Pharmacopoeia Compliance Series

Why Pharmacopoeia
Compliance Is Necessary
J. Mark Wiggins and Joseph A. Albanese

C
ompliance with requirements published by phar-
macopoeias around the world is a legal and regu-
latory requirement in those countries and regions
in which the pharmacopoeia is applicable. This
iQoncept - Stock.adobe.com

fundamental principle of pharmacopoeia compliance is

an important consideration for the bio/pharmaceutical
industry, including innovator, generic, virtual, and start-
up companies who discover, develop, manufacture, and
distribute small-molecule drug products, biotherapeutic

MJH Life Sciences products, and vaccines, as well as the drug substances and
excipients used in these products. Across the entire indus-
try and within any given company, it is crucial that there

Not for public distribution

In this series of articles, the authors provide an understanding
about the need for pharmacopoeia compliance and
practical guidance to assist those who perform this work.
The following articles can be found within this ebook
and online at www.PharmTech.com/compendia:
• Why Pharmacopoeia Compliance Is Necessary
• Why Pharmacopoeia Compliance Is Difficult
• A Brief History of Pharmacopoeias: A Global Perspective
• Global Pharmacopoeia Standards:
Why Harmonization is Needed
• Harmonization Efforts by Pharmacopoeias
and Regulatory Agencies
Upcoming articles in this series will include the following:
• Revision Process for Global/National Pharmacopoeias
• Surveillance Process for Industry: Monitoring
Pharmacopoeia Revisions
• Monograph Development: Why and When to Participate
• Monograph Development:
How to Participate; How to Harmonize
• A Practical Approach to Pharmacopoeia Compliance
• A Case Study in Pharmacopoeia Compliance:
Excipients and Raw Materials
• Pharmacopoeia Compliance:
Putting it All Together; What is on the Horizon
J. Mark Wiggins is owner and compendial
consultant with Global Pharmacopoeia Solutions
LLC. Joseph A. Albanese is the director of Analytical
Strategy and Compliance at Janssen Research and
Development, LLC.
28 Pharmaceutical Technology  REGULATORY SOURCEBOOK SEPTEMBER 2019 P h a r mTe c h . c o m
is awareness and understanding of this need for pharma-
copoeia compliance—from the CEOs of multi-national
innovator and generic-drug companies to the leadership
at small start-ups and contract manufacturers, to manag-
ers in their respective functional areas, to the analytical
bench chemists and microbiologists testing active ingre-
dients and excipients for use in drug products—so that
global patients have uninterrupted access to the critical
medicines that extend and improve their lives.
There is often insufficient understanding, however, by
stakeholders at all levels of the need to comply with re-
quirements in the pharmacopoeias. This situation can lead
to a lack of appropriate attention and resources allocated
to ensure compliance. The compliance risk can result in
observations in FDA 483s, which may be summarized as
follows: the company must comply with applicable com-
pendial standards in the United States Pharmacopeia–Na-
tional Formulary (USP–NF). A more nuanced observation
is that the company must comply with “current” compen-
dial requirements, which introduces the need to monitor
and implement updates published in USP–NF. The situa-
tion is not limited to the United States, as similar expecta-
tions to comply with the applicable pharmacopoeia exist
in Europe, Canada, Australia, Japan, China, and in laws
and regulations around the world.
The situation is made even more complex because
a company must comply with the compendial require-
ments that are applicable in a particular country, and also
with their product registrations as approved in countries
around the world. This is true whether the pharmaco-
poeia references are specifically listed in the registration,
or because the pharmacopoeias provide additional, well-
recognized quality standards. The compliance challenge
is increased by the sheer number of pharmacopoeias
that exist in important markets, often with conf licting
requirements due to lack of harmonization among the
pharmacopoeias. This lack of broad harmonization is the
current reality, despite long-term commitment and effort
by pharmacopoeias to narrow the divide between their
published standards. Somewhat balancing this high-level
view of the compliance challenge is the fact that there is
some f lexibility in how a company ensures appropriate
compliance to the multitude of compendial requirements.
But in this flexibility, there is also complexity, due to the
number of approaches that may be taken to demonstrate
compliance, with the potential for different situations to
