. Dissatisfaction does not
presume that the provider is deficient because the customer's expectations could also be
unrealistic. Extra work is required to obtain, assess, interpret, and explain the factors that
affect satisfaction (Parasuraman, 1985, Hill, 2000). These considerations appear to be
captured well by the “service gaps” theory, which characterizes the differences between
expectations and experience.
As identified by Hill and shown in Figure 10, the overall gap resulting in a
dissatisfied customer can be assessed as a function of one or more of five contributing

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gaps (Hill, 2000): 1) Promotional gap – the inability of the business organization to
fulfill expectations created in the minds of customers mainly by their marketing
communications; 2) Understanding gap – the gap that occurs when managers in the
organization fail to understand customer needs and priorities; 3) Procedural gap – the
gap that occurs when translating customer expectations into appropriate operating
procedures and systems with the business organization; 4) Behavioral gap – the
difference between customer expectations and the organization’s performance; and 5)
Perception gap: the difference between the perceptions of a customer regarding the
organization’s performance and the reality of that performance. Any of the five gaps can
affect views regarding the overall gap in service quality that can make a customer
dissatisfied. According to Hill (Hill, 2000), these gaps usually arise because of
differences in customers’ perception between what the service provider/business thought
it was providing and what customers believe they had received.

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Figure 10: Service Gaps as Identified by the Hill Model

Source: (Grigoroudis, 2010, Hill, 2000)
Zeithaml further explained this service quality gap using the conceptual model
shown in Figure 11 below. The first four gaps are identified as functions of how service
is provided, whereas Gap 5 pertains to the customer’s perceptions and expectations. Gap
5 alone can be considered a valid measure of service quality. However, closing Gap 5
often depends on repairing problems contributing to Gap 1-4. These service quality gaps
can have different causes, so that different strategies and tactics may be needed to close
each gap (Zeithaml, 1990).

78
Figure 11: Conceptual Model of Service Quality

Source: Extract from (Zeithaml, 1990)
Gap 5 has received more attention from theorists because it is harder to measure.
Grigoroudis (Grigoroudis, 2010) suggests how perception can be modeled by introducing
what is known as the “zone of tolerance” (Figure 12). The zone of tolerance identifies
two levels: the desired service level (the quality level that the customer expects that he or
she should and can receive) and the adequate service level (the minimum quality level
that the customer is willing to accept).

79
Figure 12: Zone of Tolerance relevant to Service Perceptions

Source: Extract from (Grigoroudis, 2010)
In the present study, the Hill model that decomposes satisfaction was used to
dissect the views and experience of academic and SME entrepreneurs who might be at
different levels of engagement with the regulatory agencies of the U.S. or Japan to seek
guidance through their consultative programs as described above. Thus, the survey based
its questions on a framework guided by the five service gaps.

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Chapter 3. Methodology
3.1 Introduction
The present study has four phases: Phase 1 – the development of a specialized
survey instrument that will be used to explore the research questions; Phase 2 – a focus
group analysis to validate and clarify the survey instrument; Phase 3 – the dissemination
of the survey to identified participants from representative organizations; and Phase 4 –
the analysis of the collected data.
3.2 Phase 1 – Development of Survey Instrument
The survey instrument was based on the framework of the theory of “service
gaps” described by Hill (Hill, 2000). The U.S. and Japanese surveys had 36 and 37
questions, respectively. Six beginning questions identified certain demographic
characteristics of the respondents and filtered individuals who might not be qualified to
proceed. The remaining study questions were structured to focus on the five service gaps
– the promotional gap, the understanding gap, the procedural gap, the behavioral gap, and
the perception gap. Question formats included multiple-choice, matrix or scale
measuring, and open-ended questions. A feedback or comment field was used at the end
of each section so that the respondent could provide any additional information that he or
she felt relevant. Some questions were appropriate for only one of the countries under
study, so skip-logic was used to assure that inappropriate questions were not presented to
respondents based on their previous answers regarding demographic profile or
experience. Questions were formatted into an electronic document using Qualtrics
(www.Qualtrics.com), a web-based enterprise tool that can send the survey to interested
participants.

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3.3 Phase 2 – Focus Group Analysis: Validation of the Survey Instrument
Before the survey was finalized and deployed, questions were reviewed both by
faculty members and by a focus group composed of experienced professionals (e.g.,
regulatory affairs or business development professionals) knowledgeable about medical
product development and SMEs or academia. The major purpose of the focus group was
to provide constructive feedback on the quality, flow, and relevance of the survey
questions. Before the focus group meeting, an electronic copy of the draft survey was
provided to all participants so that they had time to consider the questions. Due to the
COVID-19 pandemic, the focus group was held via a web conference. This web stream
was recorded to ensure that the ideas presented by the focus group were captured
completely. The meeting was approximately 90 minutes in duration. It began with a
short presentation of the intended study and its purpose, followed by a discussion of
survey questions. Written suggestions from the focus group were collected at the end of
the focus group session. Then, the survey was finalized from the feedback and
suggestions.
For the Japanese survey, I tried to align the questions to those in the U.S. survey
to permit some comparisons of respondents’ views without introducing bias. To
minimize potential errors in the interpretation of the questions in the Japanese survey
tool, several Japanese medical device or pharmaceutical experts reviewed the survey
design and Japanese translation to make sure that the wording and choice of survey
questions were compatible with the Japanese culture and had the same meanings as the
English version.

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3.4 Phase 3 – Dissemination of the Survey
The survey was distributed via email to 126 and 56 participants in the United
States and Japan. In addition, an anonymous link was made available to a limited
number of potential participants recommended by others. Target participants were senior
managers responsible for R&D, regulatory affairs, or business development in small
medical product companies or universities. Most respondents had experience working
with the FDA or PMDA either through joint ventures advanced by academic investigators
or as SMEs attempting to commercialize their products.
Individuals in the potential respondent pool were sought using social networking
platforms, professional association memberships, or personal referrals. They were
contacted by email or via a professional social community (e.g., LinkedIn) to solicit their
participation in the survey. Recipients were given the option to provide the contact
information of other personnel in their organization or network whom they considered
being qualified to complete the survey. These individuals were included in the panel for
distribution, and the survey was distributed concurrently to the entire distribution panel.
At the beginning of the survey, respondents were assured that their responses would
remain completely anonymous and that their identities would be protected. No financial
compensation or incentive was offered to encourage participation. Email reminders were
used to encourage the return of the surveys after 30 days.
3.5 Phase 4 – Analysis of Collected Data
Survey results were collected and saved electronically. The collected data was
then analyzed by using simple descriptive statistics. All Japanese responses to open-
ended questions were translated into English for evaluation. Then, open-ended questions

83
were evaluated and grouped according to themes. Qualtrics had the option to conduct
cross-tabulations on some types of questions so that some results could be stratified
according to certain demographic characteristics. Some questions allowed the respondent
to make a graded response, for example, from very satisfied to very unsatisfied. In these
questions, the strength of the response was assigned a weighting function so that the
“average” response could be calculated across the respondent pool by adding the
weighted values of the chosen responses and then dividing by the number of participants
answering the question. In these calculations, a respondent who had no opinion
expressed by answers such as “cannot say” or “not applicable” was not included in the
calculation.

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Chapter 4. Results
4.1 Survey Participants
The U.S. survey was disseminated from February 28 to June 6, 2021. Surveys
were sent to 126 participants using individual links developed through the Qualtrics
Mailer. Forty-eight persons opened the survey for an access rate of 38% (48/126), and 45
completed at least one question, corresponding to a response rate of 36% (45/126). Forty-
three of 45 participants completed the survey, providing a completion rate of 34%
(43/126). Additionally, 17 individuals used an anonymous link to access the survey, and
nine completed it. By combining these two participation methods, 65 individuals
accessed the survey link, 62 respondents completed at least one question, and 52
respondents completed the survey (36%; 52/143). No trend could be discerned as to
where most drop-offs occurred. About 1% (8/143) opened the survey but did not answer
any questions. Because all participants had the option to answer some but not all
questions, the number of responses for each question could vary, so was identified for
each question below.
From February 5 to June 6, 2021, the Japanese survey was disseminated to 56
individuals via email through Qualtrics Mailer. Before sending the survey link, 257
individuals had been contacted via email, LinkedIn messages and company websites, and
56 of those individuals agreed to participate in the survey. Of the 56 individuals, 43
opened the survey link for an access rate of 77% (43/56); 40 completed at least one
question, providing a response rate of 71% (40/56). Thirty-six completed the survey,
providing a completion rate of 64% (36/56). Additionally, five individuals used an
anonymous link to access the survey, and two completed it. By combining these two

85
participation methods, 48 individuals accessed the survey link, 43 respondents completed
at least one question, and 38 respondents completed the survey (62%; 38/61). Drop-offs
also did not seem to occur at any specific point. About 1% (5/61) opened the survey poll
but did not answer any of the questions. Because some participants answered only some
of the questions, the number of responses to a particular question is identified for each
question below.
4.2 Demographic Profile of Respondents
The first block of questions collected demographic information about the
respondents’ organizations, including their types (Figure 13), numbers of employees
(Figure 14), and developed products (Figure 15).
As shown in Figure 13, most respondents worked at a startup company in the U.S.
(82%, 46/56) and Japan (88%, 38/43). Among the U.S. participants, 32% worked at a
university (18/56), 20% at a research institute (11/56), and 27% at a company with
commercialized products (15/56). No one worked at a government laboratory.
Compared to the U.S. participants, 35% of the Japanese participants worked at a
company with commercialized products (15/43). Only 7% of the Japanese participants
worked at a university (3/43), and only a single participant worked at either a research
institute or a government laboratory (each 2%, 1/43). Four respondents in the U.S. self-
identified as “other”; three answered “CRO,” “independent non-profit,” and “NPO,” and
one provided a list of company names that have not been identified here for reasons of
confidentiality. Three of the Japanese also self-identified as “other,” including “none”
(1), “drug development venture” (1), and “founding agency” (1).

86
Figure 13: Types of Organizations Represented by Participants
Please list the types of organizations in which you have worked to develop medical
products in the last five years. (Please select all that apply).

Most respondents in the U.S. and Japan were employed by small companies with
less than 100 employees (Figure 14). Within that group, a majority were in the smallest
of the five categories, which had up to 20 employees (U.S. 75%, 42/56; Japan 67%,
29/43). Distributions across the larger companies included those with 21-100 employees
(U.S. 11%, 6/56; Japan 23%. 10/43); 101-300 employees (U.S. 4%, 2/56; Japan 5%,
2/43); 301-500 employees (U.S. 4%, 2/56; Japan 0%, 0/0); and more than 501 employees
(U.S. 7%, 4/56; Japan 5%, 2/43).

87
Figure 14: Size of Company by Number of Employees
Which statement best describes the size of your primary organization/Company? (If you
are at a university, hospital, or government agency, what is the size of your development
group?)

Participants were asked about the types of medical products developed by their
organization (Figure 15). In the United States, 96% of respondents worked on medical
devices (54/56), followed by biologics (20%, 11/56), drugs (20%, 11/56), medical
software (14%, 8/56), and/or IVDs (14%, 8/56). Twenty-four of 54 medical device
companies (44%) were involved in developing medical devices for pediatric patients
because of enrichment due to the enthusiastic assistance with survey distribution by
certain pediatric consortia. One respondent responded as “Other” and identified as
“digital health.” In Japan, half of the respondents worked with drugs (53%, 23/43), and
more than a third worked with medical devices (37%, 16/43), regenerative products
(26%, 11/43), IVDs (16%, 7/43), and biologics (12%, 5/43). One respondent chose
“Other,” identified as “new treatment.” The number of selections exceeded the number

88
of participants in both groups, suggesting that some companies worked on products of
different types.
Figure 15: Types of Medical Products Developed by Respondent’s Organization
Which statement best describes the product(s) that your present laboratory/company
develops? Please select all that apply.

Information was also sought regarding the respondents' levels/titles (Figure 16)
and functions (Figure 17) within their respective organizations. In the United States,
most respondents were the Founders of their organizations (62%, 34/55). The remaining
respondents self-identified as C-suite/Senior Management (47% 26/55), Researcher
(20%, 11/55), Professor (20%, 11/55), Director (15%, 8/55), Manager (4%, 2/55), and
Specialist/Associate (2%, 1/55). Three respondents (5%, 3/55) identified themselves as
“Other” and provided the position titles of “CEO” (1), “We are pre-launch” (1), and
“consultant” (1). More than half of the U.S. respondents identified more than one role

89
(55%, 30/55). Most commonly, the dual selection was observed for the founders, 15 of
whom (44%, 15/34) also had roles in the C-suite/Senior Management.
In Japan, most respondents were also Founders (47%, 20/43) or C-suite/Senior
Management (53%, 23/43). The remaining respondents self-identified as Researcher
(12%, 5/43), Professor (7%, 3/43), Director (19%, 8/43), Manager (9%, 4/43), or
Specialist/Associate (5%, 2/43). Two respondents (5%, 2/43) identified themselves as
“other” and provided the position title of “General Manager” (1) and “Founding
member/President and Representative Director” (1). Amongst Japanese respondents,
approximately one-third identified more than one role (33%, 14/43). The dual roles were
commonly seen for Founders, ten of whom (23%, 10/43) also had roles in C-suite/Senior
Management.
Figure 16: Organizational Level of Respondents
What title best describes your current responsibilities in your primary
organization/company? If more than one position is held, please select all that apply.

90
As shown in Figure 17, most of the U.S. participants worked in R&D (76%,
42/55), followed by Project Management (56%, 31/55), Business Development (56%,
31/55), Regulatory Affairs (47%, 26/55), Clinical Affairs, (27%, 15/55), and Board of
Advisors (13%, 7/55). The seven identified as “Other” specified the following roles: “all
for now” (1), “We are a 4-person device company, so we all share many of jobs” (1),
“Quality” (1), “Operations and Quality” (1), “Marketing, Commercialization Strategy”
(1), “Finance” (1), and “CEO” (1). Japanese participants worked more commonly in
Business Development (63%, 26/41), followed by R&D (46%, 19/41), Project
Management (22%, 9/41), Clinical Affairs (20%, 8/41), Regulatory Affairs (15%, 6/41),
and Board of Advisors (2%, 1/41). The four identified as “Other” specified roles in
“Software Development” (1), “Sales” (1), “General management” (1), and “Business
administration” (1). Many more answers than respondents were seen in both groups,
suggesting that respondents often had multiple roles. This suggestion is reinforced by
data from a crosstabulation that identified job functions for companies of different sizes
(Table 13). Respondents in the smallest companies with up to 20 employees selected
more than two roles per individual (Table 13).

91
Figure 17: Functional Roles of Respondents within the Company/Organization
Which job function(s) do you represent in your present organization/company? Please
select all that apply.

92
Table 13: Crosstabulation of Size of the Company with Job Functions Held
U.S.
Size of Respondents' Primary Organization/Company
Total 1 - 20 21 - 100 101 - 300 301 - 500 > 500
Job
Function(s)
of the
Respondents
Total Count (Answering) 56 42 6 2 2 4

Business Development 31 28 1 1 1 0
Board of Advisors 7 7 0 0 0 0
Clinical Affairs 15 13 0 1 0 1
Project Management 31 28 0 1 1 1
Regulatory Affairs 26 17 3 2 2 2
Research & Development 42 35 3 1 1 2
Other (Please specify) 7 4 2 0 1 0

Japan
Size of Respondents' Primary Organization/Company
Total 1 - 20 21 - 100 101 - 300 301 - 500 > 500
Job
Function(s)
of the
Respondents
Total Count (Answering) 43 29 10 2 0 2

Business Development 26 19 4 1 0 2
Board of Advisors 1 1 0 0 0 0
Clinical Affairs 8 7 1 0 0 0
Project Management 9 8 0 0 0 1
Regulatory Affairs 6 2 3 1 0 0
Research & Development 19 13 4 1 0 1
Other (Please specify) 4 3 1 0 0 0

Most companies in both countries were in the early stages of product development
(Figure 18): “Proof of Concept” (U.S. 44%, 24/54; Japan 51%, 22/43), “Non-clinical
Studies” (U.S. 41%, 22/54; Japan 47%, 20/43), “Phase I clinical trial” (U.S. 9%, 5/54;
Japan 19%, 8/43), “Phase II clinical trial” (U.S. 2%, 1/54; Japan 19%, 8/43), “Phase III
clinical trial” (U.S. 4%, 2/54; Japan 12%, 5/43), “Feasibility study (medical device)”
(U.S. 20%, 11/54; Japan 14%, 6/43), and “Pivotal study (medical device) (U.S. 2%, 1/54;
Japan 2%, 1/43). One respondent in each group answered, “I do not know.” Four of the
U.S. respondents (7%, 4/54) and three of the Japanese respondents (7%, 3/43) answered
“Other,” and their comments are shown in Table 14.

93
Figure 18: Development Stage when Planning a Regulatory Filing Strategy
At what stage in the development of a new product does your organization usually begin
to plan its regulatory filing strategy for market approval? If you work for more than one
organization or group, please reflect on the one with which you have the most
experience.

Table 14: U.S. and Japanese Respondents’ Comments on “Other”, Figure 18
U.S. respondents
1. Our mobility devices are Class 1 Exempt Devices.
2. 1) determine market need 2) determine product description 3) draft potential IFU/claims and
corresponding strategy
3. The development of the regulatory plan uses a phase appropriate approach that begins following
product nomination (initiation of nonclinical studies); as such the regulatory plan at this time
focuses on the regulatory requirements for FIH/Phase 1 studies. Thereafter, the regulatory plan
shifts to address the upcoming product development stage. We are currently working on a formal
Global Regulatory Plan (GRP), that will require the first version of the GRP at the time of the
conduct of the nonclinical studies (as described above) and will be updated to inform each
meaningful upcoming product development stage (eg, Phase 2, Phase 3, NDA preparation, and
NDA maintenance).
4. clinical /analytical validation/sample procurement
Japanese respondents
1. The business plan was based solely on efficacy in animal cells.
2. In our company, we established the company from the start of clinical trials based on the clinical
research data we had collected up to that point. At the same time, we began to formulate a
regulatory strategy in consultation with the regulatory authority.
3. From the start of R&D

94
4.3 U.S. Survey Results
A series of questions explored the U.S. respondents’ level of awareness,
experiences, and overall satisfaction with regulatory services offered to SMEs by the
FDA. First, the respondents were asked whether they knew that the FDA has services
that provide technical and regulatory assistance to small manufacturers, academic
laboratories, and research organizations to help them comply with regulatory
requirements. Of 56 responses, 57% answered Yes (32/56), and 43% answered No
(24/56) (data not illustrated). The 32 respondents who answered Yes were asked where
they found information on the FDA’s services (Figure 19). Most respondents found
information on the FDA’s website (80%, 24/30). Other sources included consultants
(50%, 15/30), other researchers/colleagues/technology transfer offices (33%, 10/30),
published articles, presentations, or seminars (27%, 8/30), or venture capital/business
development meetings (13%, 4/30) (Figure 19). Six respondents (20%, 6/30) selected
“Other” and provided their response as follows: “CTIP [the West Coast Consortium for
Technology & Innovation in Pediatric] (FDA funded Pediatric Device Consortium)” (1),
“Direct communication with relevant FDA division” (1), “from FDA meetings” (1),
“Local district office meetings” (1), “Past experience” (1), and “previous work history”
(1).

95
Figure 19: Sources of Information on the FDA’s Services to Support SMEs.
Where have you found information on the FDA’s services to provide technical and
regulatory assistance for small- to medium-sized businesses and academia?

When asked if the support of SMEs on the FDA’s website was easy to find, four
of the 30 respondents answered that it was not applicable to them. Of the remaining 26,
more than two-thirds (69%, 18/26) felt that it was easy to find, and a little less than one-
third (31%, 8/26) felt that it was not (Figure 20). When asked whether the different
services offered by the FDA were explained clearly, two answered that it was not
applicable for them. Of the remaining 27, more than half agreed that they were
(56%,15/27), and somewhat less than half disagreed (44%, 12/27) (Figure 21).

96
Figure 20: Was Information about the Support of SMEs on FDA’s Website Easy
to Find?
Was the information on the FDA’s website for supporting SMEs easy to find?

Figure 21: Did FDA Explain Clearly its Offered Services?
Has the FDA explained clearly about the different services that it offers?

A further question asked the respondents whether they were aware of specific
services designed to support SMEs (Figure 22). Eleven respondents identified that this
question did not apply to them (37%, 11/30). Of the remaining 19 respondents, only a
few respondents (21%, 4/19) were aware of “Technical and Regulatory Assistance
provided by the Division of Industry and Consumer Education (DICE) within CDRH,”
and less than half (42%, 8/19) were aware of the “Small Business and Industry

97
Assistance (SBIA) program” offered by the CDER. A little over one-third of respondents
(37%, 7/19) were familiar with both services. A crosstabulation of the services offered
by the FDA with respect to product type is presented in Table 15.
Figure 22: Awareness of the Following Services Offered by the FDA
Have you heard about the following services offered by the FDA?

