www.biopharminternational.com March 2020 BioPharm International eBook 27
cies to gain marketing approval for
the product in countries around
the world. During the regulatory
rev iew process, differences can
emerge in the quality requirements
that are approved for the product,
based on determinations made by
the health authorities in individ-
ual countries. These differences are
often minor, but may also be quite
significant, creating challenges for
compliance in all countries where
the product is approved.
A n extreme, but not uncom-
mon, example can be imagined
for a drug product that contains
a genotoxic impurit y. Differing
views by different regulators as
to the appropriate control for this
impurity can lead to more than
20 different country-specific lim-
its for the impurity. The company
can then test and release the drug
product to the individual limits
that are approved in each coun-
try. A more common approach,
however, is to apply the tightest
approved limit to enable worldwide
release of the product. Even with
this global approach, individual
certificates of analysis are required
to reflect the approved limits in
individual countries. Continuing
several years further in the prod-
uct lifecycle, the pharmacopoeias
eventually develop monographs for
the drug substance and product,
which can introduce additional
differences in testing requirements.
Compliance with requirements
p ubl i she d by pha r macop o e ia s
around the world is a legal and
regulatory requirement in those
countries and regions in which the
pharmacopoeia is applicable (3).
The situation is even more com-
ple x because a compa ny must
comply with the pharmacopoeial
requirements that are applicable
in a particular country, and also
with their product registrations as
approved in countries around the
world. There are many challenges
that make pharmacopoeia compli-
ance difficult, including the need
to address differences between the
pharmacopoeia and approved reg-
istrations (4).
There are reasons why a com-
pany might choose to proactively
submit information to the phar-
macopoeias to enable monograph
elaboration, but different com-
panies may make different deci-
sions (1). One option is for the
company not to participate in the
process, due in part to the diffi-
culty in resolving differences that
may emerge in the pharmacopoeia
monograph; the later the mono-
g raph is developed, the longer
the company can defer address-
ing the differences. These differ-
ences in the monograph, compared
to the requirements contained in
the product registrations, occur
even though the monograph is usu-
ally based on specifications that are
approved by regulatory authorities,
as stated in the Good Pharmacopoeial
P ract ices (GPh P) g u ida nce (5).
Differences between the monograph
requirements and the registrations
must be resolved so the company
remains in compliance. There is
some flexibility in how the company
complies, with a range of options to
resolve the differences, but in this
flexibility, there is also complexity.
Another choice a company might
make is to participate in monograph
development, but to submit the
necessary information when mul-
tiple companies are involved in the
process. This may be considered an
intermediate approach, based on the
timing for the submission, which still
may result in compliance challenges
if the monograph differs from the
company's approved registrations (1).
Regulatory Sourcebook Pharmacopoeia Compliance Series
A Practical Guide to Pharmacopoeia Compliance: A Series
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
to establish effective processes, partnerships, and tools to maintain appropriate and
timely compliance across the bio/pharmaceutical industry to the benefit of patients.
The following articles can be found within this ebook and online at
www.BioPharmInternational.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
• 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