drive the approach in different directions. Companies must comply with
It is against this challenging backdrop that the authors
have undertaken the preparation of a series of articles compendial requirements
to provide a common understanding of this far-reaching
and complex situation and to detail practical ways that
and must also remain up to
pharmacopoeia compliance may be addressed. The ar- date with changes made to
MJH Life Sciences
ticles intend to give consistent language to, and aware-
the requirements.
ness of, the tasks associated with the effort and to give
specific guidance to those groups and individuals within a
Not for public distribution
company who are charged with ensuring ongoing compli-
ance with pharmacopoeia requirements. While focusing
on the situation for innovator and generic companies, the
information is also potentially helpful in bringing greater
awareness and understanding to regulatory and pharma-
copoeia authorities.
Along with the understanding and assistance provided
to those who perform this work, there is the goal of ensur-
ing continued availability of medicines with consistent
quality, which comply with compendial and regulatory
expectations. Achieving compliance for these medicines
ensures meeting the needs of patients around the world,
regardless of where the patients live, where the medicines
are manufactured, or which pharmacopoeias may apply.
The legal and regulatory basis
for pharmacopoeia compliance
Pharmacopoeias are often referenced in the laws and regu-
lations of countries around the world to help ensure drug
quality, safety, and efficacy. In the United States, the Fed-
eral Food, Drug, and Cosmetic Act (FD&C Act) defines
the term “official compendium” as the official USP–NF or
any supplement to it and the term “drug” to include ar-
ticles recognized in the official USP–NF. FDA has respon-
sibility to enforce compliance with USP–NF requirements.
In Europe, the European Union Directives on Medicines
for Human and Veterinary Use (2001/82/EC and 2001/83/
EC) maintain the mandatory character of European Phar-
macopoeia (Ph. Eur.) monographs, which are applicable to
all substances, preparations, and pharmaceutical forms
appearing in it when requesting marketing authorization.
In Japan, the Law on Securing Quality, Efficacy, and Safety
of Products including Pharmaceuticals and Medical De-
vices indicates the need for compliance with the Japanese
Pharmacopoeia (JP) in order to standardize and control
the quality of drugs. The legal and regulatory framework
for pharmacopoeia compliance in these and other coun-
tries can be found in a useful summary prepared by the
World Health Organization (WHO) in conjunction with
recent International Meetings of World Pharmacopoeias
(IMWP) (1). This information, with appropriate updates
by the authors, is provided for several countries/regions
in Table I, along with a list of the authorities that have re-
sponsibility for publishing the associated pharmacopoeias.
In an article published in 2004 on the bio/pharmaceuti-
cal industry’s pharmacopoeial surveillance process (2), the
need to remain compliant with “current” compendial re-
quirements was emphasized to ensure updated standards
are incorporated into a company’s testing procedures.
If there is no process for surveillance, or if the process
is ineffective in identifying and addressing compendial
changes, the resulting lack of compliance may be listed
in regulatory observations. Specific examples from FDA
483s are included in the article, with observations such
as: “… the firm did not follow the current USP specifi-
cations … failed to implement changes to testing meth-
odology as required by USP … and did not address raw
material monograph updates.” Examples of more recent
compendial compliance observations from FDA 483s are
summarized in Table II. The common theme in all these
observations is the need to maintain alignment with ap-
plicable pharmacopoeia requirements, even as the require-
ments change over time. Similar regulatory expectations
to comply with current pharmacopoeia requirements
can be found in Europe, Japan, and other countries, be-
cause the regulatory and compendial landscape is truly
global. A review of data from inspections conducted by
the European Directorate for the Quality of Medicines
and HealthCare (EDQM) between 2006 and 2018 includes
compliance issues with Ph. Eur. general methods and gen-
eral monographs among the deficiencies observed (3). The
Pharmaceutical Technology  REGULATORY SOURCEBOOK SEPTEMBER 2019 29
Pharmacopoeia Compliance Series
Table I. Legal/regulatory basis for pharmacopoeia compliance (1). Source: World Health Organization.
Publication Published by Legal/regulatory basis