98
Table 15: Crosstabulation of Awareness of the FDA’s Services by Product Type

Table 16 shows the familiarity with various other services offered to support
SMEs. More than half were not familiar with “CDER Learn” (50%, 15/30) and “Device
Advice” (50%, 15/30), followed by “CDRH Learn” (47%, 14/30), “Small Biz Buzz”
(47%, 14/30), “conference and workshops” (37%, 11/30), “direct communication
services” (30%, 9/30), and “Webinars/Podcasts/Videos” (17%, 5/30). The services with
which respondents are either “familiar with the services but not searched” or “have
searched but not used” are “conferences and workshops” (43%, 13/30), “CDER Learn”
(33%, 10/30), “CDRH Learn” (33%, 10/30), “Webinars/Podcasts/Videos” (33%, 10/30),
“Device Advice” (30%, 9/30), “direct communication services” (30%, 9/30), and “Small
Biz Buzz” (27%, 8/30). “Webinars/Podcasts/Videos” were identified as the most used
service (50%, 15/30), followed by “direct communication services” (40%, 12/30), “Small
Biz Buzz” (27%, 8/30), “CDRH Learn” (20%, 6/20), “Conferences and workshops”
(20%, 6/20), “Device Advice” (20%, 6/20), and “CDER Learn” (17%, 5/30). Only one
respondent (11%, 1/9) who answered the question shown in Table 16 was involved in
drugs or biologics development and was unfamiliar with CDER Learn. On the other

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hand, 57% of 21 respondents (12/21) involved in medical devices or IVD development
were unfamiliar with CDRH Learn (Table 17).
Table 16: Familiarity with Services Offered to Support SMEs
Are you familiar with the following services to support small- and medium-sized
businesses?
n=30
Not familiar
Familiar but
have not
searched
Have
researched
but not used
Have Used
CDER Learn - Web-based learning tutorials 15 50% 7 23% 3 10% 5 17%
CDRH Learn - Web-based learning tutorials 14 47% 9 30% 1 3% 6 20%
Conferences and workshops, e.g.,
Regulatory Education for Industry (REdI)
conferences
11 37% 7 23% 6 20% 6 20%
Device Advice - Comprehensive regulatory
assistance (web-based)
15 50% 9 30% 0 0% 6 20%
Direct communication services 9 30% 5 17% 4 13% 12 40%
Webinars/Podcasts/Videos 5 17% 8 27% 2 7% 15 50%
Small Biz Buzz - email updates on new
regulations, guidance, and meetings
14 47% 6 20% 2 7% 8 27%
Table 17: Crosstabulation of Awareness by Product Categories

4.3.1 Experiences with U.S. FDA’s Services to Support SMEs
Seventeen respondents who had used at least one of the services mentioned above
were asked whether the FDA website gave them a sufficient explanation regarding the
services that it provided. Fourteen respondents answered Yes (82%, 14/17), and three
answered No (18%, 3/17) (data not illustrated). They were also asked if they think that
the FDA understands the needs of SMEs from the materials available on the FDA
website. Eleven respondents answered Yes (65%, 11/17), and six (35%, 6/17) answered
No (data not illustrated).

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Then, they were asked about their level of satisfaction in more detail. Six percent
(1/17) answered “not applicable” for all (data not illustrated). The overall satisfaction
rate with FDA’s web content was 69% (11/16) (Figure 23). In addition, 69% were
satisfied with the “look and feel of the contents,” “sufficient depth of information,” and
“appropriate quality of information.” A little over 50% were satisfied with the
“performance of search function” (56%, 9/16). Fewer, about half (50%, 8/16), were
satisfied with the “ease of navigation” and “specific topic items for new medical
products.” Dissatisfaction was less common; 13% (3/16) were dissatisfied with the
FDA’s web services overall. However, 31% (5/16) were dissatisfied with the
“performance and search function” and the “ease of navigation” followed by “specific
topic items for new medical product” (19%, 3/16), “look and feel of contents” (13%,
2/16), “appropriate quality of information” (6%, 1/16), and “sufficient depth of
information” (6%, 1/16). The percentages of respondents who answered “neither
satisfied nor dissatisfied” were 31% for “specific topic items for new medical product,”
25% for “appropriate quality of information” and “depth of information,” 19% for “ease
of navigation” and “look and feel of contents,” 6% for “performance of search function.”
Three respondents made additional comments (Table 18).

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Figure 23: Satisfaction or Dissatisfaction with the FDA’s Web Contents to
Support SMEs
What is your satisfaction/dissatisfaction with the FDA’s web content for small- and
medium-sized businesses?

Table 18: Comments on Content of FDA’s Website
U.S. respondents
1. It needs to be mobile device formatted and friendly to millennials.
2. Search features are poorly targeted, often either missing topics or returning too many
unwanted hits.
3. The volume of information to be digested is overwhelming.

Respondents were then asked whether they thought that FDA understood the
specific needs of those who develop products in SMEs or academia as a result of reading
web content, watching podcasts, attending webinars and/or conferences, or reading a

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newsletter for example. Of 16 respondents, 69% (11/16) answered either “very well” (1)
or “somewhat well” (10), and 31% (5/16) answered either “not very well” (4) or “not at
all” (1).
When asked, “did the FDA provide the service or information that you needed to
your satisfaction the first time?” one respondent identified that the question was not
applicable. Of the remaining 15, about three-quarters answered Yes (73%, 11/15), and
four answered No (27%, 4/15) (data not illustrated). When asked where the information
was found (Table 19), 16 respondents answered. Most obtained the information from
multiple sources. The most commonly identified route was the internet (88%, 14/16) but
many respondents also consulted or used a “podcast/webinar” (56%, 9/16), “telephone”
(50%, 8/16), “conference/workshop (in-person) (44%, 7/16), “newsletter” (38%, 6/16),
and/or “facsimile” (6%, 1/16).
Table 19: Routes Used to Obtain Information
How did you receive the information/service that you had been seeking?
n=16
Route No. of Responses
Internet website 14
Podcast/Webinar 9
Telephone 8
Conference/Workshop (in-person) 7
Newsletter 6
Facsimile 1
Respondents were also asked to identify their preferred routes of communication
(Table 20).

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Table 20: Actual Communication Route Vs. Preferred Route
Was that route of communication your preferred method?
U.S. respondents (n = 14)
1. All have their place.
2. Digital – Email or similar
3. Email
4. I believe the webinars are very informative. The website serves as an excellent source of
drug development information as well.
5. Internet
6. Prefer the internet or webinar, but at the early stages, it seems like the navigation for early-
stage companies has to be done with a consultant or by talking with FDA employees at
conferences. They are terrific, but they have to cover a lot of ground, especially with start-
ups that are learning the process.
7. Website
8. Conference
9. Email and webinar
10. Webinars are helpful.
11. Yes (4)

Table 21 shows respondents’ impressions concerning the FDA’s enthusiasm for
supporting SMEs. More than half (56%, 9/16) agreed that the FDA appeared to be
enthusiastic, whereas 38% (6/16) neither agreed nor disagreed, and only one respondent
(6%) disagreed. Similarly, when asked whether the FDA’s support had increased
respondents’ confidence level, more than half (56%, 9/16) agreed, whereas 44% (7/16)
neither agreed nor disagreed, and no respondents disagreed (Table 22).
Table 21: Views Regarding FDA’s Enthusiasm about Supporting Respondents
After using the FDA’s services (web-based information, webinar, meeting, etc.), did you
gain the impression that the FDA was enthusiastic about helping you?

n = 16
Agree 9 56%
Disagree 1 6%
Neither agree nor disagree 6 38%

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Table 22: Ability of FDA Services to Increase Confidence
Throughout the FDA’s services, did you think that the FDA helped you increase your
confidence in understanding regulatory activities to develop a medical product?

n = 16
Agree 9 56%
Disagree 0 0%
Neither agree nor disagree 7 44%

Then, respondents were asked to comment on any positive or negative experience
with their interactions, and 11 responses were received (Table 23).
Table 23: Comments on the FDA’s Services for SMEs
To what extent has your experience been realized? Please describe any positive or
negative experience you have had with the FDA’s services for small- and medium-sized
businesses.

U.S. respondents (n = 11)
1. The FDAs expectations are sometimes reasonable and other time wholly impossible for small
companies to manage. I am often surprised by FDA.
2. FDA services are helpful but may be different for someone in a small company without much
experience vs someone that has experience of multiple filings.
3. It is expensive to hire a consultant to navigate FDA affairs. It will be great to know about the
FDA complimentary services.
4. After attending the webinars, I felt confident contacting the FDA via email and I plan to
complete a Q submission soon.
5. FDA can be very supportive and open to discussing proposed studies in advance, helping to use
limited resources efficiently.
6. I'm impressed that the FDA offers assistance to small- and medium-sized companies via the
outreach provided in its website.
7. There is no consistency in the quality of the reviewers.
8. Our execution with the FDA has been disappointing to say the least. While they speak of
supporting these avenues, they are not directly or indirectly connected to those that formally
9. I don’t think it’s necessarily FDAs responsibility to be as proactive in education industry as
your questions seem to be implying they should. I also think it’s unreasonable for FDA to
tailor their outreach to the thousands of startup companies that exist in medtech. I would
certainly say that their website needs work but what do you expect? It’s a giant government
organization.
10. 70% positive, 30% negative due to ambiguity
11. I think each review branch provides different level of service. Some are better than others.

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Respondents were asked if they needed to interact with, or tried to interact with,
someone at the FDA. Twelve respondents (75%, 12/16) felt that they needed to interact
with someone at the FDA, and 11 (69%, 11/16) that they tried to contact someone at the
FDA (data not illustrated). The 14 respondents who answered Yes to one or both
questions were then asked whether they could reach the FDA staff when necessary
(Figure 24). When asked if the FDA staff were easily accessible, one respondent
answered that it did not apply to her/him. Of the remaining 13, more than two-thirds
(69%, 9/13) answered “most of the time” (5) or “some of the time” (4); four found them
to be “rarely accessible” (31%, 4/13). Likewise, one identified that the question
regarding “FDA staff was quick to respond” did not apply to her/him. Of the remaining
13, more than half of respondents (77%, 10/13) responded either “most of the time” (5)
or “some of the time” (5); three (23%, 3/13) found that they were “rarely” quick to
respond. Ninety-two percent (11/12) felt that the FDA staff provided high-quality advice
either “most of the time” (5) or “some of the time” (6); one answered that they “rarely”
provided high-quality advice (8%, 1/12), and two answered “not applicable.”
In addition, when the 14 respondents were asked whether they thought that the
FDA staff had sufficient knowledge to answer their questions, one respondent answered
that this question did not apply to him/her. Of the remaining 13 respondents, 12 (92%,
12/13) agreed, and one (8%, 1/13) disagreed (data not illustrated). Nine commented on
the positive or negative experiences when interacting with the FDA personnel (Table 24).

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Figure 24: Experience with Reaching the FDA Staff When Necessary
Were you able to reach the FDA staff when necessary?

Table 24: Positive/Negative Experience When Trying to Interact with the FDA
U.S. respondents (n = 9)
1. They were knowledgeable, thorough, and professional.
2. Informal discussions with FDA staff are wasted in my opinion. FDA staff are hesitant to respond outside of
formal documented discussions. Sometimes the FDA is eager to help yet, other times I have been denied
meetings when that is really the only route likely to help a start-up company.
3. I spoke with consultants directly instead of trying to gather detailed information from the FDA itself.
4. I received a very lengthy email responding to my question about digital health device.
5. FDA was accommodating on the positive side, but advice was ambiguous in some aspects on the negative side.
6. Experienced communication difficulties during budget-related shutdown.
7. Each review branch is different, and I had both very positive and very negative experiences with the FDA staff.
8. DICE email is responsive but tends to provide formulaic answers and referrals.
9. Collaborating with “subject matter experts” within the FDA is, in short, laughable. Those that we have
specifically engaged with show little to no comprehension of a category in which they're responsible for. They
are slow, intentionally leveraging the COVID 19 pandemic to suggest they are low on resources, however when
you do finally engage with them, they show no valid understanding of specific files, and attempts to push
execution further down chain.

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4.3.2 Feedback from Respondents who did not Use the FDA’s Services to Support
SMEs
The respondents who were either familiar or unfamiliar with the FDA’s services
for SMEs but had not used them (see Table 16) were asked why they had not accessed
those services (Table 25).
Table 25: Reason(s) Not to Access the FDA’s Services for SMEs
U.S. respondents (n = 10)
I did not have time to read such information (4)
I could not find information that I was seeking (4)
The website is not user friendly. (2)
The contents of the website/webinar/conference were not what I had expected. (1)
They were also asked, “what if anything more would you like to see the FDA do
to accelerate the commercialization of new medical products developed in academia or
SMEs?” Six respondents commented, as shown in Table 26.
Table 26: Comments Regarding Additional FDA Support
U.S. respondents (n = 6)
1. A) clear guidance in pathway - the vagueness is killing medtech innovation B) clear
guidance on timeline for approval - the vagueness is killing medtech innovation C) clear
guidance on cost
2. I have not initiated my Regulatory strategy as of yet. Still pre-launch and bogged down in
engineering and user feedback
3. Nothing comes to mind. Also, I am not clear on the previous question I was not aware of
this, so technically the answer I chose is not accurate. I said I did not read it, whereas I was
not aware of it and thus did not look for it Thanks.
4. Eliminate requirement for high-volume manufacturing to be in-place prior to EUA
consideration.
5. Based on survey and lack of my knowledge of some services, FDA and I could do a better
job of familiarizing/educating on services available.

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U.S. respondents (n = 6)
6. Small non-academic businesses and inventors are on their own when it comes to
commercialization. It doesn't matter how many Utility and Design Patents an Inventor has
or how innovative those devices are. There is no direct outreach from the FDA for patented
innovative mobility devices registered with the FDA. There are no standards for class 1
exempt mobility devices such as cane, crutches and walkers in terms of long-term
continued use and the way those devices misalign and force the body to move to maintain
balance. When you force the body to be misaligned and move in ways it was not designed
for to maintain balance you create secondary disability unrelated to injury, age or
condition. The FDA should have direct outreach to new small business that have
innovative new devices that are registered with the FDA to help them with
commercialization.
4.3.3 Respondents Unaware of the FDA’s Services to Support SMEs
Twenty-four respondents who were unaware of FDA’s technical and regulatory
assistance programs were asked if they would now be interested in the FDA’s
services/information for SMEs. Seventy-five percent answered Yes (Table 27), 21%
answered maybe, and only one (4%) answered No.
Table 27: Interest in the FDA’s services for SMEs
The FDA offers various services and information via the FDA’s website, podcast,
webinar, conference, and newsletter to support SMEs. Are you interested in such
services or information?
n = 24
Yes 18 75%
Maybe 5 21%
No 1 4%

These 24 respondents were asked if there was anything that they would like to see the
FDA do to accelerate the commercialization of new medical products developed in
academia or SMEs. Their comments are shown in Table 28.

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Table 28: Comments Recommending Additional FDA Services to Assist
Commercialization
The FDA is trying to support SMEs. What, if anything, would you like to see the FDA do
to accelerate the commercialization of new medical products developed in academia or
SMEs?

U.S. respondents (n = 18)
1. 1. Continue to provide industry specific guidance documents to clarify expectation, 2. Upper
management is terrified to ask FDA questions, so an anonymous non-binding question and answer
service would allow engineers and clinicians to ask questions they cannot ask now.
2. Cut down regulation. We are in a competitive environment. Other countries (e.g., China) has much
friendlier regulation. We need to look at their models, especially in cell therapy, if USA wants to
stay competitive.
3. Examples of successful devices/start-ups, and what was required to get them through - even if they
are fake examples. For instance, a quality system may be plug and play (simple) for an experienced
device developer, but for a new startup it's a total mystery what it's supposed to look like
4. FDA clearance or approval represents a huge regulatory risk for investors. Consequently, there
seems to be a lot of funding available for companies that have achieved FDA clearance, but little
funding for companies earlier in the process. And it's not advisable to try to get a 510(k) without a
final device, which often requires a significant engineering effort and expense. If the FDA wants to
support small businesses, they should develop a process of regulatory de-risking milestones along
the path to 510(k) clearance.
5. Funding opportunities
6. Guidance on development pathways for combination devices (specifically 3D printing) and
description of key concerns in safety regarding these devices.
7. Help plan for GMP and for 510(k) filing
8. I have not put much thought into this. Perhaps, have facilitators work with pre-revenue companies
to help them move through the process without the need for the same quantity of consultants.
9. Identify the most suitable path for regulatory approval
10. Informal conversations/ Tech watch style web meetings/presentations for early guidance. Pre-
submission is a route, but still very "formal" and often costly & time-consuming and prevents early-
stage startups to get early feedback
11. More specific focus on and support for pediatric devices to address the complexities and uniqueness
of both the technology and the process.
12. Presub process is pretty straightforward and clear. Funding mechanisms are where I struggle now,
but I am currently engaging different programs to see where I am applicable.
13. Provide accelerated timing for pre-sub meetings
14. Provide services or in-kind support to these organizations. Many small businesses don't have the
funds to generate a $100k FDA application. The rigor of testing is super important so they should
lax that but may have innovative ways to support this process.
15. Streamline requirements for clinical studies sponsored by small business concerns.
16. Targeted grants specifically for pediatric devices as they are a small market. Grants give companies
incentives to develop products for this market. Grants can be for R&D, clinical trials, and
commercialization.

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U.S. respondents (n = 18)
17. This survey has intimated that the FDA has support services for small and medium businesses. So
naturally I went to the website to find out how to register, sign up, or contact someone about the
support. After 30 minutes of looking for anything that sounds like what the survey has suggested, I
gave up. It may exist, but it certainly isn't easy to find, and I don't have the time to perform a
forensic search of the website and associated literature to find it. I have read every link the FDA
publishes about how to prepare for a med device submission...and I still do not know how to do it by
myself. This is why people hire regulatory consultants rather than engage with the FDA directly.
The published information is complex, sometimes contradictory, and it is extraordinarily difficult to
determine what is relevant to a specific project based on the information provided. It would be
hugely helpful to have the equivalent of a "customer service rep", basically the FDA's own
regulatory consultant, help with deciphering the requirements. It sounds from the questions on this
survey that the FDA does offer such a service. I have been unable to find it, which ultimately means
the FDA isn't all that helpful to a small business trying to figure out the submission process and
requirements. I will continue to employ a regulatory consultant for now.
18. Provide quick and more expedient feedback through less formal channels

4.3.4 Respondent Experiences Regarding Personal Interactions with the FDA
All respondents were asked whether they had personal interactions with the FDA,
for example, through face-to-face meetings or videoconferences. Of 50 respondents, half
(52%, 26/50) had such experience (Table 29).
Table 29: Experience with Personal Interaction with the FDA
Have you had any chance to hold a meeting, including a face-to-face meeting, zoom
conference, teleconference, or personal interaction with an individual at the FDA about
the medical product you are developing?
n = 50
Yes 26 52%
No 24 48%

Twenty-six respondents who had interacted with the FDA were asked about their
satisfaction with various elements of the consultation service (Table 30). Most were
satisfied with their “overall” interactions (S: 73%, 19/26, Neither: 12%, 3/26, NS: 15%,
4/26); with the “quality of consultation service” (S: 73%, 19/26, Neither: 15%, 4/26, NS:
12%, 3/36 ); with the “value of the consultation service” (S: 69%, 18/26, Neither: 19%,
5/26, NS: 12%, 3/26); and with the “timeline of the consultation service” (S: 62%, 16/26,

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Neither: 15%, 4/26. NS: 23%, 6/26). However, less than half were satisfied with the
“convenience of forms and documentation” (S: 44%, 11/25, Neither: 36%, 9/25, NS:
20%, 5/25, and N/A: 1/26).
Table 30: Satisfaction with Personal Interactions with the FDA
Think about your most recent experience with personal interaction with an individual at
the FDA. What is your level of satisfaction with each of the following?

