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Views on global harmonization of pharmacopeial standards: a survey of key stakeholders

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VIEWS ON GLOBAL HARMONIZATION OF PHARMACOPEIAL STANDARDS:
A SURVEY OF KEY STAKEHOLDERS

by
Catherine M. Sheehan

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

May 2020

Copyright 2020 Catherine M. Sheehan

ii
DEDICATION
I dedicate this dissertation to my family. To my husband, John for his abundance of
patience, understanding, love and endless support and encouragement to “keep going” on this
journey of learning. To my children, John, Camille and Jackie, for your understanding and
support during this process. I hope I can be there to provide you all the support you need to
achieve your goals. To my brother, Billy and sister, Jakki who were also supportive and
encouraging, despite being so far away in Ireland - it meant alot.

iii
ACKNOWLEDGEMENTS
This dissertation is the result of many years of study and research. During this time, I
was guided and supported by many people, to whom I wish to take this oppportunity to
thank and acknowledge that this would not have been possible without them. First, I wish
to thank my advisor, Dr. Eunjoo Pacifici, Ph.D. for her tremendous knowledge, insight,
and ongoing guidance, support, and friendship. I will be forever grateful for her patience,
insight and direction and unrelenting dedication to her students. Her encouragement
helped me complete this chapter of my life. I would also like to thank Dr. Frances
Richmond, Ph.D for all of her guidance and support for moving me in the right direction.
Second, I wish to acknowledge my committee members, including Dr’s. Nancy Pire-
Smerkanich, Susan Bain and Michael Jamieson for their invaluable questions, comments,
and assistance with my survey. Third, I wish to acknowledge members of my focus
group, for providing insights on stakeholders, prospective respondents, and overall
support. I wish to thank the rest of the regulatory science staff that provided me the help
to navigate all of my administrative hurdles. Fourth, in closing, I would like to thank the
other students in the 2012 Doctoral Cohort for their support professionally and personally
and for making this such an enjoyable endeavor. I would also like to thank many of my
USP colleagues – for all of your support in my career, educational and personal goals.

iv
TABLE OF CONTENTS
DEDICATION .................................................................................................................... ii
ACKNOWLEDGEMENTS ............................................................................................... iii
LIST OF TABLES ........................................................................................................... viii
LIST OF FIGURES ........................................................................................................... xi
ABSTRACT ..................................................................................................................... xiii
CHAPTER 1. OVERVIEW ........................................................................................ 1
1.4 Delimitations, Limitations, Assumptions ....................................................... 7
1.5 Organization of Thesis Proposal .................................................................. 11
1.6 Definitions .................................................................................................... 11
CHAPTER 2. LITERATURE REVIEW .................................................................. 14
2.1 History and Origin of the Pharmacopeia ...................................................... 14
2.1.1 Introduction of Public Standards to Ensure Quality of
Medicines ....................................................................................... 15
2.1.2 Establishment of the United States Pharmacopeia (USP) .............. 16
2.2 The Modern Pharmacopeia .......................................................................... 19
2.3 Legal Recognition of National and Regional Pharmacopeias ...................... 22
2.4 Harmonization of Pharmacopeias ................................................................ 26
2.4.1 The Pharmacopeial Discussion Group (PDG) ................................ 28
2.4.2 PDG Working Procedure Reforms ................................................. 35
2.4.3 ICH and PDG Work Together on Common Quality Topics .......... 36

v
2.4.4 Challenges Faced by PDG .............................................................. 38
2.4.5 Changing Pharmaceutical Landscape ............................................. 39
2.4.6 Role of WHO in Global Pharmacopeial Harmonization ................ 41
2.5 Challenges to Achieving Global Pharmacopeial Harmonization ................. 43
2.6 Examination of Stakeholders in the Pharmacopeial Harmonization
Process ......................................................................................................... 47
2.7 Research Framework.................................................................................... 48
CHAPTER 3. METHODOLOGY ............................................................................ 54
3.1 Introduction .................................................................................................. 54
3.2 Survey Development and Finalization ......................................................... 55
3.2.1 Focus Group Input to Survey Development ................................... 55
3.2.2 Survey Deployment and Analysis .................................................. 58
CHAPTER 4. RESULTS .......................................................................................... 61
4.1 Profiles of Respondents ............................................................................... 62
4.2 Experience with Standards ........................................................................... 72
4.3 Experience with Harmonization ................................................................... 74
4.4 Views on Harmonization ............................................................................. 76
4.5 Views on Collaboration and Relationship building ..................................... 82
4.6 Global Challenges with Standardized Pharmacopeial Practices and
Regulatory acceptance ................................................................................. 91
4.7 Views of the Pharmacopeial Authorities ................................................... 105

vi
4.8 Pharmacopeial Discussion Group (PDG) .................................................. 109
4.8.1 Views on PDG’s performance ...................................................... 113
4.8.2 Challenges with implementing PDG harmonized standards ........ 117
4.8.3 Should PDG harmonization be modified? .................................... 120
4.9 Usage of Pharmacopeial Standards around the World ............................... 124
4.10 Additional Information or Comments on Pharmacopeial Harmonization . 127
4.11 Future Survey Participation ....................................................................... 130
CHAPTER 5. DISCUSSION .................................................................................. 131
5.1 Global Harmonization of Pharmacopeial Standards .................................. 131
5.2 Methodological Considerations ................................................................. 131
5.3 Consideration of Results ............................................................................ 135
5.3.1 Views on Harmonization .............................................................. 136
5.3.2 Views on Collaboration and Relationship building ...................... 140
5.3.3 Global Challenges in Standardized Pharmacopeial Practices
and Regulatory Acceptance .......................................................... 143
5.3.4 Views on Pharmacopeial Authorities ........................................... 147
5.3.5 Pharmacopeial Discussion Group ................................................. 148
5.3.6 Usage of Pharmacopeial Standards around the World ................. 151
5.4 Conclusions and Future Directions ............................................................ 151
REFERENCES ............................................................................................................... 153
APPENDIX A ................................................................................................................. 162

vii
APPENDIX B ................................................................................................................. 170
APPENDIX C ................................................................................................................. 198

viii
LIST OF TABLES
Table 1: Definitions of Key Terms and Acronyms .......................................................11
Table 2: Carboxymethylcellulose Calcium, 37 Tests before Harmonization ...............34
Table 3: Carboxymethylcellulose Calcium, 10 Tests after Partial
Harmonization ................................................................................................35
Table 4: Categories of Stakeholders .............................................................................50
Table 5: CRRRS Worksheet: Organizing Stakeholder Views and Top-Level
Needs for Global Pharmacopeial Harmonization ...........................................53
Table 6: Focus Group Participants ................................................................................57
Table 7: Research Question Categories ........................................................................58
Table 8: Cross Tabulation of Organizational Affiliation on Company Size ................71
Table 9: Number of Pharmacopeial Standards with which You Have Been
Involved (Monographs, Chapters, and Reference Standards) .......................74
Table 10: Cross Tabulation Of Organizational Affiliation On Urgency To
Achieve Globally Harmonized Standards ......................................................78
Table 11: Objectives of Global Pharmacopeial Harmonization .....................................80
Table 12: Level of Agreement with the Importance of Globally Harmonized
Standards ........................................................................................................81
Table 13: Benefits of Pharmacopeial Collaboration .......................................................83
Table 14: Cross Tabulation of Organizational Affiliation on Benefits of
Pharmacopeial Collaboration on Minimizing Duplication of Efforts ............85
Table 15: Cross Tabulation of Organizational Affiliation on Benefits of Sharing
Scientific Resources .......................................................................................86

ix
Table 16: Level of Collaboration among Different Pharmacopeias ...............................87
Table 17: Cross Tabulation of Organizational Affiliation on Level of
Collaboration among Different Pharmacopeias in Stakeholder
Engagement ....................................................................................................89
Table 18: Cross Tabulation of Organizational Affiliation on Level of
Collaboration Among Different Pharmacopeias in Promoting Work-
Sharing Activities Between Pharmacopeias ...................................................91
Table 19: Challenges Facing Pharmacopeial Bodies at the Global Level ......................93
Table 20: Cross Tabulation of Organizational Affiliation on Level of Challenge
Implementing WHO's Good Pharmacopeial Practices Guidance
(GPP) ..............................................................................................................95
Table 21: Cross Tabulation of Organizational Affiliation on Level of Challenge
Implementing ICH Quality guidances ............................................................96
Table 22: Differences across Pharmacopeias to Produce Harmonized Standards ..........97
Table 23: Cross Tabulation of Organizational Affiliation on Differences across
Pharmacopeias in their Public Inquiry/Comment Processes ........................100
Table 24: Cross Tabulation of Organizational Affiliation on Differences across
Pharmacopeias with Misaligned Publication Schedules ..............................101
Table 25: Greatest Challenges for Pharmacopeias in Developing Pharmacopeial
Standards ......................................................................................................102
Table 26: Cross Tabulation of Organizational Affiliation on Challenges With
Developing Standards with Lack of Adequate Scientific Resources ...........104

x
Table 27: Cross Tabulation of Organizational Affiliation on Challenges in
Developing Standards with a Lack of Ability to Develop Reference
Material Standards ........................................................................................105
Table 28: Satisfaction with your Pharmacopeia’s Performance ...................................106
Table 29: Views on PDG’s Performance ......................................................................114
Table 30: Cross Tabulation of Organizational Affiliation on PDG Performance
in Developing Standards in a Timely Manner ..............................................116
Table 31: Cross Tabulation of Organizational Affiliation on PDG Performance
in Engaging Stakeholders in Standards Setting ............................................117
Table 32: Factors that Present the Biggest Challenges to Implementing PDG
Harmonized Standards .................................................................................118
Table 33: Cross Tabulation of Organizational Affiliations’ Views on Whether
Reference Standards are too Costly ..............................................................120
Table 34: Cross Tabulation of Organizational Affiliations’ Views on Whether
PDG Harmonization Should be Modified ....................................................122
Table 35: Changes in the PDG Process ........................................................................123
Table 36: “Other” comments regarding views on Pharmacopeial
harmonization ...............................................................................................128
Table 37: Request for Results Summary ......................................................................130

xi
LIST OF FIGURES
Figure 1: Citric Acid, Early Monograph, USP First Edition (United States
Pharmacopeial Convention, 1820, p9 (65)) ....................................................20
Figure 2: Citric Acid Monohydrate, Modern Monograph, USP 40–NF 35 First
Supplement (United States Pharmacopeial Convention, 2017c) ....................21
Figure 3: Stages of the PDG Harmonization Process ....................................................29
Figure 4: Sign-off Cover Sheet for Citric Acid Monohydrate (PDG, 2010)..................32
Figure 5: Stakeholder Category and Their Interfaces ....................................................51
Figure 6: Timeline of Qualtrics Survey Launch.............................................................62
Figure 7: Role of Respondents .......................................................................................63
Figure 8: Geographic Areas of Responsibility ...............................................................64
Figure 9: Organization/Company Affiliation .................................................................66
Figure 10: Industry Representation ..................................................................................68
Figure 11: Size of Organization/Company .......................................................................69
Figure 12: Number of People at the Organization Working with Pharmacopeial
Standards ........................................................................................................72
Figure 13: Level of Experience with Pharmacopeial Standards ......................................73
Figure 14: Level of Experience With Retrospective Harmonization (of existing
pharmacopeial standards) ...............................................................................75
Figure 15: Level of Experience with Prospective Harmonization (where no
standards exist) ...............................................................................................75
Figure 16: Views on Importance of Global Pharmacopeial Harmonization ....................76
Figure 17: Urgency to Achieve Globally Harmonized Standards ....................................77

xii
Figure 18: Meetings Regularly Attended .......................................................................107
Figure 19: Resources Consulted .....................................................................................109
Figure 20: Frequency of use of National/ Regional Pharmacopeias of
Pharmacopeial Discussion Group (PDG) Members .....................................110
Figure 21: Use of PDG Standards in Enforcement Activities? ......................................111
Figure 22: Use of PDG harmonized Standards to Increase Efficiency ..........................112
Figure 23: Modification of the PDG Harmonization .....................................................121
Figure 24: Frequency of use of WHO's International Pharmacopeia ...........................124
Figure 25: Frequency of use of Other pharmacopeias Beyond USP, Ph. Eur., and
JP ..................................................................................................................126

xiii
ABSTRACT
Pharmacopeial standards help to ensure quality of medicines by establishing official
specifications used in their manufacture, distribution, and post-market surveillance.
Unfortunately, these quality standards vary from region to region, making it difficult for
manufacturers and suppliers who market their products globally to comply with these
different specifications. Harmonizing the different pharmacopeias in use around the
world into a single global standard would eliminate duplication of efforts, decrease costs
and time, and reduce regulatory burden. However, what constitutes harmonization and
how it is to be achieved is not clear. Efforts to achieve greater harmonization of
pharmacopeial standards and practices have been ongoing for many decades, but have
produced limited results and we are far from realizing this goal. This study surveyed key
stakeholders at the organizational affiliation level to identify their vews and needs on
challenges experienced as a result of differences between pharmacopeial standards.
Results suggested that most stakeholders view pharmacopeial harmonization as important
and necessary but that the process needs to be more pragmatic, efficient, and inclusive. It
further suggested that although PDG has limited results, it is clear their work is utilized
and appreciated but that its work should be expanded and its process simplified.
Moreover, most respondents across all stakeholder organizations believed that
collaboration between pharmacopeial bodies was very important in harmonizing
standards and practices, but had mixed views on how successful and effective efforts
have been to date in addressing key challenges such as, reducing the testing burden,
removing pharmacopeial and regulatory differences and implementing good
pharmacopeial practices in development of harmonized standards.

1
CHAPTER 1. OVERVIEW
1.1 Introduction
Over the centuries, drug formulations have followed recipes, which have evolved to
become relatively standardized to ensure consistency in quality of medicines. Many of
those early recipes were collected into compendia called pharmacopeias, a term with
Greek origin that combines pharmako (drug) and poi (make) to convey directions for
preparation of drugs (Sonnedecker, 1993; WHO, 2013a). Originally composed of simple
lists of ingredients and basic instructions, these recipes have since evolved to include
extensive requirements based on advances in analytical sciences and technology. Today’s
pharmacopeias contain detailed technical standards known as monographs, with
specifications that include tests, analytical procedures and acceptance criteria used to
confirm the identity, strength (or amount), potency, quality and purity of medicines and
their ingredients, and general test chapters (Bhattacharyya, 2004; ICH, 1999).
Pharmacopeias are typically produced by national or regional pharmacopeial authorities
or commissions, often in collaboration with manufacturers and drug authorities, to
stipulate quality standards for medicines allowed in their jurisdictions (United States
Pharmacopeial Convention, 2015). Some pharmacopeias may recognize or adopt, entirely
or in part, standards developed by other pharmacopoeias instead of developing their own
based on its capabilities (WHO, 2018). Pharmacopeias play an important role throughout
a product’s lifecycle and in the global supply chain (Layloff et al., 2000). Manufacturers
use pharmacopeial standards to control the quality of products that they produce and
regulatory authorities rely on them to assess compliance during pre-market registration,

2
commercial release, and post-market surveillance (Artiges, 2001; Hutton, 1999; Keitel,
2010; Layloff et. al., 2000). With the exception of the United States Pharmacopeia (USP),
which is an independent nonprofit organization, pharmacopeial authorities are embedded
in their respective national or regional legal/regulatory authorities, typically within their
national ministries of health (see WHO Index of Pharmacopoeias) (WHO, 2018).
In the absence of any obligation to coordinate their activities, pharmacopeias around the
world have evolved separately according to their own constituencies, laws, and
organizational capabilities. Consequently, we now have individual pharmacopeias that
are slightly or, sometimes, greatly different from one another in the way that they develop
standards and set specifications. This dissonance represents a significant burden to the
pharmaceutical industry, which must navigate across different quality standards and
conduct redundant testings to satisfy different national and regional pharmacopeial
requirements. Likewise, industry is required to comply with national or regional
regulations and laws. Given as much, it has become evident that…
There is an increased need for consistent and appropriate quality requirements
for medicines because disharmonized standards do not provide additional value
or benefit, but rather increase the cost and complexity of bringing medicines to
patients worldwide (Wiggins & Schneider, 2012).

Pharmaceutical manufacturing in today’s global landscape employs a complicated supply
chain in which products are manufactured and commercialized across both developed and
emerging markets. The establishment of a harmonized pharmacopeial standard would
help to ensure consistency in the quality of the drug, reduce the testing burden on the

3
industry, and allow sharing of information and work across the pharmacopeias (Wiggins
& Schneider, 2012). In fact, the potential advantages of a globally harmonized
pharmacopeia were recognized over a century ago, in 1865, when the First International
Pharmaceutical Congress was formed. The group, including a delegation from USP, met
regularly throughout the nineteenth century and engaged in technical discussions but
made little progress toward harmonization. Over the succeeding years, the harmonization
work continued under various international initiatives. For example, in 1937, the League
of Nations was tasked with creating an International Pharmacopoeia and formed the
Technical Commission of Pharmacopoeial Experts. Unfortunately, the League of Nations
was dissolved shortly thereafter and, hence, the unfinished work was left to the newly
formed World Health Organization (WHO) led by the Expert Committee on the
Unification of Pharmacopeias. In 1951, the WHO published the first International
Pharmacopeia (Ph.Int.) for adoption by its member states, which were looking to
establish quality standards for medicines in their population (WHO, 2016).
The WHO’s Ph.Int., however, was not developed to be a global pharmacopeia or to
replace pharmacopeias like USP and others that were already well-established. Hence,
the need for harmonization across the different pharmacopeias remained unsatisfied.
Over the next several decades, other organizations including the Council of Europe,
Pharmacopeial Discussion Group (PDG), International Council for Harmonisation (ICH)
and the International Council of Drug Regulatory Authorities (ICDRA) have all been
active in efforts to harmonize pharmacopeial standards. However, the harmonization
process has been challenging and achieving a single global pharmacopeial standard

4
approach presently seems to be beyond reach. One area of challenge is the disparity in
analytical capabilities of different pharmacopeias. Modern advances in science and
technology have transformed the way in which substances in food, drugs, dietary
substances, and cosmetics are measured. Today’s sophisticated instrumentation, along
with new spectrographic and chromatographic techniques, allow for the detection and
measurement of impurities, contaminants and adulterants at levels in the parts per trillion
(Janssen, 1981). However, not all regions around the world have equal access to
advanced technology. For this reason, WHO’s Ph.Int. provides less technically
demanding alternatives where needed - for adoption by Member States (WHO, 2018;
2019). This disparity contributes to the current pharmacopeial dissonance and poses
challenges for those undertaking efforts to create globally harmonized pharmacopeial
standards and practices.
One can appreciate the complex and redundant nature of pharmacopeial testing by
examining how multiple drug manufacturers across different regions develop and supply
the same drug products and ingredients for worldwide distribution. For example, there are
approximately 20 different manufacturers that produce ibuprofen dosage forms for the
U.S. alone (Bhattacharyya, 2004). All must comply with the USP Ibuprofen monograph
established by the United States Pharmacopeia (USP) in order to market the product in
U.S. (United States Pharmacopeial Convention, 2015). However, because many other
regions have their own pharmacopeias, each manufacturer needs to conduct additional
testing to meet the pharmacopeial requirements that correspond to each region where its
product is to be distributed. This added work represents a great burden to the stakeholders

5
(industry, pharmacopeias, and regulators) without providing any additional benefit to the
patient or impact to public health or the society (Wiggins & Schneider, 2012). To help
alleviate this concern, FDA published a Manual on Policies and Procedures (MAPP) on
“Acceptability of Standards from Alternative Compendia (BP/EP/JP)” that applies to the
CMC evaluation of new drug applications performed by the CDER/OPS/Office of New
Drug Quality Assessment. The MAPP allows industry to use alternative pharmacopeial
standards if certain pharmacopeial and regulatory requirements are met (FDA, 2017).
1.2 Statement of the Problem
Pharmacopeial standards help to ensure quality of medicines by establishing official
specifications used in their manufacture, release, distribution, and post-market
surveillance. Unfortunately, these quality standards vary from region to region, making it
difficult for manufacturers and suppliers who market their products globally to comply
with these different specifications. Harmonizing the pharmacopeial standards in use
around the world into single global standards would eliminate duplication of efforts,
decrease costs and time, and reduce regulatory burden. However, what constitutes
harmonization and how it is to be achieved is not clear. Efforts to achieve greater
harmonization of pharmacopeial standards have been ongoing for many decades but have
produced limited results and we are far from realizing this goal. The difficulties faced by
those pursuing pharmacopeial harmonization may be in part due to an insufficient
understanding of the barriers that exist, including conflicting views and incompatible
needs among and between key stakeholders (pharmacopeias, regulators, and industry).

6
1.3 Purpose of the Study
The purpose of this study is to explore the views of key stakeholders by utilizing a
framework that incorporates needs across three different categories of stakeholders and
determine their level of satisfaction with the existing pharmacopeial harmonization
process (Samaras & Samaras, 2012; Wiggins & Schneider, 2012). The results of this
study may help to understand where the challenges exist to creating a harmonized
standard and may help inform and expedite ongoing and future harmonization activities.
The stakeholders can be divided into the following categories:
• Real stakeholders - classic stakeholders who have a firm stake, support or interest;
for example, pharmaceutical drug manufacturers, ingredient manufacturers,
contract and research manufacturing organizations, contract testing laboratories,
instrument, reference standards and reagent manufacturers/suppliers and
practitioners.
• Stakekeepers - independent monitors or regulators who exert influence; for
example, national and regional regulatory authorities (RA), national and regional
pharmacopeial authorities (PA), and official medicines control laboratories
(OMCLs), national or state testing laboratories like the FDA regulatory
laboratories, EDQM laboratories, academia conducting government funded
research grants, and other associated organizations like ICH, PDG, ICDRA, PIC/S
and WHO.

7
• Stakewatchers - pressure groups or watchdogs who do not have a stake, but
represent the interests of real stakeholders; for example, research and
manufacturing trade and other associations that work to protect their individual
members, medical practitioners and other similar organizations.
Study participation will comprise selected professionals from the pharmaceutical
industry, pharmacopeial and regulatory fields, academic practitioners, and trade
associations, who are known to the investigator and associates to be working in
development, implementation, review and enforcement of pharmacopeial specifications
throughout different regions of the world. Respondents will participate by invitation only
and expanded by the use of snowball referrals.
It is anticipated that the results of this study will provide insight into the current
challenges in the development of globally harmonized pharmacopeial standards and their
impact on the pharmaceutical industry, regulatory authorities, pharmacopeia, and other
stakeholders. Furthermore, the study findings may help to advance global harmonization
efforts by informing future discussions and policy initiatives.
1.4 Delimitations, Limitations, Assumptions
Delimitations:
In this study, we will not delimit to any one geographic region. The geographic
delimitation of potential respondents has the potential to bias responses towards the views
of the pharmacopeias, regulators, pharmaceutical industry and other organizations in the

8
regions of the world from which respondents are located and may affect the utility of the
conclusions that can be drawn. To minimize this effect, respondents will be actively
sought from across the world, including regions that are outside of PDG, namely China,
India, South Korea, South East Asia, South and North America, and other WHO member
countries. Current views will be sought from the three key stakeholder categories
described above, who would be familiar with pharmacopeial standards and the challenges
associated with the harmonization process.
Another delimitation will be the number of questions that are presented to the survey
respondents based on the likelihood of assuring that they will complete the survey. In
limiting the number of questions, certain topics may not be fully explored and this in turn
may constrain the analysis.
Limitations:
Restriction of respondents to an invitation only, approach was viewed as necessary to
ensure that the participants were both experienced and subject matter experts (SME). The
selection of participants was from professional networks and snowball referrals. This
approach can potentially introduce a bias because the participants may be like-minded
individuals who may have been influenced by attending the same meetings, trainings and
workshops conducted by regulatory or pharmacopeial bodies, professional, and trade
associations. The extent to which the approach used is representative of all stakeholders
in this field will determine the degree to which the external validity of the study may be
open to question.

9
There are other real and potential limitations and risks outside of the researcher’s control.
One of the concerns is that the majority of survey participants are expected to be
analytical chemists, pharmacists, pharmaceutical scientists and regulatory scientists who
are SMEs with active roles in the technical development, validation, implementation,
review and enforcement of pharmacopeial specifications. Their responses may be biased
by the fact that their views reflect those of their organizations. In addition, obtaining
sufficient numbers of respondents to ensure a balanced analysis may be difficult, given
that busy individuals may be reluctant to participate in the study. Finally, some
respondents may be constrained by the confidential nature of their activities and the type
of information, which they are able to share.
The survey tool may also prove limited in its ability to solicit feedback from different
stakeholder catagories at the organizational level in a comparable manner. Using a focus
group to critique and help construct the survey will provide valuable input from various
perspectives but does not guarantee that all questions will be useful or, that important
questions will not be missed. Finally, given the variability between the requirements of
pharmacopeial standards setting for each pharmacopeia, stakeholder experience may vary
and thus pose challenges during the interpretation of the findings.
The results of this survey may be influenced by the fact that the survey pool may be small
and participants may be difficult to recruit or may not be known to the researcher at the
time of initial survey dissemination. Given that the primary researcher of this study is
currently employed by a pharmacopeia within PDG, experimenter expectancy is a

10
potential source of bias. Additionally, the development of the survey may be handicapped
by the relative inexperience of the investigator with such methods.
Assumptions
I am making a certain number of assumptions. First, I will assume that all respondents are
truthful in their appraisals and that they are expressing their own opinions, which will be
based on their knowledge of and experience with the subject matter. Sensitivity to this
issue will require an assurance of anonymity and such limits the ability to relate specific
data to identifiers of the respondents and their employers. I also will assume that
participants who will complete the survey will have a sufficient understanding of the
subject matter to provide meaningful answers to the questions. Likewise, I will make the
assumption that I will be able to exercise balance and objectivity during the conduct of
the study and analysis of the results. However, bias may persist to some degree. The
study assumes that the companies represented by respondents are manufacturing
pharmaceutical ingredients and pharmaceutical products requiring approval and licensing
by FDA or other competent regulatory authorities. The researcher also assumes that the
respondents will be familiar with individual U.S., European, Japanese, Chinese, Indian
and other pharmaceutical laws, regulations and pharmacopeial specifications relevant to
standards setting, ICH Quality topics, and regulatory guidance documents associated with
pharmacopeial analytical methods development, validation, compliance and enforcement
activities. Finally, the assumption is that all respondents invited to participate in the
survey after agreeing to do so, will actually participate.

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1.5 Organization of Thesis Proposal
Chapter 1 introduces the problem to be studied in this thesis, explains the approach that
will be taken, and describes the delimitations, limitations and assumptions. Chapter 2
provides a more detailed overview of pharmacopeial standards setting and harmonization
efforts throughout history and summarizes the relevant academic and regulatory literature
that frames the problem in sufficient detail to inform on the exact nature of the issue.
Chapter 3 describes the research methodology that will be used in conducting the survey.
Chapter 4 analyzes the research conducted using the survey instrument. Chapter 5
provides a discussion on the research results, conclusion, and suggestions for a path
forward. Appendices to this thesis include, Appendix A: Additional Cross Tabulations,
Appendix B: Final Verison of the Survey, and Appendix C: Number of Monographs in
Pharmacopeias in WHO region.
1.6 Definitions
As used within this study, the following key terms and acronyms are defined in Table 1.
Table 1: Definitions of Key Terms and Acronyms
APhA – American Pharmacists Association
API – Active pharmaceutical ingredient (See DS)
CFDA – China Food and Drug Administration (People’s Republic of China, or PRC)
CFR – US Code of Federal Regulation
cGMP – Current Good Manufacturing Practices
ChP – Chinese Pharmacopoeia
CMC – Chemistry Manufacturing and Controls
CMO – Contract Manufacturing Organization
CRO – Contract Research Organization
CTL – Contract Testing Laboratory
DP– Drug Product See 21 CFR 314.50(d)(1) and 314.94(a)(9)(i).
DRA – Drug Regulatory Authority (see regulatory authority)
DS – Drug substance See 21 CFR 314.50(d)(1) and 314.94(a)(9)(i). (See API)
ECSPP – WHO Expert Committee on Specifications for Pharmaceutical Preparations
EDQM – European Directorate for the Quality of Medicines and HealthCare
EFPIA – European Federation of Pharmaceutical Industries and Associations
EMA – European Medicines Agency

12
EMEA – European Agency for the Evaluation of Medicinal Products
EP – European Pharmacopoeia (See Ph. Eur.)
EU – European Union
FDA – United States Food and Drug Administration
FFDCA – US Federal Food Drug and Cosmetic Act
GMP – Good Manufacturing Practice
GPhA – Generics Pharmaceutical Association (now called Association for Accessible Medicines)
GPhP – WHO Good Pharmacopeial Practices Guidance (TRS 996)
ICDRA – International Conference of Drug Regulatory Authorities
ICH – International Council on Harmonization (prior to Oct. 2015, known as International Conference
on Harmonization of Technical Requirements for Registration of Pharmaceuticals)
IMWP – International Meeting of World Pharmacopoeias
IPRP – International Pharmaceutical Regulators Programme
IP – Indian Pharmacopoeia
JP – Japanese Pharmacopoeia
MHLW – Ministry for Health Labor and Welfare
NDA – New Drug Application
NPA – National Pharmacopeial Authority
NRA – National Regulatory Authority
OMCL – Official Medicines Control Laboratory
PA – Pharmacopeial Authority ( see National Pharmacopeial Authority and Regional Pharmacopeial
Authority)
PDG – Pharmacopeial Discussion Group
Ph. Eur. – European Pharmacopoeia (See EP)
Ph. Eur. Commission – European Pharmacopoeia Commission
Ph. Int.– International Pharmacopoeia
PMDA – Japanese Pharmaceuticals and Medical Device Association
PIC/S – Pharmaceutical Inspection Co-operation Scheme
RA – Regulatory Authority (see Drug Regulatory Authority)
RPA – Regional Pharmacopeial Authority
USC – United States Code
USP – United States Pharmacopeia
USPC – United States Pharmacopeia Convention
WHO – World Health Organization
Harmonization: According to PDG, a pharmacopeial general chapter or other pharmacopeial document
is harmonized when a pharmaceutical substance or product tested by the document's harmonized
procedure yields the same results and the same accept/reject decision is reached.
Harmonization by Attribute: PDG allows partial harmonization whereby only certain elements or
attributes (e.g., definition, and tests for identification, assay and impurities) of a monograph are
harmonized while others remain unchanged.
ICH Q4B Interchangeable methods: According to ICH Q4B, where such status is indicated, any of the
official texts from JP, EP, or USP can be substituted one for the other (appropriately referenced) in the
ICH regions for purposes of the pharmaceutical registration/approval process. Using any of the
interchangeable methods, an analyst will reach the same accept or reject decisions irrespective of which
PDG pharmacopeia is used (FDA, 2008; ICH, 2002; ICH 2007).
Monograph: A minimum standard to confirm identity, strength, potency, quality and purity of a
pharmaceutical ingredient or product.
Specification: According to ICH Q6A, is a list of tests, references to analytical procedures, and
appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests
described.
Analytical procedure: According to ICH Q2(R1), it refers to the way of performing the analysis It
should describe in detail the steps necessary to perform each analytical test. This may include but is not
limited to: the sample, the reference standard and the reagents preparations, use of the apparatus,
generation of the calibration curve, use of the formulae for the calculation, etc.

13
Validated analytical procedure: According to ICH Q2(R1), the objective of validation of an analytical
procedure is to demonstrate that it is suitable for its intended purpose. Typical procedures requiring
validation include identification, impurities and assay (content or potency). Typical parameters used in
validation studies include:
Accuracy: Closeness of agreement between the value which is accepted either as a
conventional true value or an accepted reference value and the value found.
Precision: Closeness of agreement (degree of scatter) between a series of measurements
obtained from multiple sampling of the same homogeneous sample under the prescribed
conditions. Expressed as the variance, standard deviation or coefficient of variation of a series
of measurements.
Specificity: Unequivocally assess the analyte in the presence of components which may be
expected to be present. Typically, these might include impurities, degradants.
Limit of quantitation (LOQ): The lowest amount of analyte in a sample which can be
quantitatively determined with suitable precision and accuracy. Is used mostly for the
determination of impurities and/or degradation products.
Limit of detection (LOD): The lowest amount of analyte in a sample which can be detected
but not necessarily quantitated as an exact value.
Linearity: Ability (within a given range) to obtain test results which are directly proportional
to the concentration (amount) of analyte in the sample.