United States Pharmacopeia
and National Formulary
(USP–NF)
European Pharmacopoeia
(Ph. Eur.)
British Pharmacopoeia (BP)
Japanese Pharmacopoeia
(JP)
Chinese Pharmacopoeia
(ChP)
Published by the USP Convention
(a private, not-for-profit organization
that is independent of the US
government).
Published by the European
Directorate for the Quality of
Medicines and HealthCare (EDQM).
Published by the British
Pharmacopoeia Commission under
the guidance of the Medicines and
Healthcare Products Regulatory
Agency (MHRA).
Published by the Japanese
government as a ministerial
notification by the Ministry of Health,
Labour and Welfare (MHLW).
Published by the Chinese
Pharmacopoeia Commission of
the National Medical Products
Administration (NMPA), formerly the
The USP and NF are recognized as official compendia
under the Federal Food, Drug and Cosmetic Act (FD&C
Act). See, for example, 501(b), 502(e)(3)(b) and others. See
also USP general notices section 2.30.
European Union (EU) Directives 2001/82/EC and 2001/83/
EC, as amended, on medicines for human and veterinary
use maintain the mandatory character of European
Pharmacopoeia monographs.
The BP is authorized under terms of the Medicines Act
1968 (Section 99), superseded by the Human Medicines
Regulations, 2012 (Section 317(1)).
The JP is published in accordance with the Act of
Securing Quality, Efficacy, and Safety of Products
including Pharmaceuticals and Medical Devices, which is
the most fundamental law for pharmaceutical regulation in
Japan.
The ChP is published under laws established in 1950 by
the Ministry of Health. The Drug Administrative Law issued
by the National People’s Congress, effective from 2001
and updated in 2015, states that the Pharmacopoeia of the
People’s Republic of China and the drug standards issued
by the drug regulatory department under the State Council

MJH Life Sciences

China Food and Drug Administration
shall serve as the national drug standards. The Drug
(CFDA).
Registration regulation issued by CFDA in 2007 defines the
role of ChP in drug registration.

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Indian Pharmacopoeia (IP)
Russian Pharmacopoeia (SP
RF)
Published by the Indian
Pharmacopoeia Commission on
behalf of the Ministry of Health
The IP is authorized under the Indian Drugs and Cosmetics
and Family Welfare of India, with
Act (1940) and Rules (1945).
oversight from the Central Drugs
Standard Control Organization
(CDSCO).
The State Pharmacopoeia of the
Rules of elaborating general monographs and
Russian Federation (SP RF) is
monographs and including them in the State
published by the Ministry of Health
Pharmacopoeia were enacted by Federal Law No. 61-FZ
(MoH) as the authorized federal
on Circulation of Medicines (2010).
executive body.