Nineteen commented on positive or negative experiences related to their
interactions with the FDA personnel. Their comments are shown in Table 31.
Table 31: Positive/Negative Experience with Interactions with the FDA
U.S. respondents (n = 19)
1. After 30 years of working with FDA, I have too many good and bad experiences to describe! I think
the most impactful negative thing is when FDA denies a meeting with a company. They are left
guessing and it hurts fundraising efforts as well.
2. We received pre-IND advice. It was timely and clear.
3. Difficult to get information other than standard feedback
4. The FDA staff provided highly valuable information regarding design and goals of studies to be
conducted by the company.
5. My only interaction with the FDA's Division of Industry and Consumer Education (DICE) or
CDER's Small Business & Industry Assistance (SBIA) is via their website portals. Essentially all of
our formal interactions with CDER are via the PDUFA Meeting framework. Informal interactions
(eg, via Email) with CDER occur, but are primarily brief and many times logistics/administrative in
nature. Interestingly, in the context of Pre-IND requests for Type B interactions, CDER has been
designating these Pre-IND Meetings as "Written Responses".
6. They are really territorial so it’s like walking on eggshells.
7. It has been very long time ago, but experience was very positive and person was helpful.
8. My face-to-face interactions with the FDA have always been positive. They have seen the value in
our product and have been supportive of our project. And I've been impressed by their competence.
9. had a useful presub meeting with FDA
10. We found FDA staff to be engaged in the science of our technology and the intended use of our
device.
11. The process of submitting the presubmission forms is incredibly cumbersome.
12. To repeat, those representing the FDA from our engagement has left an extremely sour taste,
showing no true attempt at supporting execution, but acting as an opaque wall towards what should
be a collaborative and transparent endeavor.
Timeline of the consultation service 16 62% 4 15% 6 23% 0 0%
Convenience of forms and documentatiion 11 42% 9 35% 5 19% 1 4%
Quality of the consultation service 19 73% 4 15% 3 12% 0 0%
Value of the consultation service 18 69% 5 19% 3 12% 0 0%
Overall experience 19 73% 3 12% 4 15% 0 0%
n=26
Satisfied
Neither safisfied
nor dissatisfied
Dissatisfied Not applicable

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U.S. respondents (n = 19)
13. Only timeline and convenience/ease of use of submission form expectations.
14. Project manager was accommodating
15. Timing/urgency and focus on the key tasks at hand were lacking
16. Again, senior management tends not to reach out because they think they will lose control of the
questions that are asked could negatively impact the submission.
17. Unfortunately, our most recent experience with the FDA was very negative. Our company ended up
involving the Ombudsman to resolve a few of the issues (for example, lack of communication, no
interactive reviews, extended timelines of submission reviews).
18. This was a presubmission for 510k meeting. Very helpful. (though it was on the phone - I may have
answered the question incorrectly).
19. We had a Zoom presubmission meeting for our product, as well as a follow up meeting with OOPD
to discuss focusing the product on pediatrics. I was very impressed by everyone's advice. Negatives:
Having to send in a physical hard drive with presubmission documents; and having to send it again
twice because of silly issues and even though the files were fine! Including during the pandemic.
Seriously?

Twenty-six respondents who had interacted with the FDA were then asked
whether the face-to-face meeting or personal interaction was more beneficial than their
experience with other types of FDA services (website, webinars, conference, etc.) Of 25
respondents, 19 answered Yes (76%, 19/25), three answered No (12%, 3/25), and three
mentioned other (12%, 3/25). Respondents were also asked for additional comments,
shown in Table 32.
Table 32: Comments on Personal Interaction with the FDA
U.S. respondents answered “Yes” (n = 10)
1. Face-to-face meetings always provide more value.
2. Face to face are preferred, but not an option during COVID.
3. Advanced preparation of formal teleconference meeting was thorough, time efficient and provided
much needed information.
4. Able to get somewhat more direct feedback.
5. I can't imagine that any teleconference tool could take the place of being in a room with FDA staff.
It's important for us to read body language and have the best opportunity to develop a relationship
with regulatory staff.
6. Due to the pandemic, we have been limited to digital engagement. It does no favors for them to be
able to just turn off a WebEx after showing no preparation for an active discussion. A face-to-face
would aid engagement tremendously.
7. More relevant information is provided that cannot be obtained from website. Perhaps the use of
small business services would add some value beyond web site.
8. It's better to talk to an actual person, but if it takes 6 months to get the opportunity, it is a
tremendous challenge
9. Specific topic meetings are useful but what happens is the staff changes frequently and you must
start from scratch, or the new team wants something else.
10. Face-to-face meetings are the most valuable time you can have with the fda.

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U.S. respondents answered “Other” (n = 3)
1. N/A
2. It was a zoom but they turned their cameras off
3. Sorry, it was a phone meeting.

Twenty-four respondents who answered No in Table 29 were asked whether they
thought that personal interactions with an individual at the FDA could give them more
personalized or tailored support for their efforts to commercialize medical products.
Fifty-eight percent (14/24) answered Yes, and 29% (7/24) answered Maybe; no one
answered No (data not illustrated). Thirteen percent (3/24) checked “other” and
expanded in comments shown in Table 33.
Table 33: Comments on Whether Personal Interactions with FDA Provides
More Personalized or Tailored Supports
U.S. respondents (n = 3)
1. Yes, but the concern is at what level do you bring in FDA engagement if ‘all the ducks aren’t in a
row’ yet so to speak
2. Multiple regulatory consultants have already advised FDA would not consider out product under
EUA due to current low-volume manufacturing status
3. yes, but only if it is straightforward to engage.
4.4 Japanese Survey Results
A parallel series of questions explored the use of SME support and consultation
systems offered by the Japanese PMDA for respondents working in Japanese
organizations. First, the respondents were asked whether they were aware of these
consultation services. Of 43 respondents, 86% answered Yes (37/43), and 14% answered
No (6/43) (data not illustrated). The 37 respondents who answered Yes were asked where
they found the information on PMDA’s consultation services (Figure 24). More than a
half learned about the services from other researchers, colleagues, or technology transfer
offices (56%, 20/36). Other sources included PMDA’s website (36%, 13/36), published
articles, presentations, and seminars (28%, 10/36), venture capital/business development

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meetings (19%,7/36), consultants (14%, 5/36), or PMDA’s poster (6%, 2/36). Seven
respondents (19%,7/36) selected “Other” and provided the responses shown in Table 34.
Figure 24: Source of Information on the PMDA’s Consultation Services to
Support SMEs.
Where did you find information on PMDA's Pharmaceutical Affairs Consultation on
Research and Development Strategy - RS General Consultation and RS Strategy
Consultation (R&D)? Please select all that apply.

Table 34: Comments on “Other”, Figure 24
JP respondents (n = 7)
1. Meeting with the PMDA at Bio Japan
2. A PMDA reviewer suggested the use of the RS strategy consultation.
3. I have attended [before].
4. Medical Device Development Program (of Biodesign)
5. From an employee who had development experience at a pharmaceutical company
6. Had prior experience
7. I had been involved in the development of the product from the time of the clinical trial notification,
prior to the introduction of Pharmaceutical Affairs Consultation on R&D and RS Consultation
meetings.

When asked if the information was easy to find, four answered that the question
was not applicable. Of the remaining 32 respondents, 81% (26/32) felt that the
information regarding the PMDA’s Pharmaceutical Affairs Consultation on R&D,
Strategy, or RS General Consultation and RS Consultation (R&D) was easy to find, but
19% (6/32) that it was not (Figure 25).

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Figure 25: Was Information regarding PMDA’s Consultation Meetings Easy to
Find?
Was the information on PMDA's Pharmaceutical Affairs Consultation on Research and
Development Strategy - RS General Consultation and RS Strategy Consultation (R&D) -
easy to find?

When asked whether the different consultation services were explained clearly,
eight answered “not applicable.” Of the remaining 28, 71% agreed that they were
(20/28), and 29% (8/28) disagreed (Figure 26).
Figure 26: Were PMDA Consultation Services Explained Clearly?
Has the PMDA explained clearly about the different consultation services it offers for
SMEs or academia?

Respondents were also asked if the materials published about the programs, for
example, PMDA’s website or poster, suggested that PMDA understands the needs of
SMEs or academia. Five answered, “not applicable.” Of the others, more than half
agreed (58%, 18/31), but 42% disagreed (13/31) (Figure 27).
19%
81%
0 5 10 15 20 25 30
No
Yes
Number of Responses
n= 32

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Figure 27: Does PMDA Appear to Understand the Needs of SMEs or Academia?
Do you think from materials available from the PMDA website, poster, etc., the PMDA
understands the needs of SMEs or academia?

Respondents were asked about their satisfaction with various aspects of the
information provided about the consultation services. When asked about overall
satisfaction with the contents of PMDA’s consultation services, eight respondents
answered that it did not apply to them. Of the remaining 28, 11 were satisfied (39%,
11/28), 8 were dissatisfied (29%, 8/28), and one third were neither satisfied nor
dissatisfied (32%, 9/28). Nine respondents answered that the question regarding
“sufficient topic items for consultation services” did not apply to them. Of the remaining
27, 11 (41%,11/27) were satisfied, four were dissatisfied (15%, 4/27), and 12 were
neither satisfied nor dissatisfied (44%, 12/27). Eleven respondents identified that the
question regarding “sufficient depth of information” did not apply to them. Of the
remaining 25, four were satisfied (16%, 4/25), three were dissatisfied (12%, 3/25), and 18
were neither satisfied nor dissatisfied (72%, 18/25). Nine respondents identified that the
question regarding “appropriate quality of information” did not apply to them. Of the
remaining 27, six were satisfied (22%, 6/27), 5 were dissatisfied (19%, 5/27), and 16
were neither satisfied nor dissatisfied (59%, 16/27) (Figure 28). Twelve respondents
made comments (Table 35).

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Respondents were asked whether they have applied for or have had a
“Pharmaceutical Affairs Consultation on Research and Development (R&D) strategy,”
“RS General Consultation,” or “RS Strategy Consultation (R&D).” Of 37 respondents,
26 answered Yes (70%, 26/37) and 11 (30%, 11/37) answered No (data not illustrated).
Figure 28: Satisfaction or Dissatisfaction with the Contents of PMDA’s
Consultation Service for SMEs and Academia
Was the content of the Pharmaceutical Affairs Consultation on Research and
Development (R&D) Strategy, RS General Consultation or RS Strategy Consultation
(R&D) what you were looking for?

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Table 35: Comments related to Figure 28
JP respondents (n = 12)
1. PMDA’s consultation does not provide their opinion clearly. It is always vague. It may be a cultural
thing, but it is indeed very outdated. They need to start taking responsibility for what they
recommend since it is a paid service.
2. I would like [the PMDA] to study more from a development perspective. The approval situation of
drug discovery in the world is changing every moment.
3. There was courteous support for academia and venture companies. On the other hand, it was
assumed that the level of support would be different from that of pharmaceutical companies. (In
both good and bad ways, it was not for a development aimed to obtain approval, but rather advice
for academia and venture companies to take steps externally.)
4. The positive point is that PMDA suggested using RS Strategy Consultation before the company
investigates it. The negative point is that RS consultation is divided into cell/tissue processing
products and gene therapy products. When both categories apply to one product, at least four
consultations are required; the quality and non-clinical safety of cell/tissue processed products and
the quality and nonclinical safety of gene therapy products. The PMDA examiner, who consults on
the quality and non-clinical safety of the same product and meets in a formal consultation, is the
same. I do not understand why the cell/tissue processing products and gene therapy products should
be separated. If four consultation meetings are required, it will be a heavy burden for the venture.
5. It was not clear which one to consult specifically. Therefore, I have inquired about multiple
consultation services.
6. Lack of creativity. From our experience of consulting with Western authorities, (Japanese regulatory
authorities) have no idea of creating a creative industry. Before that, it is questionable that they do
not identify themselves at the consultation meeting. Is avoiding responsibility the reason? The exact
opposite of a creative attitude.
7. None in particular. At the previous company, I had an RS Strategy Consultation; the PMDA was
also groping and could not get a clear answer.
8. Sufficient information could be obtained by directly contacting the PMDA for consultation.
9. Although the degree of sufficiency or inadequacy of the information submitted by those who consult
is sometimes pointed out, constructive advice on what measures can be taken to improve it is rarely
provided
10. I have the impression that the PMDA listened enthusiastically to an inexperienced venture company,
and even though they could not specify them, they were able to correct our directions.
11. It is inconvenient that all the materials are embedded in a file form.
12. I was very disappointed that a consultation request could only be made by fax. I was surprised that
the email was not accepted.

4.4.1 Experience with Japanese PMDA’s Consultation Service to Support SMEs
Twenty-six respondents who had applied for PMDA’s consultation services to
support SMEs were asked about the type of PMDA consultation their organization or
company had participated. Twenty-three responded. Half applied for or had an RS
Strategy Consultation (R&D) (52%, 12/23), and a similar number had a Pharmaceutical
Affairs Consultation on R&D Strategy (48%, 11/23). Fewer had an RS General

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Consultation (22%, 5/23), and two (9%, 2/23) answered they did not remember (Figure
29). Four (17%, 4/23) answered “other” and made comments (Table 36).
Figure 29: PMDA Consultation Meetings Respondents Had
Which PMDA consultation meeting did your organization/company have? Please select
all that apply.

Table 36: Comments related to Figure 29
JP respondents (n = 4)
1. I am having a consultation before I go to the PMDA.
2. I had an RS strategy Consultation when I was at a previous company. At my current company, I use
a regular Pre-Phase II consultation meeting.
3. Free face-to-face consultation
4. I am not sure.

Twenty-six respondents who had applied for or had one of the PMDA’s
consultation services were also asked, “was a sufficient explanation of the consultation
process provided in advance?” Twenty-three responded. Five answered that this
question did not apply to them. Of the remaining 18 respondents, 13 answered Yes
(72%, 13/18), and five answered No (28%, 5/18) (data not illustrated).
Respondents were then asked whether they thought that the PMDA understands
the specific needs of those who develop products in SMEs or academia based on the
material available from the PMDA website or poster, for example. Of 23 respondents,

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four answered that this did not apply to them. Of the remaining 19 respondents, 74%
(14/19) answered either “very well” (4) or “somewhat well” (10), and 26% (5/19)
answered either “not very well” (3) or “not at all” (2) (data not illustrated).
When asked where the information was found (Table 37), 21 respondents
answered. Most obtained the information from multiple sources. Most commonly
identified were “conference or workshop” (52%. 11/21) and “internet” (52%. 11/21),
followed by “email” (48%, 10/21), “telephone” (33%, 7/21), and facsimile (5%, 1/21).
One answered “other.” Three respondents made comments (Table 38).
Table 37: Route Used to Obtain Information
How did you receive the information/service that you had been seeking prior to the
consultation meeting?
n=21
Route No. of Responses
Conference or workshop (in person) 11
Internet website 11
Email 10
Telephone 7
Facsimile 1
other 1
Table 38: Comments related to Table 37
JP respondents (n = 3)
1. Using a consultant
2. From a colleague (who had experience in medical device development)
3. From an acquaintance

Respondents were also asked to identify their preferred communication routes (Table 39).

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Table 39: Actual versus Preferred Communication Route
Was that route of communication your preferred method?

JP respondents (n = 16)
1. The fax should be eliminated. Nobody uses fax these days.
2. The PMDA is basically communicated by phone, and only decisions come by email. I, personally,
prefer to receive everything by email.
3. Web meeting
4. I do not think it will change much, so I do not have expectations.
5. I want to be able to contact the PMDA via email.
6. The free consultation provided only general answers far from the regulatory consultation that a bio
venture hopes for.
7. I do not know because I am not directly involved.
8. I do not understand the question.
9. I have had the opportunity to speak with them directly on the phone, and I have no complaints about
their communication methods.
10. Yes, they responded by email instead of fax.
11. Yes (6)

When asked, “Did the PMDA provide the consultation service that you needed to
your satisfaction the first time?”, four respondents identified that the question was not
applicable. Of the remaining 17, 71% answered Yes (12/17), and five answered No
(29%, 5/17) (data not illustrated).
Table 40 shows respondents’ impressions concerning the PMDA’s enthusiasm for
supporting SMEs and academia. Two respondents answered that this question was not
applicable. Of the remaining 19 respondents, about two-thirds (63%, 12/19) agreed that
the PMDA appeared to be enthusiastic, whereas 26% (5/19) neither agreed nor disagreed,
and only two respondents disagreed (11%, 2/19). Similarly, when asked whether the
PMDA’s consultation had increased respondents’ confidence level, three respondents
answered that this question was not applicable. Of the remaining 18 respondents, more
than half (56%, 10/18) agreed, whereas 33% (6/18) neither agreed nor disagreed, and
11% (2/18) disagreed (Table 41).

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Table 40: Perceptions of PMDA’s Enthusiasm for Supporting Respondents
After the PMDA’s consultation service, did you gain the impression that the PMDA was
enthusiastic about helping you?
n=21 n=19
Agree 12 57%
63%
Neither agree nor disagree 5 24%
26%
Disagree
2 10%
11%
Not applicable 2
10% n/a
Table 41: Effect of Consultation on Respondents’ Confidence
Throughout the consultation process, did you think that the PMDA helped you increase
your confidence in understanding regulatory activities to develop a medical product?
n=21
n=18
Agree 10 48%
56%
Neither agree nor disagree 6 29%
33%
Disagree
2 10%
11%
Not applicable 3
14% n/a

Then, respondents were asked to comment on any positive or negative experience
with their interaction, and 12 responses were received (Table 42).

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Table 42: Comments on the PMDA’s Consultation Services for SMEs or
Academia
To what extent have your expectations have been realized? Please describe any positive
or negative experience that you have had with the PMDA’s consultation service for SMEs
or academia.

JP respondents (n = 12)
1. Again, their comments are always vague, and you are forced to read between the lines.
2. The PMDA does not give us definitive answers, but they give us approximate suggestions and
intentions, which I think is sufficient. The PMDA has never said that "that content will pass our
review"; however, they suggest things like "you need this". In addition, they consider proposals that
match our development status, and I think they understand the position and environment of venture
companies very well.
3. The results of the face-to-face consultation meeting with the PMDA were explained to a third party,
which helped advance the business forward.
4. I do not think the PMDA changes the quality of its services because the applicant is a small business
or an academic institution.
5. When we presented them with the appropriate information, they were sincere in their efforts. But, if
we tried to proceed with insufficient information, the PMDA would ask us to consider further.
Based on my own experience, I believe we had a reasonable exchange.
6. I was able to get an opinion from a neutral point of view. No need to be strangely positive.
7. There were times that the tone of the PMDA up until the preliminary consultation meeting and that
at the official consultation meeting had been changed; in a way, I felt betrayed by the PMDA.
8. In the case of the pharmaceuticals evaluation division, if the content of the formal consultation
meeting is not what the PMDA expects, they only say "No" and do not provide an alternative plan.
However, in the case of the regenerative medicine products evaluation division, the correct method
to consider is explained in detail at the time of the PMDA opinion letter and can be addressed to
some extent in response to the opinion letter; and, some meaningful outcome can be obtained
through an official consultation meeting
9. It was satisfactory enough
10. As the conversation is going nowhere in Japan, we decided to go ahead with Europe and the U.S.
11. Scientific knowledge is so poor
12. About 80%

Respondents were asked if they needed to interact with, or tried to interact with,
somebody at the PMDA. Almost all respondents (96%, 23/24) felt they needed to
interact with someone at the PMDA. Fifteen (63%, 15/24) tried to contact someone at
the PMDA (data not illustrated). The 23 respondents who answered Yes to one or both
of these questions were then asked whether they could reach the PMDA staff when
necessary (Figure 30). When asked “the PMDA staff were easily accessible,” four
respondents answered that it did not apply to them. Of the remaining 17 respondents,
more than three-quarters (76%, 13/17) were “satisfied,” one was “neither satisfied nor

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dissatisfied” (6%, 1/17), and three were “dissatisfied” (18%, 3/17). Likewise, when
asked whether “PMDA staff was quick to respond,” three respondents answered that it
did not apply to them, and one did not respond. Of the remaining 17 respondents, more
than half of respondents (64%, 11/17) were “satisfied,” four (24%, 4/17) were “neither
satisfied nor dissatisfied,” and two (12%, 2/17) were “dissatisfied. Concerning the
questions whether “the PMDA staff provided high-quality advice,” three respondents
answered that it did not apply to them. Of the remaining 18 respondents, forty-four
percent (8/18) were “satisfied,” six were “neither satisfied nor dissatisfied” (33%, 6/18),
and four (22%, 4/18) were “dissatisfied.”
Figure 30: Reaching the PMDA Staff When Necessary
During the consultation process, were you able to reach PMDA consultants?

In addition, the respondents were asked whether they thought that the PMDA staff
had sufficient knowledge to answer their questions. Four answered that it did not apply
to her/him. Of the remaining 16 respondents, 12 (75%, 12/16) agreed, and four (75%,
4/16) disagreed (data not illustrated). Eight commented on the positive or negative
experiences when interacting with the PMDA personnel (Table 43).

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Table 43: Positive/Negative Experience Interacting with PMDA
JP respondents (n = 8)
1. The PMDA has extensive knowledge about GxP but none about science.
2. If you have a long relationship with the PMDA, you can distinguish knowledgeable personnel and
those who are not. If the contact person is not familiar with the situation, we will check directly with
the chief or reviewer level. However, for those who have a consultation meeting for the first time,
the difference in advice between those who are knowledgeable and those who are not may be a little
confusing.
3. The PMDA went into quite a bit of detail, which helped us understand more about the regulations in
Japan.
4. Galapagosization. They do not know much about the world.
5. The person in charge is too busy to contact.
6. If the officer in charge cannot immediately answer, they review it separately in the team and answer.
7. They will never tell us anything definitive, so the company will have to make the final judgment and
decision by itself. They often say that "I can say that this is right”.
8. I had the impression that they could accommodate my low level of knowledge.

