www.biopharminternational.com March 2018 BioPharm International eBook 21
Outsourcing Resources Quality Agreements
In another example, a contract
facility used certain materials in
production of a drug substance for
a sterile drug product. In addition
to failing to thoroughly investi-
gate product quality deviations,
the contract facility did not com-
municate with FDA about changes
i n it s mate r ia ls, eve n t houg h
t he cha nges should have been
rev iewed and approved by FDA
before being implemented. FDA
issued a warning letter and sent a
courtesy copy to the owner. "You
and your customer, …, have a qual-
ity agreement regarding the man-
ufacture of … Regardless of this
agreement, you and … are both
responsible for the quality of drugs
released and ultimately adminis-
tered to patients. You are required
to ensure that drugs are made in
accordance w ith section 501(a)
(2)(B) of the FD&C Act to ensure
safety, identity, strength, quality,
and purity."
CONCLUSION
Neither owners nor contract facili-
ties can contract around CGMP.
FDA recommends that owners and
contract facilities use quality agree-
ments to help ensure that both
parties understand and document
the actions they will take to ensure
compliance with CGMP. Without a
well-drafted quality agreement, the
quality of products manufactured
under contract may be affected and
patient safety may be jeopardized.
REFERENCES
1. FDA, Contract Manufacturing
Arrangements for Drugs:Quality
Agreements, Guidance for Industry (CDER,
Silver Spring, MD, November 2016), www.
fda.gov/downloads/drugs/guidances/
ucm353925.pdf
2. Federal, Food, Drug, and Cosmetic
Act, United States Code, Title 21,
www.fda.gov/RegulatoryInformation/
LawsEnforcedbyFDA/FederalFoodDrugand
CosmeticActFDCAct/default.htm
3. Food and Drug Administration
Safety and Innovation Act, Public
Law 112–144, July 9, 2012, www.
fda.gov/RegulatoryInformation/
LawsEnforcedbyFDA/
SignificantAmendmentstotheFDCAct/
FDASIA/default.htm
4. FDA, Warning Letters, FDA.gov, www.
fda.gov/ICECI/EnforcementActions/
WarningLetters/default.htm
BP
to stating and agreeing on the quality unit's responsibilities.
Second, some agreements are interpreted in a manner
that deviates from CGMP expectations (e.g., a contract
manufacture interprets that they do not need to perform
an investigation of an out-of-specification result that they
generate since the drug company is responsible for release of
commercial batches), which may lead to observations being
cited during an inspection. Third, a mechanism to periodically
assess and revise—if necessary—the agreement is
not always included in agreements. Lastly, some quality
agreements include commercial contract or business aspects
and should only focus on quality management aspects as
laid out in current regulations, such as 21 Code of Federal
Regulations (CFR ) 211 (5) or guidance documents such
as ICH Q7 (2) or Q10 (6). Additional helpful information on
avoiding these mistakes can be found in FDA's current
guidance for industry (1).
BioPharm: How can drug companies and contract
manufacturers create quality agreements that clearly
outline each company's responsibilities?
Iser: The best way for drug companies and contract
manufacturers to create quality agreements that clearly
outline each company's responsibilities is to follow the
recommendations for roles and responsibilities that are
found in current guidance documents. Current agency
documents clearly lay out expectations for documenting
roles and responsibilities that are directly linked to the
quality unit responsibilities included in CGMPs; and
pharmaceutical quality system aspects found in health
authority guidance and ICH guidelines.
References
1. FDA , Contract Manufacturing Arrangements for Drugs:
Quality Agreements Guidance for Industry (CDER, CBER,
CV M, November 2016), w w w.fda.gov/downloads/Drugs/
GuidanceC omplianceRegulator y Information /Guidances /
UCM353925.pdf
2. I C H , Q7 G o o d M a n u f a c t u r i n g P r a c t i c e G u i d a n c e
f o r A c t i v e P h a r m a c e u t i c a l I n g r e d i e n t s ( I C H ,
S e p t e m b e r 2 0 16 ) , w w w. f d a . g o v /d o w n l o a d s / D r u g s /
GuidanceC omplianceRegulator yInformation /Guidances /
UCM073497.pdf
3. FDA, Guidance for Industry and FDA Staff: Current Good
Manufacturing Practice Requirements for Combination Products,
Final Guidance (FDA, Silver Spring, MD, January 2017),
www.fda.gov/downloads/RegulatoryInformation/Guidances/
UCM429304.pdf
4. European Commission, EudraLex The Rules Governing Medicinal
Products in the European Union, Volume 4 EU, Guidelines for
Good Manufacturing Practice for Medicinal Products for Human
and Veterinary Use, Chapter 7 Outsourced Activities, (EC, June
28, 2012), https://ec.europa.eu/health/sites/health/files/files/
eudralex/vol-4/vol4-chap7_2012-06_en.pdf
5. 21 CFR 211
6. ICH, Q10 Pharmaceutical Quality System (ICH, April 2009).
—Susan Haigney
Expectations in Quality Agreements (Cont.)