takeaway message is clear; companies must comply with the guidance of WHO, to discuss collaboration and har-
compendial requirements and must also remain up to date monization in today’s globalized compendial, regulatory,
with changes made to the requirements. This ongoing re- and supply situation for drugs. The main suggestion to
vision to the pharmacopoeias around the world poses one come out of these meetings was the development of Good
of the main challenges for companies and will be further Pharmacopoeial Practices (GPhP) recently published by
addressed in later articles in this series. WHO (4).
WHO’s GPhP states, “The primary objective of the
Purpose and content GPhP guidance is to define approaches and policies in
of pharmacopoeias establishing pharmacopoeial standards with the ultimate
Having highlighted the need to comply with compendial goal of harmonization” (4). This focus on compendial har-
requirements, with examples of observations resulting monization is ref lected in the origins of several of the
from non-compliance, it is helpful to have an overall un- pharmacopoeias (to be detailed in another article in this
derstanding of the role pharmacopoeias play to support series) and is critical to the ongoing goal of providing
the availability of medicines. This understanding may medicines with consistent quality to patients around the
be found in the history, purpose, and content of phar- world. The WHO document goes on to list the purpose
macopoeias. Many of the pharmacopoeias from around and role of the pharmacopoeias: “A pharmacopoeia’s core
the world have met during the past several years, under mission is to protect public health by creating and making
30 Pharmaceutical Technology  REGULATORY SOURCEBOOK SEPTEMBER 2019 P h a r mTe c h . c o m
available public standards to help ensure the quality of
medicines. Pharmacopoeia standards support regulatory
authorities in controlling the quality of pharmaceutical
substances, their finished pharmaceutical products (FPPs),
and related materials and will provide a tool with which
the user or procurer can make an independent judgment
regarding quality, thus safeguarding the health of the
public.”
A search through the pharmacopoeias reveals that they
contain general notices, general chapters, general mono-
graphs, specific monographs for drug products, drug sub-
stances and excipients, and additional information related
to packaging, labeling, storage, etc. All this information
must be taken together to determine the specific quality
requirements for bio/pharmaceutical products.
Within each pharmacopoeia, there is a section referred
to as general notices, which is critical to the full under-
standing of the scope and technical approaches in that
pharmacopoeia. As stated in the USP–NF, the general
notices section presents the basic assumptions, defini-
tions, and default conditions for the interpretation and
application of the USP–NF, and the requirements apply to
all articles recognized in the compendia and to all general
chapters, unless specifically stated otherwise. Similarly,
cific monograph components, considerations for the use
of alternative methods, rules for rounding, and a defini-
tion of “about”. They have been described anecdotally as
the most important pages of the pharmacopoeia that most
users have never read. Thus, reading and understanding
the general notices is critical to ongoing pharmacopoeia
compliance.
During formulation
development, consideration
must also be given to
compendial monographs for
excipients.
There are more than 350 general chapters in USP–NF,
and more than 370 general texts in Ph. Eur., including
general monographs and chapters. Many of the general
chapters in the pharmacopoeias are mandatory and en-
forceable by regulatory authorities, containing informa-

MJH Life Sciences

the general notices in Ph. Eur. and other pharmacopoeias
apply to all monographs and other texts in the pharmaco-
poeia. The general notices provide a wide range of impor-
tion on specific chemical, biological, and microbiological
test methods and assays, as well as specific requirements
for particulate contamination and packaging components,

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tant information, from a statement of what conformance
to compendial standards means, to a description of spe-
for example. Other general chapters may instead be in-
formational and not necessarily enforceable, intended to

Table II. Examples of compendial compliance observations from FDA 483s. USP is United States Pharmacopeia.
Year Observation
The firm has not established that your purified water system is adequately designed, controlled, maintained, and
2018 monitored to ensure it consistently produces water that meets Purified Water USP monograph specifications and
appropriate microbial limits.
The firm has not established or implemented all appropriate specifications for the active pharmaceutical ingredient
2017 in accordance with the accepted USP standards and consistent with the manufacturing process. Specifically, the
firm has not included a control of all process impurities such as residual solvents.
The firm does not always follow official USP monographs when testing drug products for release and distribution to
2017
the United States.
2016 Growth promotion test is not performed in accordance with standard pharmacopeia.
The USP test method for Loss on Drying, which is used for the release of finished product to market has not been
2016
verified.
The firm could not provide documentation to show that you did not use an expired batch of USP reference standard.
2016
The laboratory staff does not document and record the expiration dates for official USP standards.
USP-grade active pharmaceutical ingredients are not always fully tested against USP monographs (e.g.,
2013
Identification, Acidity, Alkalinity, Chloride, Sulfate, Residue on Ignition).
Compendial methods for active pharmaceutical ingredients are not verified under actual conditions of use (e.g.,
2012
Water Determination, Loss on Drying, Reside on Ignition).
The firm does not perform current USP monograph testing (e.g., Assay, Identification, Distillation Range) on the final
2010
active pharmaceutical ingredients prior to distribution for use in human and veterinary drug products.
USP active pharmaceutical ingredients have been released for distribution by the firm prior to testing and/or which
2009
did not meet USP specifications (e.g., Assay, Loss on Drying).
The firm’s procedure for stability testing is insufficient. The firm does not test the stability samples of USP-grade
2009
material to ensure compliance with the USP method and limit for moisture content.

Pharmaceutical Technology  REGULATORY SOURCEBOOK SEPTEMBER 2019 31

 Pharmacopoeia Compliance Series
Figure 1. Impact of pharmacopoeia throughout drug product lifecycle.