Then, they were asked in more detail about their satisfaction during the PMDA
consultation services. Two respondents answered that these questions did not apply to
them. Of the remaining 20 respondents, about half were satisfied with their “overall”
experience with the service (S: 55%,11/20, Neither: 25%, 5/20, NS: 20%, 4/20)
(Figure 31). In particular, more than half were satisfied with the “value of the
consultation” (S: 65%, 13/20, Neither: 20%, 4/20, NS: 15%, 3/20) and about half with the
“cost of the consultation service” (S: 55%, 11/20, Neither: 15%, 3/20, NS: 30%, 6/20)
and with the “quality of the consultation service” (S: 55%, 11/20, Neither: 25%, 5/20,
NS: 20%, 4/20). Forty percent were satisfied with the “timeline of the consultation
service” (S: 40%, 8/20, Neither: 20%, 4/20, NS: 40%. 8/20), and 20% (4/20) with the
“convenience of forms and documentation” (S: 20%, 4/20, Neither: 50%, 10/20, NS:
25%, 5/20). Seven made additional comments (Table 44).

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Figure 31: Satisfaction/Dissatisfaction with the PMDA Consultation Service
Think about your most recent experience with PMDA’s Pharmaceutical Affairs
Consultation on Research and Development Strategy – RS General Consultation and RS
Strategy Consultation (R&D). What is your level of satisfaction for each one of the
following?

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Table 44: Satisfaction/Dissatisfaction with the PMDA’s Consultation Service
JP respondents (n = 7)
1. PMDA still requires documents to be submitted with hard copies. They need to live out of their
caves.
2. As the schedule of the PMDA is quite tight, we often face the problem that the date/time of the
consultation meeting has become later than expected when scheduling a consultation meeting these
days. I think there may be a shortage of staff.
3. We were able to get responses on the general process, but due to the novel nature of the drug, we
were not able to get clear answers on the technical details.
4. Our company had people with development experience, so there was no problem, but I got the
impression that the format [of the consultation meeting] was very unique, so it would be difficult for
other companies to experience this for the first time.
5. It is cumbersome to have to print out and bring a large number of application forms. During the
spread of the coronavirus, e-mails and CDs have been accepted, but in the past, it was necessary to
print out dozens of copies of thousands of pages of documents and bring them with us. I hope this
will change in the future
6. We recognize that the applicant’s lack of preparation (experience, knowledge, and human resources)
is a problem.
7. The response to consultation items, inquiries, and opinions has been generally positive, with
messages being easy to understand and the intentions and circumstances of the consulted parties
being understood.

4.4.2 Feedback from Respondents who did not Use the PMDA’s Consultation
Services to Support SMEs and Academia
Eleven respondents who had not applied for or had not had a PMDA consultation
meeting were asked why they did not apply/use the consultation service (Table 45).
Table 45: Reason(s) Not to Apply or Have the PMDA Consultation Service
JP respondents (n = 8)
1. I could not find detailed information on how to apply for the consultation meeting. (4)
2. The contents of the consultation meeting were not what I had expected. (3)
3. The timeline toward the consultation meeting did not meet my expectation. (1)

They were also asked, “what if anything more would you like to see the PMDA
do to accelerate the commercialization of new medical products developed in SMEs or
academia?” Two respondents commented, as shown in Table 46.

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Table 46: Reasons for Not Pursuing PMDA Consultation Services
JP respondents (n = 2)
1. Startups are short on money and talent. It would be very helpful if they could further lower the
hurdle to start drug development, for example, a system that allows people to easily consult with the
PMDA on how to create a development plan.
2. Since our company is still in the early stage, we have not encouraged people to consult with the
PMDA. However, we would like the PMDA to understand what it is like to develop a medical
product in a small or medium-sized venture without funds.

When asked whether they were interested in attending a consultation meeting to
support universities, research institutes, and SMEs, all six respondents answered Yes
(100%, 6/6) (data not illustrated). These six respondents were asked if there was
anything that they would like to see the PMDA do to accelerate the commercialization of
the new medical products developed in SMEs or academia. Their comments are shown
in Table 47.
Table 47: Comments on Potential Ways to Accelerate Commercialization
JP respondents (n = 6)
1. I would like to see publicly-funded POC studies, as the NIH is doing.
2. It is not easy to find where to go to get information about the PMDA.
3. I still have a strong impression that they are regulators. I expect the PMDA to send out information
in quantity and quality as much as they can
4. Young companies, such as SMEs and startups, have to go through a development phase and build a
product concept with limited funds, but the product concept needs to be as efficient as possible to
obtain marketing approval. It is useful for these companies to have advice on developing products
based on the PMDA’s thinking as a regulatory authority. Such services are useful not only for SMEs
and startups but also for large enterprises, but they are especially valuable for SMEs and startups
5. I would like the PMDA to support the transition period from in vitro studies at the cellular level to
non-clinical animal studies. In animal studies, the amount of drug administered differs by orders of
magnitude from that in cellular studies, and the analysis methods used to demonstrate efficacy are
also at the individual level, requiring corresponding analysis know-how. This phase requires a much
greater amount of money and resources than the cellular phase, and it is the first barrier to clinical
trials, as venture companies from universities do not have the capacity or financial resources to
handle animal trials, and development may stop without moving to this phase. Proving the efficacy
of a drug at the cellular level is relatively simple and cost-effective, but animal studies are
completely beyond that scope. Therefore, it is difficult for a venture company that had previously
been a university research facility to envision its landscape, even for animal testing itself, how
exactly to do it and how to come up with the funds. I would like to see the PMDA comes up with
focused and concrete support measures for these university-originated R&D-based drug discovery
ventures.
6. I would like the PMDA to provide further support in financing, development strategy, and patent
strategy. Normally, the PMDA can only give us a perfunctory comment. I expect more useful
support.

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4.4.3 Respondents’ Awareness of PMDA’s Web Contents
All respondents were asked whether they knew that contents for “academia’ or
“industry” were present on the PMDA’s website. About a third (37%, 15/41) answered
Yes, but most (63%, 26/41) answered No.
The 15 respondents who answered Yes were asked about their level of satisfaction
in more detail. Thirteen responded. When asked “overall satisfaction with PMDA’s
Web services,” one respondent answered that it did not apply to her/him. Of the
remaining 12, only a quarter was “satisfied” (S: 25%, 3/12, Neither: 58%, 7/12, NS: 17%,
2/12) (Figure 32). Regarding “sufficient topic items for new medical product,” two
responded that the question did not apply to them. A little more than one-third were
“satisfied”(S: 36%, 4/11, Neither: 36%, 4/11, NS: 27%, 3/11). One identified that the
“look and feel of contents” satisfaction did not apply to her/him. Of the remaining 11,
about a quarter were “satisfied” (S: 27%, 3/11, Neither: 72%, 8/11, NS: 9%, 1/11). For
the “appropriate quality of information,” two answered that it did not apply to them.
More than a quarter were “satisfied” (S: 27%, 3/11, Neither: 62%, 8/11, NS: 0%, 0/11).
Only 18% were satisfied with the “performance of search function” (S: 18%, 2/11,
Neither: 72%, 8/11, NS: 9%, 1/11, N/A: 2), or “sufficient depth of information” (S: 18%,
2/11, Neither: 55%, 6/11, NS: 27%, 3/11, N/A: 2). Less than 10% were satisfied with the
“ease of navigating the website” (S: 8%, 1/12, Neither: 66%, 8/12, NS: 25%, 3/12, N/A:
1). Four respondents made additional comments (Table 48).

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Figure 32: Satisfaction with PMDA’s Web Contents for Academia/Industry
Based on your experience with the PMDA’s website, what is your level of satisfaction for
each of the following?

Table 48: Comments on Satisfaction with the PMDA’s Web Contents
JP respondents (n=4)
1. Navigation is difficult due to the bureaucratic web structure.
2. I cannot say anything as I have not studied their website carefully.
3. The English version does not match the Japanese version perfectly, and some of the contents seem
to be missing, making it difficult to use.
4. Since the PMDA is a government administration, I think the information they can provide is limited,
but I think they have detailed information on guidance for various procedures. However, I think the
search/navigation function could be improved

4.4.4 Respondents Unaware of the PMDA’s Website for “Academia” or “Industry”
Twenty-five respondents were unaware of PMDA’s website for “academia” or
“industry.” When asked, “Do you think that web contents specific to “academia” or
“industry” may give you more personalized/tailored support for your efforts to
commercialize medical products?” only one answered Yes (4%, 1/25) (Table 49),

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16 (64%) answered Maybe, 4 (16%) answered No and 4 (16%) answered Other. The
comments of those answering “other” are shown in Table 50.
Table 49: Respondents’ Thoughts about the PMDA’s Web Contents Specific to
“Academia” or “Industry”
Do you think that web content specific to “academia” or “industry” may give you more
personalized/tailored support for your efforts to commercialize medical products?
n = 25
Yes 1 4%
Maybe 16 64%
No 4 16%
Other 4 16%
Table 50: Comments related to Table 49
JP respondents (n=4)
1. Perhaps the direction of policy should be determined from how they want to develop and support the
pharmaceutical industry at a higher level.
2. In a sense, it seems reasonable to separate the web contents for academia from those for corporations
(large companies). (Large) companies will have a vision as a company and will proceed with
commercialization according to their size to realize that vision. This is difficult for startups
originating from academia, so the government may have to envision what they are aiming for. Of
course, it's best if startups can do it independently, but I think they should support them there
3. I do not know what they are; so, I do not know
4. With the current system, I feel that it is difficult to specialize in the various emerging ventures.

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Chapter 5. Discussion
5.1 Overview
The medical product industry must replenish its pipelines with a constant supply
of novel products. In both the United States and Japan, universities, research institutes,
and small- and medium-sized enterprises (SMEs) play a critical role by developing new
drugs and devices from their promising seed research or technologies. The academic
centers and small biotech companies are the fertile grounds for innovation (Khanna,
2012). However, they face significant hurdles as they attempt to advance those
development activities because they often have insufficient knowledge of the regulatory
system, marginal financial assets, and poor strategies for product development. These
issues can sideline emerging businesses and result in the loss of potentially valuable
therapies. Therefore, programs to assist academia and SMEs in navigating regulatory
impediments have been in place in both the United States and Japan for over a decade.
However, little systemic research has explored the opportunities and challenges related to
programs offered by the FDA and PMDA for potential end-users. This preliminary study
aimed to explore the experiences and views of the end-users and/or potential users for
these programs.
5.2 Consideration of Study Methodology
5.2.1 Delimitations
Defining scope: This study was deliberately delimited by focusing on the
satisfaction of academic and/or SME researchers or companies that had participated, been
participating, or would participate in at least one of the FDA or PMDA’s programs to
support them in medical product development. To guide the exploration of that question,

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I used the conceptual framework of “service gaps” described by Hill (Hill, 2000). This
framework proved helpful to organize a focused analysis by grouping survey results
according to how they addressed one or more of five areas of service gap. However,
what this approach achieves in focus, it loses in breadth. Thus, findings in other areas,
such as the use of other regulatory resources and the match between regulatory
expectations and logistical capabilities, are beyond the boundaries of the work described
here.
Choice of respondent group: This research was further delimited to explore the
views of only one group of stakeholders, SMEs, who are the potential “clients” of the
services offered by the FDA or PMDA. It, therefore, does not include the views of the
service providers (the FDA or PMDA) or other potential stakeholders, such as private
funding groups that might also be working with academia or SME researchers. The
delimitation was felt to be needed to ensure a more homogeneous pool of academic and
SME respondents with experience in medical product development. In the past, the
views and needs of this group were often lost as policies were shaped by large medical
product companies with the resources to place assigned employees on advisory
committees, standards, and policy-setting groups (Gilbert et al., 2004). In comparison,
academia and SMEs have few resources and modest regulatory knowledge/skills to
inform policies and take advantage of programs unless they are well advertised (Moscicki
and Tandon, 2017).
Confinement to regulatory support programs: Academic or SME researchers face
many challenges during product development, such as securing financial support and
hiring teams. This study focused specifically on regulatory hurdles along the

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development path and was further delimited to stakeholders in only two countries, the
U.S. and Japan. Such a geographic focus was considered appropriate because, for
medical devices, the U.S. and Japanese systems have similar underlying approaches to
regulatory approvals for innovative/novel medical products. Regulatory agencies do their
reviews (Altenstetter, 2012, Lobmayr, 2010), an approach that is not taken, for example,
by the EU, where privately held notified bodies conduct most reviews. Inclusion of other
countries at this early stage would be therefore challenging because programs to enhance
the participation of SMEs vary substantially and often are not implemented by the health
authorities. A follow-on study examining how programs are structured to enhance
innovation through regulatory support would now be interesting to carry out in other
countries. Such studies would give additional insight into the degree of support and
satisfaction that the respondents receive when trying to enter markets globally. However,
such a study in the EU, an obvious large player, would be difficult at this moment in time
because the EU regulatory system is in transition. Many companies are coping with the
new European Medical Device Regulations, which are much more stringent (EU, 2020).
Whether the smaller companies and academic laboratories find this transition to be
challenging and whether the notified bodies and European governments also develop
supportive programs will be important to understand after the new MDR system has
become adopted widely.
5.2.2 Limitations
Several limitations to this preliminary study were anticipated. Some were due to
the challenges common to any research study; others were derived from this specific
research study.

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Lack of Previous Literature/Research: Little has yet been written about the views
and experiences of the broader community of investigators or SMEs that have been or
will be potential users of the regulatory service provided by the FDA and PMDA. Most
surveys done before have focused on the views of larger companies. For example, the
research of Berndt and colleagues (Berndt et al., 2006) focused on the interaction
between the FDA and the biopharmaceutical companies that perform drug R&D was
conducted on 49 professionals at medium to large companies. However, previous
research usually lays the theoretical foundations for the research problem for subsequent
researchers. Without that background research, it is more challenging to develop a
survey that allows for an analysis of trends and an exploration of central issues seen
previously. Thus, it appeared essential to critique the questions in the survey with a
different approach by using a focus group convened to discuss each survey question. The
focus group provided insights into how the questions might be improved and what areas
should be examined more carefully from the practitioners’ point of view. Previous
studies (Gower, 1993) have used such a focus group to improve the wording and content
of the questions and to provide a measure of “face validity” (Schwab and Margaritis,
2020) to the survey tool as a whole.
Finding Representative Participants: The validity of results from a survey
depends in part on the representativeness of the respondents. Representativeness refers to
how well the sample drawn for the study compares with the population it purports to
represent (Fincham, 2008). The greatest potential limitation to achieving this
representativeness was securing enough professionals in academia or SMEs with
knowledge and experience related to the government programs of interest. The number

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of experienced professionals with such a profile is relatively small and difficult to find.
No systematic list or directory is available nationally for such academic enterprises or
small companies because they typically have no commercialized products or promotional
activities.
Further, the limited literature related to this question did not provide a good
source for names of potential participants whose backgrounds would be appropriate.
Thus, other ways were explored to find potential respondents from reliable sources.
Pediatric accelerators in the U.S., such as the West Coast Consortium for Technology &
Innovation in Pediatrics (CTIP) (Espinoza et al., 2020), were particularly useful sources
for such companies. These organizations have a broad reach and were willing to reach
out to their memberships to solicit participation. In the U.S. survey, 24 of 54 medical
device companies that developed medical devices for pediatric patients were therefore
recruited nationally from this pool of companies; these companies often were developing
devices for more general markets at the same time. Such an enrichment raises the
question of whether challenges in developing a pediatric medical device would differ
from those developing adult devices and would bias the survey's overall results with
respect to devices in general. The concern was, to some extent, allayed by cross
tabulating the results from respondents who reported that they worked on medical devices
generally and those who specified pediatric medical device companies; both groups
showed similar trends in their responses for those questions whose sample sizes were
large enough to be assured that the answers had similar distributions (Appendix C and
Appendix D).

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Nevertheless, caution is advised in generalizing the results of this survey too
widely. For example, most of the companies I approached had associations with
accelerators or organizations designed to help SMEs. Some companies may be so new
that they are not even part of these organizations, so they were more difficult to find and
recruit into the survey. However, those new companies may have even less knowledge
of regulatory systems than the typical respondents represented here, whose associated
networks can often help them understand at least the basic elements of that path and can
provide certain resources that might be of value. For example, the finding that many
respondents learned about the FDA’s support programs from consultants and technology
support organizations may point to the importance of these sources of information as a
conduit to finding governmental programs. However, the ability to mine more deeply the
backgrounds of the participants was constrained by the study’s design to ensure
confidentiality and anonymity.
Assuring sufficient and accurate responses: The fact that relatively little
information is available about respondents in the study also has implications for assessing
the respondents' level of knowledge and willingness to participate. Researchers have
limited control over which and how many participants fill out the questionnaire in survey
studies such as this. This lack of control can reduce the survey's trustworthiness (Lefever
et al., 2007). The first major issue that can reduce validity is the survey completion rate.
The overall completion rate (36%, 52/143) for U.S. participants was lower than for
participants in Japan (62%, 38/61).
Nevertheless, these response rates are still considered within the typical and
acceptable range of response rates in studies involving industry professionals. For

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example, in his meta-analysis of response rate in 175 different academic studies, covering
about 200,000 respondents, Baruch reported an average response rate of 36.1% with a
standard deviation of 13.3 in studies involving top management or organizational
representatives. (Baruch, 1999).
Another potential concern when recruiting participants is obtaining input from
those with sufficient experience and experience. The demographic profiles provided
good evidence that the survey reached the appropriate population. Of those who
responded, most were at the Director level or above, and most worked in small
organizations/companies with less than 20 employees (75% for the U.S. and 67% for
Japan). In these small companies, leaders often play multiple roles (Jing et al., 2014), an
observation consistent with the finding that many respondents gave multiple answers
when asked about their roles. The relatively senior profiles of most respondents support
the conclusion that the individuals had enough experience to answer the questions in a
knowledgeable way. Although the sample size was too small to conduct sophisticated
statistical analyses, the number and quality of responses from the participants in
academia and SMEs suggest that I acquired a sufficient cross-section of the target group
to obtain some measure of saturation (Baruch, 1999).
Cross-cultural concerns: This survey was administered to respondents from two
cultures. Cross-cultural surveys can pose significant conceptual, methodological, and
organizational challenges (Smith, 2020). One such challenge, for example, is the
willingness of the participants to answer what they perceive as sensitive questions, a
concern that might be affected by cultural differences. Therefore, it was critical to
identify relevant variables to ensure that the participants interpreted the questions as

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intended by the researcher. These considerations are particularly important when
subjects have different cultural backgrounds and when the researcher does not have the
opportunity to interact or answer questions face to face (Becky et al., 2017).
Comparisons are also complicated because the programs offered in the United
States and Japan are different. Thus, I tried to align the questions to permit some
comparisons of respondents’ views without bias. To minimize potential errors in the
interpretation of the questions in the Japanese survey tool, several Japanese medical
device or pharmaceutical experts reviewed the survey design and Japanese translations to
assure that the wording and choice of survey questions were compatible with the
Japanese culture and had the same meanings as the English version. An area of some
concern was the possibility that the participants might be reticent to share what they
might consider sensitive information. This concern was, in fact, not a problem that
seemed supported by the detailed and honest views expressed by many Japanese as well
as U.S. respondents. In this regard, it seemed that respondents felt that they could be
forthcoming given the promise of anonymity.
5.3 Insights of Results
The “service gap” theory aims to characterize the differences between
expectations and experience with respect to a particular service program and is often used
when examining customer satisfaction. Hill has identified that the root causes of
dissatisfaction can be assessed by analyzing contributions in one or more of five areas:
promotional gap, understanding gap, procedural gap, behavioral gap, and perception
gap (Hill, 2000). These five taken together can affect overall perceptions of service

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quality that can make a customer satisfied or dissatisfied. Thus, key findings of this
exploratory research are considered below in the context of this set of service gaps.
5.3.1 Promotional Gap
As described in chapter 2, the promotional gap describes “the inability of the
business organization to fulfill expectations created in the minds of customers mainly by
marketing communications.” In other words, “what is said about service differs from the
standards actually delivered” (Grigoroudis, 2010). Often, the source of the problem can
stem from misleading or insufficient information about relevant services (Hill, 2000).
In this study, regulatory agencies seemed particularly challenged when trying to
ensure that academia and SMEs even knew about the special services that they provided.
This problem seemed greater in the U.S. than in Japan; 43% of the U.S. respondents and
14% of the Japanese respondents did not know that their regulatory authority offers
various services to support academia and SMEs. Such differences could be explained by
sampling differences if, for example, one group had a greater proportion of small
organizations whose less mature products did not motivate them to learn about regulatory
activities. However, cross-tabulations suggested that the Japanese respondents in the
smallest organizations were more aware of relevant services; nearly half of the U.S.
respondents in the smallest companies were unaware compared to fewer than 20% of
those in Japan (Table 51). Did this lack of awareness stem from a lack of interest? When
those who were unaware found out about those services during this survey, most
respondents in both the U.S. and Japan were interested in learning more. This is not
surprising because small and medium-sized medical product developers are well-known
to be confused and concerned about how to navigate the regulatory path for their products

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(Hudson and Khazragui, 2013) and would no doubt welcome any help to support these
efforts.

