Transcript Regulatory Aspects of Pharmaceutical Excipients

Regulatory Aspects of
Pharmaceutical Excipients
PQRI Workshop
Nick Buhay
Acting Director
Division of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research
Food and Drug Administration
Marriott Hotel and Convention Center
October 10, 2006
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Oversight of Excipient
Manufacturing Quality
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Current oversight program
– Monitoring the uses/types of excipients
– Monitoring excipient quality
– Monitoring of manufacturing problems based on
excipient quality
– Recognition of use of Voluntary CGMP
– Participation in review of standards, industry
input
– Oversight of user control of excipients:
application conditions of approval, CGMP
– ‘For cause’ inspection of excipient mfg as drug;
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other regulators’/other FDA inspection
Excipient Manufacturing
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Subject to statutory requirements in
section 510 (a) (2) (B) of the Food,
Drug and Cosmetic Act
– Excipients must be manufactured,
processed, packaged and held in
conformity with Current Good
Manufacturing Practice (CGMP)
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Models for CGMP
Conformance
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FDA has not developed regulations or
specific guidance on CGMP
conformance for excipients
ICH Q7A GMP Guidance for APIs
contains applicable guidance
However, FDA is supportive of the
IPEC GMP Guide for Bulk
Pharmaceutical Excipients
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Drug Excipient Quality
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Quality characteristics of excipients are
significant to the overall quality of the
drug products in which they are used
Drug product manufacturers rely on
excipient manufacturers to provide
excipients of uniform quality, physical
and chemical characteristics, e.g.,
levels of impurities
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Drug Excipient
Manufacturers
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Specification development based on
critical quality attributes
Process controls that ensure consistent
conformance with specifications
Every batch is tested to ensure
conformance with all specifications
Provide reliable test data to drug
product manufacturers
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Drug Product
Manufacturers
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Identify excipients needed for drug
product formulations, including
physical and chemical characteristics
Conformance with the CGMP
regulations in 21 CFR 211.84
Qualify sources of excipients
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Drug Product
Manufacturers
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21 CFR 211.84(d)(2) requires the user/drug
product manufacturer to test every batch of
drug excipient for conformity with written
specifications, for purity, strength and
quality
However, drug product manufacturers can
rely on their suppliers for this testing,
provided that the reliability of the suppliers’
test results is validated at appropriate
intervals
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Drug Product
Manufacturers
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The CGMPs are not specific as to the
method and frequency of validating
test results provided by suppliers
Drug product manufacturers should
have SOPs detailing a scientifically
sound approach to ensure periodic
validation of suppliers’ test results
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Drug Product
Manufacturers
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For excipients that are critical to the
quality of the finished dosage form,
testing by the drug product
manufacturer may be necessary to
verify the critical attributes of every
batch
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Drug Excipient Quality
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Send us information
Contribute input
– Science-based
– Risk assessment

Questions????
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