www.biopharminternational.com March 2020 BioPharm International eBook 35
Regulatory Sourcebook Pharmacopoeia Compliance Series
p r e v i o u s l y r e c e i v e d a p p r o v a l
for their method in Europe. In
essence, the currently approved
met ho d i s now con side r e d a n
alternative method to that in the
Ph. Eur. monograph.
Compliance is
complicated when
there are differences
between compendial
requirements and
approved drug product
registrations.
For the drug substance, there is
another way to ensure European
r e g u l a t o r y a g r e e m e nt t o u s e
methods other than those listed
i n t he cor resp ond i ng Ph. Eu r.
monog raph. T he procedure for
"Cer t if icat ion of Su itabilit y to
the Monographs of the European
Pharmacopoeia" (CEP), described
on the European Directorate for
t he Q u a l it y of Me d ic i nes a nd
HealthCare (EDQM) website (12),
provides for a centralized assess-
ment of applications describing
the manufacture and quality con-
trol of drug substances to facil-
it ate a nd s i mpl i f y e xc h a n ge s
between regulators and industry
to ensure compliance w ith the
Ph. Eur. and therefore w ith the
requirements of the relevant EU
legislation. The procedure com-
plements and bridges the Ph. Eur.
monograph and the submission
of a marketing authorization dos-
sier for a dr ug product. Also as
noted on the EDQM website, CEPs
are recognized by the signatory
parties of the Ph. Eur. Convention
and are also recognized by many
other countries around the world,
including Canada, Australia, New
Zealand, Tunisia, and Morocco.
CONCLUSION
C ompl i a nc e w it h c omp e nd i a l
standards is a legal and reg ula-
tory requirement in those coun-
tr ies and reg ions in which the
pharmacopoeia is applicable and
i s e ss e nt ia l to e n s u r e cont i n-
ued availability of medicines to
patients. However, compliance is
complicated when there are dif-
fe r e nc e s b e t we e n c omp e nd i a l
requirements and approved drug
product registrations. Challenges
may arise in the elaboration of
monog raphs by the phar maco -
poeia, when differences emerge
in the tests, methods, and accep-
t a n c e c r it e r i a — r a n g i n g f r o m
m i nor to sig n i f ica nt— bet ween
t he monog raph s a nd reg i st ra-
t ion s . T he s e d i f fe r e nc e s mu st
be addressed to ensure ongoing
compliance. Options include the
addition of more quality testing or
updates to product registrations to
bridge any gaps.
For met ho d d i f ferences, t he
choices are limited, as expressed
in the "MARK" principle: Merge,
Add, Replace, or Keep. To achieve
compliance decisions that meet
both regulatory and compendial
requirements, dialogue is needed
bet ween impacted stakeholders
in a company, including quality,
reg u lator y, compend ia l a f fa irs,
a nd ma ny ot hers. A lig ning on
an implementation strateg y and
m a i n t a i n i n g c o m m u n i c a t i o n
throughout the execution of the
plan are essential to achieve the
best compliance outcome for the
company.
ACKNOWLEDGMENT
The authors gratefully acknowl-
edge the contribution of Susan J.
Schniepp for her technical review
and helpful suggestions during the
preparation of this series of articles.
REFERENCES
1. J.M. Wiggins and J.A. Albanese,
"Monograph Development: Why
and When to Participate," BioPharm
International Regulatory Sourcebook
eBook, 12-24 (March 2020).
2. J.M. Wiggins and J.A. Albanese,
"Monograph Development: How to
Participate; How to Harmonize," www.
BioPharmInternational.com (March
2020).
3. M. Wiggins and J.A. Albanese, "Why
Pharmacopoeia Compliance Is
Necessary," BioPharm International
Regulatory Sourcebook eBook, 18-25
(September 2019).
4. J.M. Wiggins and J.A. Albanese,
"Why Pharmacopoeia Compliance
Is Difficult," BioPharm International
Regulatory Sourcebook eBook
(September 2019).
5. WHO, Good Pharmacopoeial
Practices, WHO Expert Committee
on Specifications for Pharmaceutical
Preparations Fiftieth Report, Technical
Report Series No. 996, Annex 1, pp.
67–85 (2016).
6. J. M. Wiggins, "Adventures in
Compliance: Converging on Global
Regulatory and Compendial Standards
for Drug Substances and Products,"
Presentation at the 1st PDA Europe
Pharmacopoeia Conference:
Convergence, Harmonization and the
Future Direction of Pharmacopoeias,
Vienna, Austria (May 29–30, 2018).
7. ICH Q3A(R2) Impurities in New Drug
Substances (ICH, Oct. 25, 2006).
8. ICH Q3B(R2) Impurities in New Drug
Products (ICH, June 2, 2006).
9. M. Wiggins and J.A. Albanese,
"Surveillance Process for Industry:
Monitoring Pharmacopoeia Revisions,"
BioPharm International Regulatory
Sourcebook eBook, 26–39 (December
2019).
10. J. M. Wiggins and J. A. Albanese,
"A Brief History of Pharmacopoeias:
A Global Perspective," www.
BioPharmInternational.com (September
2019).
11. EDQM, General Notices, Section 1.1
General Statements—Alternative
Methods, Ph. Eur. 10th Edition (Jan. 1,
2020).
12. EDQM, "Certification of Suitability—
About the Procedure—Mission &
Organisation," EDQM.eu. BP