Table 51: Crosstabulation of Awareness of by the Size of the Company
US (n=51) Did you know that the FDA has services that provide technical and regulatory
assistance to small manufacturers, academic laboratories, and research
organizations to help them comply with regulatory requirements?
Total
1-20
employees
21-100
employees
101-300
employees
301-500
employees
Yes 30 23 4 2 1
No 21 19 2 0 0

Japan (n=41)

Have you heard about PMDA’s Pharmaceutical Affairs Consultation on
Research and Development Strategy – RA General Consultation and RS
Strategy Consultation (R&D)?
Total
1-20
employees
21-100
employees
101-300
employees
301-500
employees
Yes 36 24 10 2 0
No 5 5 0 0 0

Results also suggest that academic organizations and SMEs commonly use
websites or computer searches to find information about regulatory support systems. The
increasing use of online resources is consistent with current trends across all sectors of
the economy. As stated by Åkesson et al., service encounters, a term used to describe the
primary contacts between a service provider and its customer, have relied on personal
interactions between frontline employees and customers in the past. More recently,
however, such interactions have been mediated increasingly by technology (Åkesson et
al., 2008). Properly managed, these service systems can be a powerful way to introduce
programs and manage entry into what will be a longer-term regulator-company
relationship. Regulators might thus be able to increase the uptake and satisfaction of
SMEs with their targeted regulatory offerings if those programs were to be promoted

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more widely and if the government websites were reevaluated so that SMEs could
navigate to relevant pages of those websites more efficiently.
5.3.2 Understanding Gap
The understanding gap is explained as “the gap that occurs when managers in the
organization fail to understand customer needs and priorities” (Hill, 2000), “due to the
inaccurate understanding of customer needs and priorities by the managers of the
organization” (Grigoroudis, 2010). If the organization is not aware of what is important
to customers, it is less likely to “do best what matters most to customers” (Hill, 2000). In
other sectors, a service design approach is used explicitly to understand key customer
drivers and find customer-centric ways to achieve organizational objectives. This view
starts with acknowledging that regulators and their “customers” (e.g., academia or SMEs)
can have different needs and perspectives. These different perspectives can create
tension between the two groups (Reason et al., 2015).
However, it is not clear from the literature whether the regulatory agencies have
specific methods to assess their success in this regard. Thus, it seemed helpful to probe
whether SMEs felt that the FDA or PMDA understood their needs and priorities. This
cannot always be simple to assess, but it can be gauged by asking whether the offered
materials and advice appear to meet the client’s needs. One aspect can be the perceived
appropriateness of explanations regarding the targeted programs. In this regard, more
than half of those respondents who knew about the programs in both groups found it easy
to locate the information that they needed. Only one U.S. respondent decided not to
access the FDA services for SMEs because the website, webinar, or conference contents
were not what she/he expected. Most U.S. participants felt that the FDA website had

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given a sufficient explanation of its service (82%) and that the FDA understood the
specific needs of those who develop products in academia or SMEs (69%). The U.S.
participants’ overall satisfaction with the FDA’s web-based services was 69%.
Nonetheless, one respondent expressed that it should not be the FDA’s job to gauge the
needs of the industry related to customer support and education.
[U.S. respondent] I don’t think it’s necessarily FDAs [sic]
responsibility to be as proactive in education [sic] industry as your
questions seem to be implying they should. I also think it’s
unreasonable for FDA to tailor their outreach to the thousands of
startup companies that exist in medtech. I would certainly say that their
website needs work but what do you expect? It’s a giant government
organization.
A lower proportion of Japanese respondents appeared to feel that the PMDA
provided a sufficient explanation of the consultation process provided in advance (72%),
and about three-quarters felt that the PMDA understood the specific needs of those who
develop products in academia or SMEs, as reflected in the materials available from the
PMDA (74%). However, the respondents’ overall satisfaction with the PMDA’s
consultation services was 55%. Four respondents who had not applied for a consultation
meeting also reported that the contents or timelines of the consultation meeting were not
what they had expected. As suggested by one Japanese respondent,
[Japanese respondent] I would like [the PMDA] to study more from a
development perspective. The approval situation of drug discovery in
the world is changing every moment.

The fact that many respondents in both groups felt that the regulatory agencies
understood their needs seems to endorse the current efforts by regulators to understand
the needs of academia and SMEs. Still, satisfaction levels in both samples varied. Some

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companies appeared to be comfortable with how online and other types of information
are presented, but others were confused or critical. The varying levels of satisfaction are
interesting because they suggest that what is often viewed as an undifferentiated group of
“SMEs” includes a broad spectrum of companies with different needs and experiences
concerning regulatory interactions. It would be interesting to explore further why these
programs seem straightforward to navigate for some but difficult for others.
The concerns of a minority may suggest some room for improvement. One way
that regulatory agencies could improve their understanding is by conducting a more
formalized needs assessment. Such assessment could help regulators tailor the
information that they deliver and revisit the priorities assigned to different customer
needs. The CDER at the FDA has started to embrace this approach through its
Professional Affairs and Stakeholder Engagement (PASE) initiative to promote a culture
of two-way engagement. As part of this initiative, FDA states its intention to ensure that
the CDER has a thorough understanding of partner, stakeholder, and public opinion about
issues of interest to the CDER through appropriate research (FDA, 2019d). In addition,
the CDRH Learn website has a link to a survey that allows its stakeholders to
communicate their recommendations so that it can improve its services (FDA, 2021d).
Used wisely, analyses of these valuable resources might suggest improvements to reduce
the gap.
5.3.3 Procedural Gap
The procedural gap is explained as “the gap that occurs when translating customer
expectations into appropriate operating procedures and systems with the business
organization” (Hill, 2000). In other words, “customer’s expectations are not translated

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into appropriate operating procedures/systems” (Grigoroudis, 2010). This aspect is
perhaps the most logistically demanding of the five “gaps” because it focuses on the
procedures and processes associated with “service encounters.” These service encounters
are typically consultation meetings or written responses to inquiries but could include
training events or presentations and discussions at meetings and workshops. For
example, the FDA has a learning portal for students, academia, and industry to provide
education and resources related to FDA’s regulation, product quality, and safety (FDA,
2018b); people can search training programs by subject (or type of products) or by FDA
organization. The FDA’s website has also had Guidance Webinar Series to foster
collaboration and transparency in developing guidance documents via direct outreach to
the affected stakeholders (FDA, 2017e), which unfortunately has not been updated since
June 2017. However, “CDERLearn” and “CDRH Learn” training and education websites
have various up-to-date materials, including webinars, case studies, podcasts, and videos
(FDA, 2021c, FDA, 2021d).
PMDA also has a more modest set of web materials for academia and industry
(PMDA, 2021a). Such resources represent a valuable opportunity by which it could
increase its satisfaction with the service (Åkesson et al., 2008). This help would be
welcome reflected in some comments of respondents, who pointed to difficulties in
finding information:
[Japanese respondent] It is not easy to know where to go to get
information about the PMDA.
[U.S. respondent] … I have read every link the FDA publishes about
how to prepare for a med device submission...and I still do not know
how to do it by myself. This is why people hire regulatory consultants
rather than engage with the FDA directly. The published information is
complex, sometimes contradictory, and it is extraordinarily difficult to

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determine what is relevant to a specific project based on the
information provided. It would be hugely helpful to have the equivalent
of a "customer service rep", basically the FDA's own regulatory
consultant, help with deciphering the requirements….

Even though websites can be helpful, 80% of the U.S. respondents and 100% of
the Japanese respondents believe they need to interact with someone at the FDA or the
PMDA. Well-structured procedures and timelines are required for such interactions, and
the feedback here suggests that improvement in this domain is much needed. As
suggested by two Japanese respondents,
[Japanese respondent] As the schedule of the PMDA is quite tight, we
often face the problem that the date/time of the consultation meeting
has become later than expected when scheduling a consultation
meeting these days….
[Japanese respondent] Our company had people with development
experience, so there was no problem, but I got the impression that the
format [of the consultation meeting] was very unique, so it would be
difficult for other companies to experience this for the first time.

As the respondents identified above, the consultation process may not be straightforward
for a beginner. For example, Figure 33 shows a typical process flow and timeline of the
Regulatory Science (RS) strategy consultation meeting with the PMDA. Similarly,
consultations in the U.S. take many weeks to schedule and require the submission of
detailed briefing information, steps that can be resource-intensive and intimidating for
small organizations.

147
Figure 33: RS Strategy Consultation Process Flow (Example)

Some concerns expressed in this survey were more specific. For example, one
way that consultation experiences might be improved from a procedural point of view is
to examine how documentation is handled. One Japanese respondent was critical of the
need to bring many printed documents to a PMDA meeting. That respondent was
encouraged by the change in requirements for such paper records, made necessary by the
constraints of the COVID-19 pandemic. Another commented that the PMDA had
replaced its reliance on facsimiles and paper copies by accepting emails and CDs during
the pandemic and hoped this would be carried over in the future as standard
communications methods. It will be interesting to see whether the revisions of
procedures and documentation will become incorporated more permanently when
pandemic conditions recede. Current experiences might also give helpful lessons to
avoid returning to a less satisfactory procedural state. For example, respondents working

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with the PMDA had concerns about the convenience of forms and documentation and
frustrations with scheduling.
[Japanese respondent] The PMDA’s schedule is quite tight, so we often
face a later date than expected when scheduling a consultation meeting
these days. I think there may be a shortage of staff.
[Japanese respondent] We recognize that the applicant’s lack of
preparation (experience, knowledge, and human resources) is a
problem.

These types of comments are useful because they could be used to prioritize areas that
might be characterized as “low hanging fruit,” which could be improved in a targeted
way.
Given that helpful programs do exist, it would make sense for regulators to
provide more information to academia and SMEs about how to navigate their “service
encounters.” A well-designed service system should operate seamlessly across
departmental and other organizational boundaries if it is to provide consistent service
quality (Lytle et al., 1998). This can be difficult for regulatory agencies because,
traditionally, medical devices are handled in a different way and by a different center
than drugs, for example (FDA, 2019a, PMDA, 2021b). However, in today’s world,
combination products and advanced therapies that sit at the boundaries are often
developed by innovative academic or startup companies. These companies might need a
more integrated and comprehensive way to understand how different components will be
regulated within the U.S. or Japanese frameworks because each component is subject to
different regulations and will be evaluated by different review groups.

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The PMDA levies fees for their consultation services. These may be a
disincentive for under-resourced small companies to seek assistance in Japan, as reflected
below:
[Japanese respondent] … The negative point is that RS consultation is
divided into cell/tissue processing products and gene therapy products.
Both may apply to one product, in which case at least four
consultations are required: the quality and non-clinical safety of
cell/tissue processes products and those of gene therapy products. … If
four consultation meetings are required, it will be a heavy burden for
the venture.”

Perhaps, regulators in Japan should consider improving the integration of the existing
consultation process to lessen the financial burden for some of these SMEs.
5.3.4 Behavioral Gap
The behavioral gap is defined as “the difference between customer expectations
and the organization’s performance” (Hill, 2000). In other words, it defines whether the
“service that is delivered is different from the specification of the service.” (Grigoroudis,
2010). Service specifications are typically written guidance materials or instructions that
clarify the needs and objectives for each step and contact point of the service experience.
They often include the design concepts that inspired the project and helped define the
anticipated experience's foundation (sdt, 2021).
It is difficult in a study such as this to match the service specifications of the
regulatory agencies against the behaviors of the participants in the regulatory exchanges.
First, it is not clear to what extent such documentation exists. Regulatory interactions are
more sophisticated and personalized than often studied transactions such as sales calls or
online purchasing. Thus, a stereotypic set of protocols may be difficult to formulate.

150
Second, if such specifications do exist, they may be internal to the agency. Certainly,
such documents are not found in the literature or on any of the FDA websites that have
been examined as part of the literature review. However, the FDA has made some
attempts to specify the service that it provides through its mission and vision statements:
CDER SBIA’s mission is to engage with small pharmaceutical business
and industry by providing timely and accurate information on human
drug development and regulation.
Our vision is to ensure that every industry representative can always
find the resources they need, allowing for a clear and efficient approval
process and safe and effective human drugs options. (FDA, 2021b)

It is also clear that the FDA is making efforts to improve customer service. One
way to gain feedback on behavioral gaps can be by soliciting concerns from the
stakeholders. Thus, it is interesting to observe that emails from the FDA often contain
the following language, an option for providing feedback (Figure 34).
Figure 34: At the Bottom of the FDA’s Email (Example)

Excellent customer service is important to us.
Please take a moment to provide feedback regarding the customer service you have received:
Click here for survey

However, it is not clear whether this feedback is used in any way to gather feedback on
the satisfaction of small businesses with the services it provides.
In Japan, a comparable mission/vision statement specific to academia and SMEs
cannot be found on the PMDA website; however, in its “Profile of Service” brochure,
they explained their Regulatory Science Strategy Consultation program as follows:

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“PMDA offers consultations to universities, research institutions, and
companies that develop medical products to give guidance and advice
on development strategy, clinical trial protocols, and data packages for
regulatory submissions. A variety of consultations are available for
users’ convenience, so that companies can request a consultation
suitable for their needs at any stage of development of a medical
product (PMDA, 2019).”

Nevertheless, clients of regulatory interactions seem to have an implicit view on
what might be considered “service specifications,” which base their scrutiny of the
interactions. Anecdotal statements and informal surveys often critique the behaviors and
performance of reviewers or inspection teams because these individuals are the human
interface with their industry clients (Brennan, 2015). Commonly the views have focused
on the inconsistencies in approaches or recommendations from different regulatory staff
members with whom they have interacted, particularly when mixed messages are
received from the staff at different job levels or branches (Milne and Kaitin, 2012). For
example, Berndt et al. conducted interviews with 49 senior R&D/Regulatory Affairs
officials at 17 biotech, biopharmaceutical, pharmaceutical, and CRO organizations. In
almost every company interview, they reported that respondents mentioned “a high
degree of variability in competence, communications and implementation of rules and
regulations across divisions at the FDA (Berndt et al., 2006).” Thus, it was not surprising
that some respondents in this study were concerned about similar inconsistencies when
communicating with the FDA or the PMDA.
[The U.S. Respondent] There is no consistency in the quality of the
reviewers.
[The U.S. respondent] Each review branch is different, and I had both
very positive and very negative experiences with the FDA staff.

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[Japanese respondent] There were times that the tone of the PMDA up
until the preliminary consultation meeting and that at the official
consultation meeting had been changed; in a way, I felt betrayed by the
PMDA.

An important element that is not often captured in service specifications is the
enthusiasm and encouragement that the regulatory personnel should project when they
engage with industry representatives. In a business context, effective communication
requires information that is not only timely and accurate but also communicated in an
empathic, courteous, and enthusiastic manner (Webster and Sundaram, 2009). In this
study, a relatively positive behavioral environment was suggested by half of the
respondents, who regarded the FDA as enthusiastic about helping them. Those
interactions also appeared to increase the confidence of most respondents with their
regulatory activities. Interestingly, although the overall satisfaction rate of the Japanese
respondents was lower than that of the U.S. respondents, similar to the U.S. respondents,
half of the Japanese respondents agreed that the PMDA staff were enthusiastic about
helping them. One Japanese respondent, for example, commented that the PMDA
listened enthusiastically to an inexperienced venture company.
[Japanese respondent] I have the impression that the PMDA listened
enthusiastically to an inexperienced venture company, and even though
they could not specify them, they were able to correct our directions.

Nonetheless, not all comments and views appeared so positive. Given the
importance of regulatory interactions to small businesses, it was not surprising to find
industry personnel who were critical of the attitudes and behaviors of regulatory contacts.
One area seen to be problematic was the ability of the regulatory personnel to help the
client with its problems by providing adequate information in response to questions;

153
some commented on the vague nature of the advice they received. However, it is hard to
know to what extent those negative evaluations were fully deserved. Small businesses
and academic groups can have high, and maybe unrealistic, expectations for those
interactions. They may expect the regulators to serve as their consultants and may be
disappointed when regulators cannot strategize to develop a detailed program plan but
rather limit their feedback by answering only specific preprepared questions. The
difference in expectations between regulators and SMEs may be particularly problematic
when the SME has paid a fee for the consultation, as is required in Japan, and is
discussed more fully below.
Regulators must expect that most SMEs will be naïve about regulatory
interactions and are often anxious about the advice. New companies can be blindsided by
the amount of development work that regulators insist is needed beyond that anticipated
prior to the start of the interactions. Therefore, it might be useful for regulatory agencies
to develop specific service specifications for their staff related to the special challenges of
interacting with SMEs. As previously mentioned, the CDER’s PASE and CDRH Learn
are trying to find ways to improve their service level by conducting their evaluations of
SME interactions. This research might be a good starting point to create curricula for the
FDA reviewers who interact with SMEs so that they can anticipate the special
sensitivities of that group and improve the consistency and depth of advice. They might
study the types of questions that SMEs ask most frequently during those consultations so
that reviewers are prepared with consistent answers or appropriate guidance materials
such as Frequently Asked Questions (FAQs) or publicly available educational resources.
The results might also reinforce the importance of communicating enthusiasm and

154
engagement when dealing with small companies and academicians, for which regulators
were already given positive ratings by most.
5.3.5 Perception Gap
The perception gap is defined as “the differences between the perceptions of a
customer regarding the organization’s performance and the reality of that performance”
(Hill, 2000). In other words, “the level of service perceived by customers differs from
the service actually provided” (Grigoroudis, 2010). Thus, it relates in some ways to the
behavioral gap. However, it is differentiated in this framework because it anticipates that
the customer's perceptions relative to the reality of the interaction can be examined by
looking from the outside at the interaction that took place. The “reality of the
performance” is very difficult to assess when dealing with regulatory consultations. It
would require that the actual consultation be watched, analyzed, and rated to see if the
customer's negative or positive opinions were aligned with an outside assessment of
consultation using some other, preferably standardized, metric.
Three problems are present. First, regulatory consultations, interactions, and
responses to questions are considered confidential at this early stage (PMDA, 2021d,
FDA, 2017a); with few exceptions, video/voice recording is disallowed to protect the
proprietary information shared by the SMEs in the sessions (PMDA, 2020b). Therefore,
only attendees know what exactly was discussed in these consultation meetings. Second,
even if it were possible to capture the actual workings of the consultation or interaction,
what would be the metric to determine if that interaction was at, above, or below the
standard on which the participants pass judgment? Thus, when respondents identify that
the FDA or the PMDA provided the service or information they needed to their

155
satisfaction the first time, it remains to be determined whether that rating was appropriate
related to the “reality” of the interaction. It could be that the expectations of the
participant were unreasonably low. Alternatively, when respondents have negative
views, it may be that their expectations were unrealistically high. Third, even if it were
possible to evaluate the interactions, the needs of small companies can be highly diverse.
They are developing different types of products, but they may also be at different stages
of development or have specific questions related to certain aspects of that development.
For example, one academic group might be confused about the requirements for animal
testing, another about the requirements related to analytical or quality aspects of drug
formulations or device prototypes. Thus, any external metric to define a “superior” or
“inferior” consultation would be difficult to set.
Nevertheless, the comments in some cases were specific enough to be worth
consideration. Comments that praise the quality and depth of information are likely to
reflect the “reality” that a good quality of service was provided. Notably, positive
evaluations were more frequent for the FDA than PMDA. However, the differences may
not relate only to differences in the quality or nature of the services; they could also relate
to the fact that the service, including the consultation meeting with the FDA, came “free”
in the U.S. whereas that from the PMDA had a price. Zeithaml et al. explain that price
can set expectations for the quality of service (Zeithaml, 1990). Detailed fees for
Regulatory Science (RS) Consultations at the PMDA are shown in Table 52 below.
Although fees have been reduced for qualified academic organizations or SMEs, the fact
that they exist may increase expectations concerning the expected value of the