14
CHAPTER 2. LITERATURE REVIEW
2.1 History and Origin of the Pharmacopeia
Efforts to establish public standards to control the quality of medicines and safeguard the
public have a long history that can be traced back to the written records of ancient
civilizations. Perhaps the history most familiar to many is that associated with early
Hellenic culture. The Hippocratic Corpus, containing over 1500 ancient pharmaceutical
recipes, was named after the Greek physician, Hippocrates who lived from 460 to 370 B.
C. (Hanson, 2007). Recipes contained in this corpus represented early attempts to
standardize the quality of ingredients and medicines that were prepared and dispensed by
physicians (Totelin, 2009). The Hippocratic Corpus was followed by a more detailed
record produced by the Greek physician and pharmacologist Dioscorides who wrote a
five-volume book called De Materia Medica ("On Medical Material", c.100 A.D.). This
catalogue, considered the precursor to all modern pharmacopeias, provided names and
geographic locations, descriptions, properties and methods of preparation for each listed
article. Each book was devoted to a single substance (herbal, animal, or mineral) with its
description, preparation, and therapeutic properties (Norton, 2006). Practices
meticulously detailed in the De Materia Medica were adopted throughout Medieval and
Renaissance periods by guilds and professional societies of physicians and pharmacists.
Similar trends in systematizing drug compendia were also occurring in parallel in other
countries, including China with Traditional Chinese Medicine and India with Ayurveda
(Hao & Jiang, 2015).

15
2.1.1 Introduction of Public Standards to Ensure Quality of Medicines
As trade between the Middle East and Europe increased in the ninth century, a growing
list of newly introduced medicinal ingredients and products required specialized
professionals to prescribe, compound, and dispense the medicines. The pharmacy
profession was, in fact, born out of the necessity to provide the public with medicines that
are carefully prepared with quality ingredients using standardized methods (Sonnedecker,
1993). However, without a publically mandated quality standard, adulterated and
counterfeit medicines proliferated in the marketplace (Sonnedecker, 1993), thereby
prompting local guilds and professional societies to develop and establish their own
standards. Starting in the 1300s, cities in Europe recognized local pharmacopeias and
official apothecaries, facilitating a system of ‘self-regulation’. Several pharmacopeias
became influential beyond their own municipal borders and were widely adopted. A few
even gained national recognition. For example, in 1499, a physician in Florence named
Lodvice dal Pozzo Toschanelli produced a book of drug recipes for the local physician’s
guild. This book, known as the Nuovo Receptario, became popular and was recognized
throughout the city-state of Florence, Italy. Another example is the Dispensatorium
Pharmacopolarum, which was the official pharmacopeia of Nürnberg, but became an
obligatory set of standards in over 60 cities across Germany (Sonnedecker, 1993). With
the introduction of the printing press in the 15
th
century, pharmacopeias became less
costly, more widely accessible, and increasingly important for controlling and
standardizing the quality of medicines across Europe (Sonnedecker, 1993).

16
2.1.2 Establishment of the United States Pharmacopeia (USP)
The development of a U.S. pharmacopeia appeared to lag behind that of European
countries. By 1864, for example, the British Pharmacopeia published a unified
pharmacopeia representing London, Edinburgh, and Dublin to become the official
national pharmacopeia of the Great Britain. However, as a young country, the U.S. lacked
a sufficient pool of trained medical or pharmacy professionals and a legal framework to
oversee the preparation of pharmaceutical products. Without a public quality standard or
laws to regulate the practice of medicine or pharmacy, the U.S. market in the early 1800’s
was flooded with dangerous and ineffective drugs that were either counterfeit,
contaminated, diluted, and/or decomposed (Janssen, 1981). Consequently, the U.S.
eventually became a dumping ground for adulterated drugs from abroad (FDA, 2015b).
According to a British statesman and prominent pharmacist Jacob Bell,
…manufacturers understood that drugs reduced by decay or ingenuity were still
good enough for America (FDA, 2015b).
Concerned physicians and pharmacists in the U.S. were sensitive to the immaturity of
their own systems. They borrowed methods obtained from various foreign sources
including the French military formularies and the Russian Pharmacopoeia to prepare
medicines for their patients (Sonnedecker, 1994b). Throughout the late 1700’s and early
1800’s, several of the medical societies throughout the four regional districts of the U.S.
i.e. the North, Middle, South and West, developed pharmacopeias for their own members
and local pharmacists. Notably, in 1808, the Massachusetts Medical Society in the North
District created the Massachusetts Pharmacopoeia, based on Scotland’s Edinburgh
Pharmacopoeia, which was soon widely adopted and eventually became a prominent

17
regional pharmacopeia (Haller, 1982; Sonnedecker, 1994b). It was later incorporated,
along with other regional pharmacopeial input, into the first national compendium, the
United States Pharmacopeia (USP), which was finalized in 1820, through efforts
spearheaded by Dr. Lyman Spalding, a distinguished member of the Medical Society of
New York (North District) (Sonnedecker, 1994b).
The newly established USP provided a national quality standard that could be used to
prepare medicines. Still, the lack of a legal mandate to adhere to USP standards allowed
the sale of so called “patent drugs” by unscrupulous manufacturers. Products like the
"Warner's Safe Cure for Diabetes" with its unsubstantiated claims, as well as counterfeit
medicines and preparations containing dangerous ingredients like opium, morphine,
heroin, and cocaine misled and harmed patients (Janssen, 1981). Moreover, because the
manufacturers were not obligated to list ingredients or warnings on the product labels, the
public was uninformed about what they were purchasing or consuming. The need for a
legal framework to control the quality of medicines became strikingly evident when,
during the Mexican War (1846-1848), counterfeit medications provided to U.S. military
troops to treat malaria resulted in thousands of deaths. The resulting public outrage and
calls for legislative action (Walch, 2002) facilitated the passage of the Import Drugs Act
of 1848, which, for the first time, legally recognized the USP as the official compendium
of the U.S. (Flannery, 2001).
By the early 1900s, formulation of medicines through traditional compounding by local
pharmacists and apothecaries gave way to manufacturing by the newly emerging
pharmaceutical industry that took pride in using advances in science and technology to

18
make high quality drug products. However, without a legal framework to regulate these
products, it was difficult to differentiate products manufactured by legitimate companies
from those produced by unscrupulous ‘patent’ medicine peddlers. The fight to protect the
public from inferior and harmful food and drugs was taken up by Dr. Harvey Wiley, the
director of the newly established U.S. Bureau of Chemistry. He pushed for new
legislation to oversee food and drugs by publicizing the findings of his “Poison Squad”
laboratory showing that the marketplace was full of poisonous and adulterated drugs
(FDA, 2019; Janssen, 1981). Dr. Wiley’s work was instrumental to the passage of the
Pure Food and Drug Act of 1906 that prohibited the manufacture, sale, or transportation
of adulterated, misbranded, poisonous or deleterious foods and drugs. Unfortunately,
scientific methods of analysis available at that time were primitive and insufficient to
control the quality of medicines on the market. In addition, the 1906 Act did not require
that the manufacturer demonstrate safety of its product. It was not until 1938, after a
poisonous formulation of sulfanilamide killed over 100 people, mostly children, that a
stronger law was enacted (Cannon, 1937; Holloway et al., 2010). The 1938 Federal Food,
Drug and Cosmetic Act (FD&C Act) included a drug section that provided a new system
for drug control requiring all medicines placed on the market to be safe to use under the
directions for use (Abernethy et al., 2009; FDA, 1938). The FD&C Act defines the term
“official compendium” to include USP, thereby establishing the critical role of USP in
demonstrating quality of a product and their ingredients and linking it to the adulteration
and misbranding provisions of the law (Bhattacharyya, 2004; United States
Pharmacopeial Convention, 2017a).

19
In anticipation of the new law, many of the major American pharmaceutical companies
such as Parke Davis and Eli Lilly established their own laboratories to standardize the
quantity and quality of pharmaceutical ingredients and the amount and potency of their
commercial products (Parascandola, 1995). By the 1940s, large scale manufacturing of
finished drug products and chemical ingredients was well established in the U.S., United
Kingdom, and Europe with German pharmaceutical industry giants like Bayer, Hoechst
and BASF dominating the global industry (Cramer, 2015). The passage of the 1962
Kefauver Harris Amendment further strengthened the U.S. legal framework by
establishing manufacturing quality controls, later to be called Good Manufacturing
Practices (GMP), and linking manufacturing to quality control standards appearing in the
USP (United States Pharmacopeial Convention, 2017b; Wiggins et al., 2008).
2.2 The Modern Pharmacopeia
The pharmacopeial standards in the early versions of USP were relatively primitive when
compared to the standards of today (Du Mez, 1917; Sonnedecker, 1994a). Over the last
two centuries, advances in biology and chemistry have become central to the
development of modern pharmacopeial standards. As a result, monograph standards grew
from simple pass/fail wet chemistry methods to more complex, quantitative analytical
methods. A typical monograph from the previous era, shown in Figure 1 for Citric Acid,
included basic descriptions such as nomenclature, identity, quantity of ingredients and,
sometimes, recommendations related to the compounding process (Sonnedecker, 1993).

20
Figure 1: Citric Acid, Early Monograph, USP First Edition (United States
Pharmacopeial Convention, 1820, p9 (65))

21
Figure 2: Citric Acid Monohydrate, Modern Monograph, USP 40–NF 35 First
Supplement (United States Pharmacopeial Convention, 2017c)

https://www.usp.org/sites/default/files/usp/document/harmonization/excipients/e15_current_webp
age_stage_6_monograph_updated_14_oct_2011.pdf Accessed, March, 2017.

22
In contrast, the modern version differentiates the two forms of citric acid into anhydrous
and monohydrate. As shown in Figure 2, the modern monograph is much more detailed
than its predecessor and includes the name (title) of the ingredient or preparation; the
definition; packaging, storage, and labeling requirements; and the specification. The
specification consists of information on tests (including methods and instrumentation
needed to demonstrate that the substance is of the appropriate strength, quality, and
purity) and acceptance criteria. It also includes detailed information on detecting and
quantifying impurities and contaminants, which is an important consideration for a
substance like citric acid, which is often used as an excipient.
Today’s monographs incorporate advanced methods that use modern instruments like
high-performance liquid chromatography (HPLC), gas chromatography (GC), and mass
spectrometry (MS), which provide a high degree of accuracy for determining the identity
and purity of pharmaceutical drug products and their ingredients (Görög, 2012). Many of
these analytical procedures call for using official reference standards (RS) that are highly
purified and well-characterized physical materials used in demonstrating compliance with
legal requirements (United States Pharmacopeial Convention, 2015).
2.3 Legal Recognition of National and Regional Pharmacopeias
For standards in a pharmacopeia to be legally binding, it must be incorporated into
national or regional legislation. The U.S. Federal Food, Drug, and Cosmetic Act (FD&C
Act), Part A – Drugs and Devices, requires that a drug must conform to the USP-NF
standard in order for it not to be considered adulterated, misbranded or both (United
States Pharmacopeial Convention, 2017a; FFDCA, 2016; Layloff et al., 2000):

23
A drug or device shall be deemed adulterated if it purports to be or is represented
as a drug the name of which is recognized in an official compendium, and …
differs from…the standard set forth in such compendium (FFDCA, 2016)
A drug with a name recognized in USP-NF must comply with compendial identity
or be deemed adulterated, misbranded, or both (501(b) & 502(e)(3)(b)). (Layloff
et al., 2000)
The U.S. FDA refers to the United States Pharmacopeia and the National Formulary
(USP-NF) standards as part of its drug product quality review evaluations (FFDCA,
2016; United States Pharmacopeial Convention, 2015; FDA, 2015a; Layloff et al., 2000).
It is important to note that historically the USP and NF were separate compendia until
1975 when they were combined into a single entity. Currently, the USP section of USP-
NF specifies standards for drug substance and dosage forms whereas the NF section
specifies standards for excipients. The 2017 edition, USP 39-NF 34 second supplement,
contains over 5900 monographs and over 3300 reference standards. According to U.S.
laws, a drug must meet the USP compendial standard for strength, quality, and purity,
unless it is labeled to declare all differences so as not to be considered adulterated
(FFDCA, 2016).
Many other countries have their own pharmacopeias bound by their national or regional
pharmacopeial authorities and laws. According to a World Health Organization (WHO)
questionnaire conducted during the 2012 International Meeting of World Pharmacopoeias
(IMWP), from the 49 active pharmacopieal commissions, 33 national pharmacopeias, 2
regional, and 1 international pharmacopoeias are currently employed by 140 countries
around the world and are listed in the 2013 Index of Pharmacopoeias (WHO, 2013a;
2018). The following are three examples of legally binding national pharmacopeias:

24
• Japan: The Japanese Pharmacopoeia (JP) was established in June 1886 and
implemented on July 1887 (Suzuki, 1887) by the Ministry of Health, Labour and
Welfare (MHLW) of the Japanese Government. It is referenced in Japan’s main
drug law, the Pharmaceutical Affairs Law (PAL), and maintained by the
Pharmaceuticals and Medical Devices Agency (PMDA), which is an Incorporated
Administrative Agency that works at arm’s length to the Japanese government
(PMDA, 2016). The JP 17 edition, contains 1962 monographs and 394 reference
standards.
• China: The Pharmacopoeia of the People's Republic of China (ChP) was
established in 1953 by the Chinese Pharmacopoeia Commission (ChPC), an
institution affiliated with the China Food and Drug Administration (CFDA)
currently known as the China National Medical Products Association (CNMPA).
The tenth edition, of ChP was published in 2015 and has a total of 5608 quality
standards, roughly half of which are traditional Chinese medicines (TCM)
(Chinese Pharmacopoeia Commission, 2019).
• India: The Indian Pharmacopoeia (IP) was established in 1955 and is now under
the authority of the Indian Pharmacopoeia Commission (IPC), formed in 2009
under administrative control of the Ministry of Health & Family Welfare. The IP
VII edition, published in 2014, contains close to 3000 monographs and 422
reference standards. The IPC plans to publish the eighth edition in 2018 (Indian
Pharmacopoeia Commission, 2017).

25
In Europe, discussions to replace the national pharmacopeias with a single regional
pharmacopoeia started in 1964 by the eight founding countries of the Convention on the
Elaboration of a European Pharmacopoeia (Convention), namely Belgium, France, the
Federal Republic of Germany, Italy, Luxembourg, the Netherlands, Switzerland, and the
United Kingdom (Artiges, 2001). These discussions were soon followed by the
establishment of the European Pharmacopeia Commission, which published the official
European Pharmacopeia (Ph.Eur.) in 1967. To date, the European Pharmacopoeia
Commission has remained as the decision-making body, but the European Directorate for
the Quality of Medicines & Healthcare (EDQM), created in 1996, now provides scientific
and administrative support. As stipulated by the European Union (EU) Directives
2001/82/EC, 2001/83/EC, and 2003/63/EC on medicines for human and veterinary use,
the Ph. Eur. is legally mandated for market authorization in the European Union (EDQM,
2014a). Furthermore, these directives have been transposed into national legislation of
EU Member States, thereby establishing Ph.Eur. as the quality standard within each
country (Janssen, 1981; WHO, 2013a). The Ph.Eur. is widely recognized and used
beyond the borders of the EU, with the Convention standing today at 38 member
signatories and 27 observer countries (Commission, 2014). The Ph.Eur. is the first and
only regionally harmonized pharmacopeia that is comprehensive and kept current with
regular updates (Wiggins et al., 2008). The 9
th
edition of Ph.Eur, released in 2016,
contains over 2300 monographs and 2700 reference standards (EDQM, 2019). The only
other regional pharmacopeia, the African pharmacopoeia, is limited to 96 plants and
drugs (WHO, 2018).

26
In 2017, the Pharmacopoeia of the Eurasian Economic Union (EAEU) was formed with
participation from Armenia, Belarus, Kazakhstan, Kyrgyzstan, and the Russian
Federation. The first draft Pharmacopoeia of the EAEU is being prepared by the
Pharmacopoeial Committee of the EAEU. The Pharmacopoeial Committee of the EAEU
consists of representatives from each member state of EAEU (WHO, 2018).
For countries that do not have their own pharmacopeias, the World Health Organization
(WHO), as mentioned earlier, has developed an International Pharmacopoeia (Ph. Int.).
The first volume of the Ph. Int., published by the WHO in 1951, became available for
implementation and use by any of WHO’s Member States (WHO, 2014a, 2014c). It is
important to note that the Ph. Int. has no legal standing until a national or regional
authority adopts it into that country’s legislation (Lezotre, 2014; WHO, 2014c). Whereas
the national and regional pharmacopeias focus on medicines used in their areas, WHO’s
Ph. Int. focuses primarily on the “Model Lists of Essential Medicines”, like medicines for
children and treatments for malaria, tuberculosis and HIV/AIDS, which are considered
important in developing countries, (WHO, 2013a). The Ph.Int. is evaluated and
maintained by two WHO Expert Committees and published as part of the WHO
Technical Report Series (WHO TRS) (ECSPP, 2014, WHO, 2014a). The latest, Ninth
Edition, was released in 2019 (WHO, 2019). An excerpt of number of monographs in
WHO pharmacopeias is listed in Appendix C.
2.4 Harmonization of Pharmacopeias
The modern pharmacopeia plays a major role in the regulatory process and quality
control of drug substances, excipients and drug products and is essential to the work

27
performed by pharmaceutical manufacturers and regulatory authorities, including official
testing laboratories (Bhattacharyya, 2004; Layloff et al., 2000). However, pharmacopeial
monographs vary from one country to another based on local specifications that were
developed without the knowledge of or consultation with other constituencies. The need
to harmonize international quality standards became pressing in the 1980’s as the
pharmaceutical industry expanded globally and was burdened with the requirement to
duplicate many laboratory, animal, and human tests to market its products internationally.
Therefore, it is not surprising that several important harmonization initiatives were started
at that time. In 1980, the International Conference of Drug Regulatory Authorities
(ICDRA) was established to provide a forum for regulators from WHO member states to
develop international consensus on demonstration of safety, efficacy, and quality of
medicines (ICDRA, 2002, 2004; WHO, 2014b). The Pharmacopeial Discussion Group
(PDG) was formed in 1989 with representatives from the pharmacopeias of U.S., Europe,
and Japan, to discuss harmonization of pharmacopeial standards (excipient monographs
and selected general chapters) across the three regions. At the time of PDG’s formation,
the three areas collectively represented 80% of the world’s pharmaceutical market
(Timmermans, 2004). The activities of PDG roughly coincided with the work of the
International Conference on Harmonization (ICH) formed in 1990 by drug regulatory
authorities and the pharmaceutical industry of U.S., Europe, and Japan to harmonize the
technical requirements for pharmaceutical product registration (McCarthy, 2001; WHO,
2000, 2009). Since its inception, the ICH has developed many important guidelines to
address safety, quality and efficacy topics that have become widely adopted around the
world. As ICH enters its third decade of activity, it is responding to the changing market

28
landscape by extending its reach beyond the ICH regions. The recent changes to ICH
include changing its name in 2015 to “International Council on Harmonization” and a
more inclusive membership that in 2018 includes regulators from Brazil, Canada, China,
Japan, South Korea, and Switzerland; and industry members who now represent the
generic and the biotechnology sectors (ICH, 2015, 2018).
With increasing external pressures on ICH to include more countries and stakeholders at
the table, three years on from its reform, ICH announced in November 2018 their
successful implementation of all organizational changes. ICH now has sixteen members
and twenty-eight observers, USP and EDQM amongst the most recently added observers.
However, with the current onboarding of members and observers, the challenges now
faced by ICH include, ensuring that all current ICH members and observers have training
on implementation of ICH guidelines, work scope, governance and process, and
identifying participating industry imbalance (innovator-focused) (ICH, 2018).
2.4.1 The Pharmacopeial Discussion Group (PDG)
The Pharmacopeial Discussion Group (PDG) was formed to create common quality
standards for drug products that would eliminate redundant testings like those described
in Chapter 1 for ibuprofen (Artiges, 2001; United States Pharmacopeial, 2018; Keitel,
2010). The PDG aims to harmonize both selected excipient monographs and general test
chapters so that they will be interchangeable within the ICH regions of US, Japan, and
Europe (WHO, 2011; DeStefano & Moore, 2012). PDG defined harmonization as:
A pharmacopeial general chapter or other pharmacopeial document is
harmonized “when a pharmaceutical substance or product tested by the

29
document's harmonized procedure yields the same results and the same
accept/reject decision is reached. (United States Pharmacopeial Convention,
2003)

The PDG process was reformed in 2018 and is discussed later under PDG working
procedure reforms. The harmonization process prior to April 1, 2018, had seven stages
(Figure 3).
Figure 3: Stages of the PDG Harmonization Process

https://www.uspnf.com/notices/pdg-procedure-changes Accessed, Jan., 2019.
Prior to April, 2018 the first three stages were conducted internally, i.e. within PDG
membership, whereas Stage 4 was open and public. During stage 4, which was called the
“official public inquiry”, stakeholders were invited to comment on any proposed changes
to the standard undergoing harmonization, which may impact their official national or
regional pharmacopeial standard. For the PDG, the process was complete when it reached

30
Stage 5A (Consensus) and sign-off (Stage 5B). From that point, each of the three
pharmacopeias become responsible for the adoption, publication, implementation, and
indication of harmonization (Stage 6) in their national or regional pharmacopeia (United
States Pharmacopeial, 2018; PDG, 2010). The average time for a monograph standard to
reach stage 6 is approximately 3 to 5 years.
A fully harmonized pharmacopeial monograph or general chapter is valuable because it
allows an analyst to perform the same testing procedures and reach the same accept/reject
decisions irrespective of which PDG pharmacopeia is referenced in a drug application.
For PDG stakeholders, this represents a tremendous opportunity to move away from
setting standards based on local regulatory requirements and, instead, have a single global
quality standard that would be interchangeable by all three ICH regions (DeStefano &
Moore, 2012). This is helpful to both the drug manufacturers who distribute into the three
PDG regions and regulators who review and enforce the standards in the drug
applications (Keitel, 2013).
Unfortunately, it soon became evident to the PDG that harmonizing the entire content of
the three pharmacopeias with thousands of monographs and standards would be nearly
impossible. Therefore, the group limited its focus on the most commonly used excipients
and general analytical procedures (ICH, 2002; WHO, 2013a). PDG also introduced the
term “harmonization by attribute” to allow partial harmonization of key elements of a
monograph in cases where full harmonization was not achievable (DeStefano & Moore,
2012; Liu, Moore & Sheehan, 2016).

31
With the “harmonization by attribute” concept, only selected elements of a monograph or
general chapter would be harmonized while others are left untouched. When a
monograph or test chapter is harmonized by attribute, interchangeability is achieved only
with respect to the harmonized elements (DeStefano & Moore, 2012). Non-harmonized
attributes are indicated in a text by black diamonds ( ). For these attributes, a
company must comply with the specific pharmacopeial requirements of each region
(Calam, 1995; Chowhan, 1999). Tests in a monograph or test chapter that apply to only
one pharmacopeia are known as a ‘local requirements’ or ‘specific local attributes’ and
are indicated by a white diamond (See Figure 2. USP Citric Acid Monohydrate).
Harmonization by attribute allows monographs to advance more easily to stage 6A
(regional adoption) and then to stage 6B (implementation) without all specifications
being harmonized. To accommodate harmonization by attribute, a special sign-off cover
sheet (Figure 4) is prepared along with the monograph for sign-off (PDG, 2010) to
provide information on the attributes that are fully harmonized, non-harmonized, and
local requirements but with a commitment to attain full monograph harmonization over
time by advancing to stage 6C (indication of harmonization) (United States
Pharmacopeia Convention, 2003).

32
Figure 4: Sign-off Cover Sheet for Citric Acid Monohydrate (PDG, 2010)

https://www.usp.org/sites/default/files/usp/document/harmonization/excipients/2010-06-
10_citric_acid_monohydrate_rev2_sign_off.pdf Accessed, March, 2016.
However, stage 6 monographs could be confusing and create challenges for both the
industry and regulatory authorities. For example, the sign-off cover page for “Citric Acid,
Monohydrate”, depicted in Figure 4 shows ten harmonized attributes that are included in
the harmonized monograph table. It appears that all but one (aluminum – indicated by the
‘-‘) of the ten attributes listed are adopted and implemented by the three pharmacopeias.
However, for the aluminum specification, although JP agrees with the harmonized
attribute, it will not include the aluminum test procedure in its monograph. The sign-off
sheet also lists tests for Heavy metals, Characters, Labeling, Bacterial Endotoxins and

33
Storage as non-harmonized attributes. Additional tests required for a single
pharmacopeial authority are a Sterility test for USP and Identification test for water for
Ph.Eur. Accordingly, the Citric Acid, Monohydrate monograph in Figure 2 reflects the
PDG sign-off page in that heavy metals, labeling, bacterial endotoxins and storage tests
are denoted with black diamonds ( ) to indicate that they are non-harmonized
attributes. This example demonstrates the complexities associated with harmonizing a
single monograph and underscores the enormous challenges associated with harmonizing
an entire pharmacopeia that contains thousands of monographs.
Although incomplete, a monograph that is partially harmonized is still significantly better
than one that is not harmonized at all. For example, carboxymethylcellulose calcium
(CMC) standard prior to harmonization was represented by 37 separate tests for the three
pharmacopeias (Table 2) (Liu, Moore & Sheehan, 2016).

34
Table 2: Carboxymethylcellulose Calcium, 37 Tests before Harmonization
(Liu, Moore & Sheehan, (2016).

After undergoing the PDG harmonization process, the number of tests was reduced to just
10 (Table 3).

35
Table 3: Carboxymethylcellulose Calcium, 10 Tests after Partial
Harmonization
Test USP
Monograph
JP
Monograph
EP
Monograph
Harmonized
Monograph
Identification Identical Identical Identical Identical
Alkalinity Identical Identical Identical Identical
Loss on drying 105C 105C 100 - 105C 105C
Residue on
ignition
450 - 550C 450 to 550C 600 +/- 50C 450 - 550C
Chloride 0.36% 0.36% 0.5% 0.36%
Sulfate 0.96% 0.96% 1% 1.0%
Heavy Metals Non-
Harmonized
Non-
Harmonized
Non-
Harmonized
Non-
Harmonized

2.4.2 PDG Working Procedure Reforms
PDG agreed to the implementation of significant changes to the work structure. Effective
April 1, 2018, PDG will utilize a reduced 5-stage approach for retrospective
harmonization of existing monographs or chapters, or prospectively for new monographs
or chapters. In this new Stage 1 structure, the current Stage 1, Stage 2 and Stage 3 will be
officially consolidated to streamline and reduce the level of complexity. It is critical to
PDG’s success to be able to identify any difficulties within the different
regulatory/pharmacopeial regions at stage 1 before moving a revision to the PDG stage 2
that could ultimately delay or prevent sign-off. The stage 1 will include the use of
technical telecons with all three pharmaocpieas that will be ciritical to determining
elegibility to advance to stage 2 of the PDG workplan. The previous stages 4, 5, 6 and 7
are now labeled 2, 3, 4 and 5.

36
Additionally, PDG has restructured its meeting format that includes the opportunity to
engage more effectively at the technical level with regards to resolving issues on specific
topics. PDG will maintain a twice-yearly meeting frequency with a focus on strategic
direction setting (United States Pharmacopeia, 2018).
2.4.3 ICH and PDG Work Together on Common Quality Topics
Because pharmacopeial standards are integral to the quality aspects of pharmaceutical
manufacturing, ICH and PDG activities are interdependent. For example, ICH’s Quality
guideline Q6A, addresses selecting analytical test procedures for new drug substances
and new drug products while PDG harmonizes these types of procedures. Thus, certain
ICH guidelines are dependent on PDG’s output and, in fact, refer to the PDG’s
harmonization efforts:
The full utility of this Guideline is dependent on the successful completion of
harmonization of pharmacopoeial procedures for several attributes commonly
considered in the specification for new drug substances or new drug products.
The Pharmacopoeial Discussion Group (PDG) of the European Pharmacopoeia,
the Japanese Pharmacopoeia, and the United States Pharmacopeia has expressed
a commitment to achieving harmonization of the procedures in a timely fashion
(ICH, 1999).
As ICH’s Q6A guideline became finalized in 1999, the ICH Steering Committee (SC)
expressed to PDG the urgent need to harmonize the15 pharmacopeial analytical
procedures chapters (General Methods relevant to ICH Q6A) that are critical to the full
utilization of the ICH Q6A guideline. PDG responded and, by November 2010, the 15
harmonized chapters were posted as annexes on the ICH website (FDA, 2008; ICH, 2002,
2007, 2012). Prior to this type of cooperation, pharmaceutical companies had to
investigate the similarities and differences across the pharmacopeias of interested

37
regions, determine the interchangeability of the data, and submit their findings and
recommendations to the corresponding regulatory authorities (FDA, 2008; ICH, 2007,
2012).
With recent ICH reforms, the Assembly approved a new maintenance process for the
Q4B Annexes which cover pharmacopoeial texts to be considered as interchangeable.
ICH agreed that this process will be coordinated by the Pharmacopeial Discussion Group,
which includes ICH Observers, EDQM and USP, who will keep the ICH Assembly
updated on the need for ICH approval of any updated annexes.
With increased attention on ICH and PDG reforms, in May 2018, international
stakeholders convened at the PDA Europe Pharmacopoeia Conference held in Vienna,
Austria to discuss ways to address the difficult challenges of complying with and
harmonizing compendial and regulatory requirements in the effort to ensure availability
of medicines around the world (PDA, 2018). Stakeholders recognize the need to comply
with compendial requirements of the USP, JP and Ph. Eur. However, compliance with the
varying requirements in other pharmacopeias published worldwide – including those of
China, Russia, Korea, India, and Brazil – is not as well understood, and further
challenged by differences in the general chapters and monographs for drug products,
active ingredients and excipients. During this meeting, USP, Ph. Eur., and JP discussed
the current status and future role of pharmacopoeias, and described specific initiatives to
facilitate compendial convergence, including recent process improvements to PDG.
There was agreement that some harmonization is better than none and that small steps
still move in the right direction (International Pharmaceutical Quality Newsletter, 2019).

38
2.4.4 Challenges Faced by PDG
PDG faces several difficult challenges in its work to harmonize the pharmacopeias across
the ICH regions. They include a narrow scope of work and membership, a seeming lack
of transparency, incomplete participation by stakeholders and a long timeline to complete
the harmonization process.
PDG’s harmonization efforts have a very narrow scope in that it is currently limited to 60
excipient monographs and 36 test chapters, leaving thousands of chapters and
monographs for drug substances, excipients, and finished dosage forms unharmonized
(United States Pharmacopeia Convention, 2003; WHO, 2013b). Even with this narrow
scope of work, PDG has had difficulties in achieving harmonization. It is especially
difficult to harmonize official pharmacopeial standards that may be referenced in
numerous existing drug applications. For example, glycerin is a common pharmaceutical
excipient and is currently included in the formulation of 1288 medicines in the U.S.A.
(NIH, 2017). Hence, in 2009, when the USP Glycerin pharmacopeial monograph was
updated with the addition of a new identification test to detect diethylene glycol in
glycerin, companies were required to submit regulatory updates to all corresponding drug
applications on file with the FDA (Holloway et al., 2010). This process, referred to as
retrospective harmonization, is slow and resource intensive.
Another challenge faced by PDG is its lack of transparency, which prevents timely
participation and input by key stakeholders, including the industry (DeStefano & Moore,
2012). An example of this particular issue can be seen with the USP-NF Sucrose
standard, harmonization of which was led by Ph. Eur. which reached stage 6 in the

39
process with a monograph that reflected sucrose derived only from beet sugar. Once that
occurred, USP began receiving comments from its stakeholders indicating that U.S.
sucrose is derived from cane sugar and thus U.S. manufacturers could not meet the stage
6 harmonized specifications for conductivity and color value (Liu, Moore & Sheehan,
2016). Consequently, until the harmonized stage 6 Sucrose specification was revised, the
U.S. sucrose industry experienced difficulties in releasing their product for
pharmaceutical use because it was deemed out of compliance with the stage 6
harmonized monograph (PDG, 2010).
The PDG process typically takes 3 to 5 years to reach Stage 4 (previously stage 6). This
is considerably longer than the average 12-18 months needed for regular revisions to
individual pharmacopeias, either USP or Ph. Eur. standards. This longer timeline creates
a burden for stakeholders, especially the manufacturers, who may be in a hurry to get
their products registered and commercialized.
Other challenges faced by PDG include differences in legal and/or regulatory
requirements, differing scientific opinions of experts engaged in the discussions, different
commentary processes, language differences and varying publication schedules of the
pharmacopeias in different regions.
2.4.5 Changing Pharmaceutical Landscape
While PDG continued its work, the biopharmaceutical landscape underwent a dramatic
transformation, whereby emerging economies saw an incredible growth in their
pharmaceutical manufacturing base and market size, the result of which is that the

40
ICH/PDG region of U.S., Europe, and Japan no longer represent 80% of the world’s
pharmaceutical business (Timmermans, 2004). Furthermore, with the manufacturing of
brand and generic ingredients now taking place mostly in non-PDG regions like China,
India and Brazil, some authors believe it is arguable whether PDG’s work is truly
representative of international pharmaceutical industry standards (Woo, Wolfgang, &
Batista, 2008). Given the change in pharmaceutical manufacturing locations, it is not
surprising that the national pharmacopoeias of India and China requested membership in
PDG in 2014 and 2015, respectively. However, PDG rejected both requests, choosing to
move instead to increase the transparency of its activities. For example, PDG now posts
Meeting Highlights on the websites of its member pharmacopeias and provides updates
on stage 2 official inquiry proposals at the WHO International Meeting of World
Pharmacopeias (IMWP). Yet, these changes do not appear adequate to meet the needs of
the new stakeholders. During global forums like the International Conference of Drug
Regulatory Authorities (ICDRA) and the World Health Organization (WHO), many
countries continue to call for a more inclusive process that engages stakeholders beyond
the PDG region (ICDRA, 2002, 2004; WHO, 2014b). However, broadening PDG
harmonization discussions may uncover new challenges that would likely slow the
process further. The challenges include uncertainties regarding legal and regulatory
barriers, national and regional differences in quality standards and differing
organizational resources and infrastructure. At this point, given the recent PDG process
reforms it is not clear how or in what way the PDG harmonization process will be able to
move forward.