API Development Regulatory Submission/Approval

Dosage Form Development Marketing Exclusivity

Clinical Trials Patent Expiration

Generic Entry

Early Development Commercialization Supply

Nomenclature API Monographs

Excipient Monographs Product Monographs

General Chapters (e.g.): Water/Loss on Drying, Elemental Impurities, Residual

Solvents, Chromatography, Dissolution, Dose Uniformity, Microbial Limits, Sterility

MJH Life Sciences

provide background knowledge and practical consider-
ations that are useful to bio/pharmaceutical manufac-
turers’ understanding of the production, testing, and
eral chapters numbered <1> through <5> serve the same
function as the Ph. Eur. general monographs, and include
quality requirements for injections, oral drug products,

Not for public distribution

overall quality of their products. In the USP–NF, these
informational chapters are numbered above <1000> and
topical and transdermal products, mucosal products, and
inhalation products.
include <1079> “Good Storage and Distribution Practices
for Drug Products,” <1121> “Nomenclature” and <1226>
“Verification of Compendial Procedures.” The Ph. Eur., Specific monographs
JP, and other pharmacopoeias similarly contain general
chapters that are mandatory and enforceable, as well as provide the minimum quality
chapters that are stated as being for information and non-
mandatory. It is worth noting that Ph. Eur. Chapter 5.4
requirements that must be
“Residual Solvents” represents the information contained
separately in the International Council for Harmoniza-
met for drug products and
tion (ICH) Q3C guideline, a reminder of the important ingredients, and apply to
connection that may exist between regulatory guidance
and pharmacopoeia requirements. This is also true for all manufacturers of these
Ph. Eur. Chapter 5.20 “Elemental Impurities,” USP <232>
“Elemental Impurities–Limits,” and the ICH Q3D Guide- materials.
line on Elemental Impurities, along with the associated
removal of the compendial test for heavy metals from the Specific monographs provide the minimum quality re-
pharmacopoeias, which further serves as an example of quirements that must be met for drug products and ingredi-
FIGURE COURTESY OF THE AUTHORS.