156
consultation. Thus, caution must be used to avoid an “apples-to-apples” comparison
between the services offered by the FDA and PMDA.
Table 52: PMDA Regulatory Science Consultation Fees
Consultation Category Fees (JPY)
University, research
institution, or
venture company,
meeting specified
requirements
RS Strategy Consultation (R&D) for Drugs ¥1,541,600 ¥154,100
RS Strategy Consultation (R&D) for Medical Devices ¥874,000 ¥87,400
RS Strategy Consultation (R&D) for Regenerative Medical
Products
¥874,000 ¥87,400
Consultation on Quality and Safety of Regenerative
Medical Products
¥1,541,600 ¥154,100
Additional/Follow-up Consultation on Quality and Safety
of Regenerative Medical Products
¥496,800
RS Strategy Consultation (R&D) on Pharmaceuticals
Development Plans, etc.
¥73,600
Source: An Excerpt from PMDA Website, translated into English and partially modified (PMDA, 2021c)
Part of the disconnect between SMEs and regulatory agencies may also occur
because the relationship between regulators and clients is not unidirectional. Regulators
also have expectations of companies that shape their interactions. Haigney recommended
that pharmaceutical companies see regulators as partners and use them as a tool in their
efforts to develop and market their products, given that they share the same goal, to
provide safe and effective treatments to people who need them (Haigney, 2016). As part
of this “partnership,” however, it seems that big pharmaceutical companies raise the bar
on the perceived responsibilities of applicants, and this may be contributing to the high
expectations of the FDA about their “partner” companies. A PhRMA’s white paper
focused on “Best Practices for Communication between FDA and Applicants during the
NDA Review Cycle” summarizes some of these responsibilities, for example:

157
Applicants must accept responsibility to be fully knowledgeable about, and
follow, the FDA’s GRMP [Good Review Management Principles and
Practices] guidance document”…“applicants must meet their
responsibility to submit a complete application in order to merit a
comprehensive and complete review by FDA within a specified time
(Cocchetto et al., 2008)

These expectations may be unrealistic for SMEs only beginning to understand the
regulatory requirements related to the ideas that they are trying to develop into products.
Most SMEs are quite unfamiliar with the myriad laws, regulations, and guidance
materials that must frame their development strategies. Further, they lack the necessary
methods/people to navigate the system (Jamieson and Richmond, 2014). In contrast,
large enterprises generally have strong regulatory capabilities and loud voices, which
may dominate the regulators’ experience and expectations. Thus, regulatory agencies
may fail to recognize and understand the unmet needs of academia/SMEs despite the best
of intentions.
5.4 Conclusions and Recommendations for Future Direction
Regulatory agencies recognize the importance of SMEs. In their forward-looking
plans, FDA acknowledges that it “needs to continue to keep pace with evolving science
and technology” and to educate students, academia, and industry about “FDA’s
regulatory, product quality, safety responsibilities, and research” (FDA, 2021a).
Similarly, in 2021, the MHLW published the “Pharmaceutical industry Vision 2021,”
which included a plan to assist academia or venture companies in strengthening drug
discovery capabilities through continuous innovation. The plan acknowledged that
established pharmaceutical companies are successful because they know how to navigate
the complex regulatory, reimbursement, intellectual property, and quality systems

158
associated with medical product development. However, it also recognized that SMEs
lack such knowledge and will require involvement, advice, and guidance at an earlier
stage to commercialize discoveries with therapeutic promises coming out of academia
and SMEs (MHLW, 2021). To this end, it seems clear that governments see the
programs targeted at SMEs and academic organizations as necessary for national
economic and medical reasons worthy of special effort.
The present study suggests that the emerging enterprises also value the targeted
programs. However, those programs can sometimes miss the mark in anticipating and
responding to the needs of their stakeholders. Gaps in satisfaction are most evident in
procedures, which are often characterized as slow, bureaucratic, and unhelpful by some
respondents. Results suggest that programs could be improved if regulators take account
of the less mature state and knowledge of newly formed companies and, using this lens,
modify these programs logistically if they are to produce more effective outcomes.
Improvements in services are essential, but both regulatory agencies and clients
may need to compromise. For example, the FDA has recently noted that one of its
overburdened divisions, the Office of Tissues and Advanced Therapies (OTAT), will in
the future be unable to provide as much individual attention to SMEs as they have had in
the past. This instruction appears driven by the increasing workload of OTAT in the face
of serious personnel constraints; it has 40 staff openings at the time of this writing.
Further, OTAT wants companies soliciting help to do a better job in preparing for
interactions. OTAT is planning to update its website to implement “root
communications” that will distribute messages related to meeting preparations and
interactions by next year. OTAT Director, Willian Bryan, commented:

159
“…one challenge is that we are getting IND applications or a meeting
request that really is so grossly deficient that we can’t communicate
effectively with the stakeholders and that is taking up a lot of our time.
… That is not productive and is not helping the sponsor much either.”
(Eglovitch, 2021).

OTAT is a division that deals with advanced therapies and may not reflect the
attitudes or intentions of other parts of the FDA. Further, it cannot represent the views of
the PMDA. However, it illustrates the tension between academia/SMEs looking for
detailed and frequent interactions and regulators who have insufficient time, experience,
and authority to play the role of facilitator and consultant. Perhaps what may be needed
is to recognize that small businesses require a different approach than that traditionally
taken for large established companies. Some potentially worthwhile changes might range
from the formation of “tiger teams” of individuals trained to deal specifically with the
needs of small businesses to modified procedures that might help facilitate their
questions, submissions, and reviews. Also, it might be important to have more frequent
and earlier interactions and educational sessions to help small companies facing the
“valley of Death” (Pitts and Brady, 2018, Joelle Greenberg et al., 2017). Perhaps such
changes should not be placed entirely on the shoulders of regulators. The better
preparation of new companies with critical technologies, drugs, and devices is in
everyone’s interest and may require a team approach to protect. Thus, regulatory
agencies, universities, and the business community might consider a broader and more
deliberate effort through public-private partnerships to share the work now mostly left to
the regulatory agencies.

160
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175
Appendix A: U.S. Survey Questionnaire

176
U.S Survey Questionnaire
Q1. Thank you for participating in this survey. I value your views and needs related to
regulatory support programs that the FDA has developed to foster new medical
product development.
Your responses will be kept anonymous and presented only as part of a cumulative
analysis. Your identity will also be protected. You may not be able to answer every
question, so you can skip a question if you wish.

Please click  to start.

Go to Q2

Q2. Please list the types of organizations in which you have worked to develop medical
products in the last five years. Please select all that apply.
▢ A start-up
▢ A company with commercialized products
▢ A university
▢ A research institute in a university or hospital
▢ A government laboratory
▢ Other (Please specify) ________________________________________________

Go to Q3

Q3. Which statement best describes the size of your primary organization/company? (If
you are at a university, hospital, or government agency, what is the size of your
development group?)
o 1 - 20 employees
o 21 - 100 employees
o 101 - 300 employees
o 301 - 500 employees
o More than 500 employees

Go to Q4

177
Q4. Which statement best describes the product(s) that your present laboratory/company
develops? Please select all that apply.
▢ Drugs
▢ Biologics
▢ In Vitro diagnostics
▢ Regenerative products
▢ Medical devices
▢ Medical devices - pediatric
▢ Medical software
▢ Combination products
▢ Other (Please specify) ________________________________________________

Go to Q5

Q5. What title best describes your current responsibilities in your primary
organization/company? If more than one position is held, please select all that apply.
▢ Founder
▢ C-Suite/Senior Management
▢ Director
▢ Manager
▢ Specialist/Associate
▢ Professor
▢ Researcher
▢ Other (Please specify) ________________________________________________

Go to Q6

178
Q6. Which job function(s) do you represent in your present
organization/company? Please select all that apply.
▢ Business Development
▢ Board of Advisors
▢ Clinical Affairs
▢ Project Management
▢ Regulatory Affairs
▢ Research & Development
▢ Other (Please specify) ________________________________________________

Go to Q7

Q7. At what stage in the development of a new product does your organization usually
begin to plan its regulatory filing strategy for market approval or clearance? If you
work for more than one organization or group, please reflect on the one with which
you have the most experience.
▢ Proof of concept
▢ Non-clinical studies
▢ Phase I clinical trial
▢ Phase II clinical trial
▢ Phase III clinical trial
▢ Feasibility study (medical device)
▢ Pivotal study (medical device)
▢ Other (Please specify) ________________________________________________
▢ I do not know.

Go to Q8

Q8. Did you know that the FDA has services that provide technical and regulatory
assistance to small manufacturers, academic laboratories, and research organizations
to help them comply with regulatory requirements?
o Yes
o No

If “Yes”, go to Q9
If “No”, go to Q31

179
Q9. Where have you found information on the FDA's services to provide technical and
regulatory assistance for small- to medium-sized businesses and academia? Please
select all that apply.
▢ On FDA's website
▢ From FDA's poster
▢ From published articles, presentations or seminars
▢ From other researchers/colleagues/technology transfer offices
▢ From venture capital/business development meetings
▢ From consultants
▢ Other (Please specify) ________________________________________________

Go to Q10

Q10. Was the information on the FDA's website for supporting small- and medium-sized
businesses easy to find?
o Yes
o No
o Not applicable

Go to Q11

Q11. Has the FDA explained clearly about the different services that it offers?
o Yes
o No
o Not applicable

Go to Q12

Q12. Have you heard about the following services offered by the FDA?
o Technical and regulatory assistance provided by the Division of Industry and Consumer
Education (DICE) within the Center of Devices and Radiological Health (CDRH)
o Small Business and Industry Assistance (SBIA) program offered by the Center of Drug
Evaluation and Research (CDER)
o Both of the above-mentioned services
o Not applicable

Go to Q13

180
Q13. Are you familiar with the following services to support small- and medium-sized
businesses?
Not familiar
familiar but have
not researched
Have researched
but not used
Have used
CDER Learn - Web-based
learning tutorials
o o o o
CDRH Learn - Web-based
learning tutorials
o o o o
Conferences and
workshops, e.g.,
Regulatory Education for
Industry (REdI)
conferences
o o o o
Device Advice -
Comprehensive regulatory
assistance (web-based)
o o o o
Direct communication
services
o o o o
Webinars/Podcasts/Videos
o o o o
Small Biz Buzz - email
updates on new
regulations, guidance, and
meetings.
o o o o
Other (Please specify)
o o o o

If “Have used” (count) is greater than or equal to “1”, go to Q14
Otherwise, go to Q29

Q14. Did the FDA website give a sufficient explanation of the services that it provided?
o Yes
o No
o Not applicable

Go to Q15

181
Q15. Do you think, from the materials available from the FDA website, show that that
they understand the needs of small- and medium-sized businesses?
o Yes
o No
o Not applicable

Go to Q16

Q16. What is your satisfaction/dissatisfaction with the FDA's web content for small- and
medium-sized businesses?
Satisfied
Neither satisfied
nor dissatisfied
Dissatisfied Not applicable
Look and feel of
contents
o o o o
Ease of navigating
the website
o o o o
Performance of
search function
o o o o
Sufficient topic
items for a new
medical product
o o o o
Sufficient depth of
Information
o o o o
Appropriate
quality of
Information
o o o o
Overall
satisfaction with
FDA's web
services
o o o o

Go to Q17

Q17. Do you have any further comments on the FDA's web-based information?
________________________________________________________________
________________________________________________________________

Go to Q18

182
Q18. In your opinion, by reading the content of the FDA's website, watching podcasts
and/or webinars, attending a conference, or reading a newsletter, how well does the
FDA understand the specific needs of those who develop products in small- and
medium-sized businesses or academia?
o Very well
o Somewhat well
o Not very well
o Not at all
o Not applicable

Go to Q19

Q19. Did the FDA provide the service or information that you needed to your satisfaction
the first time?
o Yes
o No
o Not applicable

Go to Q20

Q20. How did you receive information/service that you had been seeking?
Yes No Not applicable
Conference or workshop
(in-person)
o o o
Telephone
o o o
Facsimile
o o o
Podcast/Webinar
o o o
Internet website
o o o
Newsletter
o o o
Other (Please specify)
o o o

Go to Q21

183
Q21. Was that route of communication your preferred method?
________________________________________________________________
________________________________________________________________

Go to Q22

Q22. After using FDA's services (web-based information, webinar, meeting, etc.), did
you gain the impression that the FDA was enthusiastic about helping you?
o Agree
o Neither agree nor disagree
o Disagree
o Not applicable

Go to Q23

Q23. Throughout the FDA's services, did you think that the FDA helped you increase
your confidence in understanding regulatory activities to develop a medical
product?
o Agree
o Neither agree nor disagree
o Disagree
o Not applicable

Go to Q24

Q24. To what extent have your expectations have been realized? Please describe any
positive or negative experience that you have had with the FDA's services for
small- and medium-sized businesses.
________________________________________________________________
________________________________________________________________

Go to Q25

184
Q25. Please reflect on your interactions with personnel at the FDA when you were trying
to collect information to support small- and medium-sized businesses from the
FDA's services (web-based information, webinar, meeting, etc.)

Yes No Not applicable
Did you feel like you
needed to interact with
someone at the FDA?
o o o
Did you try to interact
with someone at the
FDA?
o o o

If “Yes” is greater than or equal to “1”, go to Q26
Otherwise, go to Q33

Q26. Were you able to reach the FDA staff when necessary?

Most of the time Some of the time Rarely Not applicable
FDA staff was
easily accessible
o o o o
FDA staff was
quick to respond
o o o o
FDA staff
provided high-
quality advice
o o o o

Go to Q27

Q27. Did the FDA have the knowledge to answer your questions (if you asked them
questions)?
o Yes
o No
o Not applicable

Go to Q28

Q28. Please describe any positive and negative experiences you had when you were
trying to interact with the FDA personnel.
________________________________________________________________
________________________________________________________________

185
Go to Q33

Q29. Please describe the reason(s) why you have not accessed the FDA's service for
small- and medium-sized businesses. Please select all that apply.
▢ The website is not user friendly.
▢ I could not find information that I was seeking.
▢ The contents of the website/webinar/conference were not what I had expected.
▢ I did not have time to read such information.

Go to Q30

Q30. What if anything more would you like to see FDA do to accelerate the
commercialization of new medical products developed in academia or small- and
medium-sized businesses?
________________________________________________________________
________________________________________________________________
Go to Q33

Q31. The FDA offers various services and information via the FDA website, podcast,
webinar, conference, and newsletter to support small- and medium-sized
businesses. Are you interested in such services or information?
o Yes
o Maybe
o No

Go to Q32

Q32. The FDA is trying to support small- and medium-sized businesses. What if
anything would you like to see the FDA do to accelerate the commercialization of
new medical products developed in academia or small- and medium-sized
businesses?
________________________________________________________________
________________________________________________________________

Go to Q33

186
Q33. Have you had any chance to hold a meeting, including a face-to-face meeting, zoom
conference, teleconference, or personal interaction with an individual at the FDA
about the medical product that you are developing?
o Yes
o No

If “Yes”, go to Q34
If “No”, go to Q37

Q34. Think about your most recent experience with a personal interaction with an
individual at the FDA. What is your level of satisfaction with each of the
following?

Satisfied
Neither satisfied
nor dissatisfied
Dissatisfied Not applicable
Timeline of the
consultation
service
o o o o
Convenience of
forms and
documentation
o o o o
Quality of the
consultation
service
o o o o
Value of the
consultation
service
o o o o
Your overall
experience
o o o o

Go to Q35

Q35. Please describe any positive or negative experience that you have had when
interacting with an individual at the FDA.
________________________________________________________________
________________________________________________________________

Go to Q36

187

Q36. Compared to your experience on other services (website, webinars, conferences,
etc.) offered by the FDA, did you think the face-to-face meeting was more
beneficial for you? Can you comment on your experience?
o Yes ________________________________________________
o No ________________________________________________
o Other (Please specify) ________________________________________________

Go to Q38 (the end)

Q37. Do you think that a personal interaction with an individual at the FDA may give
you more personalized/tailored support for your efforts to commercialize medical
products?
o Yes
o Maybe
o No
o Other (Please specify) ________________________________________________

Go to Q38 (the end)

Q38. Thank you very much for participating in the survey. I appreciate your time and
input on this topic. I will be providing a brief summary of the results to those who
have participated in the survey once the analysis of the survey is completed. If you
wish to receive the summary, please provide your email address below.
________________________________________________________________

188
Appendix B: Japanese Survey Questionnaire

189
Japanese Survey Questionnaire
右上の［English ˅］をクリックすると、日本語に切り替えることができます。

Q1. Thank you for participating in this survey. I value your views and needs related to regulatory
support programs that the PMDA has developed to foster new medical product development.
Your responses will be kept anonymous and presented only as part of a cumulative
analysis. Your identity will also be protected. You may not be able to answer every
question, so you can skip a question if you wish.

Please click  to start.

Go to Q2

Q2. Please list the types of organization in which you have worked to develop medical products
in the last five years. Please select all that apply.
▢ A start-up
▢ A company with commercialized (or approved/certified) products in Japan
▢ A university
▢ A research institute in a university or hospital
▢ A government Laboratory
▢ Other (Please specify) ________________________________________________

Go to Q3

Q3. Which statement best describes the size of your primary organization/company? (If you are at
a university, hospital, or government agency, what is the size of your development group?)
o 1 - 20 employees
o 21 - 100 employees
o 101 - 300 employees
o 301 - 500 employees
o More than 501 employees

Go to Q4

190

Q4. Which statement best describes the product(s) that your present laboratory/company
develops? Please select all that apply.
▢ Drugs
▢ Biologics
▢ In Vitro diagnostics
▢ Regenerative products
▢ Medical devices
▢ Medical devices - pediatric
▢ Medical software
▢ Combination products
▢ Other (Please specify) ________________________________________________

Go to Q5

Q5. What title best describes your current responsibilities in your primary
organization/company? If more than one position is held, please select all that apply.
▢ Founder
▢ C-Suite/Senior Management
▢ Director
▢ Manager
▢ Specialist/Associate
▢ Professor
▢ Researcher
▢ Other (Please specify) ________________________________________________

Go to Q6

Q6. Which job function(s) do you represent in your present organization/company? Please select
all that apply.
▢ Business Development
▢ Board of Advisors
▢ Clinical Affairs
▢ Project Management
▢ Regulatory Affairs
▢ Research & Development
▢ Other (Please specify) ________________________________________________

191
Go to Q7

Q7. At what stage in the development of a new product does your organization usually begin to
plan its regulatory filing strategy for market approval? If you work for more than one
organization or group, please reflect on the one with which you have the most experience.
▢ Proof of concept
▢ Non-clinical studies
▢ Phase I clinical trial
▢ Phase II clinical trial
▢ Phase III clinical trial
▢ Feasibility study (medical device)
▢ Pivotal study (medical device)
▢ Other (Please specify) ________________________________________________
▢ I do not know.