41
2.4.6 Role of WHO in Global Pharmacopeial Harmonization
Calls for a more inclusive pharmacopeial harmonization process in recent years have
brought together pharmacopoeias from around the world to collaborate and work toward
greater harmonization. They have also strengthened WHO's role in developing global
quality standards for the production and testing of medicines (WHO, 2013a). The World
Health Assembly (WHA) has adopted many resolutions requesting the WHO to develop
international standards, recommendations and instruments to assure the quality of
medicines, whether produced and traded nationally or internationally (WHO, 2003).
Through creation of the WHO International Meeting of the World Pharmacopeias
(IMWP), pharmacopeias from non-ICH and non-PDG regions have established a forum
to voice their views. WHO posed a short questionnaire of 11 questions to attending
pharmacopeias at the first international meeting of world pharmacopeias in 2012 to
obtain the name of the pharmacopeia, latest publication, update frequency and if they
collaborate with other pharmacopeias (WHO, 2018).
Since its first meeting in 2012, the IMWP has met a total of ten times and initiated a
process of global harmonization of quality control specifications by developing a Good
Pharmacopoeial Practices (GPhP) guidance (WHO, 2013b). The primary objective of the
GPhP guidance is to define approaches and policies in establishing pharmacopeial
standards, with the ultimate goal of global harmonization of quality control specifications
within the WHO member states (WHO, 2015). The GPhP guidance describes a set of
principles to be used by national and regional pharmacopeial authorities to help with
development and maintenance of pharmacopeial standards. The GPhP guidance is

42
designed to help establish common practices, facilitate adoption of the standards from
one pharmacopoeia by another pharmacopoeia (adopt/adapt), and promote collaboration
and work sharing with regional/national pharmacopeias and foster interactions with
stakeholders (WHO, 2013b, 2016). Most importantly, the GPhP guidance should support
regulatory authorities at the local level by providing a basic compendial standard for
regulatory compliance. According to Keitel, good pharmacopoeial practices are intended
to facilitate future collaboration, work-sharing and prospective harmonization between
participating pharmacopeias (Keitel, 2013).
The 7
th
IMWP meeting, held in Tokyo, Japan, in September of 2016, resulted in the
creation of a survey to solicit stakeholder input on their perceived value of the GPhP
guidance. The outcome of the survey was discussed at the 8
th
International Meetings of
World Pharmacopoeias (IMWP) held in Brasilia, Brazil in 2017. The survey results did
not demonstrate a wide awareness of WHO’s Good Pharmacopeial Practices Technical
report guidance document (TRS 996 guidance). These findings no doubt, present
challenges for the IMWP and will need to be discussed in the framework of WHO’s
overall goals and objectives. With the GPhP complete, the IMWP plan to work on
creating a white paper on the value of a pharmacopieal standard for public health.
Additionally, IMWP will continue its work on developing a strategy for collaboration
between pharmacopeias. Their last meeting took place in Geneva, March 2019. The
WHO’s recent activities under the IMWP on its development of Good Pharmacopoeial
Practices (GPhP) was also discussed during the May 2018, PDA Europe Pharmacopoeia
Conference held in Vienna, Austria (PDA, 2018; International Pharmaceutical Quality

43
Newsletter, 2019). At this meeting, Wiggins indicated that the GPhP document provides
a common approach to the development of new and revised compendial standards and
enables an “adopt/adapt” mechanism to potentially bring these standards into other
pharmacopoeias, resulting in harmonization.
2.5 Challenges to Achieving Global Pharmacopeial Harmonization
Creating a globally harmonized and modernized compendial standard is widely viewed as
an ideal solution for eliminating the burden of redundant testing (Calam, 1995).
According to Wiggins and Schneider, an ideal pharmacopeia is one that “addresses the
content, purpose and applicability of pharmacopeial standards for the current
environment” that should build on other harmonization efforts and facilitate drug
registration and quality approaches through the use of a single, global compendial
standard. Wiggins and Schneider also identified three principles which they felt were
important in achieving global pharmacopeial harmonization namely, standardized
pharmacopeial practices, pharmacopeial collaboration, and regulatory acceptance
(Wiggins & Schneider, 2012). These principles described by Wiggins et al., are also in
direct alignment with the work of ICDRA and WHO’s Good Pharmacopeial Practices
Guideline (GPhP), which advocates for standardized pharmacopeial practices, adopting
and adapting standards among the pharmacopeias and, most importantly, regulatory
acceptance (WHO, 2016). WHO wrote that complete pharmacopeial harmonization is
only possible once regulatory systems have also been harmonized. Convergence or
efforts to align around a common standard and reinforced collaboration among
pharmacopoeial committees and regulators, supported by adequate interaction with

44
industry, will assist in facing new challenges and resource constraints (WHO, 2013b).
Recently, Wiggins presented on the benefits of compendial/regulatory standards and
global convergence during the 2018 PDA Europe Pharmacopoeia Conference held in
Vienna, Austria (Wiggins, 2019). Similarily, Lezotre wrote that pharmaceutical industries
request better harmonization of requirements for the development and manufacture of
pharmaceutical products to avoid duplication of work and potential drug supply
shortages. As a result, harmonization of pharmaceutical regulations has become an
important topic of discussion among worldwide Drug Regulatory Authorities (DRAs)
(Lezotre, 2014).
However, interest in harmonization does not appear to be universally embraced by all
pharmacopeias. For example, the 2015 edition of the ChP contained standards that were
not harmonized with other pharmacopeias, including those within PDG. This prompted
commentary from the European Federation of Pharmaceutical Industries and
Associations (EFPIA) in February 2017. EFPIA’s comments on the ChP were delivered
during a Compendial Joint Industry Group webinar on the topic of global harmonization
of pharmacopoeias and addressed challenges being faced by global manufacturers in
meeting newly introduced requirements of the Chinese Pharmacopoeia (ChP) 2015:
When standards published by the pharmacopoeias are not aligned, the differences
increase the cost and complexity of compliance, and may hinder the export and
import of products between China and Europe, creating uncertainty in the supply
of medicines to the patients who need them (Compendial Joint Industry Group,
2017).
However, a recently published International Pharmaceutical Quality (IPQ) article also
discused other real concerns that exist to achieving compliance with the varying

45
requirements in the roughly three dozen other pharmacopoeias published in the world –
including those of Japan, China, Russia, Korea, India, and Brazil – is not as well
understood, and is complicated by differences in the general chapters and monographs for
drug products, active ingredients and excipients (International Pharmaceutical Quality,
2019).
The efforts of the last two decades have been a living laboratory on the hurdles that exist
in the harmonization of pharmacopeial standards, not only at the international level but
also at the level of the affected countries. Two particular hurdles may give insight into
some of these challenges. The first example, at the international level, relates to the way
analytical methods are developed and validated (WHO, 2013a). Such methods must be
developed using ICH guidelines, for example, ICH Q6 for specifications and ICH Q2 for
validation, in order to comply with regulatory requirements in ICH regions (FDA,
2015a). These methods typically use highly purified and well-characterized “reference
material standards”, (United States Pharmacopeia, 2018) which can be very expensive to
develop or purchase. Employing these standards is seen as challenging for all but the
richest of the pharmacopeial authorities, governments and companies (Hutton, 1999;
ICDRA, 2004). Indeed, many of the world pharmacopeias (including recently added
Pharmacopoeia of the Eurasian Economic Union (EAEU)) within WHO member states
associated with developing countries cannot reach this level of conformity (WHO, 2018).
As a consequence, WHO is working to develop its own set of quality standards that are
both achievable and affordable for use in regions where resources are limited (WHO,
2013a). However, the immediate result of the WHO initiative is the creation of two

46
divergent approaches to method development and validation, which has created further
dissonance between pharmacopeias and exacerbated the continuing need for removal of
redundant testing by the industry.
The second example relates to specific organizational practices and timelines. In this
regard, some pharmacopeias do not provide opportunities for public comments during the
standard setting process, do not have a revision process that ensures timely adoption of
standards, or do not publish frequent updates (Wiggins et al., 2008). These types of
problems exist typically because of a lack of technical experts, staff and other resources
to do the requisite work. Some pharmacopeias lack the laboratory equipment, materials
and capabilities needed to promulgate standards or make the changes necessary to update
official standards. Consequently, some regions of the world are at a disadvantage when it
comes to establishing pharmacopeial standards that are up-to-date and harmonized.
It is clear that the harmonization efforts by PDG to date, do not address the challenges
described above. For the PDG to become more effective, it will need to identify, engage,
and satisfy its stakeholders that includes newly added members of ICH. However, there
is presently little evidence that PDG has sought stakeholder views on or their satisfaction
with the current harmonization process (Shaheen, 2003; Williams, 2011). By PDG’s own
admission, the group lacks stakeholder engagement (EDQM, 2014b). It should increase
its engagement and interactions with regional trade associations, provide stakeholders
with timely access to proposed revisions and meeting outcomes, and involve experts
early in the process to address conflicts. As PDG does not have its own website, it has to
rely on USP, EP, and JP to help disseminate information (EDQM, 2014b). A survey of

47
key stakeholders such as this one may aid in identifying opportunities for progressing
global harmonization efforts and thereby increase stakeholder satisfaction.
2.6 Examination of Stakeholders in the Pharmacopeial Harmonization Process
It is a central tenet of most theories of policy development that attention should be paid to
the stakeholders that the policy will affect. But what is a stakeholder? The word
“stakeholder” originates from the seventeenth century, when it initially described “a third
party entrusted with the stakes of a bet” (Reed et al., 2009). More recently, an early
theorist, Freeman, defined the term as “any group or individual who is affected by or can
affect the achievement of an organization’s objectives” (Fassin, 2009). Other definitions
include that by Max Clarkson as “persons or groups that have, or claim ownership,
rights, or interests in a corporation and its activities, past present or future” (Brugha &
Varvasovszky, 2000; Clarkson, 1995). Clarkson further delineated stakeholders into
primary stakeholders, essential to the survival of the organization and secondary
stakeholders, not essential to the survival of the organization but with whom the
organization closely interacts (Clarkson, 1995).
There are many other definitions of stakeholders, but I will focus on those that may be
most applicable to my research. For example, Fassin developed a triadic stratification
using his own terminology of "real stakeholders", "stakewatchers", and "stakekeepers",
which may apply well to the pharmacopeial harmonization process (Fassin, 2009). The
“real stakeholders” would be those with a strong stake or interest in the group, while the
“stakewatchers” would include pressure groups or watchdogs that do not have a stake
themselves but protect the interests of real stakeholders. Finally, “stakekeepers” would

48
include external, independent monitors or regulators with no stake in the group but who
exert their influence by imposing external controls and regulations (Fassin, 2009, 2010).
According to Brugha and Varvasovszky, stakeholder analysis can be used to gain insights
into the intentions, interests, interrelations, and agendas of the key stakeholders and how
these factor into their decision making and implementation processes (Varvasovszky &
Brugha, 2000). These findings can then be used to inform development of future policies
(Brugha & Varvasovszky, 2000). In that sense stakeholder analysis can be both
retrospective and prospective in that it can be used to obtain information on past views
and behaviors but also predict and provide information that can be used to influence
future outcomes. Finally, stakeholder analysis could be a useful tool for engaging
stakeholders and identifying opportunities to mobilize their support for future initiatives.
2.7 Research Framework
For my research, I will use the three stakeholder approach described by Fassin in which
the stakeholders are classified as “real stakeholders”, “stakekeepers”, and
“stakewatchers” (Table 4). This concept may be most useful for application to the
present study as it includes a third level of categorization of stakeholders that may enable
a better understanding of stakewatchers and stakekeepers who neither have a direct stake
nor control or influence over the real stakeholders. Using this concept, the real
stakeholder category would include the industry that manufactures and supplies
pharmaceutical drug products and ingredients in addition to Contract Research
Organizations (CROs), Contract Manufacturing Organizations (CMOs), Contract Testing
Laboratories (CTLs), analytical equipment/reagent manufacturers, and reference standard

49
manufacturers and suppliers and practitioners. The stakekeepers would include the
pharmacopeial authorities, regulatory authorities, official medicines control laboratories,
governmental testing laboratories, academic institutions holding government research
grants and other affiliated organizations that could include PDG, ICH, ICDRA and WHO
(Table 3). Finally, the stakewatchers would include the research and manufacturing trade
and other associations, like Pharmaceutical Research and Manufacturers of America
(PhRMA) and Generic Pharmaceutical Association (GPhA), now referred to as the
Association for Accessible Medicines (AAM), that work to protect their individual
members, healthcare practitioners and other organizations. Adopting Fassin’s model, a
stakeholder initial needs analysis was created by identifying the universe of key
stakeholders and placing them into these three categories.

50
Table 4: Categories of Stakeholders
Real Stakeholder
(Firm stake, support or interest)
Pharmaceutical finished drug product manufacturers,
CMOs, CROs, CTLs, Analytical equipment and reagent
manufacturers, Reference Standards makers, suppliers
and practitioners
Pharmaceutical ingredient manufacturers, suppliers and
distributors (Drug substance and ingredients (excipients))
Stakekeeper
(No stake but influence by
imposing regulations, controls)
National /Regional Regulatory authorities – e.g., FDA,
EDQM, PMDA, their Official Medicines Control
Laboratories, and Government testing labs.
National/Regional pharmacopeial authorities – e.g., USP,
Ph. Eur., JP, IP, ChP
Regulatory and other organizations e.g., WHO, ICH, PDG,
ICDRA, government funded research bodies (e.g.,
academia)
Stakewatcher
(Watchdog, pressure groups
with no stake but protect the
interests of Real stakeholders)
Trade associations (representing both Drug Ingredient and
Drug product manufacturers – brand and generics – e.g.,
International Pharmaceutical Excipients Council (IPEC),
Pharmaceutical Research Association (PhRMA) for US
innovator drug manufacturers, GPhA (now AAM) for US
generic drug product manufacturers, European Federation
of Pharmaceutical Industries Association (EFPIA) for
European innovator drug manufactures
Healthcare providers (Pharmacist – e.g., American
Pharmacists Association), Consumer Health Care Advocacy
Groups – e.g., Consumer Health Products Association
(CHPA) ) and other associated organizations

Recognizing that many individuals, groups or organizations often belong to more than a
single stakeholder category, proper classification can sometimes be difficult. For
example, industry organizations like PhRMA could be viewed as a stakewatcher as well
as a real stakeholder because of their business or income model. Similarly, a
pharmacopeial authority like USP could be viewed both as a stakeholder and stakekeeper

51
depending on their business and income model. The Venn diagram in Figure 5 depicts
the overlap and interfaces between stakeholder categories.
Figure 5: Stakeholder Category and Their Interfaces

To understand the challenges with achieving pharmacopeial harmonization, the views of
the stakeholders were obtained with a focus on examining their dissonance. According to
Samaras and Samaras, stakeholder dissonance can be summarized as conflicts between
the needs, wants, and desires (NWD) of various stakeholders as well as the perception of
“an imbalance in power or legitimacy” (Samaras & Samaras, 2012). Samaras defines a
stakeholder ‘Need’ as a basic must have. Looking at the needs of the three stakeholder
categories, as discussed above, for example PDG member pharmacopeias are perceived
by other pharmacopeial authorities as being more advanced in their analytical standards
setting capabilities in addition to having more resources at their disposal. Hence, the PDG
readily embraces a need to develop and validate methods according to ICH quality

52
guidelines. However, many pharmacopeias around the world have limited access to
technology and lack resources making it extremely challenging to develop and validate
analytical procedures according to ICH quality guidelines. Therefore, PDG’s approach to
harmonization may be viewed by many non-PDG members as unachievable.
The views and needs of the three categories of stakeholders were identified and placed
into four categories, Collaboration & Relationships, Resources, Regulatory acceptance,
Standardized pharmacopeial practices described in the CRRRS worksheet (Table 5). The
CRRRS worksheet or research framework was used to highlight the views and needs of
the three stakeholder categories on challenges in the harmonization process. This CRRRS
worksheet has also incorporated Wiggins’ three principles (pharmacopeial collaboration,
standardized pharmacopeial practices and regulatory acceptance) (WHO, 2016; Wiggins
& Schneider, 2012).
The CRRRS worksheet will be used to inform the development of the draft survey
questions for the focus group. The survey questions will help to identify the views and
underlying needs across three different categories of stakeholders that are contributing to
pharmacopeial disharmony due to difficulties with development and validation of
analytical procedures, and implementation of and compliance with different national and
regional pharmacopeial standards. The views and needs of key stakeholders may be
useful in assessing stakeholder satisfaction/dissatisfaction with the harmonization process
and in identifying specific issues which are causative of pharmacopeial dissonance.

53
Table 5: CRRRS Worksheet: Organizing Stakeholder Views and Top-Level
Needs for Global Pharmacopeial Harmonization
(Adapted from Samaras (Samaras & Samaras, 2012)
Real Stakeholder Stakekeeper Stakewatcher
Collaboration & Relationships
(Adopt/Adapt; Work-sharing, Cooperation, Memorandum of Understanding)
Resources
(Human/laboratory resources, Experts, Transparency in standards setting process, Publication
& Commentary process)
Regulatory Acceptance
(Satisfaction; Perceived value and benefit; Efficiency in release /qualification of
product/ingredients – interchangeability in specifications)
Standardized Pharmacopeial Practices
(Satisfaction; Perceived value and benefit; Quality testing/ no redundancy in testing)
Using a survey tool directed at key stakeholders, I posed questions designed to identify
views of these stakeholders on the importance, objectives and benefits of harmonization,
collaboration and relationship building, and resources. In addition, the study explored the
challenges faced by pharmacopeial bodies with introduction of standardized
pharmacopeial practices, pharmacopeial work-sharing (development and validation of
methods) and interactions with participating pharmacopeias of WHO member states,
PDG, and other stakeholders. The study aimed to understand how key stakeholders are
impacted by a lack of alignment between different pharmacopeial standards due to
differences in regulatory/legal requirements between regions by investigating the
challenges related to a lack of resources, inadequate laboratory capabilities, inability to
develop reference standards, and a lack of transparency in standards setting processes.
The survey also included specific questions for pharmacopieal authorities to assess their
level of satisfaction with their own performance in standards setting activities, meetings
attended and resources used.

54
CHAPTER 3. METHODOLOGY
3.1 Introduction
The research has three parts: a detailed literature review that is presented in Chapter 2
and not discussed further here, a stakeholder analysis to define the survey population of
interest for this research, and an exploratory research survey. The primary purpose of the
stakeholder analysis was to assess the overall satisfaction or dissatisfaction of the key
pharmacopeial stakeholders with the pharmacopeial harmonization process, including
their views and needs on the challenges that exist in the process (Samaras & Samaras,
2012). The analysis was descriptive and qualitative in nature as there is insufficient
delineation at this point between the three stakeholder groups (real stakeholders,
stakekeepers and stakewatchers) to make quantitative comparisons. For example, the
number of respondents for both stakekeeper and stakewatcher groups at the
organizational affiliation level were small in number creating difficulties at this pont in
obtaining a balanced analysis across the three stakeholder categories. However, the
results of the study may provide insights into the nature of each of the stakeholder’s
stake.
Questions for the preliminary draft survey instrument were developed based on the
information obtained from the literature review, the CRRRS worksheet (Table 5) that
identifies four categories used to explore stakeholder views and needs, and discussions
with the research thesis committee from the USC International Center for Regulatory and
Quality Sciences.

55
Finally, an opening introduction was crafted to meet the needs of the survey respondents.
Respondents included preselected participants who were selected by invitation only, so
that the qualifications of survey participants could be matched to the criteria established.
Survey respondents were solicited from a population of professionals from the
pharmaceutical industry, pharmacopeial, regulatory, academic or research institutions,
trade and other associations, and health care professionals involved in development,
enforcement and compliance to harmonized standards; who have worked in the
pharmaceutical sciences, quality, regulatory, pharmacy, academic or consultancy fields.
Included were individuals known to the investigator and associates, as well as individuals
identified using a snowball method and individuals who are members in quality,
pharmaceutical and regulatory societies worldwide.
3.2 Survey Development and Finalization
The initial survey was constructed and managed using Qualtrics web-based survey
software (www.qualtrics.com). The draft survey included approximately 33 questions in
various formats, such as multiple-choice, matrix, scaled, rank-order, yes/no, and open
text-entry formats. The first few questions asked preliminary questions regarding the
demographics of the respondents and established the backgrounds and affiliations of the
respondents and the remaining questions focused on areas of interest identified by the
previously discussed framework.
3.2.1 Focus Group Input to Survey Development
A preliminary draft of the survey was presented to a Focus Group (FG) whose
observations, comments and recommendations were used to revise the survey. Ten

56
participants from pharmacopeial and regulatory authorities, industry, academia, and
associations with a strong knowledge of pharmacopeial harmonization and/or experience
with survey development were invited to participate in the FG. Due to an emergency, Dr.
Pire-Smerkanich was unable to attend the focus group meeting but provided her
comments post meeting.
The objective of the FG was to critique and approve the draft survey by examining its
content, formatting and clarity, application, and content of these questions (Table 6). The
FG participants were provided with an electronic version of the survey prior to a meeting
and also with a paper copy at the FG meeting held on July 31, 2018. A 2-hour face-to-
face meeting at the University of Southern California (USC) was conducted with three
participants attending in person and six via teleconference or videoconference. The
meeting began with a short presentation on the intended research and purpose of the
study, followed by a discussion on the survey questions and intended survey recipients.
The survey questions were subsequently modified to incorporate comments from the FG
participants. Included in the survey were questions probing stakeholder views and needs
on pharmacopeial authorities and PDG to explore where challenges may exist with
resources, standardized pharmacopeial practices and regulatory acceptance. Also
included were questions to explore the frequency of use of pharmacopeias around the
world.

57
Table 6: Focus Group Participants
Name Title
Frances Richmond, PhD Director and Professor, International Center For Regulatory
Science
Eunjoo Pacifici, PharmD, PhD Director, International Center for Regulatory Science
Associate Professor, Department of Regulatory and Quality
Sciences
Nancy Pire-Smerkanich, DRSc,
MS
Assistant Professor, Department of Regulatory and Quality
Sciences
Susan Bain, DRSc Assistant Professor, Department of Regulatory and Quality
Sciences
Ernest Parente, Ph.D. Director/Principal Scientist at Cardinal Health Kansas City,
Missouri Area
(currently serves as an Expert Committee member of USP
Chemical Medicines expert committee)
Mark Wiggins

Director, Compendial Affairs, Merck & Co., Inc. West Point,
Pennsylvania
(retired June 31, 2018)
Srini Srinivasan, Ph.D.

Consultant, Washington D.C. Metro Area
(Former Chief Science Officer, United States Pharmacopeia
(USP))
Anthony Destefano, Ph.D.

Sr. Bioanalytical Consultant at Nuventra Pharma Sciences,
Washington D.C. Metro Area
(Former Vice President of General Chapters, United States
Pharmacopeia)
Lawrence H. (Larry) Block, Ph.D.

Professor Emeritus at Duquesne University, Greater Pittsburgh
Area
(Currently serves as an Expert Committee member of USP
Excipients Monographs 2 Expert committee and General Chapters
Physical Analysis expert committee)
Donatus Ako-Arrey Senior Director, Regulatory Affairs at Mallinckrodt
Pharmaceuticals, Hazelwood, Missouri
The final survey was developed to have 33 questions, divided into five sections, a)
demographic information and experience with pharmacopeial harmonization, b) views on
pharmacopeial harmonization, c) views on collaboration, resourses & relationship
building, d) global challenges with standardized pharmacopeial practices and regulatory
acceptance, e) views on pharmacopeial authorities and PDG, f) usage of pharmacopeias
around the world (Table 7). The responses to the questionnaire are analyzed in the
outlined research categories as identified in Table 7.

58
Table 7: Research Question Categories
Research Category Question Number
Demographics and Background Q1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
Views on Pharmacopeial harmonization Q12, 13, 14, 15
Views on Collaboration, Resources, and Relationship
building
Q16, 17, 18
Global Challenges with Standardized Pharmacopeial
Practices and Regulatory Acceptance
Q19, 20, 21
Views of the Pharmacopeial authorities and PDG Q22, 23, 24, 25, 26, 27, 28, 29, 30, 32
Usage of Pharmacopeias around the world Q32, Q33
Additional information on views on pharmacopeial
harmonization
Q34

The final survey was validated prior to dissemination to research participants by first
sending it to several individuals who are either past or present students or faculty in the
USC doctoral program. This step was important to ensure that the email notification
arrived properly, and the answers were returned and analyzed appropriately and if
problems were identified, they would be resolved prior to survey launch. A final copy of
the survey is shown in Appendix B.
3.2.2 Survey Deployment and Analysis
Potential survey participants were identified as those who have worked with and have
knowledge of pharmacopeial harmonization and are either colleagues known to me
through professional connections or referred to me by colleagues. All potential survey
participants were contacted either by email from USC or LinkedIn invitations in order to
identify their willingness to receive the survey and also to determine whether they met
the criteria for inclusion within the surveyed populations. Subsequently, the survey link
was distributed through Qualtrics email to all who agreed to participate.

59
The survey was forwarded to the participant within 3 business days of receiving
confirmation of participation. The number of respondents was correlated to the number of
surveys distributed in order to establish the response rate. The target for this survey was
70 surveys in which the respondents have answered more than 75% of the questions.
Survey recipients also had the option to provide the names of other individuals who they
felt may be appropriate participants in the survey based on their knowledge and
participation in pharmacopeial harmonization. Some individuals had issues receiving the
survey link through Qualtrics email as some ended up in their spam folders. This was
corrected and emails with links to the survey were resent through Qualtrics to those still
willing to participate in the survey. One respondent requested that I send a paper copy of
the survey as he was unable to open the survey link in Qualtrics. Another respondent
requested that the link be resent as the survey taker accidently completed the survey
without answering all the questions.
Individuals who were not known to the investigators were asked whether they were
familiar with pharmacopeial harmonization activities of their national or regional
pharmacopeia and the laws and regulations that apply for compliance with pharmacopeial
standards. A high level overview of the survey results was offered as an incentive to all
respondents who completed the survey and indicated that they wished to receive the
survey results and provided their email; this was hoped to improve the survey response
rate. Potential respondents were assured that their responses would be anonymous. No
remuneration was provided. Participants were assured that no specific data regarding the

60
identity of the companies or organizations will be published should this work result in
publication, although it will be known to the principal investigator, Catherine Sheehan.
The survey results were collected and saved electronically. Survey responses were also
printed, and a second copy was saved electronically in a separate location. The collected
data were analyzed using various statistical methods to identify patterns, trends and
correlations between the research questions and the demographic information describing
the participant’s organization, experience and views on pharmacopeial harmonization.
The data was then displayed in a tabular or graphical format. Many comments were
received and were analyzed for trends or common topics. Descriptive data were provided
for all survey questions noting the frequency of each of the response categories.
Cross tabulation was performed for specific questions on organization/company
affiliation and used to further delineate whether differences or similarities existed
between stakeholder groups. Given the relatively modest numbers for some
organizational affiliation analysis such as stakewatcher and stakekeeper categories, most
showed relatively little correlation, but a few of the more interesting cross tabulation
analyses are presented below in Chapter 4, Results and Appendix A.

61
CHAPTER 4. RESULTS
The survey was open from August until November 2018. Initial invitations to participate
in the survey were sent to approximately 1,100 potential respondents via USC email
across multiple geographic regions. This target population was drawn from the
pharmaceutical industry, drug substance and excipient industry, pharmacopeias,
government, academia, and trade associations. From this initial invite, 149 (14%)
expressed their interest in participating in the survey and it was to this group that the
survey was sent via Qualtrics on August 12, 2018. Subsequently, four more groups were
identified from this initial pool of 1,100 and sent the survey link via Qualtrics on
September 27th, October 19th, October 24th, and November 2nd, expanding the total
respondent pool to 179. The survey remained open until November 16, 2018, at which
time 141 surveys were started (Figure 6). Of the 141 surveys started, seven were
previews and not included in the final results while five were partially completed and
included in the final results. Two respondents opted out and were taken to the end of the
survey and excluded from the final result. Therefore, the total number of respondents
who completed the survey was 134 equating to a 75% (134/179) response rate. Because
not all respondents answered every question in the survey, the number of responses
corresponding to each question is reported along with the results.

62
Figure 6: Timeline of Qualtrics Survey Launch

4.1 Profiles of Respondents
The primary functional role of respondents varied but the highest response was received
for Regulatory Specialist/Manager (21%, 27/129) (Figure 7). Other roles, in decreasing
order, were Compendial Specialist/Manager (11%, 14/129), QA/QC Laboratory
Scientist/Manager (11%, 14/129), Pharmacopeial scientist (9%, 12/129), Consultant (9%,
12/129), Government scientist (7%, 9/129), and Academic scientist (5%, 7/129). Few
responses were received for manufacturing/CMC specialist manager (5 responses), raw
material development (3 responses), formulation development specialist (2 responses),
and clinical bioanalysis (1 response). The remaining 18% (23/129) selected ‘Other’ and
further clarified their roles in the text box provided and listed below Figure 7.

63
Figure 7: Role of Respondents
What is your primary functional role at your company/organization? n=129

*Other
• Research and Development Manager
• Quality Auditor
• R&D Analytical, Technical/Regulatory support of manufacturing sites
• Material Sciences
• Professor
• Raw Material Release/Reference Standard Coordinator
• Head of Quality Department
• President-Regulatory
• Toxicologist
• Scientific Dir.
• Policy, advocacy and regulatory intelligence
• Analytical Development.
• Technical Support
1% (1)
2% (2)
2% (3)
4% (5)
5% (7)
7% (9)
9% (12)
9% (12)
11% (14)
11% (14)
18% (23)
21% (27)
0 5 10 15 20 25 30
Clinical/Bioanalysis
Formulation Development Scientist
Pharmaceutical Raw Material…
Manufacturing/CMC Specialist/Manager
Academic Scientist
Government Scientist
Consultant
Pharmacopeial Scientist
QA/QC Laboratory Scientist/Manager
Compendial Specialist/Manager
Other* (Please Specify)
Regulatory Specialist/Manager

64
• Translation and scientific review of the translated standards to ensure content equivalency
• Manager of a pharmaceutical analysis applications lab.
• Company analytical strategy leader
• Procurement Manager
• Director of department of antibiotics and excipient of department in Jiangsu Institute for food and
drug control, China
• Material Attributes and Technologies in Process Development
• Industry Liaison
• Pharmacist
• Senior manager
• Expert in the regulatory and sciences for both generic and biosimilar drug products. Also provide
guidance and recommendations related to policy for both regulatory and science matters.
When asked about their geographical responsibilities, most respondents (40%, 91/227)
selected the Americas (North and South), followed by Europe, (22%, 50/227) and Asia
(20%, 45/227) (Figure 8). Fewer respondents selected Oceania (7%, 17/227), Africa
(7%, 16/227), and ‘other’ (4%, 8/227) described in the text box provided below Figure 8.
Figure 8: Geographic Areas of Responsibility
For which of the following geographic region(s) or/ country are you primarily
responsible? (please select all that apply) n =227

Other:
• Worldwide
• I participate on the global front via the International Generic and Biosimilars Association (IGBA)

65
• USA
• Canada (captured under Americas)
• China
• India
• Thailand (captured under Asia)
When asked to identify their organizational affiliations, most reported pharmaceutical
industry (45%, 59/132), followed by pharmacopeial authority (10%, 13/132), drug
regulatory authority (8%, 11/132), trade associations (6%, 8/132), academia (5%, 7/132),
and official medicines control labs. (4%, 5/132) (Figure 9). Of the 29 respondents (22%,
29/132) who selected ‘other’, 18 listed excipient manufacturer/chemicals industry, which
would fall under the category of pharmaceutical industry (see items in bold in the text
box provided below Figure 9), but because these respondents did not select the proper
category, they were not included in the skip logic questions targeted for the
pharmaceutical industry respondents. Additional listings noted under ‘other’ were
consultant, consultant/training, non-profit testing and publisher of consumer reports,
government and hospital.