the significant challenges for the bio/pharmaceutical in-
dustry to ensure compliance with updated regulatory and
compendial requirements.
General monographs typically provide overall quality
requirements that are applicable to a specific dosage form
or route of administration for drug products. In the Ph.
Eur., there are general dosage form monographs for cap-
sules, tablets, eye preparations, nasal preparations, paren-
teral preparations and many others. In USP–NF, the gen-
32 Pharmaceutical Technology  REGULATORY SOURCEBOOK SEPTEMBER 2019 P h a r mTe c h . c o m
ents, and apply to all manufacturers of these materials, both
innovator and generic-drug companies. A monograph in-
cludes the name of the ingredient or preparation; the defini-
tion, packaging, storage, and labeling requirements; and the
specification, consisting of a series of tests, procedures and
acceptance criteria. In the USP–NF, there are currently more
than 4900 specific monographs, and in Ph. Eur., there are
more than 2400 monographs. These specific monographs
cover the entire range of bio/pharmaceutical products, in-
cluding excipients, small-molecule drug substances, biologi-
cal products, and vaccines. A few examples are the mono-
graphs for the excipient hypromellose, the drug substances
acetaminophen (as it is named in the USP) or paracetamol
(as it is named in Ph. Eur.), and sitagliptin phosphate, and a
variety of drug products, including sitagliptin tablets, inf-
liximab concentrated solution, and human papillomavirus
vaccine. Monographs often require official reference stan-
dards, which are physical materials that may be purchased
from the pharmacopoeia to be used in conjunction with
the test methods in the monograph to assess specific qual-
ity attributes of the drug product or ingredient, including
assay and impurities.
Moving to regulatory
submissions and product
commercialization, it is
important to understand the
compendial requirements
for packaging,MJH Life
storage, andSciences
distribution.
Not for public distribution
Information contained in the pharmacopoeia is inter-re-
lated, and the requirements from one section must be utilized
in conjunction with other sections. A specific monograph
may include a reference to a general dosage form monograph,
along with references to applicable general chapters, with the
basic underpinnings contained in the general notices. Bio/
pharmaceutical companies must understand and apply these
pharmacopoeial requirements within this context. A guide,
titled “How to Use the BP,” was posted on the British Pharma-
copoeia website (5) that provides an overview and illustration
of the inter-relation of pharmacopoeia content. This guide
forms a framework for navigating compendial requirements
in the BP, and should be helpful, especially for those who may
be less familiar with the structure and use of pharmacopoeias.
Pharmacopoeia impact
throughout drug product lifecycle
Pharmacopoeias impact drugs and their ingredients through-
out the entire product lifecycle (Figure 1). Beginning with the
development of a new drug substance or API, many of the
pharmacopoeia general chapters should be considered for
potential quality and functionality testing. For example, the
compendial tests listed in general chapters for water con-
tent or loss on drying, residual solvents, elemental impuri-
ties, and microbiological evaluation will likely be used for
quality release of the material later in the lifecycle. Similarly,
information listed in the chromatography chapter should be
considered during analytical method development, because
many of the compendial requirements can be incorporated
into the test procedures, such as method repeatability and
resolution for system suitability. Consideration should also
be given at the appropriate stage of product development to
compendial requirements for method validation, such as USP
<1225> “Validation of Compendial Procedures,” because this
information will ultimately be used to support the product
registration.
Once dosage form development is initiated, additional
compendial content becomes important. General chapters
and general product monographs provide requirements for
a given dosage form that must be considered before a prod-
uct is registered or licensed. Drug product quality and func-
tional characteristics should be evaluated according to these
compendial requirements, because this is the regulatory ex-
pectation. Depending on the dosage form being developed,
applicable chapters include uniformity of dosage units (con-
tent uniformity or mass variation), dissolution, particulate
contamination, microbiological tests, sterility, and chroma-
tography for assay and impurities. Pharmacopoeias also con-
tain general chapters and general dosage form monographs
that provide core requirements for drug products, including
USP <1> “Injections,” Ph. Eur. monograph [520] on Parenteral
preparations and Ph. Eur. monograph [478] on Tablets.
During formulation development, consideration must
also be given to compendial monographs for excipients. As
stated in the pharmacopoeias, and perhaps more importantly,
as expected by health authorities around the world, excipi-
ents used in drug products must comply with the applicable
monograph requirements published in the pharmacopoeias.
Lack of awareness or attention to this point jeopardizes drug
product approval and ultimate compliance. The existence of
so many pharmacopoeias around the world with excipient
monographs that do not broadly align is a significant compli-
cating factor for compendial compliance and global product
registrations.
Moving to regulatory submissions and product commer-
cialization, it is important to understand the compendial re-
quirements for packaging, storage, and distribution. Failure
to take these general chapters into account as contained in
the various pharmacopoeias may again have adverse impact
on regulatory approval and long-term compliance. Consid-
eration of these requirements may also be important when
planning for and evaluating drug product stability. The use of
compendial reference standards for pharmacopoeial testing,
or alternatively, of qualifying in-house primary or secondary
standards, must also be considered at an appropriate stage in
product and analytical development to meet the expecta-
tions of regulatory agencies.
Pharmaceutical Technology  REGULATORY SOURCEBOOK SEPTEMBER 2019 33
Pharmacopoeia Compliance Series
Once dosage form along with consideration of how the pharmacopoeias
impact drugs throughout their product lifecycle. The
development is initiated, increasingly global environment for industry, regulators,
and pharmacopoeias, where expectations and standards
additional compendial do not always agree, represents one of the significant chal-
lenges to ensuring consistent and sustained compendial
content becomes important. compliance.
Subsequent articles in this series will cover a wide range
Nomenclature used in pharmacopoeias for excipients, of topics: providing information to help in the creation of an
drug substances, and drug products must also be consid- effective compendial review process; presenting a case study
ered during the product lifecycle. The link between a prod- in compliance for excipients and raw materials; discussing
uct’s generic name and the content of the active ingredient considerations for monograph development; giving recom-
can be important in clinical trials to support dosing studies, mendations concerning global vs. national pharmacopoeias
in developing product strengths, and for filing and label- and the need for harmonization in order to establish con-
ing purposes, especially in the United States. USP <1121> sistent, global pharmacopoeia standards, which will help
states that USP–NF titles for monograph articles are legally industry deliver medicines with consistent quality to extend
recognized under the FD&C Act as the designations for use and improve the lives of patients around the world while
in labeling the articles to which they apply and relate to the meeting health authority expectations. It is the authors’ goal
adulteration and misbranding provisions of the Act. USP for these articles to provide clear understanding about the
<1121> also contains a section on the monograph naming need for pharmacopoeia compliance and practical guidance
policy for drug products containing salt drug substances. to assist those who perform this work to establish effective
The USP Salt Policy stipulates that USP will use the name of processes, partnerships and tools to maintain appropriate
the active moiety, which is the molecule or ion responsible and timely compliance across the bio/pharmaceutical in-
for the physiological or pharmacological action of the drug dustry to the benefit of patients.