Go to Q8

Q8. Have you heard about PMDA's Pharmaceutical Affairs Consultation on Research and
Development Strategy - RS General Consultation and RS Strategy Consultation (R&D)?
o Yes
o No

If “Yes”, go to Q9
If “No”, go to Q33

Q9. Where did you find information on PMDA's Pharmaceutical Affairs Consultation on
Research and Development Strategy - RS General Consultation and RS Strategy
Consultation (R&D)? Please select all that apply.
▢ On PMDA's website
▢ From PMDA's poster
▢ From published articles, presentations or seminars
▢ From other researchers/colleagues/technology transfer offices
▢ From venture capital meetings/business development meetings
▢ From consultants
▢ Other (Please specify) ________________________________________________

Go to Q10

192
Q10. Was the information on PMDA's Pharmaceutical Affairs Consultation on Research and
Development Strategy - RS General Consultation and RS Strategy Consultation (R&D) -
easy to find?
o Yes
o No
o Not applicable

Go to Q11

Q11. Has the PMDA explained clearly about the different consultation services it offers for
small- or medium-sized businesses or academia?
o Yes
o No
o Not applicable

Go to Q12

Q12. Do you think from materials available from the PMDA website, poster, etc., the PMDA
understand the needs of small- and medium-sized businesses or academia?
o Yes
o No
o Not applicable

Go to Q13

193

Q13. Was the content of the Pharmaceutical Affairs Consultation on Research and Development
(R&D) Strategy, RS General Consultation or RS Strategy Consultation (R&D) what you
were looking for?
Satisfied
Neither satisfied
nor dissatisfied
Dissatisfied Not applicable
Sufficient topic
items for the
consultation
services
o o o o
Sufficient depth of
information
o o o o
Appropriate
quality of
information
o o o o
Overall
satisfaction with
PMDA's
information
o o o o

Go to Q14

Q14. Please describe any positive or negative experiences that you have had when trying to
collect information on this particular consultation service.
________________________________________________________________
________________________________________________________________

Go to Q15

Q15. Have you applied for or had a Pharmaceutical Affairs Consultation on Research and
Development (R&D) Strategy, RS General Consultation or RS Strategy Consultation
(R&D)?
o Yes
o No

If “Yes”, go to Q16
If “No”, go to Q31

194
Q16. Which PMDA consultation meeting did your organization/company have? Please select all
that apply.
▢ Pharmaceutical Affairs Consultation on Research and Development (R&D) Strategy
▢ RS General Consultation
▢ RS Strategy Consultation (R&D)
▢ Do not remember
▢ Other (Please specify) ________________________________________________

Go to Q17

Q17. Was a sufficient explanation of the consultation process provided in advance?
o Yes
o No
o Not applicable

Go to Q18

Q18. In your opinion, by reading the materials available from the PMDA website, poster, etc.,
how well do PMDA consultants understand the specific needs of those who develop
products in small- and medium-sized businesses or academia?
o Very well
o Somewhat well
o Not very well
o Not at all
o Not applicable

Go to Q19

195

Q19. How did you receive information/service that you had been seeking prior to the
consultation meeting?
Yes No Not applicable
Conference or workshop
(in person)
o o o
Email o o o
Telephone o o o
Facsimile o o o
Internet website o o o
Others (Please specify) o o o

Go to Q20

Q20. Was that route of communication your preferred method?
________________________________________________________________
________________________________________________________________

Go to Q21

Q21. Did the PMDA provide the consultation service that you needed to your satisfaction the
first time?
o Yes
o No
o Not applicable

196
Go to Q22

Q22. After the PMDA's consultation service, did you gain the impression that the PMDA was
enthusiastic about helping you?
o Agree
o Neither agree nor disagree
o Disagree
o Not applicable

197
Go to Q23

Q23. Throughout the consultation process, did you think that the PMDA helped you increase
your confidence in understanding regulatory activities to develop a medical product?
o Agree
o Neither agree nor disagree
o Disagree
o Not applicable

Go to Q24

Q24. To what extent have your expectations have been realized? Please describe any positive or
negative experience that you have had with the PMDA's consultation services for small-
and medium-sized businesses or academia.
________________________________________________________________
________________________________________________________________

Go to Q25

Q25. Please reflect on your interactions with personnel at the PMDA during the consultation
process.
Yes No Not applicable
Did you feel like you
needed to interact with
someone at the PMDA?
o o o
Did you try to interact
with someone at
PMDA?
o o o

If “Yes” is greater than or equal to “1”, go to Q26
Otherwise, go to Q29

198
Q26. During the consultation process, were you able to reach PMDA consultants?
Satisfied
Neither satisfied
nor dissatisfied
Dissatisfied Not applicable
PMDA staff was
easily accessible
o o o o
PMDA staff was
quick to respond
o o o o
Consultants
provided high-
quality advice
o o o o

Go to Q27

Q27. Did the PMDA have the knowledge to answer your questions (if you asked them
questions)?
o Yes
o No
o Not applicable

Go to Q28

Q28. Please describe any positive and negative experiences you had when you were trying to
interact with the PMDA personnel.
________________________________________________________________
________________________________________________________________

Go to Q29

199
Q29. Think about your most recent experience with PMDA's Pharmaceutical Affairs
Consultation on Research and Development Strategy - RS General Consultation and RS
Strategy Consultation (R&D). What is your level of satisfaction for each of the following?
Satisfied
Neither satisfied
nor dissatisfied
Dissatisfied Not applicable
Cost of the
consultation
service
o o o o
Timeline of the
consultation
service
o o o o
Convenience of
forms and
documentation
o o o o
Quality of the
consultation
service
o o o o
Value of the
consultation
service
o o o o
Your overall
experience
o o o o

Go to Q30

Q30. Please describe any positive or negative experiences that you have had during the
consultation meeting with PMDA.
________________________________________________________________
________________________________________________________________

Go to Q35

Q31. Please describe the reason(s) that you have not applied/had a PMDA consultation
meeting. Please select all that apply.
▢ I could not find detailed information on how to apply for the consultation meeting.
▢ The application process was too complex to apply.
▢ The contents of the consultation meeting were not what I had expected.
▢ The timeline toward the consultation meeting did not meet my expectation.

Go to Q32

200
Q32. What if anything more would you like to see PMDA do to accelerate the commercialization
of new medical products developed in small- and medium-sized businesses or academia?
________________________________________________________________
________________________________________________________________

Go to Q35

Q33. The "Pharmaceutical Affairs Consultation for R&D Strategy" is PMDA's consultation
service to support universities, research institutes and/or small- and medium-sized
enterprises. This consultation service offers guidance and advice on clinical and regulatory
strategies and/or processes that lead to the commercialization of the product. Are you
interested in attending such a consultation meeting?
o Yes
o Maybe
o No

Go to Q34

Q34. The PMDA is trying to support small- and medium-sized businesses or academia. What if
anything would you like to see the PMDSA do to accelerate the commercialization of new
medical products developed in small- and medium-sized businesses or academia?
________________________________________________________________
________________________________________________________________

Go to Q35

Q35. Do you know that contents for "academia" and "industry" can be found on the PMDA's
website?
o Yes
o No

If “Yes”, go to Q36
If “No”, go to Q38

201
Q36. Based on your experience with PMDA's website - what is your level of satisfaction for each
of the following?
Satisfied
Neither satisfied
nor dissatisfied
Dissatisfied Not applicable
Look and feel of
contents
o o o o
Ease of navigating
the website
o o o o
Performance of
search function
o o o o
Sufficient topic
items for a new
medical product
o o o o
Sufficient depth of
information
o o o o
Appropriate
quality of
Information
o o o o
Overall
satisfaction with
PMDA's web
services
o o o o

Go to Q37

Q37. Do you have any further comments on the PMDA's web-based information?
________________________________________________________________
________________________________________________________________

Go to Q39 (the end)

Q38. Do you think that web content specific to "academia" or "industry" may give you more
personalized/tailored support for your efforts to commercialize medical products?
o Yes
o Maybe
o No
o other (Please specify) ________________________________________________

202

Go to Q39 (the end)

Q39. Thank you very much for participating in the survey. I appreciate your time and input on
this topic. I will be providing a brief summary of the results to those who have participated
in the survey once the analysis of the survey is completed. If you wish to receive the
summary, please provide your email address below.
________________________________________________________________