66
Figure 9: Organization/Company Affiliation
Which one of the following best describes your organization/company? n=132

*Other:
• Excipient Industry
• Training and consulting
• Non-profit testing and publisher of Consumer Reports
• Excipient industry
• Specialty chemicals. We produce mineral excipients.
• Consultant for pharmaceutical industry
• Consumer Products, plus excipient manufacturer
• Consultant
• Consultant
• Consulting Firm
• Technical services to pharmaceutical industry
• Pharma Consultant
• Excipient manufacturer
• Pharma Excipient Distributor
• Excipients
• Government
• Excipient Manufacturer
4% (5)
5% (7)
6% (8)
8% (11)
10% (13)
22% (29)
45% (59)
0 10 20 30 40 50 60 70
Official Medicines Control
laboratories/Governmental Testing Laboratories
Academia
Trade Association /Organization
Drug Regulatory Authority
Pharmacopeial Authority
Other* (Please specify)
Pharmaceutical Industry

67
• Excipients Industry
• Excipient Manufacturer
• Excipient Manufacturer
• Scientific Instrumentation
• Pharmaceutical Excipients company
• Chemical company
• Pharmaceutical excipient manufacturer
• Excipients manufacturer (Chemical company)
• Excipient manufacturer
• Manufacturer and supplier of excipients to the pharmaceutical industry.
• HOSPITAL
• Excipient Manufacturer

The 59 respondents affiliated with pharmaceutical industry as shown above were directed
to a separate set of questions to further probe the nature of their organizations. Most were
from generic industry (29%, 20/69) followed by innovator industry (23%, 16/69), drug
substance/API manufacturer/suppliers (20%, 14/69) and excipient manufacturer/supplier
(17%, 12/69) (Figure 10). Because respondents could select more than one answer, the
total number of responses were greater than 59. Four respondents who chose ‘Other’
specified their industry as either consultant, generic formulations or regulatory
consultant; two respondents selected Contract Research Organization and one selected
Contract Manufacturing listed below Figure 10.

68
Figure 10: Industry Representation
Which of the following best describes your industry? (Select all that apply) n= 69

Other:
• Consultant
• Generic formulations
• Regulatory consultant
• Contract Research Organization
• Contract Research Organization
• Contract Manufacturing
When asked specifically about the size of their organizations, 74% of respondents
(95/128) reported 200 or more employees with further breakdown as follows: 34%
(43/128) with more than 5000 employees, 9% (11/128) with 2000-5000 employees, and
32% (41/128) with 200-1999 employees. The remaining 26% (33/128) were affiliated
with organizations with less than 200 employees (Figure 11).
0
1% (1)
3% (2)
6% (4)
17% (12)
20% (14)
25% (16)
29% (20)
0 5 10 15 20 25
Contract Analytical Testing laboratory
(CTO)
Contract Manufacturing Organization
(CMO)
Contract Research Organization (CRO)
Other (please specify)
Excipient Manufacturer/Supplier
Drug Substance/API Manufacturer/Supplier
Innovator Industry
Generic Industry - Chemical and Biological

69
Figure 11: Size of Organization/Company
What is the size of your organization/company? n=128

To explore the differences in the size of organizational affiliations across various
stakeholder groups, a cross tabulation was performed for the question on organization
affiliation and organization/company size. However, as the number of respondents for
both stakewatcher and stakekeeper groups at the organizational affiliation levels were
low compared to the real stakeholder group, assuring a balanced analysis may be
difficult. As can be seen in Table 8, most respondents from the pharmaceutical industry
were from organizations with more than 5000 employees (41%, (24/58), followed by
organizations with 200-1999 employees (33%, 19/58), with less than 200 employees
(14%, 8/58), and with 2000-5000 employees (12%, 7/58). Most respondents from the
drug regulatory authority were also from organizations with more than 5000 employees

70
(55%, 6/11), followed by 200-1999 employees (27%, 3/11) and less than 200 employees
(18%, 2/11). All 8 respondents from the trade associations were from organizations with
less than 200 employess. Most respondents representing pharmacopeial authority were
from organizations with 200-1999 employees (85%, 11/13) while the remaining 15%
(2/13) were from organizations with less than 200 employees. Three of the four
respondents representing the OMCLs/government testing labs. were from organizations
with 200-1999 employees and the remaining one respondent was from an organization
with less than 200 employees. Respondents representing academia were equally
distributed across organizations with more than 5000 employees, with less than 200
employees, and with 200-1999 employees (each with 29%, 2/7) followed by one
respondent (14%, 1/7) from an organization with 2000-5000 employees. Most
respondents who selected ‘Other’ were from organizations with more than 5000
employees (41%, 11/27), followed by organzations less than 200 employess (37%, 10/27)
and equally distributed between organizations with 200-1999 (11%, 3/27) and 2000-5000
(11%, 3/27).

71
Table 8: Cross Tabulation of Organizational Affiliation on Company Size
Organization/company
affiliation
What is the size of your organization
Less than
200
employees
200-1999
employees
2000-5000
employees
More than
5000
employees
Total
N
Pharmaceutical Industry 14%
(8/58)
33%
(19/58)
12%
(7/58)
41%
(24/58)
100%
58
Other (please specify) 37%
(10/27)
11%
(3/27)
11%
(3/27)
41%
(11/27)
100%
27
Trade
Association/Organization
100%
(8/8)
0%
(0/8)
0%
(0/8)
0%
(0/8)
100%
8
Drug Regulatory Authority 18%
(2/11)
27%
(3/11)
0%
(0/11)
55%
(6/11)
100%
11
Pharmacopeial Authority 15%
(2/13)
85%
(11/13)
0%
(0/13)
0%
(0/13)
100%
13
OMCL/Government Testing
Labs
25%
(1/4)
75%
(3/4)
0%
(0/4)
0%
(0/4)
100%
4
Academia 29%
(2/7)
29%
(2/7)
14%
(1/7)
29%
(2/7)
101%*
7
*Total due to rounding
When asked how many people at their organizations worked on pharmacopeial standards,
highest responses were received for less than 20 people (41%, 52/128), followed by
greater than 50 people, (32%, 41/128), and 21-50 people, (20%, 25/128) (Figure 12). To
explore the differences in the number of people across various stakeholder groups, a cross
tabulation was performed on the number of people working with pharmacopeial
standards at the organization affiliation level and is captured under Appendix A.

72
Figure 12: Number of People at the Organization Working with Pharmacopeial
Standards
How many people in your organization/company work with pharmacopeial standards for
pharmaceutical application? n= 128

4.2 Experience with Standards
To understand how much experience the respondents had working with pharmacopeial
standards, they were asked to indicate their levels of experience according to the number
of years. A majority of respondents described their experiences with pharmacopeial
standards as high (>10 years) followed by moderate (1-10 years) and little or none (<1
year) for monographs (high: 71%, 89/126; moderate: 28%, 35/126; little or none: 2%,
2/126), test chapters (high: 64%, 79/124; moderate: 29%, 36/124; little or none: 7%,
9/124), and reference standards (high: 53%, 62/118; moderate: 31%, 36/118; little or
none: 17%, 20/118) (Figure 13).

73
Figure 13: Level of Experience with Pharmacopeial Standards
Please indicate your level of experience with pharmacopeial standards?

To probe further the extent of their experiences with pharmacopeial standards,
respondents were asked to provide the number of standards that they have developed or
used. As shown in Table 9, most respondents selected the lowest level of fewer than 10
standards (monographs: 32%, 41/128; test chapters: 46%, 57/123; reference standards:
57%, 69/122), followed by 10-29 standards (monographs: 19%, 24/128; test chapters:
23%, 28/123; reference standards: 18%, 22/122), 30-49 standards (monographs: 11%,
14/128; test chapters: 8%, 10/123; reference standards: 7%, 8/122), 50-100 standards
(monographs: 15%, 19/128; test chapters: 11%, 13/123; reference standards: 7%, 8/122),
and more than 100 standards (monographs: 23%, 30/128; test chapters: 12%, 15/123;
reference standards: 12%, 15/122).
n=124
n=126
n=118

74
Table 9: Number of Pharmacopeial Standards with which You Have Been
Involved (Monographs, Chapters, and Reference Standards)
With how many pharmacopeial standards have you been involved (either in development
or usage)?

<10 10-29 30-49 50-100 >100 Total N
Monographs 32% 19% 11% 15% 23% 128
Test
chapters 46% 23% 8% 11% 12% 123
Reference
Standards 57% 18% 7% 7% 12% 122
4.3 Experience with Harmonization
In addition to their experiences with standards, repondents were also asked about their
experiences with the pharmacopeial harmonization process, separated into retrospective
and prospective processes. In general, most respondents reported the highest level of
experience (>10 years) with retrospective harmonization (Figure 14) than with
prospective harmonization (Figure 15). In addition, respondents were most experienced
with monographs followed by test chapters and reference standards for both retrospective
harmonization (monographs – high: 46%, 58/127; medium: 34%, 43/127; little of none:
20%, 26/127; test chapters – high: 44%, 55/126; medium: 31%, 39/126; little or none:
25%, 32/126; reference standards – high: 32%, 39/123; medium: 30%, 37/123; little or
none: 38 %, 47/123) and prospective harmonization (monographs – high: 31%, 39/126;
medium: 38%, 48/126; little of none: 31%, 39/126; test chapters – high: 35%, 43/124;
medium: 35%, 43/124; little or none: 37%, 46/124; reference standards – high: 23%,
28/122; medium: 30%, 37/122; little or none: 47%, 57/122).

75
Figure 14: Level of Experience With Retrospective Harmonization (of existing
pharmacopeial standards)
Please indicate your level of experience with harmonization of existing pharmacopeial
standards (retrospective harmonization)?

Figure 15: Level of Experience with Prospective Harmonization (where no
standards exist)
Please indicate your level of experience with harmonization of pharmacopeial standards
where no standards exist (prospective harmonization)?

n=126
n=124
n=122
n=127
n=126
n=123

76
4.4 Views on Harmonization
When asked about their views and needs on the importance of harmonization, almost all
respondents reported that achieving global pharmacopeial harmonization was important
(very important: 81%, 104/128; somewhat important: 18%, 23/128) while one respondent
viewed it as not important (Figure 16).
Figure 16: Views on Importance of Global Pharmacopeial Harmonization
How important is it to achieve globally harmonized quality standards? n=128
Similarly, almost 90% of respondents thought the need to achieve globally harmonized
quality standards was an urgent issue (very urgent: 33%, 42/128; somewhat urgent: 55%,
71/128) while 9% (11/128) viewed it as not urgent (Figure 17).

77
Figure 17: Urgency to Achieve Globally Harmonized Standards
How urgent is it to achieve globally harmonized quality standards? n=128

Cross tabulation was conducted to explore if respondents from different organizational
affiliations had different views on the importance and the urgency of achieving globally
harmonized standards. As can be seen from Table 10, most respondents across all
organizations viewed a need to achieve globally harmonized quality standards as urgent
(very urgent: 20-43%; somewhat urgent: 40-100%) while a minority viewed it as not
urgent (7-20%) (Table 10). There were some notible difference across organizations in
that while the pharmaceutical industry was evenly split between very urgent (43%, 25/58)
and somewhat urgent (45%, 26/58), most of the other groups were skewed more toward
4
9% (11/128)
55% (71/128)
33% (42/128)
0 20 40 60 80
I don't know
Not urgent (within 6-10
years)
Somewhat urgent (within 3-
5 years)
Very urgent (within 1-2
years)

78
somewhat urgent: drug regulatory authority (very urgent: 30%, 3/10; somewhat urgent:
70%, 7/10), trade association (very urgent: 25%, 2/8; somewhat urgent: 70%),
pharmacopeial authority (very urgent: 38%, 5/13; somewhat urgent: 62%), academia
(somewhat urgent: 100%, 7/7), official control laboratories (very urgent: 20%, 1/5;
somewhat urgent: 40%, 2/5), and other (very urgent: 22%, 6/27; somewhat urgent: 59%,
16/27).
Table 10: Cross Tabulation Of Organizational Affiliation On Urgency To
Achieve Globally Harmonized Standards
Organization/company
affiliation
How urgent is it to achieve globally harmonized
quality standards?
Very urgent
(within 1-2
years)
Somewhat
urgent
(within 3-
5 years)
Not
urgent
(within
6-10
years)
I don’t
know
Total
N
Pharmaceutical Industry 43%
(25/58)
45%
(26/58)
7%
(4/58)
5%
(3/58)
(100%)
58
Other 22%
(6/27)
59%
(16/27)
19%
(5/27)
0%
(0/27)
100%
27
Trade Association/Organization 25%
(2/8)
63%
(5/8)
12%
(1/8)
0%
(0/8)
100%
8
Drug Regulatory Authority 30%
(3/10)
70%
(7/10)
0%
(0/10)
0%
(0/10)
100%
10
Pharmacopeial Authority 38%
(5/13)
62%
(8/13)
0%
(0/13)
0%
(0/13)
100%
13
Official Medicines Control
Laboratories /Government Testing
Laboratories
20%
(1/5)
40%
(2/5)
20%
(1/5)
20%
(1/5)
100%
5
Academia 0%
(0/7)
100%
7/7
0%
(0/7)
0%
(0/7)
100%
7

To understand the needs and views of respondents on the goals of harmonization, they
were provided a list of potential objectives and asked their thoughts on the importance of
each item. A high percentage of respondents viewed all of the items listed in Table 11 as

79
being important. Specifically, a majority of respondents viewed providing harmonized
standards with the same accept/reject conclusions as very important (82%, 102/124)
followed by somewhat important (15%, 18/124) and not important (3%, 4/124).
Similarly, a majority of respondents viewed facilitating international regulatory
compliance as very important (81%, 100/124) followed by somewhat important (15%,
18/124) and not important (5%, 6/124); a majory viewed facilitating recognition of
standards between regulatory bodies as very important (77%, 95/123) followed by
somewhat important (19%, 24/123), and not important (4%, 5/123); a majority viewed
reducing redundant testing burden as very important (76%, 94/123), followed by
somewhat important (21%, 26/123), and not important (2%, 3/123); a majority viewed
facilitating international regulatory filings as very important (74%, 90/121) followed by
somewhat important (21%, 26/121), and not important (4%, 5/121); and a majority
viewed safeguarding quality of medicines in the global supply chain as very important
(73%, 90/123) followed by somewhat important (21%, 26/123), and not important (6%,
7/123). In comparison, fewer respondents viewed the remaining two statements as
important: increasing transparency of public comment process (very important: 40%,
49/122; somewhat important: 48%, 58/122; not important:12%, 15/122) and accelerating
adoption of new standards into pharmacopeia (very important: 34%, 42/124; somewhat
important: 55%, 68/124; not important:11%,14/124) (Table 11).

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Table 11: Objectives of Global Pharmacopeial Harmonization
In your view, which of the following are important objectives of global pharmacopeial
harmonization?

Very
important
Somewhat
important
Not
important
Total
N
1. Providing harmonized
standards with the same
accept/reject conclusions 82% (102) 15% (18) 3% (4) 124
2. Facilitating international
regulatory compliance 81% (100) 15% (18) 5% (6) 124
3. Facilitating recognition of
standards between
regulatory bodies 77% (95) 19% (24) 4% (5) 123
4. Reducing redundant testing
burden 76% (94) 21% (26) 2% (3) 123
5. Facilitating international
regulatory filings 74% (90) 21% (26) 4% (5) 121
6. Safeguarding quality of
medicines in the global
supply chain 73% (90) 21% (26) 6% (7) 123
7. Increasing transparency of
public comment process 40% (49) 48% (58) 12% (15) 122
8. Accelerating adoption of
new standards into
pharmacopeia 34% (42) 55% (68) 11% (14) 124

The respondents were asked to provide their levels of agreement with the importance of
statements related to harmonized standards. Consistent with above findings, most
respondents agreed with all five statements listed in Table 12 as being important needs
for achieving globally harmonized standards. The highest level of agreement was
observed for Minimizing redundancy in testing requirements (agree: 95%, 109/115;
neither agree nor disagree: 4%, 5/115; disagree: 1%, 1/115) followed by slightly lower
levels of agreement for Reducing the compliance testing burden, (agree: 91%, 105/115;

81
neither agree nor disagree: 7%, 8/115; disagree: 2%, 2/115), and Maintaining alignment
between harmonized pharmacopeial standards (agree: 91%, 106/116; neither agree nor
disagree: 9%, 10/116; disagree: none). Much lower levels of agreement were observed
for Adopting good pharmacopeial practices in developing standards (agree: 79%,
89/112; neither agree nor disagree: 18%, 20/112; disagree: 3%, 3/112); and Implementing
local/ regional phamacopeial testing requirements into my QC/QA program easier
(agree: 66%, 71/107; neither agree nor disagree: 26%, 28/107; disagree: 7%, 8/107)
(Table 12).
Table 12: Level of Agreement with the Importance of Globally Harmonized
Standards
Please select your level of agreement with the importance of the following statements
related to globally harmonized quality standards?

Agree Neither
agree nor
disagree
Disagree Total
N
1. Minimizing redundancy in testing
requirements 95% (109) 4% (5) 1% (1) 115
2. Reducing the compliance testing
burden 91% (105) 7% (8) 2% (2) 115
3. Maintaining alignment between
harmonized pharmacopeial
standards 91% (106) 9% (10) 0% (0) 116
4. Adopting good pharmacopeial
practices in developing standards 79% (89) 18% (20) 3% (3) 112
5. Implementing local/regional
pharmacopeial testing requirements
into my QC/QA program is easier 66% (71) 26% (28) 7% (8) 107
Respondents were provided an option to enter text comments under ‘other’ and the seven
comments received are listed below.

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Other comments (please specify)
• Preparation of regulatory documents in the ICH CTD format can improve the review process if more
global harmonized quality standards are available and accepted by regulatory authorities.
• Generic pharmaceutical industries manufacture and supply drug products to multiple countries,
which follow regional pharmacopoeia. API and Excipient manufacturers are testing and releasing
their COAs Pharmacopoeia wise. Harmonized testing methods and pharmacopeial standards helps
generic drug industry to a greater extent with respect to 1. Can have better inventory control of
materials (APIs and Excipients) 2. One specification and testing method for different pharmacopoeia
3. Reduces cost of analysis pharmacopoeia wise 4. Reduces cost maintaining pharmacopoeia wise
reference standards ......
• It is very important to make sure that the harmonized quality standards do not negatively impact
the availability of materials which have historically been safely used in approved drug products by
unnecessarily tightening specifications or test methods when there is no safety problem. Samples
of all major global sources of a material must be evaluated before harmonizing monographs if any
limits are to be tightened so that these materials can continue to comply with the harmonized
standard.
• It is fundamentally important to enable medicines with consistent quality to be available to all
patients around the world, based on a harmonized pharmacopoeia standard.
• For me harmonization brings coherence to the standards. I mean, since the risk of a process is the
same and if the pharmacopeial standard was written to mitigate these risks, so make more sense to
have an aligned standard among different pharmacopeia and not having so different requirements.
• Facilitating acceptance of harmonized standards among all regulatory bodies.
• Eliminating bad methods in favor or newer accurate methods
4.5 Views on Collaboration and Relationship building
Results in this section reveal the views and needs of respondents on the importance and
the practical aspects of establishing collaborations and relationship building across
various pharmacopeias. When asked about their views and needs regarding the benefits
of pharmacopeial collaboration, a majority of respondents (55-83%) considered all six
items listed in Table 13 as very important with few (2-6%) considering them as not
important. Specifically, facilitating the adoption of standards between regulatory bodies
received the highest response (very important: 83%, 102/123; somewhat important: 14%,
17/123; not important: 3%, 4/123) followed by minimizing duplication of efforts (very
important: 80%, 98/123; somewhat important: 19%, 23/123; not important: 2%, 2/123),
aligning pharmacopeial standards across different regions (very important: 78%, 97/124;

83
somewhat important: 19%, 24/124; not important: 2%, 3/124), developing solutions that
can be adopted broadly (very important: 70%, 85/121; somewhat important: 27%,
33/121; not important: 2%, 3/121); sharing expertise and resources (very important:
69%, 85/123; somewhat important: 28%, 34/123; not important: 3%, 4/123), and
providing a common understanding of the regional needs and challenges (very
important: 55%, 67/122; somewhat important 39%, 48/122; not important: 6%, 7/122).
Table 13: Benefits of Pharmacopeial Collaboration
Which of the following items would you consider to be important benefits of
pharmacopeial collaboration?

Very
important
Somewhat
important
Not
important
Total
N
1. Facilitating the adoption of
standards between regulatory
bodies 83% (102) 14% (17) 3% (4) 123
2. Minimizing duplication of efforts 80% (98) 19% (23) 2% (2) 123
3. Aligning pharmacopeial standards
across different regions 78% (97) 19% (24) 2% (3) 124
4. Developing solutions that can be
adopted broadly 70% (85) 27% (33) 2% (3) 121
5. Sharing expertise and resources 69% (85) 28% (34) 3% (4) 123
6. Providing a common
understanding of the regional
needs and challenges 55% (67) 39% (48) 6% (7) 122
Comments entered under “Are we missing any other important benefits of pharmacopeial
collaboration?” are listed below. A total of eight comments were provided.
Are we missing any other important benefits of harmonization?
• Industry requires a common quality for excipients when used in global drug products.
• The collaboration should result in the best scientifically justified limits and methods developed
that are needed to provide appropriate control without going overboard and developing standards

84
that are not based primarily on what is needed for the safe use of the material. Pharmacopeial
standards should not be based on the manufacturer's capability but rather to simply set a
minimum standard for safe use in a pharmaceutical product. The standards should not address
functionality or performance. That is something that should be established between the user and
their supplier and not something that belongs in pharmacopeial monograph.
• It could generate trust. Trust on the side of patients, producers, regulators. That's what prosperity
truly comes from. If you know you will not be robbed tomorrow for your effort today. What a
release from fear.
• Results of safety (toxicology) testing using global ICH guidelines can be more acceptable to
regulatory submissions globally if the test articles (test materials) can be characterized using global
harmonized standards and analytical methods.
• Market condition - National and regional norms
• Regulators carry too much weight in decision process and they may lack direct experience.
• Reducing manufacturing costs and speeding development of drug substances and excipients
through promotion of ONE set of pharmacopeial standards across the globe.
• Also most important as a benefit of harmonization: medicines with consistent quality for all
patients, as listed on a previous response.
Several cross tabulations were performed to explore if there were differences across
stakeholder groups for items listed in Table 13. A cross tabulation between
organizational affilitation and minimizing duplication of effort as a benefit of
pharmacopeial collaboration. As seen from Table 14, the results appeared to show that
most respondents across all organizations viewed the benefit as being very important but
there were some differences. Respondents from trade association group appear to have
had the strongest views with all 8 respondents selecting the benefit as very important,
followed by drug regulatory authority (very important: 90%, 9/10; somewhat important:
10%, 1/10), pharmaceutical industry (very important: 83%, 45/54; somewhat important:
13%, 7/54; not important: 4%, 2/54), academia (very important: 83%, 5/6; somewhat
important: 17%, 1/6), government testing labs (very important: 80%, 4/5; somewhat
important: 20%, 1/5), other (very important: 74%, 20/27; somewhat important: 26%,
7/27), and pharmacopeial authority (very important: 54%, 7/13; somewhat important
(46%, 6/13) (Table 14).

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Table 14: Cross Tabulation of Organizational Affiliation on Benefits of
Pharmacopeial Collaboration on Minimizing Duplication of Efforts
Organization/company affiliation Minimizing duplication of efforts
Very
important
Somewhat
important
Not
important
Total N
Pharmaceutical Industry 83%
(45/54)
13%
(7/54)
4%
(2/54)
100%
54
Other (please specify) 74%
(20/27)
26%
(7/27)
0%
(0/27)
100%
27
Trade Association/Organization 100%
(8/8)
0%
(0/8)
0%
(0/8)
100%
8
Drug Regulatory Authority 90%
(9/10)
10%
(1/10)
0%
(0/10)
100%
10
Pharmacopeial Authority 54%
(7/13)
46%
(6/13)
0%
(0/13)
100%
13
OMCL/Government Testing Labs 80%
(4/5)
20%
(1/5)
0%
(0/5)
100%
5
Academia 83%
(5/6)
17%
(1/6)
0%
(0/6)
100%
6

A cross tabulation was also performed between organization affiliations and the
importance and need for sharing scientific resources as a benefit of pharmacopeial
collaboration. As seen from Table 15, the results appeared to show that most respondents
across all organizations felt it was very important, but again, there were some differences
across the groups. Respondents from government testing labs appeared to have the
strongest views with all 5 respondents selecting the benefit as very important, followed
by drug regulatory authority (very important: 90%, 9/10; somewhat important: 10%,
1/10), academia (very important: 86%, 6/7; somewhat important: 14%, 1/7),
pharmaceutical industry (very important: 69%, 37/54; somewhat important: 26%, 14/54;
not important: 6%, 3/54), trade association (very important: 63%, 5/8; somewhat
important: 37%, 3/8), other (very important: 62%, 16/26; somewhat important: 35%,
9/26; not important: 4%, 1/26), and pharmacopeial authority (very important: 54%, 7/13;
somewhat important (46%, 6/13).

86
Table 15: Cross Tabulation of Organizational Affiliation on Benefits of Sharing
Scientific Resources
Organization/company affiliation Sharing expertise and resources
Very
important
Somewhat
important
Not
important
Total N
Pharmaceutical Industry 69%
(37/54)
26%
(14/54)
6%*
(3/54)
100%
54
Other (please specify) 62%
(16/26)
35%
(9/26)
4 %*
(1/26)
100%
26
Trade Association/Organization 63%
(5/8)
37%
(3/8)
0%
(0/8)
100%
8
Drug Regulatory Authority 90%
(9/10)
10%
(1/10)
0%
(0/10)
100%
10
Pharmacopeial Authority 54%
(7/13)
46%
(6/13)
0%
(0/13)
100%
13
OMCL/Government Testing Labs 100%
(5/5)
0%
(0/5)
0%
(0/5)
100%
5
Academia 86%
(6/7)
14%
(1/7)
0%
(0/7)
100%
7
*Total due to rounding
When asked about their views and needs regarding the current levels of collaboration
among different pharmacopeia in their efforts to produce harmonized standards
efficiently, most respondents thought that the activities listed in Table 16, were occurring
at a high level only across some or a few pharmacopeias rather than across most.
Specifically, 35% (44/127) viewed engaging stakeholders (industry, government,
academia, other pharmacopeias) as occurring ‘high across some’ and 30% (38/127)
selected ‘high across few’, while 22% (28/127) selected ‘high across most’, and 13%
(17/127) selected ‘I don’t know’. Similarly, 33% (42/127) viewed establishing
communication channels between pharmacopeias as occurring high across some and 27%
(34/127) selected ‘high across few’, while 22% (28/127) selected ‘high across most’, and
18% (23/127) selected ‘I don’t know’. In comparison, 34% (43/127) viewed promoting
work-sharing activities between pharmacopeias as ‘high across few’ and 30% (38/127)

87
selected ‘high across some’, while 16% (20/127) selected ‘high across most’, and 20%
(26/127) selected ‘I don’t know’. Similarly, 34% (43/127) viewed promoting
transparency in standards setting as occurring ‘high across few’ and 25% (32/127)
selected ‘high across some’ while 18% (23/127) selected ‘high across most’, and 23%
(29/127) selected ‘I don’t know’ (Table 16).
Table 16: Level of Collaboration among Different Pharmacopeias
In your view, what is the current level of collaboration among different pharmacopeias in
their efforts to produce harmonized standards efficiently?

High
across
most
High
across
some
High
across
few
I don't
know
Total
N
1. Engaging stakeholders
(industry, government,
academia, other
pharmacopeias) 22% (28) 35% (44) 30% (38) 13% (17) 127
2. Promoting work-sharing
activities between
pharmacopeias 16% (20) 30% (38) 34% (43) 20% (26) 127
3. Establishing communication
channels between
pharmacopeias 22% (28) 33% (42) 27% (34) 18% (23) 127
4. Promoting transparency in
standards setting 18% (23) 25% (32) 34% (43) 23% (29) 127

Comments entered under ‘Are we missing other important information?’ are listed below.
A total of nine comments were provided.
Are we missing other important information?
• Why is it only "high" you're asking for?? Also: Pharmacopoeias + HAs never operate in isolation
some may be giving "lip service" to harmonization

88
• The globally applicable pharmacopoeias do a good job concerning collaboration with each other
and industry for prospective harmonization. The national pharmacopoeia such as ChP does not
have the level of established, transparent processes.
• Major pharmacopeia (USP.EP, JP work and collaborate well, issues with smaller pharmacopeia
wanting to be strong e.g., China, Russia etc.)
• Legal status and constraints may influence the level of international collaboration that can be
achieved.
• Interaction at the volunteer level is minimal
• Getting the pharmacopeia to want to actively harmonize is a first step that is lacking in many
regions.
• Communication between the pharmacopeias does not appear to be very good and also the
involvement of industry should take place earlier in the process in a very open way, not just after
the pharmacopeias have already drafted what they want in a monograph. Industry should be
involved BEFORE anything is drafted to get their thoughts as to what makes sense.
• Collaborating with Industry and their practices, procedures shall be assessed.
• All reference standard development should comply with ISO standards, specifically the ISO 30-34
series

To explore if there were differences across organizational affiliations in how stakeholder
engagement was viewed, cross tabulation was performed between organizational
affiliation and item 1 in Table 16, level of collaboration. As shown in Table 17, results
appeared to show that most respondents across most organizational affilitations thought
that engagement of stakeholders was occurring at a high level only across some or a few
pharmacopeias and was not occurring across most, but there were notable differences. A
higher percentage of respondents from government testing labs thought that engagement
was occurring at a high level (high across most: 60%, 3/5; high across some: 20%, 1/5;
high across few: 20%, 1/5), compared to those from drug regulatory authority (high
across most: 40%, 4/10; high across some: 30%, 3/10: high across few: 10%; don’t’
know: 20%, 2/10), trade association (high across most: 25%, 2/8, high across some: 25%,
2/8; high across few: 25%, 2/8; don’t know: 25%, 2/8), pharmacopeial authority (high
across most: 23%, 3/13; high across some: 23%, 3/13; high across few: 54%, 7/13),
pharmaceutical industry (high across most: 21%, 12/57; high across some: 33%, 19/57;

89
high across few: 28%, 16/57; don’t know: 18%, 10/57), and other (high across most:
15%, 4/27; high across some: 52%, 14/27; high across few (33%, 9/27). None from
academia thought that engagement was occurring high across most while 29% (2/7)
thought it was occurring high across some, 29% (2/7) thought it was occurring across
few, and 42% (3/7) didn’t know (Table 17).
Table 17: Cross Tabulation of Organizational Affiliation on Level of
Collaboration among Different Pharmacopeias in Stakeholder
Engagement
Organization/company affiliation

Engaging stakeholders (industry, government, academia, other
pharmacopeias
High across most High
across
some
High
across
few
I don’t
know
Total
N
Pharmaceutical Industry 21%
(12/57)
33%
(19/57)
28%
(16/57)
18%
(10/57)
100%
57
Other (please specify) 15%
(4/27)
52%
(14/27)
33%
(9/27)
0%
(0/27)
100%
27
Trade Association/Organization 25%
(2/8)
25%
(2/8)
25%
(2/8)
25%
(2/8)
100%
8
Drug Regulatory Authority 40%
(4/10)
30%
(3/10)
10%
(1/10)
20%
(2/10)
100%
10
Pharmacopeial Authority 23%
(3/13)
23%
(3/13)
54%
(7/13)
0%
(0/13)
100%
13
OMCL/Government Testing Labs 60%
(3/5)
20%
(1/5)
20%
(1/5)
0%
(0/5)
100%
5
Academia 0%
(0/7)
29%
(2/7)
29%
(2/7)
42%
(3/7)
100%
7
Cross tabulation was conducted between organizational affiliations and level of
collaboration among different pharmacopeias for promoting work-sharing activities
between pharmacopeias (item 2 in Table 16). As shown in Table 18, most respondents
across most organizational affiliations thought that promoting work-sharing activities was
occurring at a high level only across some or a few pharmacopeias and was not occurring
across most, but there were notable differences. Similar to findings shown in Table 17, a
higher percentage of respondents from government testing labs thought that promoting

90
work-sharing activies was occurring at a high level (high across most: 60%, 3/5; high
across some: 20%, 1/5; don’t know: 20%, 1/5), compared to those from drug regulatory
authority (high across most: 30%, 3/10; high across some: 30%, 3/10: high across few:
20%, 2/10; don’t’ know: 20%, 2/10), pharmacopeial authority (high across most: 16%,
2/13; high across some: 46%, 6/13; high across few: 38%, 5/13), pharmaceutical industry
(high across most: 14%, 8/57; high across some: 25%, 14/57; high across few: 39%,
22/57; don’t know: 23%, 13/57), trade association (high across most: 12%, 1/8, high
across some: 13%, 1/8; high across few: 25%, 2/8; don’t know: 50%, 4/8), and other
(high across most: 11%, 3/27; high across some: 41%, 11/27; high across few: 41%,
11/27; don’t know: 7%, 2/27). None from academia thought that engagement was
occurring high across most while 29% (2/7) thought it was occurring high across some,
14% (1/7) thought it was occurring across few, and 57% (4/7) didn’t know (Table 18).
Other cross tabulations for items in Table 16 revealed similar findings and are placed in
Appendix A.