MJH Life Sciences

substance, instead of the name of the salt, when creating
drug product monograph titles for such a drug product. Acknowledgment
The policy also stipulates that USP will base the strength The authors gratefully acknowledge the contribution of

Not for public distribution

of the product on the active moiety. Companies need to Susan J. Schniepp for her technical review and helpful sug-
be aware of the USP Salt Policy, which is enforced by FDA gestions during the preparation of this series of articles.
(6, 7), to avoid issues with the name and strength listed
on drug product labeling and in registrations. The FDA References
guidance (6) states that a drug product with labeling that 1. WHO, “Review of World Pharmacopoeias,” World Health Or-
contains a name that is inconsistent with the applicable USP ganization, Working Document QAS/12.512/Rev.1 (March
2013), www.who.int/medicines/areas/quality_safety/quality_
monograph title risks being misbranded. Another example assurance/resources/InternationalMeetingWorldPharmaco-
of the impact of pharmacopoeia nomenclature is the tran- poeias_QAS13-512Rev1_25032013.pdf?ua=1
sition from the excipient name hydroxypropyl methylcel- 2. N. A. Schwarzwalder and R. H. Bishara, American Pharmaceu-
lulose to the shortened title hypromellose, which resulted tical Review 7 (4), pp. 53-57 (July-August 2004).
in significant revisions to the ingredient listing on labels 3. EDQM, “EDQM Inspections and Trends of Deficiencies–Over-
view 2006 to 2018,” EDQM, Certification of Substances De-
and in registrations. partment, Public Document PA/PH/CEP (18) 56 (April 2019),
Once a product is launched and reaches the end of ex- www.edqm.eu/sites/default/files/cep_edqm_inspections_
clusivity, compendial monographs for drug substances and_trends_of_deficiencies_2006_2018_pa_ph_cep_18_56.
and drug products will be developed by the pharmaco- pdf
poeia. This is generally accomplished with the support 4. WHO, Good Pharmacopoeial Practices, WHO Expert Commit-
tee on Specifications for Pharmaceutical Preparations Fifti-
of companies who have received regulatory approval for eth Report, Technical Report Series No. 996, Annex 1, pp.
these products, to provide a public quality standard in the 67-85 (2016), www.who.int/medicines/publications/pharm-
pharmacopoeia that is applicable to the product or material prep/WHO_TRS_996_annex01.pdf?ua=1
from all approved sources. Considerations for monograph 5. BP, “How to Use the BP,” British Pharmacopoeia Website, www.
development, looking at the impact to both innovator and pharmacopoeia.com/how-to-use-the-bp
6. FDA, Naming of Drug Products Containing Salt Drug Sub-
generic-drug companies, will be provided in a later article stances, Guidance for Industry (CDER, June 2015), www.fda.
in this series. gov/media/87247/download
7. FDA, Naming of Drug Products Containing Salt Drug Sub-
Conclusion stances, Manual of Policies and Procedures (MAPP 5021.1
In this article, the first in a series about compendial ac- Rev.1) (CDER, Office of Pharmaceutical Quality, Effective
December 7, 2017), www.fda.gov/media/85022/download PT
tivities in the bio/pharmaceutical industry, the basis for
pharmacopoeia compliance expectations was provided,
34 Pharmaceutical Technology  REGULATORY SOURCEBOOK SEPTEMBER 2019 P h a r mTe c h . c o m