203
Appendix C: U.S. Survey Results – Medical Devices

Q2 - Please list the types of organizations in which you have worked to develop medical products in the last
five years. Please select all that apply.
30 Responses
A start-up
A university
A company with commercialized ...
A research institute in a university or ...
A government laboratory
Other (Please specify)
0 5 10 15 20
23
11
6
7
0
2
Other
NPO
independent non-profit
Go to Q3
Q3 - Which statement best describes the size of your primary organization/company? (If you are at a
university, hospital, or government agency, what is the size of your development group?)
30 Responses
1 - 20 employees
21 - 100 employees
101 - 300 employees
301 - 500 employees
More than 500 employees
0 5 10 15 20
22
2
1
2
3
Go to Q4
U.S. Survey Results - Medical Devices
204
Q4 - Which statement best describes the product(s) that your present laboratory/company develops? Please
select all that apply. - Selected Choice
30 Responses
Medical devices
Medical devices - pediatric
Drugs
Medical software
Combination products
Biologics
Regenerative products
In Vitro diagnostics
Other (Please specify)
0 5 10 15 20 25 30
30
16
4
3
3
3
2
1
0
0 Responses
Other
Go to Q5
Q5 - What title best describes your current responsibilities in your primary organization/company? If more
than one position is held, please select all that apply.
29 Responses
Founder
C-Suite/Senior Management
Researcher
Professor
Director
Manager
Specialist/Associate
Other (Please specify)
0 2 4 6 8 10 12 14 16 18
18
13
6
5
3
2
1
1
205
1 Responses
Other
CEO
Go to Q6
Q6 - Which job function(s) do you represent in your present organization/company? Please select all that
apply. - Selected Choice
29 Responses
Research & Development
Project Management
Business Development
Regulatory Affairs
Clinical Affairs
Board of Advisors
Other (Please specify)
0 5 10 15 20
24
19
17
12
9
4
2
2 Responses
Other
We are a 4 person device company, so we all share many of the jobs.
Operations and quality
Go to Q7
206
Q7 - At what stage in the development of a new product, does your organization usually begin to plan its
regulatory filing strategy for market approval or clearance? If you work for more than one organization
or group, please reflect on the one with which you have the most experience.
28 Responses
Development Stage Choice Count
Proof of concept 16
Non-clinical studies 9
Phase I clinical trial 2
Phase II clinical trial 1
Phase III clinical trial 1
Feasibility study (medical device) 6
Pivotal study (medical device) 0
I do not know. 1
Other (Please specify) 1
1 Responses
Other
Our mobility devices are Class 1 Exempt Devices
Go to Q8
Q8 - Did you know that the FDA has services that provide technical and regulatory assistance to small
manufacturers, academic laboratories, and research organizations to help them comply with regulatory
requirements?
29 Responses
Field Choice Count
Yes 15 52%
No 14 48%
Total 29
Yes, go to Q9
No, go to Q31
207
Q9 - Where have you found information on the FDA's services to provide technical and regulatory
assistance for small- to medium-sized businesses and academia? Please select all that apply. - Selected
Choice
13 Responses
On FDA's website
From consultants
From other ...
From published articles, ...
From venture capital/business ...
From FDA's poster
Other (Please specify)
0 2 4 6 8 10 12
12
7
4
2
1
0
3
3 Responses
Other
From fda meetings
Local district office meetings
Past experience
Go to Q10
Q10 - Was the information on the FDA's website for supporting small- and medium-sized businesses easy to
find?
13 Responses
Field Choice Count
Yes 7 54%
No 6 46%
Not applicable 0 0%
Total 13
Go to Q11
208
Q11 - Has the FDA explained clearly about the different services that it offers?
13 Responses
Field Choice Count
Yes 4 31%
No 9 69%
Not applicable 0 0%
Total 13
Go to Q12
Q12 - Have you heard about the following services offered by the FDA?
13 Responses
Technical and regulatory
assistance provided by the
Division of Industry and
Consumer Education (DICE)
within the Center of Devices ...
Small Business and Industry
Assistance (SBIA) program
offered by the Center of Drug
Evaluation and Research
(CDER)
Both of the above-mentioned
services
Not applicable
0
2
4
6
3
1
3
6
Go to Q13
209
Q13 - Are you familiar with the following services to support small- and medium-s...
13 Responses
Field
Not
familiar
familiar but have
not researched
Have researched
but not used
Have
used
CDER Learn - Web-based learning tutorials 7 3 2 1
CDRH Learn - Web-based learning tutorials 6 2 1 4
Conferences and workshops, e.g. Regulatory
Education for Industry (REdI) conferences
5 2 2 4
Device Advice - Comprehensive regulatory
assistance (web-based)
5 3 0 5
Direct communication services 3 2 2 6
Small Biz Buzz - email updates on new regulations,
guidance, and meetings.
8 2 1 2
Webinars/Podcasts/Videos 3 4 0 6
Other (Please specify) 10 0 0 3
3 Responses
Other
N/A
Presubs
Q-submission
If "Have used" (count) is greater than or equal to 1, go to Q14
If "Have used" (count) is equal to 0, go to Q29
210
Q14 - Did the FDA website give a sufficient explanation of the services that it provided?
7 Responses
Field Choice Count
Yes 4 57%
No 3 43%
Not applicable 0 0%
Total 7
Go to Q15
Q15 - Do you think from the materials available from the FDA website show that that they
understand the needs of small- and medium-sized businesses?
7 Responses
Field Choice Count
Yes 2 29%
No 5 71%
Not applicable 0 0%
Total 7
Go to Q16
211
Q16 - What is your satisfaction/dissatisfaction with the FDA's web content for sm...
7 Responses
Satisfied Neither satisfied nor dissatisfied Dissatisfied Not applicable
Look and feel of contents
Ease of navigating the website
Performance of search function
Sufficient topic items for a new
medical product
Sufficient depth of Information
Appropriate quality of Information
Overall satisfaction with FDA's web
services
0 0.5 1 1.5 2 2.5 3 3.5 4
Go to Q17
212
Q17 - Do you have any further comments on the FDA's web-based information?
2 Responses
Comments
It needs to be mobile device formatted and friendly to millennials.
The volume of information to be digested is overwhelming.
Go to Q18
Q18 - In your opinion, by reading the content of the FDA's website, watching podcasts and/or webinars,
attending a conference, or reading a newsletter, how well does the FDA understand the specific needs of
those who develop products in small- and medium-sized businesses or academia?
6 Responses
Field Choice Count
Very well 0 0%
Somewhat well 1 17%
Not very well 4 67%
Not at all 1 17%
Not applicable 0 0%
Total 6
Go to Q19
Q19 - Did the FDA provide the service or information that you needed to your satisfaction the first time?
6 Responses
Field Choice Count
Yes 2
No 3
Not applicable 1
Go to Q20
213
Q20 - How did you receive information/service that you had been seeking?
6 Responses
Method Yes
Internet website 5
Podcast/Webinar 3
Conference or workshop (in-person) 3
Telephone 2
Newsletter 1
Facsimile 1
Total 15
Go to Q21
Q21 - Was that route of communication your preferred method?
5 Responses
Comments
All have their place.
Digital - Email or similar
Yes
Yes
webinars are helpful
Go to Q22
Q22 - After using FDA's services (web-based information, webinar, meeting, etc.), did you gain the
impression that the FDA was enthusiastic about helping you?
6 Responses
Field Choice Count
Agree 2 33%
Disagree 1 17%
Not applicable 0 0%
Neither agree nor disagree 3 50%
Total 6
214
Go to Q23
Q23 - Throughout the FDA's services, did you think that the FDA helped you to increase your confidence in
understanding regulatory activities to develop a medical product?
6 Responses
Field Choice Count
Agree 1 17%
Neither agree nor disagree 5 83%
Disagree 0 0%
Not applicable 0 0%
Total 6
Go to Q24
Q24 - To what extent have your expectations have been realized? Please describe any positive or negative
experience that you have had with the FDA's services for small- and medium-sized businesses.
4 Responses
Comments
There is no consistency in the quality of the reviewers.
Our execution with the FDA has been disappointing to say the least. While they speak of supporting these
avenues, they are not directly or indirectly connected to those that formally execute for small businesses utilizing
their required regulatory pathway. If this was indeed to deliver value, then individuals on their own side, those who
directly collaborate with startups and medium sized companies, need to be delivering it. As it stands the FDA'
support for small and medium sized businesses has been a huge disappointment.
It is expensive to hire a consultant to navigate FDA affairs. It will be great to know about the FDA complimentary
services.
I think each review branch provides different level of service. Some are better than others.
Go to Q25
215
Q25 - Please reflect on your interactions with personnel at the FDA when you were...
6 Responses
Field Yes No Not applicable
Did you feel like you needed to interact with someone at the FDA? 4 2 0
Did you try to interact with someone at the FDA? 6 0 0
If "Yes" is greater than or equal to "1", go to Q26
Otherwise, go to Q33
Q26 - Were you able to reach the FDA staff when necessary?
6 Responses
Most of the time Some of the time Rarely Not applicable
FDA staff was easily
accessible
FDA staff was quick
to respond
FDA staff provided
high-quality advice
0
1
2
3
2
1
3 3 3
1
0 0
1 1
2
1
Go to Q27
Q27 - Did the FDA have the knowledge to answer your questions (if you asked them questions)?
6 Responses
Field Choice Count
Yes 5 83%
No 1 17%
Not applicable 0 0%
Total 6
216
Go to Q28
Q28 - Please describe any positive and negative experience you have had when you were trying to interact
with the FDA personnel.
4 Responses
Comments
They were knowledgeable, thorough, and professional.
Each review branch is different and I had both very positive and very negative experiences with the FDA staff.
DICE email is responsive, but tends to provide formulaic answers and referrals.
Collaborating with 'subject matter experts' within the FDA is, in short, laughable. Those that we have specifically
engaged with show little to no comprehension of a category in which they're responsible for. They are slow,
intentionally leveraging the COVID 19 pandemic to suggest they are low on resources, however when you do
finally engage with them they show no valid understanding of specific files, and attempts to push execution further
down chain.
Go to Q33
Q29 - Please describe the reason(s) why you have not accessed the FDA's service for small- and medium-
sized businesses. Please select all that apply.
6 Responses
Reason Choice Count
I did not have time to read such information. 1
I could not find Information that I was seeking. 4
The website is not user friendly. 1
The contents of the website/webinar/conference were not what I had expected. 1
Go to Q30
217
Q30 - What if anything more would you like to see FDA do to accelerate the commercialization of new
medical products developed in academia or small- and medium-sized businesses?
3 Responses
Comments
A) clear guideance in pathway - the vagueness is killing medtech innovation B) clear guidance on timeline for
approval - the vagueness is killing medtech innovation C) clear guidance on cost
Based on survey and lack of my knowledge of some services, FDA and I could do a better job of
familiarizing/educating on services available.
small non academic businesses and inventors are on their own when it comes to commercialization.It doesn't
matter how many Utility and Design Patents an Inventor has or how innovative those devices are. There is no
direct outreach from the FDA for patented innovative mobility devices registered with the FDA. There are no
standards for class 1 exempt mobility devices such as cane, crutches and walkers in terms of long-term continued
use and the way those devices misalign and force the body to move to maintain balance. When you force the body
to be misaligned and move in ways it was not designed for to maintain balance you create secondary disability
unrelated to injury, age or condition. The FDA should have direct outreach to new small business that have
innovative new devices that are registered with the FDA to help them with commercialization.
Go to Q33
Q31 - The FDA offers various services and information via the FDA website, podcast, webinar, conference,
and newsletter to support small- and medium-sized businesses. Are you interested in such services or
information?
14 Responses
Field Choice Count
Yes 10 71%
Maybe 4 29%
No 0 0%
Total 14
Go to Q32
218
Q32 - The FDA is trying to support small- and medium-sized businesses. What if anything would you like to
see the FDA do to accelerate the commercialization of new medical products developed in academia or
small- and medium-sized businesses?
12 Responses
Comments
1. Continue to provide industry specific guidance documents to clarify expectation, 2. Upper management is
terrified to ask FDA questions, so an anonymous non-binding question and answer service would allow engineers
and clinicians to ask questions they they cannot ask now.
Examples of successful devices/start-ups, and what was required to get them through - even if they are fake
examples. For instance, a quality system may be plug and play (simple) for an experienced device developer, but
for a new startup it's a total mystery what it's supposed to look like
FDA clearance or approval represents a huge regulatory risk for investors. Consequently, there seems to be a lot
of funding available for companies that have achieved FDA clearance, but little funding for companies earlier in the
process. And it's not advisable to try to get a 510(k) without a final device, which often requires a significant
engineering effort and expense. If the FDA wants to support small businesses, they should develop a process of
regulatory de-risking milestones along the path to 510(k) clearance.
Guidance on development pathways for combination devices (specifically 3D printing) and description of key
concerns in safety regarding these devices.
Help plan for GMP and for 510(k) filing
I have not put much thought into this. Perhaps, have facilitators work with pre-revenue companies to help them
move through the process without the need for the same quantity of consultants.
More specific focus on and support for pediatric devices to address the complexities and uniqueness of both the
technology and the process.
Presub process is pretty straightforward and clear. Funding mechanisms are where I struggle now, but I am
currently enaging different programs to see where I am applicable/
Provide services or in kind support to these organizations. Many small business don't have the funds to generate a
$100k FDA application. The rigor of testing is super important so they should lax that, but may have innovative
ways to support this process.
Streamline requirements for clinical studies sponsored by small business concerns.
Targeted grants specifically for pediatric devices as they are a small market. Grants give companies incentives to
develop products for this market. Grants can be for R&D, clinical trials, and commercialization.
219
This survey has intimated that the FDA has support services for small and medium businesses. So naturally I went
to the website to find out how to register, sign up, or contact someone about the support. After 30 minutes of
looking for anything that sounds like what the survey has suggested, I gave up. It may exist, but it certainly isn't
easy to find, and I don't have the time to perform a forensic search of the website and associated literature to find
it. I have read every link the FDA publishes about how to prepare for a med device submission...and I still do not
know how to do it by myself. This is why people hire regulatory consultants rather than engage with the FDA
directly. The published information is complex, sometimes contradictory, and it is extraordinarily difficult to
determine what is relevant to a specific project based on the information provided. It would be hugely helpful to
have the equivalent of a "customer service rep", basically the FDA's own regulatory consultant, help with
deciphering the requirements. It sounds from the questions on this survey that the FDA does offer such a service. I
have been unable to find it, which ultimately means the FDA isn't all that helpful to a small business trying to figure
out the submission process and requirements. I will continue to employ a regulatory consultant for now.
Go to Q33
Q33 - Have you had any chance to hold a meeting including a face-to-face meeting, zoom conference,
teleconference, or personal interaction with an individual at the FDA about the medical product that you are
developing?
26 Responses
Field Choice Count
Yes 15 58%
No 11 42%
Total 26
Yes, go to Q34
No, go to Q37
Q34 - Think about your most recent experience with a personal interaction with an...
15 Responses
Field Satisfied
Neither satisfied nor
dissatisfied
Dissatisfied
Not
applicable
Timeline of the consultation service 8 2 5 0
Convenience of forms and
documentation
4 6 4 1
Quality of the consultation service 10 2 3 0
Value of the consultation service 9 3 3 0
Your overall experience 9 2 4 0
220
Go to Q36
Q36 - Compared to your experience on other services (website, webinars, conference, etc.) offered by the
FDA, did you think the face-to-face meeting was more beneficial for you? Can you comment on your
experience? - Selected Choice
15 Responses
Field Choice Count
Yes 10 67%
No 3 20%
Other (Please specify) 2 13%
Total 15
Go to Q35
Q35 - Please describe any positive or negative experience you have had when interacting with an individual
at the FDA.
11 Responses
Comments
Again, senior management tends not to reach out because they think they will lose control of the questions that are
asked could negatively impact the submission.
It has been very long time ago, but experience was very positive and person was helpful
My face-to-face interactions with the FDA have always been positive. They have seen the value in our product and
have been supportive of our project. And I've been impressed by their competence.
Only timeline and and convenience/ease of use of submission form expectations.
The process of submitting the presubmission forms is incredibly cumbersome
They are really territorial so it’s like walking on eggshells.
This was a presubmission for 510k meeting. Very helpful. (though it was on the phone - I may have answered the
question incorrectly).
Timing/urgency and focus on the key tasks at hand were lacking
To repeat, those representing the FDA from our engagement has left an extremely sour taste, showing no true
attempt at supporting execution, but acting as an opaque wall towards what should be a collaborative and
transparent endeavor.
Unfortunately, our most recent experience with the FDA was very negative. Our company ended up involving the
Ombudsman to resolve a few of the issues (for example, lack of communication, no interactive reviews, extended
timelines of submission reviews).
We found FDA staff to be engaged in the science of our technology and the intended use of our device.
221
2 Responses
Other
It was a zoom but they turned their cameras off
Sorry, it was a phone meeting.
6 Responses
Yes - Text
Due to the pandemic we have been limited to digital engagement. It does no favors for them to be able to just turn
off a webex after showing no preparation for an active discussion. A face to face would aid engagement
tremendously.
Face to face meetings are the most valuable time you can have with the fda
I can't imagine that any teleconference tool could take the place of being in a room with FDA staff. It's important for
us to read body language and have the best opportunity to develop a relationship with regulatory staff.
It's better to talk to an actual person, but if it takes 6 months to get the opportunity it is a tremendous challenge
More relevant information provided that cannot be obtained from web site. Perhaps use of small business services
would add some value beyond web site.
Specific topic meetings are useful but what happens is the staff changes frequently and you must start from
scratch, or the new team wants something else.
Go to the end
Q37 - Do you think that personal interaction with an individual at the FDA may give you more
personalized/tailored support for your efforts to commercialize medical products? - Selected Choice
11 Responses
Field Choice Count
Yes 5
Maybe 4
No 0
Other (Please specify) 2
2 Responses
Other
Yes, but the concern is at what level do you bring in FDA engagement if 'all the ducks aren't in a row' yet so to
speak
yes, but only if it is straightforward to engage.
222
The end
223
Appendix D: U.S. Survey Results – Pediatric Medical Devices
Q2 - Please list the types of organizations in which you have worked to develop medical products in the last
five years. Please select all that apply.
24 Responses
A start-up
A university
A company with commercialized ...
A research institute in a university or ...
A government laboratory
Other (Please specify)
0 5 10 15 20
22
7
5
5
0
1
Other
NPO
Go to Q3
Q3 - Which statement best describes the size of your primary organization/company? (If you are at a
university, hospital, or government agency, what is the size of your development group?)
24 Responses
1 - 20 employees
21 - 100 employees
101 - 300 employees
301 - 500 employees
More than 500 employees
0 5 10 15 20
23
0
0
0
1
Go to Q4
U.S. Survey - Pediatric Medical Devices
224
Q4 - Which statement best describes the product(s) that your present laboratory/company develops? Please
select all that apply. - Selected Choice
24 Responses
Medical devices - pediatric
Medical devices
Medical software
Combination products
Biologics
In Vitro diagnostics
Other (Please specify)
Regenerative products
Drugs
0 2 4 6 8 10 12 14 16 18 20 22 24
24
16
2
1
1
1
0
0
0
0 Responses
Other
Go to Q5
Q5 - What title best describes your current responsibilities in your primary organization/company? If more
than one position is held, please select all that apply.
23 Responses
Founder
C-Suite/Senior Management
Researcher
Professor
Director
Manager
Specialist/Associate
Other (Please specify)
0 2 4 6 8 10 12 14 16 18
18
9
6
3
4
2
0
2
225
2 Responses
Other
CEO
We are pre-launch
Go to Q6
Q6 - Which job function(s) do you represent in your present organization/company? Please select all that
apply. - Selected Choice
23 Responses
Research & Development
Project Management
Business Development
Regulatory Affairs
Clinical Affairs
Board of Advisors
Other (Please specify)
0 5 10 15 20
21
17
16
9
9
4
3
3 Responses
Other
We are a 4 person device company, so we all share many of the jobs.
Marketing, Commercialization Strategy
CEO
Go to Q7
226
Q7 - At what stage in the development of a new product, does your organization usually begin to plan its
regulatory filing strategy for market approval or clearance? If you work for more than one organization
or group, please reflect on the one with which you have the most experience.
23 Responses
Development Stage Choice Count
Proof of concept 10
Non-clinical studies 9
Phase I clinical trial 2
Phase II clinical trial 1
Phase III clinical trial 0
Feasibility study (medical device) 7
Pivotal study (medical device) 0
I do not know. 0
Other (Please specify) 1
1 Responses
Other
Our mobility devices are Class 1 Exempt Devices
Go to Q8
Q8 - Did you know that the FDA has services that provide technical and regulatory assistance to small
manufacturers, academic laboratories, and research organizations to help them comply with regulatory
requirements?
24 Responses
Field Choice Count
Yes 11 46%
No 13 54%
Total 24
Yes, go to Q9
No, go to Q31
227
Q9 - Where have you found information on the FDA's services to provide technical and regulatory
assistance for small- to medium-sized businesses and academia? Please select all that apply. - Selected
Choice
11 Responses
On FDA's website
From consultants
From other ...
From published articles, ...
From venture capital/business ...
From FDA's poster
Other (Please specify)
0 1 2 3 4 5 6 7 8 9
8
9
4
1
1
0
2
2 Responses
Other
CTIP ( FDA funded Pediatric Device Consortium)
Local district office meetings
Go to Q10
Q10 - Was the information on the FDA's website for supporting small- and medium-sized businesses easy to
find?
11 Responses
Field Choice Count
Yes 4 36%
No 5 45%
Not applicable 2 18%
Total 11
Go to Q11
Q11 - Has the FDA explained clearly about the different services that it offers?
10 Responses
Field Choice Count
228
Yes 2 20%
No 7 70%
Not applicable 1 10%
Total 10
Go to Q12
Q12 - Have you heard about the following services offered by the FDA?
11 Responses
Technical and regulatory
assistance provided by the
Division of Industry and
Consumer Education (DICE)
within the Center of Devices ...
Small Business and Industry
Assistance (SBIA) program
offered by the Center of Drug
Evaluation and Research
(CDER)
Both of the above-mentioned
services
Not applicable
0
1
2
3
4
5
3
1
2
5
Go to Q13
229
Q13 - Are you familiar with the following services to support small- and medium-s...
11 Responses
Field
Not
familiar
familiar but have
not researched
Have researched
but not used
Have
used
CDER Learn - Web-based learning tutorials 6 5 0 0
CDRH Learn - Web-based learning tutorials 6 4 0 1
Conferences and workshops, e.g. Regulatory
Education for Industry (REdI) conferences
5 2 3 1
Device Advice - Comprehensive regulatory
assistance (web-based)
6 3 0 2
Direct communication services 3 3 1 4
Small Biz Buzz - email updates on new regulations,
guidance, and meetings.
6 3 1 1
Webinars/Podcasts/Videos 1 6 0 4
Other (Please specify) 9 0 1 1
2 Responses
Other
N/A
Presubs
If "Have used" (count) is greater than or equal to 1, go to Q14
If "Have used" (count) is equal to 0, go to Q29
230
Q14 - Did the FDA website give a sufficient explanation of the services that it provided?
4 Responses
Field Choice Count
Yes 1 25%
No 3 75%
Not applicable 0 0%
Total 4
Go to Q15
Q15 - Do you think from the materials available from the FDA website show that that they
understand the needs of small- and medium-sized businesses?
4 Responses
Field Choice Count
Yes 1 25%
No 3 75%
Not applicable 0 0%
Total 4
Go to Q16
231
Q16 - What is your satisfaction/dissatisfaction with the FDA's web content for sm...
4 Responses
Satisfied Neither satisfied nor dissatisfied Dissatisfied Not applicable
Look and feel of contents
Ease of navigating the website
Performance of search function
Sufficient topic items for a new
medical product
Sufficient depth of Information
Appropriate quality of Information
Overall satisfaction with FDA's web
services
0 0.5 1 1.5 2 2.5 3
Go to Q17
232
Q17 - Do you have any further comments on the FDA's web-based information?
1 Responses
Comments
It needs to be mobile device formatted and friendly to millennials.
Go to Q18
Q18 - In your opinion, by reading the content of the FDA's website, watching podcasts and/or webinars,
attending a conference, or reading a newsletter, how well does the FDA understand the specific needs of
those who develop products in small- and medium-sized businesses or academia?
3 Responses
Field Choice Count
Very well 0 0%
Somewhat well 1 33%
Not very well 1 33%
Not at all 1 33%
Not applicable 0 0%
Total 3
Go to Q19
Q19 - Did the FDA provide the service or information that you needed to your satisfaction the first time?
3 Responses
Field Choice Count
Yes 1
No 2
Not applicable 0
Go to Q20
Q20 - How did you receive information/service that you had been seeking?
3 Responses
Method Yes
Internet website 3
Newsletter 2
233
Go to Q22
Q22 - After using FDA's services (web-based information, webinar, meeting, etc.), did you gain the
impression that the FDA was enthusiastic about helping you?
3 Responses
Field Choice Count
Agree 1 33%
Disagree 1 33%
Not applicable 0 0%
Neither agree nor disagree 1 33%
Total 3
Go to Q23
Podcast/Webinar 2
Telephone 2
Conference or workshop (in-person) 1
Facsimile 0
Total 10
Go to Q21
Q21 - Was that route of communication your preferred method?
2 Responses
Comments
All have their place.
Digital - Email or similar
234
Q23 - Throughout the FDA's services, did you think that the FDA helped you to increase your confidence in
understanding regulatory activities to develop a medical product?
3 Responses
Field Choice Count
Agree 1 33%
Neither agree nor disagree 2 67%
Disagree 0 0%
Not applicable 0 0%
Total 3
Go to Q24
Q24 - To what extent have your expectations have been realized? Please describe any positive or negative
experience that you have had with the FDA's services for small- and medium-sized businesses.
2 Responses
Comments
There is no consistency in the quality of the reviewers.
Our execution with the FDA has been disappointing to say the least. While they speak of supporting these
avenues, they are not directly or indirectly connected to those that formally execute for small businesses utilizing
their required regulatory pathway. If this was indeed to deliver value, then individuals on their own side, those who
directly collaborate with startups and medium sized companies, need to be delivering it. As it stands the FDA'
support for small and medium sized businesses has been a huge disappointment.
Go to Q25
Q25 - Please reflect on your interactions with personnel at the FDA when you were...
3 Responses
Field Yes No Not applicable
Did you feel like you needed to interact with someone at the FDA? 1 2 0
Did you try to interact with someone at the FDA? 2 1 0
If "Yes" is greater than or equal to "1", go to Q26
Otherwise, go to Q33
Q26 - Were you able to reach the FDA staff when necessary?
235
3 Responses
Most of the time Some of the time Rarely Not applicable
FDA staff was easily
accessible
FDA staff was quick
to respond
FDA staff provided
high-quality advice
0
0.5
1
1.5
2
1
0
2
1 1 1
0 0 0
1
2
0
Go to Q27
Q27 - Did the FDA have the knowledge to answer your questions (if you asked them questions)?
3 Responses
Field Choice Count
Yes 2 67%
No 1 33%
Not applicable 0 0%
Total 3
Go to Q28
236
Q28 - Please describe any positive and negative experience you have had when you were trying to interact
with the FDA personnel.
2 Responses
Comments
DICE email is responsive, but tends to provide formulaic answers and referrals.
Collaborating with 'subject matter experts' within the FDA is, in short, laughable. Those that we have specifically
engaged with show little to no comprehension of a category in which they're responsible for. They are slow,
intentionally leveraging the COVID 19 pandemic to suggest they are low on resources, however when you do
finally engage with them they show no valid understanding of specific files, and attempts to push execution further
down chain.
Go to Q33
Q29 - Please describe the reason(s) why you have not accessed the FDA's service for small- and medium-
sized businesses. Please select all that apply.
5 Responses
Reason Choice Count
I did not have time to read such information. 1
I could not find Information that I was seeking. 3
The website is not user friendly. 1
The contents of the website/webinar/conference were not what I had expected. 1
Go to Q30
237
Q30 - What if anything more would you like to see FDA do to accelerate the commercialization of new
medical products developed in academia or small- and medium-sized businesses?
4 Responses
Comments
Based on survey and lack of my knowledge of some services, FDA and I could do a better job of
familiarizing/educating on services available.
Eliminate requirement for high-volume manufacturing to be in-place prior to EUA consideration.
I have not initiated my Regulatory strategy as of yet. Still pre-launch and bogged down in engineering and user
feedback
small non academic businesses and inventors are on their own when it comes to commercialization.It doesn't
matter how many Utility and Design Patents an Inventor has or how innovative those devices are. There is no
direct outreach from the FDA for patented innovative mobility devices registered with the FDA. There are no
standards for class 1 exempt mobility devices such as cane, crutches and walkers in terms of long-term continued
use and the way those devices misalign and force the body to move to maintain balance. When you force the body
to be misaligned and move in ways it was not designed for to maintain balance you create secondary disability
unrelated to injury, age or condition. The FDA should have direct outreach to new small business that have
innovative new devices that are registered with the FDA to help them with commercialization.
Go to Q33
Q31 - The FDA offers various services and information via the FDA website, podcast, webinar, conference,
and newsletter to support small- and medium-sized businesses. Are you interested in such services or
information?
13 Responses
Field Choice Count
Yes 11 85%
Maybe 2 15%
No 0 0%
Total 13
Go to Q32
Q32 - The FDA is trying to support small- and medium-sized businesses. What if anything would you like to
see the FDA do to accelerate the commercialization of new medical products developed in academia or
small- and medium-sized businesses?
11 Responses
Comments
238
Examples of successful devices/start-ups, and what was required to get them through - even if they are fake
examples. For instance, a quality system may be plug and play (simple) for an experienced device developer, but
for a new startup it's a total mystery what it's supposed to look like
FDA clearance or approval represents a huge regulatory risk for investors. Consequently, there seems to be a lot
of funding available for companies that have achieved FDA clearance, but little funding for companies earlier in the
process. And it's not advisable to try to get a 510(k) without a final device, which often requires a significant
engineering effort and expense. If the FDA wants to support small businesses, they should develop a process of
regulatory de-risking milestones along the path to 510(k) clearance.
Help plan for GMP and for 510(k) filing
I have not put much thought into this. Perhaps, have facilitators work with pre-revenue companies to help them
move through the process without the need for the same quantity of consultants.
Informal conversations/ Tech watch style web meetings/presentations for early guidance. Pre-submission is a
route, but still very "formal" and often costly & time-consuming and prevents early-stage startups to get early
feedback
Presub process is pretty straightforward and clear. Funding mechanisms are where I struggle now, but I am
currently enaging different programs to see where I am applicable/
Provide services or in kind support to these organizations. Many small business don't have the funds to generate a
$100k FDA application. The rigor of testing is super important so they should lax that, but may have innovative
ways to support this process.
Streamline requirements for clinical studies sponsored by small business concerns.
Targeted grants specifically for pediatric devices as they are a small market. Grants give companies incentives to
develop products for this market. Grants can be for R&D, clinical trials, and commercialization.
This survey has intimated that the FDA has support services for small and medium businesses. So naturally I went
to the website to find out how to register, sign up, or contact someone about the support. After 30 minutes of
looking for anything that sounds like what the survey has suggested, I gave up. It may exist, but it certainly isn't
easy to find, and I don't have the time to perform a forensic search of the website and associated literature to find
it. I have read every link the FDA publishes about how to prepare for a med device submission...and I still do not
know how to do it by myself. This is why people hire regulatory consultants rather than engage with the FDA
directly. The published information is complex, sometimes contradictory, and it is extraordinarily difficult to
determine what is relevant to a specific project based on the information provided. It would be hugely helpful to
have the equivalent of a "customer service rep", basically the FDA's own regulatory consultant, help with
deciphering the requirements. It sounds from the questions on this survey that the FDA does offer such a service. I
have been unable to find it, which ultimately means the FDA isn't all that helpful to a small business trying to figure
out the submission process and requirements. I will continue to employ a regulatory consultant for now.
provide quick and more expedient feedback through less formal channels
Go to Q33
239
Yes, go to Q34
No, go to Q37
Q34 - Think about your most recent experience with a personal interaction with an...
9 Responses
Field Satisfied
Neither satisfied nor
dissatisfied
Dissatisfied
Not
applicable
Timeline of the consultation service 4 3 2 0
Convenience of forms and
documentation
1 5 3 0
Quality of the consultation service 7 1 1 0
Value of the consultation service 7 1 1 0
Your overall experience 6 2 1 0
Go to Q35
Q33 - Have you had any chance to hold a meeting including a face-to-face meeting, zoom conference,
teleconference, or personal interaction with an individual at the FDA about the medical product that you are
developing?
22 Responses
Field Choice Count
Yes 9 41%
No 13 59%
Total 22
240
Q35 - Please describe any positive or negative experience you have had when interacting with an individual
at the FDA.
8 Responses
Comments
My face-to-face interactions with the FDA have always been positive. They have seen the value in our product and
have been supportive of our project. And I've been impressed by their competence.
Only timeline and and convenience/ease of use of submission form expectations.
The process of submitting the presubmission forms is incredibly cumbersome
They are really territorial so it’s like walking on eggshells.
This was a presubmission for 510k meeting. Very helpful. (though it was on the phone - I may have answered the
question incorrectly).
To repeat, those representing the FDA from our engagement has left an extremely sour taste, showing no true
attempt at supporting execution, but acting as an opaque wall towards what should be a collaborative and
transparent endeavor.
We found FDA staff to be engaged in the science of our technology and the intended use of our device.
had a useful presub meeting with FDA
Go to Q36
Q36 - Compared to your experience on other services (website, webinars, conference, etc.) offered by the
FDA, did you think the face-to-face meeting was more beneficial for you? Can you comment on your
experience? - Selected Choice
9 Responses
Field Choice Count
Yes 6 67%
No 1 11%
Other (Please specify) 2 22%
Total 9
241
2 Responses
Other
It was a zoom but they turned their cameras off
Sorry, it was a phone meeting.
4 Responses
Yes - Text
Due to the pandemic we have been limited to digital engagement. It does no favors for them to be able to just turn
off a webex after showing no preparation for an active discussion. A face to face would aid engagement
tremendously.
I can't imagine that any teleconference tool could take the place of being in a room with FDA staff. It's important for
us to read body language and have the best opportunity to develop a relationship with regulatory staff.
More relevant information provided that cannot be obtained from web site. Perhaps use of small business services
would add some value beyond web site.
able to get somewhat more direct feedback
Go to the end
Q37 - Do you think that personal interaction with an individual at the FDA may give you more
personalized/tailored support for your efforts to commercialize medical products? - Selected Choice
13 Responses
Field Choice Count
Yes 7
Maybe 4
No 0
Other (Please specify) 2
2 Responses
Other
multiple regulatory consultants have already advised FDA would not consider our product under EUA due to
current low-volume manufacturing status
yes, but only if it is straightforward to engage.
The end
242

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Asset Metadata

Creator Migita, Nami (author)

Core Title Regulatory programs to foster medical product development: user experience in the United States and Japan

School School of Pharmacy

Degree Doctor of Regulatory Science

Degree Program Regulatory Science

Degree Conferral Date 2022-05

Publication Date 01/24/2022

Defense Date 01/12/2022

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag FDA,OAI-PMH Harvest,PMDA,regulatory program,Satisfaction,SME,user experience

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Richmond, Frances J. (committee chair), Bain, Susan (committee member), Davies, Daryl L. (committee member), Kuo, Chiaoyun Benson (committee member)

Creator Email migita73@icloud.com,nmigita@usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-oUC110520274

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