91
Table 18: Cross Tabulation of Organizational Affiliation on Level of
Collaboration Among Different Pharmacopeias in Promoting Work-
Sharing Activities Between Pharmacopeias
Organization/company affiliation Promoting work-sharing activities between pharmacopeias
High across
most
High across
some
High
across
few
I don’t
know
Total
Pharmaceutical Industry 14%
(8/57)
25%
(14/57)
39%
(22/57)
23%*
(13/57)
100%
57
Other (please specify) 11%
(3/27)
41%
(11/27)
41%
(11/27)
7%
(2/27)
100%
27
Trade Association/Organization 12%
(1/8)
13%*
(1/8)
25%
(2/8)
50%
(4/8)
100%
8
Drug Regulatory Authority 30%
(3/10)
30%
(3/10)
20%
(2/10
20%
(2/10
100%
10
Pharmacopeial Authority 16%
(2/13)
46%
(6/13)
38%
(5/13)
0%
(0/13
100%
13
OMCL/Government Testing Labs 60%
(3/5)
20%
(1/5)
0%
(0/5)
20%
(1/5)
100%
5
Academia 0%
(0/7)
29%
(2/7)
14%
(1/7)
57%
(4/7)
100%
7
*due to rounding
4.6 Global Challenges with Standardized Pharmacopeial Practices and Regulatory
acceptance
In this section, respondents were asked to provide their views and needs on the potential
barriers to the efficient development of globally harmonized standards. As can be seen in
Table 19, most respondents thought that all activities listed were challenging but some
items were viewed as more challenging than others. Specifically, most respondents (50%,
62/125) viewed defining a common approach to developing global specifications as very
challenging while 41% (51/125) thought it was moderately challenging, 5% (6/125)
thought it was not challenging at all, and another 5% (6/125) selected cannot say.
Similarly, most respondents (46%, 59/127) viewed maintaining alignment between
different pharmacopeial standards as very challenging while 41% (52/127) thought it
was moderately challenging, 4% (5/127) thought it was not challenging at all, and 9%
(11/127) selected cannot say. In comparison, remaining five items were viewed by most

92
respondents as moderately challenging instead of very challenging: developing reference
standards (very challenging: 23%, 29/127; moderately challenging: 54%, 69/127; not
challenging: 14%, 18/127; cannot say: 9%, 11/127); implementing WHO's Good
Pharmacopeial Practices Guidance (GPP)(very challenging 12%, 15/127; moderately
challenging: 44%, 56/127; not challenging: 26%, 33/127; cannot say: 18 %, 23/127);
implementing ICH Quality guidances as challenging (very challenging: 17%, 22/127;
moderately challenging: 44%, 56/127; not challenging: 26%, 33/127; cannot say: 13%,
16/127); overcoming language differences (very challenging: 24%, 31/127; moderately
challenging: 39%, 50/127; not challenging: 26%, 33/127; cannot say: 10%, 13/127);
protecting data confidentiality (very challenging: 36%, 46/127; moderately challenging:
38%, 48/127; not challenging: 17%, 22/127; cannot say: 9%, 11/127).

93
Table 19: Challenges Facing Pharmacopeial Bodies at the Global Level
At the global level, which of the following activities do you think are most challenging for
pharmacopeial bodies in their efforts to produce harmonized standards efficiently?
Very
challenging
Moderately
challenging
Not
challenging
at all
Cannot
Say
Total
N
1. Defining a common
approach to
developing global
specifications
50% (62) 41% (51) 5% (6) 5% (6) 125
2. Maintaining
alignment between
different
pharmacopeial
standards
46% (59) 41% (52) 4% (5) 9% (11) 127
3. Protecting data
confidentiality
36% (46) 38% (48) 17% (22) 9% (11) 127
4. Overcoming
Language
differences
24% (31) 39% (50) 26% (33) 10% (13) 127
5. Developing
reference
standards
23% (29) 54% (69) 14% (18) 9% (11) 127
6. Implementing
WHO's Good
Pharmacopeial
Practices Guidance
(GPP)
12% (15) 44% (56) 26% (33) 18% (23) 127
7. Implementing ICH
Quality guidances
17% (22) 44% (56) 26% (33) 13% (16) 127
To explore if there were differences across different stakeholder groups, selected items
were chosen for cross tabulation from Table 19. A cross tabulation was conducted
between organizational affiliations and level of challenge in implementing WHO's Good
Pharmacopeial Practices Guidance (GPP) (Table 20). As shown in Table 20, most
respondents across most organizations/affiliations viewed the activity as challenging, but

94
there were notable differences. A higher percentage of respondents from pharmacopeial
authority thought that it was very challenging (very challenging: 38%, 5/13; moderately
challenging: 31%, 4/13; not challenging: 31%, 4/13) compared to respondents from
academia (very challenging: 29%, 2/7; moderately challenging: 29%, 2/7; not challenging
14%, 1/7; cannot say: 29%, 2/7), other (very challenging: 11%, 3/27; moderately
challenging: 63%, 17/27; not challenging : 7%, 2/27; cannot say: 19%, 5/27), drug
regulatory authority (very challenging: 10%, 1/10; moderately challenging: 30%, 3/10:
not challenging: 30%, 3/10; cannot say: 30%, 3/10), and pharmaceutical industry (very
challenging: 7%, 4/57; moderately challenging: 37%, 21/57; not challenging: 35%,
20/57; cannot say: 21%, 12/57). None from government testing labs thought that it was
very challenging while 80% (4/5) thought it was not challenging at all and 20% (1/5)
cannot say. Like wise, none from trade association thought that it was very challenging
while 63% (5/8) thought it was moderately challenging, 25% (2/8) thought it not
challenging, and 13% (1/8) selected cannot say (Table 20).

95
Table 20: Cross Tabulation of Organizational Affiliation on Level of Challenge
Implementing WHO's Good Pharmacopeial Practices Guidance
(GPP)
Organization/Company
affiliation
Implementing WHO's Good Pharmacopeial Practices Guidance
(GPP)
Very
challenging
Moderately
challenging
Not
challenging
at all
Cannot
say
Total N
Pharmaceutical Industry 7%
(4/57)
37%
(21/57)
35%
(20/57)
21%
(12/57)
100%
57
Other (please specify) 11%
(3/27)
63%
(17/27)
7%
(2/27)
19%
(5/27)
100%
27
Trade
Association/Organization
0%
(0/8)
63%
(5/8)
25%
(2/8)
13%*
(1/8)
100%
8
Drug Regulatory Authority 10%
(1/10)
30%
(3/10)
30%
(3/10)
30%
(3/10)
100%
10
Pharmacopeial Authority 38%
(5/13)
31%
(4/13)
31%
(4/13)
0%
(0/13)
100%
13
OMCL/Government
Testing Labs
0%
(0/5)
80%
(4/5)
20%
(1/5)
0%
(0/5)
100%
5
Academia 29%
(2/7)
29%
(2/7)
14%*
(1/7)
29%
(2/7)
100%
7
A cross tabulation was performed between organizational affiliation and the level of
challenge in implementing ICH Quality guidances (item 7 from Table 19). As shown in
Table 21, most respondents across most organizational affilitations thought that the
activity was challenging, but there were notable differences. A higher percentage of
respondents from pharmacopeial authority thought that it was challenging (very
challenging: 38%, 5/13; moderately challenging: 23%, 3/13; not challenging: 38%, 5/13)
compared to respondents from drug regulatory authority (very challenging: 30%, 3/10;
moderately challenging: 40%, 4/10: not challenging: 40%, 4/10; cannot say: 10%, 1/10),
academia (very challenging: 29%, 2/7; moderately challenging: 29%, 2/7; not
challenging: 14%, 1/7; cannot say: 29%, 2/7), pharmaceutical industry (very challenging:
14%, 8/57; moderately challenging: 30%, 17/57; not challenging: 39%, 22/57; cannot
say: 18%, 10/57), trade association (very challenging: 13%, 1/8; moderately challenging:

96
63%, 5/8; not challenging: 13%, 1/8; cannot say: 13%, 1/8), and other (very challenging:
11%, 3/27; moderately challenging: 78%, 21/27; not challenging: 4%, 1/27; cannot say:
7%, 2/27). None from government testing labs thought that it was very challenging while
80% (4/5) thought it was moderately challenging, and 20% (1/5) thought it was not
challenging at all (Table 21). Other cross tabulations for items in Table 19 are placed in
Appendix A.
Table 21: Cross Tabulation of Organizational Affiliation on Level of Challenge
Implementing ICH Quality guidances
Organization/Company
affiliation
Implementing ICH Quality guidances
Very
challenging
Moderately
challenging
Not
challenging
at all
Cannot
say
Total N
Pharmaceutical Industry 14%
(8/57)
30%
(17/57)
39%
(22/57)
18%*
(10/57)
100%
57
Other (please specify) 11%
(3/27)
78%
(21/27)
4%
(1/27)
7%
(2/27)
100%
27
Trade
Association/Organization
13%
(1/8)
63%
(5/8)
13%
(1/8)
13%*
(1/8)
100%
8
Drug Regulatory Authority 30%
(3/10)
40%
(4/10)
40%
(2/10)
10%
(1/10)
100%
10
Pharmacopeial Authority 38%
(5/13)
23%
(3/13)
38%
(5/13)
0%
(0/13)
100%
13
OMCL/Government
Testing Labs
0%
(0/5)
80%
(4/5)
20%
(1/5)
0%
(0/5)
100%
5
Academia 29%
(2/7)
29%
(2/7)
14%
(1/7)
29%*
(2/7)
100%
7
*due to rounding
To understand which of the differences across pharmacopeias are most challenging,
respondents were asked their views on a list of potential differences. As can be seen in
Table 22, most respondents thought all items listed were challenging, but not to the same
extent. Specifically, most respondents (74%, 87/118) thought disparate regulatory/legal
requirements as very challenging while 20% (24/118) thought it was moderately

97
challenging, 2% (2/118) thought it was not challenging, and 4% (5/118) selected cannot
say. In comparison, most thought diverse scientific opinions was moderately challenging
(51%, 60/118) while 38% (45/118) thought it was very challenging, 7% (8/118) thought
it was not challenging at all, and 4% (5/118) selected cannot say. Similarly, most viewed
different public inquiry /comment processes as moderately challenging (59%, 70/118)
while 25% (29/118) thought it was very challenging, 9% (11/118) thought it was not
challenging and 7% (8/118) selected cannot say. Most respondents also viewed
misaligned publication schedules as moderately challenging (47%, 56/118) but more
thought it was not challenging (25%, 29/118) than very challenging (18%, 21/118) and
10% (12/118) selected cannot say.
Table 22: Differences across Pharmacopeias to Produce Harmonized Standards
At the global level, which of the following differences across pharmacopeias do you think
are most challenging in their efforts to produce harmonized standards efficiently?

Very
challenging
Moderately
challenging
Not
challengin
g at all
Cannot
Say
Total
N
1. Disparate
regulatory/legal
requirements 74% (87) 20% (24) 2% (2) 4% (5) 118
2. Diverse scientific
opinions 38% (45) 51% (60) 7% (8) 4% (5) 118
3. Different public
inquiry /comment
processes 25% (29) 59% (70) 9% (11) 7% (8) 118
4. Misaligned
publication
schedules 18% (21) 47% (56) 25% (29) 10% (12) 118
Comments entered under Are we missing any other important differences across
pharmacopeias? are listed below. A total of 13 comments were provided.

98
Are we missing any other important differences across pharmacopeias? (please specify)
• The JP and the ChP are part of the government and are controlled by the government. Their
decision making process can be quicker that the USP since the USP utilizes a formal public
comment period. However, the USP process is more beneficial to stakeholders. Other
Pharmacopoeias such as the ChP are difficult to work with since their approach is not flexible and
not as transparent as the USP.
• Regional pharmacopeia bodies are not effectively involved in global harmonization.
• Regarding this question: At the global level, which of the following activities do you think are most
challenging for pharmacopeial bodies in their efforts to produce harmonized standards efficiently?
This one is a bit harder to answer without having more direct understanding of what that process
looks like internally at a compendium. From an outside perspective there seems to be a hurdle with
compendia bodies in wanting to align with ICH in some situations. Sort of an example concept is
with Elementary Impurities USP Commentary responses to PF content which would infer that the
role of the USP is not to directly align with ICH etc. That may be an opinion held internal to the
USP however as end users that IS the expectation. Two (or more) differently worded
requirements/criteria are not ideal. Decisions need to be data based when possible and sometimes
personal perceptions seem to drive decisions when the data should be driving the decisions.
• Political agendas trumping good science is a very challenging aspect.
• Pharmacopoeias are regulations in some settings but not in all. This makes change very difficult.
• One of the main differences is the historical background. For example, one acceptance criteria may
be different for several pharmacopeias, but having applied them for a long time before
harmonization makes it difficult to overcome. Products long-standing in the market without
problems may set a standard of quality difficult to change. Lack of reference standards in some
countries to test suitability of analytical procedures may also set limits for harmonization.
• Language=Thinking=Culture. You may think you're speaking the same language, but the semantics
and subtexts etc., are so different. Even within the same country this plays a role of course. The
semantics of the major pharmacopoeias are different, you really need to tear them all down and start
again if you want to go all the way (Not saying that's worth the effort)
• Diverse scientific opinions and disparate regulatory/legal requirements in different regions are the
biggest obstacles to global harmonization.
• Different mechanisms to incorporate industry feedback and get industry involved early in the
process. Different general notice/chapter requirements such as the policy on additives that is
different between the JP and the USP/PhEur.
• Different languages and availability of a translation.
• Different impact and resources of pharmacopeias (e.g., regional vs country)
• Different culture approaches which I simplify here: western countries and jurisdictions tend to put
responsibilities to legal entities (companies) producing drugs and allow for risk benefit evaluation
with random inspection of data and sites by regulatory authorities, This is based on trust and on the
idea that economic success is important to western countries, and that finally every authority has to
support economic success. Eastern countries are very prescriptive and regulatory authorities want to
have all details on file, This is based on distrust, and economic success is less important.
• Delay in publishing some pharmacopoeias in English or not at all makes keeping up to date with
those standards very difficult, even for a global company such as the one I work for.
Cross tabulation was conducted between organizational affiliations and level of challenge
across different pharmacopeias associated with different public inquiry/comment

99
processes, item 3 in Table 22. As shown in Table 23, most respondents across most
organizational affilitations thought that the process was challenging but there were
notable differences. A higher percentage of respondents from government testing labs
thought that it was very challenging (very challenging: 40%, 2/5; moderately challenging:
20%, 1/5; not challenging: 40%, 2/5), compared to those from other (very challenging:
30%, 8/27; moderately challenging: 63%, 17/27; not challenging: 4%, 1/27; cannot say:
4%, 1/27), pharmacopeial authority (very challenging: 25%, 2/8; moderately challenging:
63%, 5/8; not challenging: 13%, 1/8), drug regulatory authority (very challenging: 20%,
2/10; moderately challenging: 70%, 7/10: not challenging: 10%, 1/10), trade association
(very challenging: 13%, 1/8; moderately challenging: 75%, 6/8; cannot say: 13%, 1/8),
and pharmaceutical industry (very challenging: 26%, 14/53; moderately challenging:
54%, 29/53; not challenging: 9%, 5/53; cannot say: 9%, 5/53). None from academia
thought that it was very challenging while 71% (5/7) thought it was moderately
challenging, 14% (1/7) thought it was not challenging at all and 14% (1/7) cannot say
(Table 23).

100
Table 23: Cross Tabulation of Organizational Affiliation on Differences across
Pharmacopeias in their Public Inquiry/Comment Processes
Organization/Company
affiliation
Different public inquiry/comment processes
Very
challenging
Moderately
challenging
Not
challenging
at all
Cannot
say
Total
N
Pharmaceutical Industry 26%
(14/53)
54%
(29/53)
9%
(5/53)
9%
(5/53)
100%
53
Other (please specify) 30%
(8/27)
63%
(17/27)
4%
(1/27)
4%*
(1/27)
100%
27
Trade
Association/Organization
13%
(1/8)
75%
(6/8)
0%
(0/8)
13%*
(1/8)
100%
8
Drug Regulatory Authority 20%
(2/10)
70%
(7/10)
10%
(1/10)
0%
(0/10)
100%
10
Pharmacopeial Authority 25%
(2/8)
63%
(5/8)
13%*
(1/8)
0%
(0/8)
100%
8
OMCL/Government
Testing Labs
40%
(2/5)
20%
(1/5)
40%
(2/5)
0%
(0/5)
100%
5
Academia 0%
(0/7)
71%*
(5/7)
14%
(1/7)
14%
(1/7)
100%
7
*due to rounding
Cross tabulation was also conducted between organizational affiliations and level of
challenge across different pharmacopeias associated with misaligned publication
schedules, item 4 in Table 22. As shown in Table 24, most respondents across most
organizational affiliations thought that the issues was challenging, but there were notable
differences. A higher percentage of respondents from pharmaceutical industry thought it
was very challenging (very challenging: 23%, 12/53; moderately challenging: 36%,
19/53; not challenging: 32%, 17/53; cannot say: 9%, 5/53), compared to respondents
from drug regulatory authority (very challenging: 20%, 2/10; moderately challenging:
60%, 6/10: not challenging: 10%, 1/10; cannot say: 10%, 1/10), government testing labs
(very challenging: 20%, 1/5; moderately challenging: 40%, 2/5; not challenging: 40%,
2/5), academia (very challenging:14%, 1/7; moderately challenging: 43%, 3/7; not
challenging: 29%, 2/7; cannot say: 14%, 1/7), pharmacopeial authority (very challenging:

101
13%, 1/8; moderately challenging: 50%, 4/8; not challenging: 38%, 3/8), and trade
association (very challenging: 13%, 1/8; moderately challenging: 63%, 5/8; not
challenging: 13%, 1/8; cannot say: 13%, 1/8). Respondents in the other category also
thought that the issue of misaligned publication schedule was challenging (very
challenging: 30%, 8/27; moderately challenging: 63%, 17/27; not challenging: 4%, 1/27;
cannot say: 4%, 1/27) (Table 24). Other cross tabulations for items in Table 22 are
placed in Appendix A.
Table 24: Cross Tabulation of Organizational Affiliation on Differences across
Pharmacopeias with Misaligned Publication Schedules
Organization/Company
affiliation
Misaligned publication schedules
Very
challenging
Moderately
challenging
Not
challenging
at all
Cannot
say
Total N
Pharmaceutical Industry 23%
(12/53)
36%
(19/53)
32%
(17/53)
9%
(5/53)
100%
53
Other (please specify) 30%
(8/27)
63%
(17/27)
4%
(1/27)
4%*
(1/27)
100%
27
Trade
Association/Organization
13%
(1/8)
63%
(5/8)
13%
(1/8)
13%*
(1/8)
100%
8
Drug Regulatory Authority 20%
(2/10)
60%
(6/10)
10%
(1/10)
10%
(1/10)
100%
10
Pharmacopeial Authority 13%*
(1/8)
50%
(4/8)
38%
(3/8)
0%
(0/8)
100%
8
OMCL/Government
Testing Labs
20%
(1/5)
40%
(2/5)
40%
(2/5)
0%
(0/5)
100%
5
Academia 14%
(1/7)
43%
(3/7)
29%
(2/7)
14%
(1/7)
100%
7
*due to rounding
To understand what factors are considered to be the greatest challenges in developing
pharmacopeial standards, respondents were asked for their level of agreement with 6
potential factors (Table 25). Responses were varied but the highest level of agreement
was reported for a lack of adequate collaboration on work-sharing activities (agree: 41%,
39/94; neither agree nor disagree: 33%, 31/94; disagree: 26%, 25/94). This was followed

102
by a lack of a transparent standard setting process (agree: 34%, 35/102; neither agree
nor disagree: 26%, 27/102; disagree: 39%, 40/102), a lack of adequate laboratory
capabilities requiring outsourcing (agree: 26%, 26/99; neither agree nor disagree: 32%,
32/99; disagree: 41%, 41/99); a lack of adequate scientific resources (agree: 23%,
23/101; neither agree nor disagree: 29%, 29/101; disagree: 49%, 49/101); and a lack of
ability to develop reference material standards (agree: 19%, 19/98; neither agree nor
disagree: 37%, 36/98; disagree: 44%, 43/98). Lowest level of agreement was reported for
a lack of ability to remove environmentally dangerous chemical reagents (agree: 15%,
14/93; neither agree nor disagree: 39%, 36/93; disagree: 46%, 43/93).
Table 25: Greatest Challenges for Pharmacopeias in Developing Pharmacopeial
Standards
Please select your level of agreement with the following factors in presenting the greatest
challenges for developing pharmacopeial standards at your pharmacopoeia?

Agree
Neither
agree
nor
disagree
Disagree
Total
N
1. Lack of adequate collaboration on work-
sharing activities 41% (39) 33% (31) 26% (24) 94
2. Lack of a transparent standard setting
process 34% (35) 26% (27) 39% (40) 102
3. Lack of adequate laboratory capabilities
requiring outsourcing 26% (26) 32% (32) 41% (41) 99
4. Lack of adequate scientific resources 23% (23) 29% (29) 49% (49) 101
5. Lack of ability to develop reference
material standards 19% (19) 37% (36) 44% (43) 98
6. Lack of ability to remove environmentally
dangerous chemical reagents 15% (14) 39% (36) 46% (43) 93
To further explore stakeholder views and needs on what are the greatest challenges for
pharmacopeias in developing pharmacopeial standards, cross tabulations were performed

103
between organizational affiliations with the following issues: a lack of adequate scientific
resources and a lack of ability to develop reference material standards (items 4 and 5 in
Table 25). As shown in Table 26, most respondents across all organizations disagree that
a lack of adequate scientific resources presented greatest challenges, but there were some
differences. A higher percentage of respondents from academia disagreed (disagree: 71%,
5/7; agree: 29%, 2/7) compared to government testing labs (disagree: 60%, 3/5; neither
agree nor disagree: 20%, 1/5; agree: 20%, 1/5), drug regulatory authority (disagree: 57%,
4/7; agree: 43%, 3/7), pharmaceutical industry (disagree: 49%, 21/43; neither agree nor
disagree: 30%, 13/43; agree: 21%, 9/43), other (disagree: 44%, 11/25; neither agree nor
disagree: 40%, 10/25; agree: 16%, 4/25), pharmacopeial authority (disagreed: 43%, 3/7;
neither agree nor disagree: 29%, 2/7; agree: 29%, 2/7) and trade association (agree: 29%,
2/7; neither agree nor disagree: 43%, 3/7; agree: 29%, 2/7) (Table 26).

104
Table 26: Cross Tabulation of Organizational Affiliation on Challenges With
Developing Standards with Lack of Adequate Scientific Resources
Organization/company affiliation Lack of adequate scientific resources
Agree Neither agree
nor disagree
Disagree Total
N
Pharmaceutical Industry 21%
(9/43)
30%
(13/43)
49%
(21/43)
100%
43
Other (please specify) 16%
(4/25)
40%
(10/25)
44%
(11/25)
100%
25
Trade Association/Organization 29%
(2/7)
43%
(3/7)
29%*
(2/7)
100%
7
Drug Regulatory Authority 43%
(3/7)
0%
(0/7)
57%
(4/7)
100%
7
Pharmacopeial Authority 29%
(2/7)
29%*
(2/7)
43%
(3/7)
100%
7
OMCL/Government Testing Labs 20%
(1/5)
20%
(1/5)
60%
(3/5)
100%
5
Academia 29%
(2/7)
0%
(0/7)
71%
(5/7)
100%
7
*due to rounding
Cross tabulation was performed between organizational affiliations on challenges in
developing pharmacopeial standards with a lack of ability to develop reference material
standards. As shown in Table 27, most respondents across all organizations disagree but
there were some notable differences. A higher percentage of respondents from other
disagreed (disagree: 61%, 14/23; neither agree nor disagree: 30%, 7/23; agree: 9%, 2/23),
compared to pharmacopeial authority (disagreed: 57%, 4/7; neither agree nor disagree:
29%, 2/7; agree: 14%, 1/7), academia (disagree: 71%, 5/7; agree: 29%, 2/7), drug
regulatory authority (disagree: 43%, 3/7; neither agree nor disagree: 43%, 3/7; agree:
14%, 1/7), government testing labs (disagree: 40%, 2/5; neither agree nor disagree: 20%,
1/5; agree: 40%, 2/5) pharmaceutical industry (disagree: 34%, 15/44; neither agree nor
disagree: 45%, 20/44; agree: 21%, 9/44), and trade association (disagree: 34%, 2/6;
neither agree nor disagree: 33%, 2/6; agree: 33%, 2/6) (Table 27). Other cross tabulations
for items in Table 25 are placed in Appendix A.

105
Table 27: Cross Tabulation of Organizational Affiliation on Challenges in
Developing Standards with a Lack of Ability to Develop Reference
Material Standards
Organization/company affiliation Lack of ability to develop reference material
standards
Agree Neither agree
nor disagree
Disagree Total N
Pharmaceutical Industry 21%
(9/44)
45%
(20/44)
34%
(15/44)
100%
44
Other (please specify) 9%
(2/23)
30%
(7/23)
61%
(14/23)
100%
23
Trade Association/Organization 33%
(2/6)
33%
(2/6)
34%*
(2/6)
100%
6
Drug Regulatory Authority 14%
(1/7)
43%
(3/7)
43%
(3/7)
100%
7
Pharmacopeial Authority 14%
(1/7)
29%
(2/7)
57%
(4/7)
100%
7
OMCL/Government Testing Labs 40%
(2/5)
20%
(1/5)
40%
(2/5)
100%
5
Academia 33%
(2/6)
17%
(1/6)
50%
(3/6)
100%
6
4.7 Views of the Pharmacopeial Authorities
In this section, 13 respondents who are affiliated with a pharmacopeial authority as
reported in Figure 9 were directed to three questions probing their levels of satisfaction
with performance of their pharmacopeias, meetings they regularly attend, and resources
they usually consult.
When respondents were asked to provide their levels of satisfaction with six areas of
focus by their pharmacopeias, a majority reported being satisfied with half of the six
statements listed in Table 28. Although overall numbers are small, respondents reported
highest levels of satisfaction (54%) with the performance by their pharmacopeias in
stakeholder engagement through workshops and forums (satisfied: 54%, 7/13; neither
satisfied nor dissatisfied: 8%, 1/13; dissatisfied: 23%, 3/13; don’t know: 17%, 2/13),

106
scientific resources (satisfied: 54%, 7/13; neither satisfied nor dissatisfied: 23%, 3/13;
dissatisfied: 8%, 1/13; don’t know: 15%, 2/13), and transparency in public
inquiry/comment process (satisfied: 54%, 7/13; neither satisfied nor dissatisfied: 23%,
3/13; dissatisfied: 8%, 1/13; don’t know: 15%, 2/13). Respondents were less satisfied
(31-46%) with their laboratory capabilities to develop quality specifications (satisfied:
46%, 6/13; neither satisfied nor dissatisfied: 8%, 1/13; dissatisfied: 23%, 3/13; don’t
know: 23%, 3/13), alignment of standards across different pharmacopeias (satisfied:
31%, 4/13; neither dissatisfied nor satisfied: 38%, 5/13; dissatisfied: 23%, 3/13; don’t
know: 8%, 1/13), and reducing the testing burden for industry (satisfied: 31%, 4/13;
neither dissatisfied nor satisfied: 38%, 5/13: dissatisfied: 8%, 1/13; don’t know: 23%,
3/13).
Table 28: Satisfaction with your Pharmacopeia’s Performance
How satisfied are you with the adequacy of your pharmacopeia’s performance in the
following areas?
Satisfied
Neither
Satisfied nor
Dissatisfied Dissatisfied
I don't
know
Total
N
1. Stakeholder engagement
through workshops and
forums
54% (7) 8% (1) 23% (3) 17% (2) 13
2. Scientific resources 54% (7) 23% (3) 8% (1) 15% (2) 13
3. Transparency in public
inquiry/comment process
54% (7) 23% (3) 8% (1) 15% (2) 13
4. Laboratory capabilities to
develop quality
specifications
46% (6) 8% (1) 23% (3) 23% (3) 13
5. Alignment of standards
across different
pharmacopeias
31% (4) 38% (5) 23% (3) 8% (1) 13
6. Reducing the testing
burden for industry
31% (4) 38% (5) 8% (1) 23% (3) 13

107
When asked which meetings they regularly attend, the highest response was received for
pharmacopeial meetings in your region with 8 responses followed by
bilateral/multilateral meetings between pharmacopeias, PDG technical meetings, and
WHO’s IMWP meetings each with 5 responses, and ICH meetings with 4 responses
(Figure 18). The total number of responses (27) was higher than the number of
respondents (13) because each respondent could select more than one answer. Additional
meetings captured under ‘Other’ listed at the bottom of Figure 18 included Expert Panel
Meetings, workshops, and conferences related to pharmacopeial topics in Figure 18.
Figure 18: Meetings Regularly Attended
Which meetings do you regularly attend? (please select all that apply) n=27

4
5
5
5
8
0 1 2 3 4 5 6 7 8 9
ICH meetings
WHO’s International Meeting of World
Pharmacopeias (IMWP)
Pharmacopeial Discussion Group (PDG) technical
meetings
Bilateral/multilateral meetings between
pharmacopeias
Pharmacopeial meetings in your region

108
Other:
• Expert Panel Meetings
• Workshops
• Conferences related to pharmacopeial topics
When asked which resources they consult when developing, implementing or
enforcement of pharmacopeial standards, 8 responses were received for ICH Quality
topics, local/regional regulatory documents, and local pharmacopeial monographs,
chapters and reference standards; followed by 6 responses for WHO’s International
Pharmacopeial standards, PDG standards, regulatory guidances documents outside their
local/regional areas; and 4 responses for WHO Good Pharmacopeial Practices guidance
document (Figure 19). Respondents did not provide any additional resources under
‘Other’ section.

109
Figure 19: Resources Consulted
What resources do you consult when working with pharmacopeial standards? (Select all
that apply) n=46

4.8 Pharmacopeial Discussion Group (PDG)
In this section, respondents were asked about their needs and views on the harmonization
activities conducted by the Pharmacopeial Discussion Group (PDG), comprised of the
pharmacopeias of the United States, European Union, and Japan. First, the respondents
were asked how frequently they used the pharmacopeias of the three jurisdictions. The
highest frequencies of use were observed for United States Pharmacopeia (high: 80%,
97/120; medium: 10%, 12/120; little or none: 10%, 12/120) followed by European
Pharmacopeia (high: 51%, 61/119; medium: 32%, 38/119; low: 17%, 20/119) and
Japanese Pharmacopeia (high: 35%, 42/120; medium: 23%, 28/120; low 42%, 50/120)
(Figure 20).
4
6
6
6
8
8
8
0 1 2 3 4 5 6 7 8 9
WHO's Good Pharmacopeial Practices
Guidance
Regulatory guidances/documents outside
your local/regional area
Pharmacopeial Discussion Group (PDG)
..standards
WHO International Pharmacopeial standards
Local/Regional regulatory
guidances/documents
Local/Regional Pharmacopeial monographs…
International Council for Harmonisation (ICH)
Topics..Quality

110
Figure 20: Frequency of use of National/ Regional Pharmacopeias of
Pharmacopeial Discussion Group (PDG) Members
Please indicate your frequency of use of the following pharmacopeias which form the
Pharmacopeial Discussion Group (PDG)? n=120,119,121

When asked about the use of PDG standards in enforcement activities, 90% of the
respondents thought that the standards were helpful when compared to local or regional
standards (very helpful: 47%, 57/126; somewhat helpful: 43%, 54/126) while 6% (7/126)
thought that they were not helpful (Figure 21). The remaining 8 respondents (6%, 8/126)
selected other and further clarified their comments in the text box provided.

111
Figure 21: Use of PDG Standards in Enforcement Activities
In your experience, how helpful are PDG harmonized standards compared to local or
regional standards in helping regulators with enforcement activities? n=126

Other, (please specify):
• I don’t know (5)
• Unknown (1)
• FDA largely ignores opinions/ perspectives from USP (1)
• As a trade organization we do not have knowledge as to how helpful or not this process is. This
said, the more harmonized standards there are, the easier it is for industry to understand the
expectations of regulatory bodies (1)

When asked if PDG standards are helpful in increasing efficiency in their professional
functions, results were similar to above with around 90% reporting that the standards
were helpful (very helpful: 54%, 68/126; somewhat helpful: 37%, 46/126) while 6%
(8/126) selected not helpful (Figure 22). Four respondents (3%, 4/126) provided
comments in the text box provided below Figure 22 under ‘Are we missing any other
important information?’

112
Figure 22: Use of PDG harmonized Standards to Increase Efficiency
In your experience, how helpful are PDG harmonized standards to increase efficiency in
your professional function? n=126

Are we missing any other important information?
• I don’t know
• N/A’
• we are missing important information’
• ‘x’

113
4.8.1 Views on PDG’s performance
To understand how PDG’s activities were viewed by the stakeholders, respondents were
provided with 5 performance statements and asked for their levels of agreement. The
highest level of agreement was reported for PDG’s work whereby harmonization helps
pharmacopeial standards stay aligned (agree: 81%, 92/113; neither agree nor disagree:
14%, 16/113; disagree: 4%, 5/113) followed by provides a transparent public
inquiry/comment process in standards setting activities (agree: 60%, 64/106; neither
agree nor disagree: 28%, 30/106; disagree: 11%, 12/106), and provides timely access to
proposed and official standards through publication and translations (agree: 57%,
63/110; neither agree nor disagree: 34%, 38/110; disagree: 9%, 9/110). The lowest level
of agreement was reported for the statement that PDG develops standards in a timely
manner (agree: 27%, 29/106; neither agree nor disagree: 36%, 38/106; disagree: 37%,
39/106) (Table 29). Comments provided under are we missing any other important
information? are listed below Table 29.

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Table 29: Views on PDG’s Performance
Please select your level of agreement with the following statements regarding PDG
performance?
Agree
Neither
agree
nor
disagree Disagree
Total
N
1. Harmonization helps pharmacopeial
standards stay aligned 81% (92) 14% (16) 4% (5) 113
2. Provides a transparent public
inquiry/comment process in standards setting
activities 60% (64) 28% (30) 11% (12) 106
3. Provides timely access to proposed and
official standards through publication and
translations 57% (63) 34% (38) 9% (9) 110
4. Engages stakeholders during standards
setting through workshops and educational
trainings 53% (55) 38% (39) 10% (10) 104
5. Develops standards in a timely manner 27% (29) 36% (38) 37% (39) 106

Are we missing any other important information?
• The PDG process is very slow and takes too long to get agreement on what should be simple
decisions based on what current existing safe materials can meet as opposed to trying to tighten
standards in one or more regions.
• Serious consideration should be given to including the Chinese Pharmacopoeia as a member of the
PDG. ChP membership in the PDG will help improve collaboration and in turn improve
harmonization with the ChP.
• The PDG is an outdated model for compendial harmonization because they will not allow
participation by other pharmacopeia. They are also not open to industry input which could
significantly reduce the time it takes to develop harmonized methods and specifications.
• Despite the fact that the PDG process is very slow, "Does not develop standards in a timely
manner", it is still a very valuable function and is currently the only path available for
harmonization across multiple compendia.
• Although timeliness of developing harmonized standards has been slow, the dedication and
commitment by the PDG partners to still work toward a harmonized outcome is apparent and
commendable.
• Regarding the "timely access" statement above, I agree with that statement that there is timely
access to view the proposed content. However duration of the time to submit comments overall
for the PF process (including harmonization items) is insignificant. Submission times should align
with the weight of the change. A standard 90 day time period is helpful for planning staffing and
review expectations but does not align with concept of shifting staffing resources as needed for
higher priority items in some situations.

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A series of cross tabulations were performed to explore if there were differences across
organizational affiliations (items 4 and 5 listed in Table 29) in how PDG’s performance
was viewed. As shown in Table 30, a cross tabulation between organizational affiliations
and views on whether PDG develops standards in a timely manner reveals differences
across different stakeholder groups. Most respondents from pharmaceutical industry
thought that PDG did not develop standards in a timely manner (disagree: 43%, 20/47;
neither agree nor disagree: 36%, 17/47; agree: 21%, 10/47) as did most respondents from
academia (disagree: 60%, 3/5; agree: 40%, 2/5) and other (disagree: 42%, 10/24; neither
agree nor disagree: 33%, 8/24; agree: 40%, 2/5). In comparison, most respondents from
trade assoiciations thought that PDG performed in a timely manner (agree: 60%, 3/5;
neither agree nor disagree: 20%, 1/5; disagree: 20%, 1/5) as did pharmacopeial authority
(agree: 45%, 5/11; neither agree nor disagree: 27%, 3/11; disagree: 27%, 3/11). Most
respondents from drug regulatory authority selected neither agree nor disagree (78%, 7/9)
while one respondent each selected agree and disagree. Out of the five respondents from
government testing labs, two selected agree, one selected disagree, and two selected
neither agree nor disagree.

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Table 30: Cross Tabulation of Organizational Affiliation on PDG Performance in
Developing Standards in a Timely Manner
Organization/company
affiliation
Develops standards in a timely manner
Agree Neither
agree nor
disagree
Disagree Total N
Pharmaceutical Industry 21%
(10/47)
36%
(17/47)
43%
(20/47)
100%
47
Other (please specify) 25%
(6/24)
33%
(8/24)
42%
(10/24)
100%
24
Trade
Association/Organization
60%
(3/5)
20%
(1/5)
20%
(1/5)
100%
5
Drug Regulatory Authority 11%
(1/9)
78%
(7/9)
11%
(1/9)
100%
9
Pharmacopeial Authority 45%
(5/11)
27%
(3/11)
27%
(3/11)
100%
11
OMCL/Government Testing
Labs
40%
(2/5)
40%
(2/5)
20%
(1/5)
100%
5
Academia 40%
(2/5)
0%
(0/5)
60%
(3/5)
100%
5

A cross tabulation between organizational affiliations and views on PDG’s performance
in engaging stakeholders through workshops and educational trainings revealed mixed
results (Table 31). The highest agreement was seen in respondents from government
testing labs (agree: 100%, 5/5) followed by drug regulatory authority (agree: 88%, 7/8;
neither agree nor disagree: 13%, 1/8), other (agree: 67%, 16/24; neither agree nor
disagree: 29%, 7/24; disagree: 4%, 1/24), trade association (agree: 60%, 3/5; neither
agree nor disagree: 40%, 2/5), academia (agree: 60%, 3/5; disagree: 40%, 2/5),
pharmaceutical industry (agree: 37%, 17/46; neither agree nor disagree: 57%, 26/4;
disagree: 7%, 3/46), and pharmacopeial authority (agree: 36%, 4/11; neither agree nor
disagree: 28%, 3/11; disagree: 36%, 4/11). Other cross tabulations for items in Table 29
are placed in Appendix A.

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Table 31: Cross Tabulation of Organizational Affiliation on PDG Performance
in Engaging Stakeholders in Standards Setting
Organization/company affiliation Engages stakeholders during standards setting through
workshops and educational trainings
Agree Neither agree
nor disagree
Disagree Total
N
Pharmaceutical Industry 37%
(17/46)
57%*
(26/46)
7%
(3/46)
100%
46
Other (please specify) 67%
(16/24)
29%
(7/24)
4%
(1/24)
100%
24
Trade Association/Organization 60%
(3/5)
40%
(2/5)
0%
(0/5)
100%
5
Drug Regulatory Authority 88%
(7/8)
13%*
(1/8)
0%
(0/8)
100%
8
Pharmacopeial Authority 36%
(4/11)
28%
(3/11)
36%
(4/11)
100%
11
OMCL/Government Testing Labs 100%
(5/5)
0%
(0/5)
0%
(0/5)
100%
5
Academia 60%
(3/5)
0%
(0/5)
40%
(2/5)
100%
5
*due to rounding
4.8.2 Challenges with implementing PDG harmonized standards
To understand what challenges are faced by stakeholders in their efforts to implement
PDG harmonized standards in their regions, the respondents were presented with six
potential areas of challenge. Although most respondents viewed five of the six items
listed in Table 32 as not challenging, they did agree that reference standards are too
costly (agree: 41%, 42/104; neither agree nor disagree; 34%, 36/104; disagree: 25%,
26/104). The results for the remaining five statements are as follows: there is a lack of
alignment between PDG standards and our local/regional pharmacopeia (agree: 30%,
29/97; neither agree nor disagree: 30%, 29/97; disagree: 40%, 39/97), our organization
lacks adequate laboratory capabilities (agree: 19%, 20/105; neither agree nor disagree:
27%, 28/105; disagree: 54%, 57/105), our organization lacks adequate scientific
resources (agree: 17%, 18/106; neither agree nor disagree: 26%, 28/106; disagree: 57%,

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60/106), PDG standards are not recognized by our regulatory body (agree: 17%, 16/93;
neither agree nor disagree: 23%, 21/93; disagree: 60%, 56/93), and reference standards
are not easily available (agree: 15%, 16/104; neither agree nor disagree: 34%, 35/104;
disagree: 51%, 53/104). Comments under “other” provided by nine respondents are listed
below Table 32.
Table 32: Factors that Present the Biggest Challenges to Implementing PDG
Harmonized Standards
Please select your level of agreement with the following factors that present the biggest
challenges to implementing PDG harmonized standards into your region?

Agree
Neither
agree
nor
disagree
Disagree
Total
N
1. Reference standards are too costly 41% (42) 34% (36) 25% (26) 104
2. There is a lack of alignment between PDG
standards and our local/regional
pharmacopeia 30% (29) 30% (29) 40% (39) 97
3. Our organization lacks adequate
laboratory capabilities 19% (20) 27% (28) 54% (57) 105
4. Our organization lacks adequate scientific
resources 17% (18) 26% (28) 57% (60) 106
5. PDG standards are not recognized by our
regulatory body 17% (16) 23% (21) 60% (56) 93
6. Reference standards are not easily
available 15% (16) 34% (35) 51% (53) 104

Other comments (please specify)
• Recommended to include Industry people in PDG or the Best practices across Industry shall be
considered for Harmonization.
• The PDG standards are not recognized in China and India where two of our plants are unless there
is no local monograph. This creates problems for us, especially in China.
• I am in a PDG region. Strictly speaking, the above does not apply to my organization
• Adopting standards as a consultant is not difficult.

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• My company routinely implements PDG harmonized standards in the US, Europe and Japan.
• Regulatory differences combines with the difference in publication schedules can be difficult to
manage.
• Regarding this question. Please select your level of agreement with the following factors in
presenting the greatest challenges for developing pharmacopeial standards at your
pharmacopoeia? Not working at a Pharmacopeial body I can't really answer from an internal
perspective however from an outside perspective of the standard setting in general, it seems to
be a non-transparent process from when PF Comments are submitted in general to how/what is
approved regarding final content. Decisions seem to be heavily influenced by pharmacopeial
liaisons with some input from experts via committees and decisions seem less decided by a robust
process and robust "data driven" mechanism.
• As an industry representative, the question above is difficult to answer. I responded based on
implementation by my company as "our organization", with my pharmacopoeia being USP and the
regulatory body being US FDA, based on my geographical location.
• Our company requires use of Reference Standards for daily operation - so we have a formal
program to verify equivalence of USP Reference Standards to secondary standards that are used in
our facilities. We could not manage costs of the amount of USP Reference Standards we would
need to purchase for daily operation.
A cross tabulation was performed between organizational affiliations and views on
whether reference standards within PDG are too costly. As can be seen from Table 33,
the results show mixed views. Most respondents from pharmaceutical industry thought
that reference standards were too costly (agree: 43%, 21/49; neither agree nor disagree:
31%, 15/49; disagree: 27%, 13/49) as did pharmacopeial authority (agree: 43%, 3/7;
neither agree nor disagree: 29%, 2/7; disagree: 29%, 2/7). Respondents from academia
were equally split with 3 selecting agree and 3 selecting neither agree nor disagree.
Respondents from drug regulatory authority were also equally split across agree (33%,
2/6), neither agree nor disagree (33%, 2/6), and disagree (33%, 2/6). In comparison, most
respondents from the trade association selected disagree (50%, 3/6) followed by agree
(33%, 2/6) and neither agree nor disagree (17%, 1/6) whereas 40% (10/25) of
respondents in the other category selected agree, another 40% selected neither agree nor
disagree, and 20% (5/25) selected disagree. Of the five respondents from government

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testing labs, two each selected agree and neither agree nor disagree while one selected
disagree.
Table 33: Cross Tabulation of Organizational Affiliations’ Views on Whether
Reference Standards are too Costly
Organization/company affiliation Reference standards are too costly
Agree Neither agree
nor disagree
Disagree Total N
Pharmaceutical Industry 43%
(21/49)
31%*
(15/49)
27%
(13/49)
100%
49
Other (please specify) 40%
(10/25)
40%
(10/25)
20%
(5/25)
100%
25
Trade Association/Organization 33%
(2/6)
17%
(1/6)
50%
(3/6)
100%
6
Drug Regulatory Authority 33%
(2/6)
33%*
(2/6)
33%
(2/6)
100%
6
Pharmacopeial Authority 43%
(3/7)
29%*
(2/7)
29%
(2/7)
100%
7
OMCL/Government Testing Labs 40%
(2/5)
40%
(2/5)
20%
(1/5)
100%
5
Academia 50%
(3/6)
50%
(3/6)
0%
(0/6)
100%
6
*due to rounding
4.8.3 Should PDG harmonization be modified?
When asked if pharamacopeial harmonization as laid out by PDG should be modified, a
majority of respondents thought that it should be modified (53%, 67/ 127) while 24%
(31/127) had no opinion and 21%, (27/127) thought that it should be kept as is. Only 2%
(2/127) thought that the process should be eliminated (Figure 23).

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Figure 23: Modification of the PDG Harmonization
Thinking of the totality of your experience with PDG to date, pharmacopeial
harmonization as laid out by PDG should be: n=127

A cross tabulation was performed between organizational affiliation for the above results
and whether PDG harmonization should be modified. As can be seen from Table 34,
most respondents across all organizational affiliations felt that PDG harmonization
should be modified. Only one respondent from pharmacopeial authority and another
identified as ‘other’ thought that the process should be eliminated. None from
pharmaceutical industry, drug regulatory authority, trade association, official medicines
control laboratories, or academia thought that the process should be eliminated but a
considerable number (0 - 50%) reported they had no opinion. While none of the
respondents from trade associations or academia thought that the process should be kept
as is, 40% (2/5) from government testing labs thought the process should remain, as did
2% (2)
21% (27)
24% (31)
53% (67)
0 10 20 30 40 50 60 70 80
Eliminated
Kept as is
No opinion
Modified

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30% (3/10) of drug regulatory authority, 23% (13/57) of pharmaceutical industry, 23%
(3/13) of pharmacopeial authority, and 22% (6/27) of other.
Table 34: Cross Tabulation of Organizational Affiliations’ Views on Whether
PDG Harmonization Should be Modified

Organization/company affiliation Should harmonization by PDG be modified?
Kept as is Modified Eliminated No
opinion
Total
N
Pharmaceutical Industry 23%
(13/57)
54%
(31/57)
0%
(0/57)
21%
(12/57)
100%
57
Other (please specify) 22%
(6/27)
44%
(12/27)
0.3%
(1/27)
29%
(8/27)
100%
27
Trade Association/Organization 0%
(0/8)
50%
(4/80
0%
(0/8)
50%
(4/80
100%
8
Drug Regulatory Authority 39%
(3/10)
50%
(5/10)
0%
(0/10)
20%
(2/10)
100%
10
Pharmacopeial Authority 23%
(3/13)
61%
(8/13)
8%
(1/13)
8%
(1/13)
100%
13
Official Medicines Control
Laboratories/Government Testing
Laboratories
40%
(2/5)
60%
(3/5)
0%
(0/5)
0%
(0/5)
100%
5
Academia 0%
(0/7)
57%
(4/7)
0%
(0/7)
43%
(3/7)
100%
7
To understand how the PDG process should be modified, respondents were provided with
seven potential actions and asked to provide their levels of importance. As can be seen in
Table 35 most respondents considered all the actions to be important. The highest
response was received for the statment, simplify the harmonization process (important:
64%, 80/125; somewhat important: 24%, 30/125; not important: 2%, 3/125; don’t know:
10%, 12/125) followed by expanding PDG membership to include more regions
(important: 52%, 66/126; somewhat important; 27%, 34/126; not important: 9%, 11/126;
don’t know: 12%, 15/126); strengthening the linkage between PDG and ICH Q4B
(important: 52%, 63/121; somewhat important: 26%, 32/121; not important: 3%, 4/121;

123
don’t know: 18%, 21/121), increase transparency of PDG's processes and activities
(important: 50%, 63/125; somewhat important: 30%, 38/125; not important: 5%, 6/125;
don’t know: 14%, 18/125), include harmonization topics beyond excipients and general
chapters (important: 48%, 61/126; somewhat important: 28%, 35/126; not important:
10%, 13/126; don’t know: 13%, 17/126); separate harmonization activities of prospective
(new) standards from retrospective (existing) standards (important: 40%, 51/126;
somewhat important: 36%, 45/126; not important: 10%, 12/126; don’t know: 14%,
18/126), provide additional trainings and stakeholder outreach (important: 38%, 47/125;
somewhat important 39%, 49/125; not important: 8%, 10/125; don’t know: 15%, 19/125).
Table 35: Changes in the PDG Process
If you were to modify the PDG process, which of the following changes would you
consider to be important?

Important
Somewhat
important
Not
important
I don't
know
Total
N
1. Simplify the harmonization
process 64% (80) 24% (30) 2% (3) 10% (12) 125
2. Expand PDG membership to
include more regions 52% (66) 27% (34) 9% (11) 12% (15) 126
3. Strengthen the linkage between
PDG and ICH Q4B 52% (63) 26% (32) 3% (4) 18% (22) 121
4. Increase transparency of PDG's
processes and activities 50% (63) 30% (38) 5% (6) 14% (18) 125
5. Include harmonization topics
beyond excipients and general
chapters 48% (61) 28% (35) 10% (13) 13% (17) 126
6. Separate harmonization
activities of prospective (new)
standards from retrospective
(existing) standards 40% (51) 36% (45) 10% (12) 14% (18) 126
7. Provide additional trainings and
stakeholder outreach 38% (47) 39% (49) 8% (10) 15% (19) 125

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4.9 Usage of Pharmacopeial Standards around the World
To understand how frequently other pharmacopeias (outside of PDG region) are being
used, respondents were first asked about their use of WHO’s International Pharmacopeia
and were then provided with a list of national pharmacopieas and asked for their
frequency of use. As can been seen in Figure 24, most respondents (58%, 70/120) use
WHO’s pharmacopeia less than once a year while 28% (34/120) use it 1-10 times per
year and 13% (16/120) use it more than 10 times per year.
Figure 24: Frequency of use of WHO's International Pharmacopeia
Please indicate your frequency of use of WHO’s International Pharmacopeia for your
company/organization? n=120

Results of 15 other pharmacopeias within the WHO member states (British, Chinese,
Indian, Korean, Russian Federation, Ukranian, Croatian, Argentinian, Brazilian,
Mexican, Indonesian, Thailand, Philippines, African, and Eurasian) show that the British
Pharmacopoeia (BP) was most frequently used (high: 30%, 35/117; medium: 38%,

125
45/117; little or none: 32%, 37/117) followed by the Chinese Pharmacopeia (ChP) (high:
32%, 38/117; medium: 21%, 24/117; little or none: 47%, 55/117) and the Indian
Pharmacopeia (IP) (high:15%, 17/112; medium:19%, 21/112; little or none: 66%,
74/112) (Figure 25).
For five of the remaining pharmacopeias, Korea, Russian Federation, Brazil, Mexico, and
Eurasia, respondents reported less frequent use Korean Pharmacopeia (high: 3%, 3/113;
medium:14%, 16/113; little or none: 83%, 94/113), Russian Federation Pharmacopeia,
(high: 5%, 6/114; medium:16%, 18/114; little or none: 79%, 90/114), Brazilian
Pharmacopeia, (high: 7%, 8/112; medium:18%, 20/112; little or none: 75%, 84/112),
Mexican Pharmacopeia (high: 6%, 7/113; medium:16%, 18/113; little or none: 78%,
88/113), Eurasia Pharmacopeia (high:1%, 1/110; medium:15%, 16/110; little or none:
85%, 93/110). The last seven remaining pharmacopeias on the list, Ukrainian, Croatian,
Argentinian, Indonesian, Thailand, Philippines and African, were were least frequently
used: Ukranian Pharmacopeia (high: 2%, 2/112; medium 2%, 2/112; little or none: 96%,
108/112), Croatian Pharmacopeia (high: 2%, 2/116; medium: 5%, 6/116; little or none:
93%, 108/116); Argentinian Pharmacopeia, (high: 3%, 3/112; medium:11%, 12/112; little
or none: 87%, 97/112), Indonesian Pharmacopeia (high:1%, 1/113; medium: 3%, 3/113;
little or none: 96%, 109/113), Thailand Pharmacopeia (high: 3%, 3/117: medium: 4%,
5/117; little or none: 93%, 109/117), Philippian Pharmacopeia (high:1%, 1/112; medium:
3%, 3/112; little or none: 96%, 108/112), African Pharmacopeia (high:1%, 1/111;
medium: 4%, 4/112; little or none: 95%, 107/112).

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Respondents were provided a text box to add “Other” pharmacopeias that were not
included in the list. Their comments have been summarized below Figure 25.
Figure 25: Frequency of use of Other pharmacopeias Beyond USP, Ph. Eur., and
JP
Please indicate your frequency of use of other pharmacopeias listed below (categorized
into national and regional pharmacopeias) for your company/organization? If the
pharmacopeia is not listed, please add it to the "other" field provided. (Please select all
that apply)

127
“Other” (please specify)
• American and European
• Your selections of high/medium/little might not clearly relate level of experience/usage in some of
your questions. For example the classification of "high" usage, I use the BP perhaps once a week
or a bit less, I use WHO maybe once a month, I seek out 'smaller" National Pharmacopeias maybe
once every 18 months. I use the European Pharmacopeia almost daily. However I use the USP
between 5-30 times a day on average if not more. "Super users" vs 10 times a year being viewed as
high usage might reveal different perceptions/understanding.
• You forgot the Canadian Pharmacopeia!! I think we should make the Lunar Pharmacopeia the way
ELon Musk is going:) The British Pharmacopeia is empty shell since it is still mostly been replaced
by the Ph Eur. The other pharmacopeias are also slowly being replaced by the Ph Eur or USP as
well as the ease of drug approvals. The system in Japan is too cumbersome to worry about since
they have several different compendia.
• The EAEU Pharmacopoeia is upcoming I believe
• European Pharmacopoeia - High (>10 times per year)
• United States Pharmacopeia - High (>10 times per year)
• Japanese Pharmaceutical Excipients - High degree of usage.
• Japanese Pharmaceutical Codes - Moderate degree of usage.
• United States Pharmacopoeia (high)
• Kazakhstan Pharmacopoeia (medium)
• Belarussian Pharmacopoeia (none)
• We use USP and EP almost exclusively.
• Since We don't deal with much international pharmacopoeias, my opinion is limited.
• Europe Pharmacopoeia
• European Pharmacopoeia
• European Pharmacopoeia
• USP
• USP
• USP High
• Spanish Pharmacopeia
• Española

4.10 Additional Information or Comments on Pharmacopeial Harmonization
Survey respondents were offered the opportunity to provide additional information and
comments regarding their views on pharmacopeial harmonization that they feel will
contribute to the survey findings. Their comments have been divided into three themes
according to their views on pharmacopeial harmonization: positive, negative, and mixed
(Table 36).

128
Table 36: “Other” comments regarding views on Pharmacopeial harmonization
In the space provided below, please feel free to provide any additional information or
comments that you feel will contribute to my understanding of your views on
pharmacopeial harmonization.
Positive:
Pharmacopeial harmonization is a very important goal and is valuable to regulators. It permits greater
and more efficient collaboration among regulators of different geographical jurisdictions and permits
these entities to share their regulatory inspection burdens, contributing to more efficient regulation
and economy of operation. In our present world of multi-national drug manufacturing and marketing,
the importance of pharmacopeial harmonization cannot be overstated.
More frequently discussion between Experts, Scientific Liaisons and Regulators in each region should
be beneficial.
The ultimate goal of harmonization would be the inclusion of all pharmacopoeias, but this must be
balanced with the realization that this would take a considerable amount of time. Adapt/adopt with
PDG may be more realistic approach for the national/regional pharmacopoeias outside of PDG. In
addition, any harmonization of any kind must be accepted/adopted by the regulatory authorities in the
country/region, otherwise harmonization is futile.
Undoubtedly very difficult to introduce retrospectively, but harmonization of common test methods
such as those in USP <401> would be an enormous advance.
It will be very beneficial; however, can be a long and challenging process.
Very important to expand harmonization within the current PDG members and also with the larger
emerging markets. Continuing globalization of the pharmaceutical industry and the industries that
support them require scientifically sound collaboration to streamline the regulatory and quality/safety
processes for drugs and drug components.
Harmonization is great; the PDG should be expanded to include more general chapters and
monographs, including monographs for other items - not just excipients. The PDG should also consider
expanding to include the Indian Pharmacopeia.
Harmonization is very important, but it must allow for flexibility to adapt to local regulations, practices,
etc.
Pharmacopeial Harmonization has great advantages for content users to drive efficiency in providing
medicine to customers.
I believe that the current high level of collaboration among pharmacopoeias, through international
meetings, bilateral meetings, MOUs and GPhPs, is unprecedented and is to be commended. This
environment should be maintained/ strengthened to enable the long-term benefits of pharmacopoeia
harmonization to be achieved as quickly and practically as possible. The legacy of this accomplishment -
global standards in the pharmacopoeias - for now and for future patients in our global world deserves
the focus and effort.
In my view the harmonization is essential in the current context of globalization. API monographs are
seldom harmonized and only partially. I am especially deceived when some "harmonized" monographs
are revised and then become "unharmonized". The "harmonized monographs" are normally so
because they originated in the same sponsor, not by actual prospective harmonization or because one
pharmacopoeia used another one to get "inspiration".
Although as a trade organization I do not engage with or in specific activities outlined in this survey, I
do receive comments and feedback from our member companies. This said there is always benefit
when global regulatory bodies are able to harmonize their processes to remove redundancies and
burden that adds no scientific value to the review and approval of a drug product. As our members are

129
increasingly becoming more global in resourcing of raw materials and further downstream, the
marketing of the finished product, a more unified and singular standard minimizes overall cost. This
translates into savings for the end user, the patient, to ensure affordable medicines are available for
the treatment and possible cure of disease(s). Further the more streamlined and transparent a process
can be refined, the better the outcome for compliance. If the expectations are clear and concise and
also harmonized from one regulatory body to another, the easier for global sponsors to remove
unnecessary and possibly unethical testing.
Negative:
Absolute harmonization has not been successful; the process is painfully slow to an extreme, almost to
the point of being pointless. Rather than trying for a perfect alignment could the core characteristics be
harmonized and then regional differences added as a local annex? At least this would reduce the
testing burden by a significant amount to the benefit of all.
I think the ChP has become a force to be dealt with. The 2015 version caused a lot of problems. They
are very far out of alignment with other pharmacopeias in many areas. They seem to have no clear
process for input or revision. They seem to be driving toward "higher purity" without regard for if it's
really necessary or not. It will be difficult to harmonize with them if they cannot agree on a process
and engage in interactive dialog.
Harmonization should not try to reach agreement on every last detail within a monograph. However,
harmonization by attribute is not effective either. The goal should be to be able to achieve equivalent
results and to have robust methods for critical quality or safety attributes and leave the rest to makers
and users.
From what I have observed in harmonization activities between JP, EP, and USP, each pharmacopoeia
shows little willingness to compromise on points of difference
My experience has involved expert committee work for USP and attendance at one PDG meeting. The
major problem is the glacial speed at which changes are made and the frustration with making updates
to harmonized chapters.
Over 10 years ago we started a regional effort for "Harmonization of Pharmacopeias of the Americas"
among the US-Mexican-Argentinian-Brazilian Pharmacopeias. However, the differences in timing,
process, and capabilities/resources did not allow us to accomplish our goals. Also, we were waiting for
the PDG harmonized standards and the conclusion was that there was no advantage in duplicating
efforts.
The PDG process is horrendous and bureaucratic and should be scrapped. There should be one
pharmacopeia- under WHO
The process takes too long. It is a function of resource allocation and agreement on the standard.
Getting the words exactly right is also an issue. As long as in the end the tests are executed the same
way and one gets the same result with the same acceptance criteria, slight variations in the wording
should not be haggled over. Need to decide how much of a procedure needs to be harmonized. pH is
a good example. How important is the lack of agreement on the calibration of the instrument to the
final result?
Mixed:
It is critical that the PDG be expanded to include other major market pharmacopeias such as the
Chinese, Indian and Brazilian Pharmacopeias. These markets are becoming as important as the US,
Europe and Japan and if they are not included in harmonization efforts, the work the PDG is doing will
become increasingly less relevant to industry.

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Since the level of scientists and regulatory authority are different among countries, the expansion of
harmonization should be carefully considered.
Harmonization has its own challenges and needs government support in addition to other stake
holders. Political climate also plays an important role for harmonization. Harmonization to be
expedited for regulatory compliance guidelines too for making Pharmacopoeial harmonization
effective.
The communication between experts in the 3 PDG countries is very constricted with little to no direct
interaction between collaborating teams from the participating countries. Paradoxically a sizable part
of the time is spent trying to not think or come back from thinking the other guys are stupid, boorish or
both. It's like neighbors you never really see, that live right next door, and you start making up stories
to try to make sense of what little signals you do get. It's very easy to think "They have bad intent"
Having worked in general chapters harmonization and currently working in other general chapters
harmonization, I feel that direct communication between scientist of included pharmacopeias (USP-EP-
JP) should be possible, at least a couple of times before the harmonization is signed at that level,
especially when a high impact chapter is discussed. We receive letters and respond with more letters,
generally without any contacts. And unfortunately (talking about my experience), modifications even
small but necessary are difficult to be done in harmonized chapters. Evolution, which is faster and
faster nowadays, will be very difficult to be included in rigid environments. I believe that apart from
harmonization, there should be a periodic revision (yearly or each two years) to make corrections and
improvements.
Pharmacopeial harmonization is nice to have, but it's not critical.
Functional testing to be included for all excipients. For co-processed excipients, the testing and
specifications shall be made stringent. For polymers, the limits for material attributes are overlapping
and need differentiation between specific grades. Based on dosage form, the physical attributes need can
be spelled out. (eg: BD & PSD are important for solid orals but not for liquids/Injectables).
4.11 Future Survey Participation
Respondents were asked to indicate if they wished to receive a copy of the completed
survey and if they would be open to discussing their feedback for the purpose of
informing this study. A majority wished to receive the survey results and most agreed to
discuss their feedback (Table 37).
Table 37: Request for Results Summary
Yes No Total N
Would you like to receive a summary of the survey
results when I complete my study?
76%
(89/117)
24%
(28/117)
100%
117
Would you be open to discussing your feedback for
the purpose of informing this study?
55%
(64/117)
45%
(53/117)
100%
117

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CHAPTER 5. DISCUSSION
5.1 Global Harmonization of Pharmacopeial Standards
The purpose of this study was to explore the views and needs of key stakeholder
categories on the importance and challenges of achieving harmonization of
pharmacopeial standards and practices across different regulatory jurisdictions, the
effectiveness of existing levels of collaboration and transparency, the efficiency of
harmonization efforts, and the work conducted by PDG. The study also sought to
understand why efforts to harmonize pharmacopeial standards globally have produced
limited results to date. The current harmonization efforts have been criticized in the
literature for being burdensome, lengthy, and inefficient (Wiggins & Schneider, 2012;
PDA, 2018; International Pharmaceutical Quality Newsletter, 2019). For this study, I
developed a research framework adopted from Samaras (Samaras & Samaras, 2012),
which identifies four categories of needs, Collaboration and Relationships building,
Resources, Regulatory acceptance, and Standardized pharmacopeial practices, to explore
as areas of challenges in the development, implementation, and enforcement of standards
across pharmacopeias and regulatory regions.
5.2 Methodological Considerations
Survey participants were delimited to members of the three key stakeholder categories
(real stakeholder, stakekeeper, and stakewatcher), described in Chapter 2, who should be
familiar with pharmacopeial standards and the challenges associated with harmonization.
The participants were further delimited to subject matter experts (SMEs) within these
stakeholder categories who had direct experience with pharmacopeial harmonization and

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were drawn from the pharmaceutical industry, drug substance and excipient industry,
pharmacopeias, government, academia, and trade associations across multiple geographic
regions. This was accomplished by making the survey accessible only to those that had
accepted the invitation to receive the survey link. A limitation in the selection of survey
participants was the challenge of assuring that the sampled population accurately reflects
the views of the three key stakeholders as a whole. It is impossible to identify all of the
individuals who would be appropriate for such a survey. Although this approach may
have introduced bias due to the possibility that the participants might be like-minded
individuals who are similarly influenced by similar meetings, trainings and workshops,
the highly experienced respondents provided differing perspectives and insights into
various aspects of pharmacopeial harmonization. Among the respondents were those who
had considerable experience across a diversity of pharmacopeias, geographical regions,
and industry affiliations, which helps in allaying any potential concern that the survey
results do not adequately reflect the views of a broader stakeholder population. Because
most respondents were at a director/manager or specialist/scientist level, they are likely to
be experienced working with pharmacopeial standards and familiar with the
harmonization activities. Furthermore, they would likely be experienced in interacting
with both internal and external stakeholders, including regulatory bodies, pharmacopeial
bodies, pioneer and generic manufacturers, ingredient manufacturers, as well as contract
and government laboratories and academia.
Another delimitation was the number of questions presented to survey respondents. In
limiting the number of questions, certain topics might not have been fully explored and

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this in turn might have constrained the analysis. To address this, a focus group was
created to critique and help construct the survey and it provided valuable input from
various perspectives. This step was helpful but could not guarantee that all questions
would be useful or that important questions would not be missed.
This study was further delimited to a specific period of time. Whether the views
expressed here will be the same views held by respondents in a few years is open to
question. The subject of pharmacopeial harmonization is currently under active
discussion by various stakeholder groups and those discussions could result in changes to
the current process. For example, PDG has recently announced its plans to change its
process to improve efficiency (United States Pharmacopeia, 2018). The PDG may also
modify its membership to address criticism for not including other major pharmacopeias
like those of China and India similar to ICH that went through major reforms in 2017.
A major concern for this study was the potential for a low response rate that could have
limited its utility. Although some of the stakeholder categories responses like
stakewatcher and stakekeeper were low and not balanced in size compared to real
stakeholder, cross tabulation across organizational affilitation was performed as it may be
helpful to identify any noticeable differences on certain topics discussed in the survey
questions that can be explored further in future studies (Trotter, 2012). The small
numbers in some of the categories may indicate that the number of appropriately
experienced individuals currently working with pharmacopeial standards may be limited
(Figure 12). It is of course important to delimit the sample to appropriately experienced
individuals as was done and discussed above, but it was impossible to require them to

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complete the survey. However, the level of engagement of respondents who began the
survey was high. The majority of respondents who started the survey continued to the
end, and in fact, put a lot of effort into giving detailed comments in the text boxes
provided.
For respondents who agreed to participate, my concern was that a lengthy survey could
lead to a high percentage of incomplete surveys. Indeed, even with only 33 questions,
some respondents did not answer every question. This may have been due to time
limitations as many respondents chose to provide optional text responses in addition to
multiple-choice answers, in which case the survey would have taken longer than
originally intended. In some instances, an incomplete survey may reflect a respondent’s
lack of knowledge on a particular section of a question.
The ability of each question to probe the needs, views, and experience of the respondent
may have been limited by the way in which the questions were worded. For example, the
question regarding the frequency of use of pharmacopeias by a company/organization
provided possible selections of high level (>10 times per year), little or none (<1 time
/year), and medium (1-10 times per year). But this wording, in hindsight, may have been
too restrictive. For example, one respondent’s comments revealed that the frequency of
use can vary greatly depending on the specific pharmacopeia. For this responder, the
frequency of use of BP was around once a week, WHO once a month, ‘smaller’ National
Pharmacopeias once every 18 months, the European Pharmacopeia almost daily, and
USP between 5-30 times a day on average, if not more. The suggestion to add a "Super

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users" category instead of restricting to > 10 times a year as indicative of high usage may
be a better approach for future studies.
Another concern initially was that the respondents may be from a limited geographic area
and thereby bias the results towards the limited views of respondents that do not represent
those of a more broader group of stakeholders from pharmacopeias, regulators,
pharmaceutical industry, trade associations and other organizations around the world.
However, the results indicate that the survey reached a global pool of respondents
including individuals from Africa, the Americas (North and South), Asia, Europe and
Oceania, with a wide range of experiences across different sectors including
manufacturers, contract research/manufacturing organizations, academia, pharmacopeial
bodies, and regulatory bodies. The profiles of respondents clearly show that the survey
targeted the intended population of experts and provides assurance that the study results
are thus likely to be representative of the broader stakeholder population engaged in
pharmacopeial harmonization.
5.3 Consideration of Results
The primary goal of this study, to explore key stakeholder views and needs on the current
state of global harmonization, was driven by the observations as reported in the literature
and through personal experience that a lack of harmonized pharmacopeial standards has
created many challenges in the quality control of medicines and their regulation. The
findings from this study are descriptive and qualitative in nature as there is insufficient
delineation at this point across the three key stakeholder groups (Real Stakeholder,
Stakekeeper and Stakewatcher) to make quantitative comparisons. The findings reveal

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two general themes: a) lack of collaboration and relationship building and b) challenges
facing pharmacopeias due to disparities in pharmacopeial practices, regulatory
acceptance, and resources across different regulatory jurisdictions. The results suggest
that stakeholders view these factors as key contributors to the slow rate of progress
towards harmonization of pharmacopeial standards and practices. These findings
reinforce some other published findings (Wiggins & Schneider, 2012; PDA, 2018;
International Pharmaceutical Quality Newsletter, 2019) but also provide further insights.
For selected questions, a series of cross tabulations was performed to explore the
differences across organizational affiliations for the two themes described above in
addition to the views on pharmacopeial authorities and PDG (Chapter 4 and Appendix
A). However, for cross tabulation results, the number of respondents for both
stakewatcher and stakekeeper groups were low compared to the real stakeholder group,
thus making is difficult to draw conclusions.
5.3.1 Views on Harmonization
According to Wiggins, there are approximately 36 pharmacopeias published around the
world (WHO, 2018; International Pharmaceutical Quality Newsletter, 2019). Naturally,
this makes pharmacopeial harmonization a very difficult task to achieve. The findings
from this study indicate that stakeholders across all organizational affiliations view
pharmacopeial harmonization as being very important and urgent. However, despite the
overwhelming support from key stakeholders as to the importance and urgency of
pharmacopeial harmonization, little progress has been made thus far. According to the
results, we also see that a majority of respondents agreed with key objectives of global

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harmonization: to provide harmonized standards with the same accept/reject decision,
facilitate recognition of standards between regulatory bodies, and reduce the compendial
tesing burden (Table 11). The text comments below provide further insights into how
stakeholders view pharmacopeial harmonization:
Pharmacopeial harmonization is a very important goal and is valuable to
regulators. It permits greater and more efficient collaboration among regulators
of different geographical jurisdictions and permits these entities to share their
regulatory inspection burdens, contributing to more efficient regulation and
economy of operation. In our present world of multi-national drug manufacturing
and marketing, the importance of pharmacopeial harmonization cannot be
overstated.
..the current high level of collaboration among pharmacopoeias, through
international meetings, bilateral meetings, MOUs and GPhPs is unprecedented
and is to be commended. This environment should be maintained/ strengthened to
enable the long-term benefits of pharmacopoeia harmonization to be achieved as
quickly and practically as possible.
It is fundamentally important to enable medicines with consistent quality to be
available to all patients around the world, based on a harmonized pharmacopoeia
standard.
As our (trade association) members are increasingly becoming more global in
resourcing of raw materials and further downstream, the marketing of the
finished product, a more unified and singular standard minimizes overall cost.
..harmonization brings coherence to the standards…so make more sense to have
an aligned standard among different pharmacopeia and not having so different
requirements
It is also clear from some text comments that some of the stakeholders had negative
views on the current harmonization efforts:
The PDG process is horrendous and bureaucratic and should be scrapped. There
should be one pharmacopeia- under WHO
The process takes too long.

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The major problem is the glacial speed at which changes are made and the
frustration with making updates to harmonized chapters.
The results of this study indicate that key stakeholders consider global pharmacopeial
harmonization as important in maintaining alignment between harmonized standards
(Table 12). These observations are consistent with views expressed in the literature by
Wiggins et al.:
..alignment between the pharmacopeias is essential to facilitate adoption of
standards between regulatory bodies and if industry is compelled to meet
conflicting pharmacopeial and regulatory requirements, drug product availability
may be jeopardized and costs may be increased without benefit (Wiggins et al.,
2008).
As described in Chapter 2, meeting different pharmacopeial requirements is quite
challenging. With many regions having their own pharmacopeias, each manufacturer is
required to conduct additional testing to meet the individual requirements for each
jurisdiction where its products are to be distributed (Bhattacharyya, 2004). Since PDG
could not successfully accomplish ICH’s original ask for 100% harmonization of each
standard it had to provide the process of ‘harmonization by attribute’ or partial
harmonization. Some of the survey comments appear to support PDG’s revised approach:
Harmonization should not try to reach agreement on every last detail within a
monograph. However, harmonization by attribute is not effective either. The goal
should be to be able to achieve equivalent results and to have robust methods for
critical quality or safety attributes and leave the rest to makers and users.
Absolute harmonization has not been successful; the process is painfully slow to
an extreme, almost to the point of being pointless. Rather than trying for a perfect
alignment could the core characteristics be harmonized and then regional
differences added as a local annex? At least this would reduce the testing burden
by a significant amount to the benefit of all.

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Because pharmacopeial standards are integral to the quality aspects of pharmaceutical
manufacturing, ICH and PDG activities are interdependent. As such, certain ICH
guidelines are dependent on PDG’s output and, in fact, refer to the PDG’s harmonization
efforts:
The full utility of this Guideline is dependent on the successful completion of
harmonization of pharmacopoeial procedures for several attributes commonly
considered in the specification for new drug substances or new drug products.
The Pharmacopoeial Discussion Group (PDG) of the European Pharmacopoeia,
the Japanese Pharmacopoeia, and the United States Pharmacopeia has expressed
a commitment to achieving harmonization of the procedures in a timely fashion
(ICH, 1999).
Hence, not being able to achieve pharmacopeial harmonization in a timely and efficient
manner has broader implications. Although worksharing and adoption of standards
between pharmacopeial bodies would be one possible solution in facilitating
pharmacopieal harmonization in a timely way, the findings from this study indicate that
collaborations across most pharmacopeias are not occurring at a high level. According to
WHO, complete pharmacopeial harmonization is only possible once regulatory systems
have also been harmonized and that:
convergence and continued collaboration among pharmacopoeial committees and
regulators, together with industry interaction, will assist in facing new challenges
and resource constraints (WHO, 2013b).
Survey comments also showed alignment with published literature:
Preparation of regulatory documents in the ICH CTD format can improve the
review process if more global harmonized quality standards are available and
accepted by regulatory authorities.
….Harmonized testing methods and pharmacopeial standards helps generic drug
industry to a greater extent with respect to 1. Can have better inventory control of

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materials (APIs and Excipients) 2. One specification and testing method for
different pharmacopoeia 3. Reduces cost of analysis pharmacopoeia wise 4.
Reduces cost maintaining pharmacopoeia wise reference standards ......
What remains to be understood is how to reduce the pharmacopeial testing burden for
stakeholders in performing redundant testing and facilitate recognition of standards
between regulatory bodies. A possible solution that has been under discussion within
WHO’s IMWP is to build upon the approach of pursuing convergence of pharmacopeial
standards whereby all pharmacopeias would collaborate towards alignment on a common
approach to establishing quality standards and practices.
However, with a formal harmonization process that exists only across 3 pharmacopeias of
PDG out of 36 existing pharmacopeias, the process is not inclusive. As a result, many
jurisdictions require stakeholders to carry the added burden of compliance with the local
pharmacopeial standard (Bhattacharyya, 2004; Shaheen, 2003). Clearly, better
mechanisms to more efficiently align standards and requirements are urgently needed.
Similar to how ICH has engaged regulatory organizations such as International
Pharmaceutical Regulators Programme (IPRP) in buiding training sessions for regulatory
bodies for implementation of quality guidances, ICH could engage pharmacopeias and
the WHO’s IMWP in developing training on the implementation and adoption of high
use ICH guidances relating to pharmacopeial specifications and pharmacopeial chapters
listed in the ICH Q4B annexes for newly added ICH members (IPRP, 2019).
5.3.2 Views on Collaboration and Relationship building
The existing literature discussed the important benefits of harmonized pharmacopeial
standards and their ability to streamline regulatory compliance. The results of this study

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indicate that stakeholders across different organizational affiliations view the benefits of
collaboration as important in facilitating the adoption and alignment of pharmacopeial
standards between regulatory and pharmacopeial bodies (Table 13). These findings are
consistent with those described in the literature:
when standards published by the pharmacopeais are not aligned, the differences
increase the cost and complexity of compliance, and may hinder the export and
import of products between China and Europe, creating uncertainty in the supply
of medicinesto the patients who need them (Compendial Joint Industry Group,
2017).
Survey findings also indicate that stakeholders felt that important benefits of
collaboration were, sharing expertise and resources and a need to developing solutions
that can be adopted broadly. Despite these views, collaboration among different
pharmacopeias is not adequate including in the areas of engaging stakeholders, promoting
work-sharing activities, establishing communication channels, and promoting
transparency. However, as described in Chapter 2 and in the literature, many
pharmacopeias are not yet willing or cannot commit to actively collaborating on
harmonization activities. As a result, industry is burdened with having to comply with
individual national or regional pharmacopeial standards, regulations and laws that pose
limitations as described below by Wiggins & Schneider:
There is an increased need for consistent and appropriate quality requirements
for medicines because disharmonized standards do not provide additional value
or benefit, but rather increase the cost and complexity of bringing medicines to
patients worldwide (Wiggins & Schneider, 2012).
Regulatory bodies could facilitate the pharmacopeial harmonization process by
collaborating directly with pharmacopeial bodies to develop training programs on the

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implementation and adoption of pharmacopeial standards as the US FDA has done in
recent years by issuing guidances on Analytical Procedures and Methods Validation for
Drugs and Biologic and policy on Acceptability of Standards from Alternative
Compendia (FDA 2017; 2015a). Stakeholder alignment on the need for a common
approach to harmonization of standards will also help global regulators. The text
comment below from the survey points to a desire for a pragmatic but scientific approach
to developing standards:
The collaboration should result in the best scientifically justified limits and
methods developed that are needed to provide appropriate control without going
overboard and developing standards that are not based primarily on what is
needed for the safe use of the material.
In the long term, more effort is needed from both pharmacopeial and regulatory bodies to
support and facilitate alignment of standards between pharmacopeias, which will be key
to reducing the industry testing burden. There has been some progress in satisfying the
need for global collaboration. For example, ICH Q4B Expert Working Group was
successful in determining interchangeability of 15 general test chapters (annexes) for
purposes of pharmaceutical registration, approval and compliance testing (ICH, 2007).
While only 15 annexes are currently declared as interchangeable by ICH Q4B, their work
has the potential to be adopted more broadly by the newly reformed and expanded ICH
membership and should be considered one of the possible discussion topics and training
opportunities during future ICH meetings. What remains to be seen is whether ICH, in its
new organizational structure, still values the work of ICH Q4B and will increase its
global efforts to expand its current workplan. Also, efforts should be made between PDG
and ICH members participating in ICH Q4B activities to promote stronger

143
collaboration. The following text comments provide additional insights related to
collaboration:
Getting the pharmacopeia to want to actively harmonize is a first step that is
lacking in many regions.
Communication between the pharmacopeias does not appear to be very good and
also the involvement of industry should take place earlier in the process in a very
open way, not just after the pharmacopeias have already drafted what they want
in a monograph. Industry should be involved BEFORE anything is drafted to get
their thoughts as to what makes sense.
Collaborating with Industry and their practices, procedures shall be assessed.

5.3.3 Global Challenges in Standardized Pharmacopeial Practices and Regulatory
Acceptance
Survey results suggested that adopting and implementing standardized pharmacopeial
practices was challenging because of a lack of a common approach to developing global
specifications and the difficulties in maintaining alignment between different
pharmacopeial harmonized standards (Table 19). A good example of a challenge
described in the current literature is that of the 2015 edition of the ChP. ChP introduced
several new and revised standards that were not harmonized with but instead different to
other pharmacopeias, including those within PDG (Compendial Joint Industry Group,
2017). As a result, the 2015 edition of ChP created major challenges for industry
stakeholders as described in Chapter 2. Text comments in the survey also supported the
findings in the literature and provide further insight:
The 2015 version caused a lot of problems. They are very far out of alignment
with other pharmacopeias in many areas. They seem to have no clear process for
input or revision….. It will be difficult to harmonize with them if they cannot
agree on a process and engage in interactive dialog.

144
Serious consideration should be given to including the Chinese Pharmacopoeia
as a member of the PDG.
Pharmacopoeias such as the ChP are difficult to work with since their approach
is not flexible and not as transparent as the USP.

As ChP is currently not a PDG member, an urgent need for a higher level of stakeholder
engagement and collaboration to achieve alignment between PDG and ChP standards
should be further considered.
Much has been written about the importance and benefits of establishing good
pharmacopeial practices (GPhP). The obvious benefits for implementing GPhP are, the
ease of recognition of harmonized standards by different regulatory bodies, helps
promote collaboration and work sharing with regional/national pharmacopeias and fosters
interactions with stakeholders (WHO, 2013b, 2016). In this study, a majority of
respondents agreed with the importance of adopting Good Pharmacopeial Practices
(GPhP) in developing harmonized standards (Table 19). This response was similar across
all organizations and is consistent with the literature (International Pharmaceutical
Quality Newsletter, 2019). But the respondents also found implementing WHO's Good
Pharmacopeial Practices Guidance (GPP) to be challenging (Table 20) and
pharmaceopeial bodies are not using GPhP as much as other references (Figure 19).
Hence, what remains to be seen is how pharmacopeial bodies will successfully
implement GPhP in their efforts to produce globally harmonized standards efficiently and
collaboratively. Such will be a difficult task to accomplish given the differences existing
between pharmacopeias and levels of available resources (WHO, 2016). These
differences include the use of technology reflected in each pharmacopeia as well as the

145
breadth of medicines covered by each pharmacopeia (WHO, 2016). Given these
differences, some pharmacopeias may be unable, for example, to work together on
standards that would be outside their scope or resource capabilities. A possible solution is
to pursue the WHO IMWP’s desire to collaborate with all stakeholders on pharmacopeial
convergence towards a common approach to developing standards and practices.
Study results suggested that implementing ICH quality guidelines was also viewed as
challenging (Table 19 & 21). As mentioned earlier, some pharmacopeias may not have
the resources and be capable of implementing ICH quality guidances relating to
pharmacopeial standard setting such as ICH Q2, 3, 4, and 6. This will pose challenges for
some pharmacopeias in their efforts to standardize and align practices as outlined by
GPhP in developing and validating test methods and acceptance criteria.
Study results showed that disparate regulatory/legal requirements existing for different
pharmacopeias were challenging in developing harmonized standards (Table 22). Given
the literature, it is not surprising that the majority of respondents viewed disparate
regulatory/legal requirements as challenging. DeStefano and Moore describes that
differences in the regulatory and legal requirements of each country can make
pharmacopeial harmonization difficult, or even impossible (DeStefano & Moore, 2012).
The text comments further shed light on their concerns:
Pharmacopoeias are regulations in some settings but not in all. This makes
change very difficult.
Diverse scientific opinions and disparate regulatory/legal requirements in
different regions are the biggest obstacles to global harmonization

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Different impact and resources of pharmacopeias (e.g., regional vs country)

On the subject of greatest challenges for pharmacopeias in developing pharmacopeial
standards in areas including the lack of adequate collaboration on work-sharing activities
(Table 25), adequate scientific resources, and lack of ability to develop reference
material standards, the results suggested that stakeholders felt there was a lack of
collaboration but adequate resources. A cross tabulation performed across organizational
affiliations on lack of adequate scientific resources suggested mixed views as most
respondents representing the real stakeholder category, disagreed; stakewatcher category,
neither agree nor disagree; and stakekeeper category, agreed (Table 26). Similarly, for
lack of ability to develop reference material standards, cross tabulation results suggested
that most respondents representing the real stakeholder category, neither agree nor
disagree; stakewatcher category, mixed views, and stakekeeper category, mostly
disagreed (Table 27). The text comments provide additional concerns:
Products long-standing in the market without problems may set a standard of
quality difficult to change. Lack of reference standards in some countries to test
suitability of analytical procedures may also set limits for harmonization.

However, for these cross tabulation results, the number of respondents for both
stakewatcher and stakekeeper groups were low compared to the real stakeholder group
thus making is difficult to draw conclusions.
The purpose of all pharmaceutical regulations is to ensure the quality, safety and efficacy
of medicines in the supply chain, thereby ensuring patient safety and well being. As such,

147
pharmacopeial standards should include only those tests necessary (reducing the testing
burden) to ensure quality and safety of medicines and their components in a global supply
chain. While a great deal of commonality in regulatory approaches likely already exists,
perhaps where differences exist, regulators should play a more collaborative role in
global pharmacopeial harmonization and endeavor to find ways to ensure a uniform
global regulatory approach. For example, some drug regulators are also taking a similar
approach in their efforts to achieve convergence for new drug marketing application
(NDA) requirements, as its focus is on converging pharmacopeial requirements in order
to simplify global harmonization of pharmacopeial standards (Sandler, 2018). It remains
to be seen whether pharmacopeial bodies can follow their lead, but whatever the
approach ultimately agreed upon, it should be a more collaborative, inclusive, and
provide a more efficient way of producing harmonized standards that are interchangeable
and acceptable between regulatory bodies. Given the challenges faced by key
stakeholders in complying with legal and regulatory requirements in different
jurisdictions, the approach put forward by WHO’s IMWP members on convergence
towards common standards and practices should continue to be pursued.
5.3.4 Views on Pharmacopeial Authorities
The survey results indicate that pharmacopieal authorities generally view their efforts at
engaging with stakeholders, transparency in their public inquiry/comment process and
scientific resources in a positive light (Table 28). However, the survey findings from the
pharmacopeias do not reflect the challenges found in the literature that highlights the
inability of industry to provide timely input on proposed revisions expressed through

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EFPIA comments submitted during the 2017 Compendial Joint Industry Group meeting.
The EFPIA encouraged the Chinese Pharmacopoeial Commission to increase availability
of its publications to users outside of China, preferably in English, in electronic format,
with a six month implementation time. If this could be done, it would facilitate
compliance by multi-national companies by maximizing the time available for
assessment and implementation of changes (Compendial Joint Industry Group, 2017).
This activity would foster improved relationships between the three key stakeholder
categories. A survey comment also suggested that a longer implementation period might
be appropriate for major changes, e.g. general chapters with significant impact. If this
type of engagement was pursued, there is a potential that it would reduce stakeholder
challenges with the public inquiry process and facilitate easier access to proposed
changes. This could allow industry the chance to provide feedback and better prepare for
implementation of these changes once changes are official. However, survey comments
are reflective of the concerns found in the literature, most likely to include views of the
other two key stakeholders, real stakeholders and stakewatchers:
Other Pharmacopoeias such as the ChP are difficult to work with since their
approach is not flexible and not as transparent as the USP.
Different languages and availability of a translation.
Regulatory differences combines with the difference in publication schedules can
be difficult to manage.
5.3.5 Pharmacopeial Discussion Group
Although some respondents in this study agree that pharmacopeias collaborate well in
certain arenas, such as in PDG (USP, EP, JP), most viewed the level of collaboration

149
among different pharmacopieas as inadequate. Many have written about the importance
of Pharmacopeial Discussion Group (PDG) and its efforts to harmonize pharmacopieal
standards (Keitel, 2013; Liu, Moore & Sheehan, 2017). Although PDG has limited results
in successful harmonization of standards, it is clear from this study that their work is
appreciated and utilized. The following survey comments reveal similar finding in this
study:
….it is still a very valuable function and is currently the only path available for
harmonization across multiple compendia.
Despite the fact that the PDG process is very slow, "Does not develop standards
in a timely manner", it is still a very valuable function and is currently the only
path available for harmonization across multiple compendia.
Although timeliness of developing harmonized standards has been slow, the
dedication and commitment by the PDG partners to still work toward a
harmonized outcome is apparent and commendable.

Overall, the use of standards developed by individual jurisdictions that form PDG was
high; the highest frequencies of use (high >10 times/year) were observed for USP: 80%
(97/120) followed by 51% (61/119) for Ph. Eur. followed by 35% (42/120) for JP.
The study results suggested that a majority of repondents were satisfied that PDG
performs well in certain areas. The survey results suggested that there are still challenges
with alignment of pharmacopeial standards, reducing the testing burden, and transparency
in public inquiry/comment processes (Table 28). The survey results also indicated that
there are still challenges with timely access to proposed and revised standards,

150
engagement of stakeholders, and developing standards in a timely manner (Table 29).
The text comments further supported these concerns:
Submission times should align with the weight of the change. A standard 90 day
time period is helpful for planning staffing and review expectations but does not
align with concept of shifting staffing resources as needed for higher priority
items in some situations.

Overall, the survey results showed that most respondents agree that PDG standards are
helpful to their work, but thought there was a need for the process to be modified,
simplified, inclusive and transparent. At the same time, text comments show that some
respondents disagree:
From what I have observed in harmonization activities between JP, EP, and USP,
each pharmacopoeia shows little willingness to compromise on points of
difference
The PDG is an outdated model for compendial harmonization because they will
not allow participation by other pharmacopeia. They are also not open to
industry input which could significantly reduce the time it takes to develop
harmonized methods and specifications.

Perhaps, a good way forward to address some of the concerns raised may be to further
engage members of WHO’s IMWP to assist with communication of proposed PDG
proposed revisions to all 36 WHO member pharmacopieas. IMWP could help obtain
broad input from all concerned pharmacopeial stakeholders early in the PDG standards
setting process to ensure their timely involvement. IMWP could also collaborate with
both PDG and ICH to gain further input and alignment on ways to facilitate education on
and implementation of GPhP building a foundation towards a common approach to

151
developing pharmacopeial standards and practices. Both these efforts could facilite
alignment on standards by key stakeholders.
5.3.6 Usage of Pharmacopeial Standards around the World
It was interesting to see the usage of pharmacopeias around the world beyond those of
PDG. Most respondents use WHO’s International pharmacopeia less than once a year.
From a list of 15 national pharmacopeias, the British Pharmacopoeia (BP) was most
frequently used followed by the Chinese Pharmacopeia (ChP) and the Indian
Pharmacopeia (IP).
5.4 Conclusions and Future Directions
The results of this survey provided the views and needs of key stakeholders on factors
that impact global harmonization of pharmacopeial standards. The responses suggested
that achieving pharmacopeial harmonization is still viewed by key stakeholders as being
very important and urgent in establishing standards and reducing the testing, regulatory
and legal burdens. The survey results also suggested that a lack of collaboration and
transparency across pharmacopeias creates challenges in efforts towards pharmacopeial
harmonization and agreement towards development and implementation of a common
standard and pharmacopeial practices. The survey also indicated that identifying ways to
address industry dissatisfaction with the time it takes to develop standards, provide a
more transparent public inquiry and a more flexible stakeholder - friendly comment
processes in standards setting activities are other areas which need further consideration
and alignment.

152
The survey results also suggested that pharmacopeias collaborate well in certain arenas,
such as the work carried out by PDG. Although PDG has limited results in terms of the
number of successfully harmonized standards, it is clear from this study that their work is
appreciated and utilized. However, the survey results indicated that PDG harmonization
efforts need to be more inclusive, transparent, efficient and its scope of work modified
and expanded. Since the results from the survey highlighted the ever increasing number
of challenges faced by key stakeholders with regard to development and implementation
of common pharmacopeial standards and practices in different regulatory regions, it may
be helpful to identify a more simplified approach such as convergence towards a common
quality standard and practices in order to achieve alignment between different
pharmacopeial standards and their regulatory authorities. One approach is for members of
WHO’s IMWP, PDG, and ICH to collaborate more and establish training programs for
implementing the GPhP and ICH pharmacopeial related guidances. As this can be a huge
resource burden for some stakeholders, identifying and adopting mechanisms to
collaborate on establishing formalized trainings and work-sharing activities will be an
important step towards achieving global harmonization. In doing so, more progress could
be made towards global alignment of pharmacopeial standards which could help facilitate
recognition and interchangeability of standards between regulatory bodies. As such, more
support is needed from regulators and pharmacopeias to achieve these goals. One would
hope that the results from this study could be a useful tool for engaging stakeholders and
identifying opportunities to mobilize their support for future collaborative initiatives.

153
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APPENDIX A
ADDITIONAL CROSS TABULATIONS
Additional cross tabulation was performed for specific questions and used to sub stratify
the survey so that organizational/company affiliation differences could be further
identified.
A.1 Profiles of Respondents
A.1.1 Cross Tabulation of Number of People at the Organization Working with
Pharmacopeial Harmonization

Organization/company
affiliation
Number of People in your Organization working on
pharmacopeial standards
Less than
20
employees
21-50
employees
>50
employees
I don’t
know
Total
N
Pharmaceutical Industry 35%
(20/57)
19%
(11/57)
39%
(22/57)
7%
(4/57)
100%
57
Other (please specify) 59%
(16/27)
15%
(4/27)
22%
(6/27)
4%
(1/27)
100%
27
Trade
Association/Organization
100%
(8/8)
0%
(0/8)
0%
(0/8)
0%
(0/8)
100%
8
Drug Regulatory Authority 18%
(2/11)
9%*
(1/11)
45%
(5/11)
27%
(3/11)
100%
11
Pharmacopeial Authority 23%
(3/13)
46%
(6/13)
31%
(4/13)
0%
(0/13)
100%
13
OMCL/Government Testing
Labs
0%
(0/5)
40%
(2/5)
60%
(3/5)
0%
(0/5)
100%
5
Academia 43%
(3/7)
14%
(1/7)
14%
(1/7)
29%
(2/7)
100%
7
*due to rounding

163
A.2 Views on Collaboration and Relationship Building
A.2.1 Cross Tabulation of Organizational Affiliation on Level of Collaboration
Among Different Pharmacopeias on Establishing Communication Channels
Between Pharmacopeias
Organization/company affiliation Establishing communication channels between
pharmacopeias
High across
most
High
across
some
High
across
few
I don’t
know
Total
Pharmaceutical Industry 21%
(12/57)
28%
(16/57)
26%
(15/57)
25%
(14/57)
100%
57
Other (please specify) 19%
(5/27)
41%
(11/27)
33%
(9/27)
7%
(2/27)
100%
27
Trade Association/Organization 12%
(1/8)
13%*
(1/8)
38%
(3/8)
38%
(3/8)
100%
8
Drug Regulatory Authority 30%
(3/10)
40%
(4/10)
20%
(2/10)
10%
(1/10)
100%
10
Pharmacopeial Authority 23%
(3/13)
46%
(6/13)
31%
(4/13)
0%
(0/13)
100%
13
OMCL/Government Testing Labs 60%
(3/5)
40%
(2/5)
0%
(0/5)
0%
(0/5)
100%
5
Academia 14%
(1/7)
29%
(2/7)
14%
(1/7)
43%
(3/7)
100%
7
*due to rounding
A.2.2 Cross Tabulation of Organizational Affiliation on Level of Collaboration
Among Different Pharmacopeias in Promoting Transparency in Standards Setting
Organization/company affiliation Promoting transparency in standards setting
High across
most
High across
some
High
across
few
I don’t
know
Total
Pharmaceutical Industry 21%
(12/57)
16%
(9/57)
39%
(22/57)
25%*
(14/57)
100%
57
Other (please specify) 11%
(3/27)
30%
(8/27)
37%
(10/27)
22%
(6/27)
100%
27
Trade Association/Organization 12%
(1/8)
25%
(2/8)
25%
(2/8)
38%
(3/8)
100%
8
Drug Regulatory Authority 10%
(1/10)
40%
(4/10)
20%
(2/10)
30%
(3/10)
100%
10
Pharmacopeial Authority 23%
(3/13)
31%
(4/13)
38%
(5/13)
8%
(1/13)
100%
13
OMCL/Government Testing Labs 40%
(2/5)
60%
(3/5)
0%
(0/5)
0%
(0/5)
100%
5
Academia 14%
(1/7)
29%
(2/7)
29%
(2/7)
29%
(2/7)
100%
7
*due to rounding

164
A.3 Global Challenges with Standardized Pharmacopeial Practices and Regulatory
acceptance
A.3.1 Cross Tabulation of Organizational Affiliation on Challenges Facing
Pharmacopeias on Defining a Common Approach to Developing Global
Specifications
Organization/Company
affiliation
Defining a common approach to developing global specifications
Very
challenging
Moderately
challenging
Not
challenging
at all
Cannot
say
Total N
Pharmaceutical Industry 51%
(29/56)
34%
(19/56)
4%
(2/56)
11%
(6/56)
100%
56
Other (please specify) 44%
(12/27)
56%
(15/27)
0%
(0/27)
0%
(0/27)
100%
27
Trade
Association/Organization
75%
(6/8)
25%
(2/8)
0%
(0/8)
0%
(0/8)
100%
8
Drug Regulatory Authority 30%
(3/10)
70%
(7/10)
0%
(0/10)
0%
(0/10)
100%
10
Pharmacopeial Authority 67%
(8/12)
0%
(0/12)
33%
(4/12)
0%
(0/12)
100%
12
OMCL/Government Testing
Labs
0%
(0/5)
100%
(5/5)
0%
(0/5)
0%
(0/5)
100%
5
Academia 57%
(4/7)
43%
(3/7)
0%
(0/7)
0%
(0/7)
100%
7
A.3.2 Cross Tabulation of Organizational Affiliation on Level of Collaboration
in Maintaining Alignment Among Different Pharmacopeias
Organization/company
affiliation

Maintaining alignment between different pharmacopeial standards
Very
challenging
Moderately
challenging
Not
challenging
at all
Cannot
Say
Total
N
Pharmaceutical Industry 44%
(25/57)
37%
(21/57)
3%
(2/57)
16%
(9/57)
100%
57
Other (please specify) 63%
(17/27)
37%
(10/27)
0%
(0/27)
0%
(0/27)
100%
27
Trade
Association/Organization
25%
(2/8)
63%
(5/8)
12%
(1/8)
0%
(0/8)
100%
8
Drug Regulatory Authority 40%
(4/10)
60%
(6/10)
0%
(0/10)
0%
(0/10)
100%
10
Pharmacopeial Authority 54%
(7/13)
23%
(3/13)
15%
(2/13)
8%
(1/13)
100%
13
OMCL/Government Testing
Labs
60%
(3/5)
40%
(2/5)
0%
(0/5)
0%
(0/5)
100%
5
Academia 14%
(1/7)
72%
(5/7)
0%
(0/7)
14%
(1/7)
100%
7

165
A.3.3 Cross Tabulation of Organizational Affiliation on Level of
Collaboration on Overcoming Language Challenges
Organization/Company
affiliation
Overcoming Language differences
Very
challenging
Moderately
challenging
Not
challenging
at all
Cannot
say
Total N
Pharmaceutical Industry 21%
(12/57)
32%
(18/57)
30%*
(17/57)
18%
(10/57)
100%
57
Other (please specify) 33%
(9/27)
37%
(10/27)
26%
(7/27)
4%
(1/27)
100%
27
Trade
Association/Organization
0%
(0/8)
75 %
(6/8)
12 %
(1/8)
13 %*
(1/8)
100%
8
Drug Regulatory Authority 30%
(3/10)
50%
(5/10)
20%
(2/10)
0%
(0/10)
100%
10
Pharmacopeial Authority 38%
(5/13)
38%*
(5/13)
23%
(3/13)
0%
(0/13)
100%
13
OMCL/Government Testing
Labs
0%
(0/5)
60%
(3/5)
40%
(2/5)
0%
(0/5)
100%
5
Academia 29%
(2/7)
43%
(3/7)
14%
(1/7)
14%
(1/7)
100%
7
*due to rounding

166
A.4 Differences Across Pharmacopeias To Produce Harmonized Standards
A.4.1 Cross Tabulation of Organizational Affiliation on Differences Across
Pharmacopeias for Disparate Regulatory/Legal Requirements
Organization/Company
affiliation
Disparate regulatory/legal requirements
Very
challenging
Moderately
challenging
Not
challenging at
all
Cannot
Say
Total
N
Pharmaceutical Industry 72%
(38/53)
21%
(11/53)
0%
(0/53
7%
(4/53)
100%
53
Other (please specify) 81%
(22/27)
19%
(5/27)
0%
(0/27)
0%
(0/27)
100%
27
Trade
Association/Organization
63%
(5/8)
25%
(2/8)
0%
(0/8)
12%
(1/8)
100%
8
Drug Regulatory Authority 80%
(8/10)
10%
(1/10)
10%
(1/10)
0%
(0/10)
100%
10
Pharmacopeial Authority 75%
(6/8)
25%
(2/8)
0%
(0/8)
0%
(0/8)
100%
8
OMCL/Government Testing
Labs
80%
(4/5)
0%
(0/5)
20%
(1/5)
0%
(0/5)
100%
5
Academia 57%
(4/7)
43%
(3/7)
0%
(0/7)
0%
(0/7)
100%
7

A.4.2 Cross Tabulation of Organizational Affiliation on Differences Across
Pharmacopeias for Diverse Scientific Opinions

Organization/Company
affiliation
Diverse scientific opinions
Very
challenging
Moderately
challenging
Not
challenging
at all
Cannot
say
Total
N
Pharmaceutical Industry 43%
(23/53)
40%
(21/53)
9%
(5/53)
8%
(4/53)
100%
53
Other (please specify) 37%
(10/27)
59%
(16/27)
4%
(1/27)
0%
(0/27)
100%
27
Trade
Association/Organization
25%
(2/8)
63%
(5/8)
0%
(0/8)
13%*
(1/8)
100%
8
Drug Regulatory Authority 40%
(4/10)
60%
(6/10)
0%
(0/10)
0%
(0/10)
100%
10
Pharmacopeial Authority 25%
(2/8)
63%
(5/8)
13%*
(1/8)
0%
(0/8)
100%
8
OMCL/Government Testing
Labs
0%
(0/5)
80%
(4/5)
20%
(1/5)
0%
(0/5)
100%
5
Academia 57%
(4/7)
43%
(3/7)
0%
(0/7)
0%
(0/7)
100%
7

167
A.5 Greatest Challenges for Pharmacopeias in Developing Pharmacopeial
Standards
A.5.1 Cross Tabulation of Organizational Affiliation on Challenges with Lack of
Adequate Collaboration on Work-Sharing Activities
Organization/company affiliation Lack of adequate collaboration on work-sharing
activities
Agree Neither agree
nor disagree
Disagree Total N
Pharmaceutical Industry 51%
(22/43)
30%
(13/43)
19%
(8/43)
100%
43
Other (please specify) 32%
(7/22)
41%
(9/22)
27%
(6/22)
100%
22
Trade Association/Organization 29%*
(2/7)
29%*
(2/7)
43%
(3/7)
100%
7
Drug Regulatory Authority 20%
(1/5)
60%
(3/5)
20%
(1/5)
100%
5
Pharmacopeial Authority 14%
(1/7)
57%
(4/7)
29%
(2/7)
100%
7
OMCL/Government Testing Labs 60%
(3/5)
0%
(0/5)
40%
(2/5)
100%
5
Academia 60%
(3/5)
0%
(0/5)
40%
(2/5)
100%
5
*due to rounding
A.5.2 Cross Tabulation of Organizational Affiliation on Challenges with Lack of
a Transparent Standard Setting Process
Organization/company affiliation Lack of a transparent standard setting process
Agree Neither agree
nor disagree
Disagree Total
N
Pharmaceutical Industry 47%
(21/45)
24%
(11/45)
29%
(13/45)
100%
45
Other (please specify) 24%
(6/25)
36%
(9/25)
40%
(10/25)
100%
25
Trade Association/Organization 29%
(2/7)
14%
(1/7)
57%
(4/7)
100%
7
Drug Regulatory Authority 14%
(1/7)
14%
(1/7)
72%
(5/7)
100%
7
Pharmacopeial Authority 29%
(2/7)
14%
(1/7)
57%
(4/7)
100%
7
OMCL/Government Testing Labs 40%
(2/5)
40%
(2/5)
20%
(1/5)
100%
5
Academia 17%
(1/6)
33%
(2/6)
50%
(3/6)
100%
6

168
A.5.3 Cross Tabulation of Organizational Affiliation on Challenges with Lack of
Adequate Laboratory Capabilities Requiring Outsourcing
Organization/company affiliation Lack of adequate laboratory capabilities
requiring outsourcing
Agree Neither agree
nor disagree
Disagree Total N
Pharmaceutical Industry 51%
(22/43)
30%
(13/43)
19%
(8/43)
100%
43
Other (please specify) 32%
(7/22)
41%
(9/22)
27%
(6/22)
100%
22
Trade Association/Organization 29%*
(2/7)
29%*
(2/7)
43%
(3/7)
100%
7
Drug Regulatory Authority 20%
(1/5)
60%
(3/5)
20%
(1/5)
100%
5
Pharmacopeial Authority 14%
(1/7)
57%
(4/7)
29%
(2/7)
100%
7
OMCL/Government Testing Labs 60%
(3/5)
0%
(0/5)
40%
(2/5)
100%
5
Academia 60%
(3/5)
0%
(0/5)
40%
(2/5)
100%
5

A.5.4 Cross Tabulation of Organizational Affiliation on Challenges in Developing
Standards With a Lack of Ability to Remove Environmentally Dangerous Chemical
Reagents
Organization/company affiliation Lack of ability to remove environmentally
dangerous chemical reagents
Agree Neither agree
nor disagree
Disagree Total N
Pharmaceutical Industry 16%
(7/43)
40%
(17/43)
44%
(19/43)
100%
43
Other (please specify) 9%
(2/22)
50%
(11/22)
41%
(9/22)
100%
22
Trade Association/Organization 0%
(0/5)
20%
(1/5)
80%
(4/5)
100%
5
Drug Regulatory Authority 17%
(1/6)
50%
(3/6)
33%
(2/6)
100%
6
Pharmacopeial Authority 14%
(1/7)
29%
(2/7)
57%
(4/7)
100%
7
OMCL/Government Testing Labs 40%
(2/5)
20%
(1/5)
40%
(2/5)
100%
5
Academia 20%
(1/5)
20%
(1/5)
40%
(3/5)
100%
5

169
A.6 Views of the Pharmacopeail Authorities/Views on PDG performance
A.6.1 Cross Tabulation of Organizational Affiliation on PDG Performance in
Providing Transparent Public/Inquiry Comment Process

Organization/company affiliation Provides a transparent public inquiry/comment process in
standards setting activities
Agree Disagree Neither agree
nor disagree
Total
Pharmaceutical Industry 53%
(24/45)
16%
(7/45)
31%
(14/45)
100%
45
Other (please specify) 62%
(16/26)
8%
(2/26)
31%*
(8/26)
100%
26
Trade Association/Organization 100%
(5/5)
0%
(0/5)
0%
(0/5)
100%
5
Drug Regulatory Authority 67%
(6/9)
0%
(0/9)
33%
(3/9)
100%
9
Pharmacopeial Authority 58%
(7/12)
17%
(2/12)
25%
(3/12)
100%
12
OMCL/Government Testing Labs 75%
(3/4)
0%
(0/4)
25%
(1/4)
100%
4
Academia 60%
(3/5)
20%
(1/5)
20%
(1/5)
100%
5
*due to rounding
A.6.2 Cross Tabulation of Organizational Affiliation on PDG Performance on
Timely Access to Standards Through Publication and Translations
Organization/company affiliation Provides timely access to proposed and official standards
through publication and translations
Agree Disagree Neither agree
nor disagree
Total
Pharmaceutical Industry 52%
(25/48)
13%
(6/48)
35%
(17/48)
100%
48
Other (please specify) 54%
(14/26)
4%
(1/26)
42%
(11/26)
100%
26
Trade Association/Organization 60%
(3/5)
0%
(0/5)
40%
(2/5)
100%
5
Drug Regulatory Authority 89%
(8/9)
0%
(0/9)
11%
(1/9)
100%
9
Pharmacopeial Authority 58%
(7/12)
17%
(2/12)
25%
(3/12)
100%
12
OMCL/Government Testing Labs 60%
(3/5)
0%
(0/5)
40%
(2/5)
100%
5
Academia 60%
(3/5)
20%
(1/5)
20%
(1/5)
100%
5

170
APPENDIX B
FINAL VERSION OF SURVEY

Dear Survey Respondent, This survey seeks to understand stakeholder views on global
harmonization of pharmacopeial standards, both documentary (monographs and general
test chapters/methods) and associated reference material standards (used as
comparison standards in tests and assays). It is part of research associated with the
Doctor of Regulatory Science degree at the University of Southern California. Your
answers are important to the success of the study and are completely anonymous. At
the end of the survey, there will be an option to voluntarily participate in a follow-up
phone interview. You can also receive the survey results upon request once the study is
completed. Thank you in advance for your participation.

Q1 Demographics and Background Information. This section captures your background
and current involvement and experience with pharmacopeial standards which
include both documentary standards (monographs and test chapters) and associated
reference standards.

Q8 Which one of the following best describes your organization/company?
o Pharmaceutical Industry (1)
o Drug Regulatory Authority (2)
o Pharmacopeial Authority (4)
o Official Medicines Control laboratories/Governmental Testing Laboratories (5)
o Academia (6)
o Trade Association /Organization (3)
o Other (please specify) (7)
________________________________________________

171
Skip To: Q9 If Which one of the following best describes your organization/company? =
Pharmaceutical Industry

Display This Question:
If Which one of the following best describes your organization/company? = Pharmaceutical
Industry

Q9 Which of the following best describes your industry? (please check all that apply)
▢ Innovator Industry (1)
▢ Generic Industry - Chemical and Biological (2)
▢ Drug Substance/API Manufacturer/Supplier (3)
▢ Excipient Manufacturer/Supplier (4)
▢ Contract Research Organization (CRO) (5)
▢ Contract Manufacturing Organization (CMO) (6)
▢ Contract Analytical Testing laboratory (CTO) (7)
▢ Other (please specify) (8)
________________________________________________

Q6 What is the size of your organization/company?
o Less than 200 employees (1)
o 200-1999 employees (2)
o 2000-5000 employees (3)
o More than 5000 employees (4)

172

Q7 How many people in your organization/company work with pharmacopeial standards
for pharmaceutical application?
o < 20 (1)
o 21-50 (2)
o > 50 (3)
o I don't know (4)

Q10 What is your primary functional role at your company/organization?
o Formulation Development Scientist (1)
o Compendial Specialist/Manager (2)
o Regulatory Specialist/Manager (3)
o Manufacturing/CMC Specialist/Manager (4)
o QA/QC Laboratory Scientist/Manager (5)
o Academic Scientist (6)
o Government Scientist (7)
o Pharmacopeial Scientist (8)
o Consultant (9)
o Pharmaceutical Raw Material Development/Manufacture/Distribution (10)
o Clinical/Bioanalysis (11)
o Other (please specify) (12)
________________________________________________

173

Q2 Please indicate your level of experience with pharmacopeial standards?

High (>10 years)
(1)
Moderate (1-10
years) (2)
Little or none (< 1
year) (3)
Monographs (1)
o o o
Test Chapters (2)
o o o
Reference
Standards (3)
o o o

Q3 Please indicate your level of experience with harmonization of existing
pharmacopeial standards (retrospective harmonization) ?

High (>10 years)
(1)
Medium (1-10
years) (2)
Little or none (
Monographs (1)
o o o
Test chapters (2)
o o o
Reference
standards (3)
o o o

174
Q4 Please indicate your level of experience with harmonization of pharmacopeial
standards where no standards exist (prospective harmonization)?

High (>10 years)
(1)
Medium (1-10
years) (2)
Little or none (
Monographs (1)
o o o
Test chapters (2)
o o o
Reference
standards (3)
o o o

Q5 With how many pharmacopeial standards have you been involved (either in
development or usage)?
<10 (1) 10-29 (2) 30-49 (3) 50-100 (4) >100 (5)
Monographs
(1)
o o o o o
Test chapters
(2)
o o o o o
Reference
Standards (3)
o o o o o

Page Break

175

Q11 For which of the following geographic region(s) or/ country are you primarily
responsible? (please select all that apply)
▢ Africa (1)
▢ Asia (2)
▢ Europe (3)
▢ Americas (4)
▢ Oceania (Australia, New Zealand, Polynesia, Micronesia (Kosrae,Yap,
Chuuk, and Pohnpei), Melanesia (Vanuatu, the Solomon Islands, Fiji, and Papua
New Guinea) (5)
▢ Other (9) ________________________________________________

Page Break

176
Q00 Section Two This section explores your views regarding the importance of global
pharmacopeial harmonization.

Q12 How important is it to achieve globally harmonized quality standards?
o Very important (1)
o Somewhat important (2)
o Not important (3)
o I don't know (4)

Q13 How urgent is it to achieve globally harmonized quality standards?
o Very urgent (within 1-2 years) (1)
o Somewhat urgent (within 3-5 years) (2)
o Not urgent (within 6-10 years) (3)
o I don't know (4)

177
Q14 In your view, which of the following are important objectives of global
pharmacopeial harmonization?

Very important
(1)
Somewhat
important (2)
Not important
(3)
I don't know
(4)
Reducing
redundant
testing burden
(1)
o o o o
Providing
harmonized
standards with
the same
accept/reject
conclusions (2)
o o o o
Safeguarding
quality of
medicines in the
global supply
chain (3)
o o o o
Accelerating
adoption of new
standards into
pharmacopeia
(4)
o o o o
Increasing
transparency of
public comment
process (5)
o o o o
Facilitating
recognition of
standards
between
regulatory
bodies (6)
o o o o
Facilitating
international
regulatory
compliance (7)
o o o o
Facilitating
international
regulatory filings
(8)
o o o o

178
Q15 Please select your level of agreement with the importance of the
following statements related to globally harmonized quality standards?
Agree (1)
Neither agree
nor disagree
(2)
Disagree (3)
I don't know
(4)
Minimizing
redundancy in
testing
requirements (1)
o o o o
Reducing the
compliance
testing burden
(2)
o o o o
Maintaining
alignment
between
harmonized
pharmacopeial
standards (3)
o o o o
Implementing
local/regional
pharmacopeial
testing
requirements
into my QC/QA
program is
easier (4)
o o o o
Adopting good
pharmacopeial
practices in
developing
standards (5)
o o o o

179
Q15a Other (please specify)

________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

Page Break

180

Q00 Section Three:
This section explores your views on specific aspects of collaboration and relationship
building related to global pharmacopeial harmonization.

Q16 In your view, what is the current level of collaboration among different
pharmacopeias in their efforts to produce harmonized standards efficiently?

High across
most (1)
High across
some (2)
High across
few (3)
I don't know
(4)
Engaging
stakeholders
(industry,
government,
academia, other
pharmacopeias)
(1)
o o o o
Promoting work-
sharing activities
between
pharmacopeias
(2)
o o o o
Establishing
communication
channels
between
pharmacopeias
(3)
o o o o
Promoting
transparency in
standards
setting (4)
o o o o

Q16a Are we missing other important information? (Please specify)
________________________________________________________________

181
Q17 Which of the following items would you consider to be important benefits of
pharmacopeial collaboration?

Very important
(1)
Somewhat
important (2)
Not important
(3)
I don't know
(4)
Minimizing
duplication of
efforts (1)
o o o o
Sharing
expertise and
resources (2)
o o o o
Aligning
pharmacopeial
standards
across different
regions (3)
o o o o
Providing a
common
understanding
of the regional
needs and
challenges (4)
o o o o
Facilitating the
adoption of
standards
between
regulatory
bodies (5)
o o o o
Developing
solutions that
can be adopted
broadly (6)
o o o o

Q17a Are we missing any other important benefits of pharmacopeial
collaboration? (please specify)
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

182
Q18 At the global level, which of the following activities do you think are most
challenging for pharmacopeial bodies in their efforts to produce harmonized standards
efficiently?

Very
challenging (1)
Moderately
challenging (2)
Not
challenging at
all (3)
Cannot Say
(4)
Defining a
common
approach to
developing
global
specifications
(1)
o o o o
Developing
reference
standards (2)
o o o o
Protecting data
confidentiality
(3)
o o o o
Implementing
WHO's Good
Pharmacopeial
Practices
Guidance (GPP)
(4)
o o o o
Implementing
ICH Quality
guidances (5)
o o o o
Overcoming
Language
differences (6)
o o o o
Maintaining
alignment
between
different
pharmacopeial
standards (7)
o o o o

183
Q18a At the global level, which of the following differences across pharmacopeias do
you think are most challenging in their efforts to produce harmonized standards
efficiently?

Very
challenging (1)
Moderately
challenging (2)
Not
challenging at
all (3)
Cannot Say
(4)
Diverse
scientific
opinions (1)
o o o o
Disparate
regulatory/legal
requirements (2)
o o o o
Different public
inquiry
/comment
processes (3)
o o o o
Misaligned
publication
schedules (4)
o o o o

Q18b Are we missing any other important differences across pharmacopeias? (please
specify)
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

Page Break

184
Display This Question:
If Which one of the following best describes your organization/company? = Pharmacopeial
Authority

Q00 Section Four This section addresses performance of your pharmacopeia
in standards setting and collaborating with other pharmacopeias.

Display This Question:
If Which one of the following best describes your organization/company? = Pharmacopeial
Authority

Q19 How satisfied are you with the adequacy of your pharmacopeia’s performance in
the following areas?
Satisfied (1)
Neither
Satisfied nor
Dissatisfied (2)
Dissatisfied (3)
I don't know
(4)
Laboratory
capabilities to
develop quality
specifications (1)
o o o o
Scientific
resources (2)
o o o o
Reducing the
testing burden
for industry (3)
o o o o
Transparency in
public
inquiry/comment
process (4)
o o o o
Stakeholder
engagement
through
workshops and
forums (5)
o o o o
Alignment of
standards
across different
pharmacopeias
(6)
o o o o

185
Q20 Please select your level of agreement with the following factors in presenting the
greatest challenges for developing pharmacopeial standards at your pharmacopoeia?
Agree (1)
Neither agree
nor disagree
(2)
Disagree (3)
I don't know
(4)
Lack of
adequate
scientific
resources (1)
o o o o
Lack of
adequate
laboratory
capabilities
requiring
outsourcing (2)
o o o o
Lack of ability to
develop
reference
material
standards (3)
o o o o
Lack of
adequate
collaboration on
work-sharing
activities (4)
o o o o
Lack of a
transparent
standard setting
process (5)
o o o o
Lack of ability to
remove
environmentally
dangerous
chemical
reagents (6)
o o o o

186
Display This Question:
If Which one of the following best describes your organization/company? = Pharmacopeial
Authority

Q21 Which meetings do you regularly attend? (please select all that apply)
▢ WHO’s International Meeting of World Pharmacopeias (IMWP) (1)
▢ ICH meetings (2)
▢ Bilateral/multilateral meetings between pharmacopeias (3)
▢ Pharmacopeial Discussion Group (PDG) technical meetings (4)
▢ Pharmacopeial meetings in your region (5)

Display This Question:
If Which one of the following best describes your organization/company? = Pharmacopeial
Authority

Q21a Other (please specify)
________________________________________________________________

187
Display This Question:
If Which one of the following best describes your organization/company? = Pharmacopeial
Authority

Q22 What resources do you consult when working with pharmacopeial standards?
(Select all that apply)
▢ Local/Regional Pharmacopeial monographs, reference standards and
general chapters (1)
▢ WHO International Pharmacopeial standards (2)
▢ Local/Regional regulatory guidances/documents (3)
▢ Regulatory guidances/documents outside your local/regional area (4)
▢ International Council for Harmonisation (ICH) Topics on Quality (e.g., ICH
Q1, Q2,Q3,Q4,Q5,Q6) (5)
▢ Pharmacopeial Discussion Group (PDG) harmonized standards (6)
▢ WHO's Good Pharmacopeial Practices Guidance (7)

Display This Question:
If Which one of the following best describes your organization/company? = Pharmacopeial
Authority

Q22a Other (please specify)
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

Page Break

188
Q00 Section Five This section addresses specific aspects of implementing
standardized pharmacopeial practices currently utilized by the Pharmacopeial
Discussion Group (PDG). (One answer)

Q23 Please indicate your frequency of use of the following pharmacopeias which
form the Pharmacopeial Discussion Group (PDG)?

High (>10 times
per year) (1)
Medium (1-10
times per year) (2)
Little or none (< 1
year) (3)
Japanese
Pharmacopeia (1)
o o o
European
Pharmacopeia (2)
o o o
United States
Pharmacopeia (3)
o o o

189
Q24 Please select your level of agreement with the following factors that present the
biggest challenges to implementing PDG harmonized standards into your region?
Agree (1)
Neither agree
nor disagree
(2)
Disagree (3)
I don't know
(4)
Our
organization
lacks adequate
scientific
resources (1)
o o o o
Our
organization
lacks adequate
laboratory
capabilities (2)
o o o o
There is a lack
of alignment
between PDG
standards and
our
local/regional
pharmacopeia
(3)
o o o o
Reference
standards are
not easily
available (4)
o o o o
Reference
standards are
too costly (5)
o o o o
PDG standards
are not
recognized by
our regulatory
body (6)
o o o o

Q24a Other (please specify)
________________________________________________________________
________________________________________________________________
________________________________________________________________

190
________________________________________________________________
________________________________________________________________

Q25 In your experience, how helpful are PDG harmonized standards compared to
local or regional standards in helping regulators with enforcement activities?
o Very helpful (1)
o Somewhat helpful (2)
o Not helpful at all (3)
o Other (please specify) (4)
________________________________________________

Q26 In your experience, how helpful are PDG harmonized standards to increase
efficiency in your professional function?
o Very helpful (1)
o Somewhat helpful (2)
o Not helpful at all (3)
o Any we missing important Information (4)
________________________________________________

Page Break

191

Q27 Please select your level of agreement with the following statements regarding PDG
performance?
Agree (1)
Neither agree
nor disagree
(2)
Disagree (3)
I don't know
(4)
Develops
standards in a
timely manner
(1)
o o o o
Harmonization
helps
pharmacopeial
standards stay
aligned (2)
o o o o
Engages
stakeholders
during standards
setting through
workshops and
educational
trainings (3)
o o o o
Provides a
transparent
public
inquiry/comment
process in
standards
setting activities
(4)
o o o o
Provides timely
access to
proposed and
official
standards
through
publication and
translations (5)
o o o o

192
Q27a Are we missing important information regarding PDG performance (please
specify)

________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

Q28 How do PDG harmonized documentary standards help you in your work?
Agree (1)
Neither agree
nor disagree
(2)
Disagree (3)
I don't know
(4)
By reducing
redundant
testing (1)
o o o o
By providing
standards with
the same
accept/reject
conclusions (2)
o o o o
By facilitating
recognition of
standards
between
regulatory
bodies (3)
o o o o
By facilitating
international
filings (4)
o o o o
By facilitating
regulatory
compliance (5)
o o o o

193
Q29 Thinking of the totality of your experience with PDG to date, pharmacopeial
harmonization as laid out by PDG should be:
o Kept as is (1)
o Modified (2)
o Eliminated (3)
o No opinion (4)

194
Q31 If you were to modify the PDG process, which of the following changes would you
consider to be important?
Important (1)
Somewhat
important (2)
Not important
(3)
I don't know
(4)
Expand PDG
membership to
include more
regions (1)
o o o o
Simplify the
harmonization
process (2)
o o o o
Separate
harmonization
activities of
prospective
(new) standards
from
retrospective
(existing)
standards (3)
o o o o
Increase
transparency of
PDG's
processes and
activities (4)
o o o o
Include
harmonization
topics beyond
excipients and
general
chapters (5)
o o o o
Provide
additional
trainings and
stakeholder
outreach (6)
o o o o
Strengthen the
linkage between
PDG and ICH
Q4B (7)
o o o o

Page Break

195
Q32 Please indicate your frequency of use of WHO's International Pharmacopeia for
your company/organization?
o High (>10 times per year) (1)
o Medium (1-10 times per year) (2)
o Little or none (< 1 time per year) (3)

Q33 Please indicate your frequency of use of other pharmacopeias listed
below (categorized into national and regional pharmacopeias) for
yourcompany/organization? If the pharmacopeia is not listed, please add it to the "other"
field provided. (Please select all that apply)

High (>10 times per
year) (1)
Medium (1-10 times
per year) (2)
Little or none (< 1
time year) (3)
British Pharmacopeia
(1) o o o
Chinese
Pharmacopeia (2) o o o
Indian Pharmacopeia
(3) o o o
Korean Pharmacopeia
(4) o o o
Russian Federation
Pharmacopeia (5) o o o
Ukranian
Pharmacopeia (6) o o o
Croatian
Pharmacopeia (7) o o o
Argentinian
Pharmacopeia (8) o o o
Brazilian
Pharmacopeia (9) o o o
Mexican
Pharmacopeia (10) o o o
Indonesian
Pharmacopeia (11) o o o
Thailand
Pharmacopeia (12) o o o

196

High (>10 times per
year) (1)
Medium (1-10 times
per year) (2)
Little or none (< 1
time year) (3)
Philippines
Pharmacopeia (13) o o o
African Pharmacopeia
(14) o o o
Eurasian
Pharmacopeia
(Armenia; Belarus;
Kazakhstan;
Kyrgyzstan; and the
Russian Federation)
(15)
o o o

Q33a Other (please specify)
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

Q34 In the space provided below, please feel free to provide any additional information
or comments that you feel will contribute to my understanding of your views on
pharmacopeial harmonization. Thank you
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

197
Q35 Please provide an email contact for a colleague whom you feel would be able to
take this survey? Thank you
________________________________________________________________

End of Survey

Request for Results Summary Please select all that apply
Yes (1) No (2)
Would you like to receive a
summary of the survey
results when I complete my
study? (1)
o o
Would you be open to
discussing your feedback
for the purpose of informing
this study? (2)
o o

Skip To: QID126 If Request for Results Summary Please select all that apply = Would you like to
receive a summary of the survey results when I complete my study?
Skip To: QID126 If Request for Results Summary Please select all that apply = Would you like to
receive a summary of the survey results when I complete my study?
Skip To: End of Survey If Request for Results Summary Please select all that apply = Would you
be open to discussing your feedback for the purpose of informing this study?
Skip To: End of Survey If Request for Results Summary Please select all that apply = Would you
be open to discussing your feedback for the purpose of informing this study?

Please enter an email where you would like us to contact you ?Thank you
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

198
APPENDIX C
Number of Monographs in Pharmacopeias in WHO region
Excerpt Table 3, pages 12-13: Number of Monographs included in Pharmacopoeias
Source: (WHO, 2013b), Accessed April 18, 2014

Abstract (if available)

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Asset Metadata

Creator Sheehan, Catherine Margaret (author)

Core Title Views on global harmonization of pharmacopeial standards: a survey of key stakeholders

School School of Pharmacy

Degree Doctor of Regulatory Science

Degree Program Regulatory Science

Publication Date 02/14/2020

Defense Date 01/24/2020

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

Tag good pharmacopeial practices,harmonization,monograph standard,OAI-PMH Harvest,pharmacopeia,pharmacopeial discussion group,regulatory interchangeability

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Pacifici, Eunjoo (committee chair), Clemens, Roger (committee member), Davies, Daryl (committee member), Richmond, Frances (committee member)

Creator Email cmsheeha@usc.edu,dcsheehans@comcast.net

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c89-270135

Unique identifier UC11673387

Identifier etd-SheehanCat-8174.pdf (filename),usctheses-c89-270135 (legacy record id)

Legacy Identifier etd-SheehanCat-8174.pdf

Dmrecord 270135

Document Type Dissertation

Rights Sheehan, Catherine Margaret

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the a...

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA