Good Manufacturing Practice ( GMP ) Compliance:: Gmps Explained
Good Manufacturing Practice ( GMP ) Compliance:: Gmps Explained
Good Manufacturing Practice ( GMP ) Compliance:: Gmps Explained
GMPs EXPLAINED
Presented by
The Fourth Annual Pharmaceutical Regulatory and Compliance Congress and Best Practices Forum November 13, 2003
minimum GMP for methods to be used, and the facilities or controls to be used for, the manufacture, processing, packing or holding of a drug to assure that the drug is:
Safe
International sites
Schering Plough ($500 Million) Abbott Laboratories ($100 Million) WyethAyerst Laboratories ($30 Million) Individual Defendants
International cooperation
ICH: International Conference on Harmonisation
Proposed
Control
Quality
Assurance
Documentation
Before entering into contract, review regulatory history Monitor regulatory compliance
Air
Sanitation
21 C.F.R. 211.42-58
7
Must have written procedures and testing of product while being manufactured to assure batch uniformity and integrity Control procedures shall be established to monitor output and to validate manufacturing processes that could cause variability 21 C.F.R. 211.110
9
To assure that a drug product meets applicable standards of identity, strength, quality and purity at the time of use, it shall bear an expiration date determined by appropriate stability testing described in Section 211.166.
21 C.F.R. 211.137 (a)
Expiration dates shall be related to any storage conditions stated on the labeling, as determined by stability studies described in Section 211.166.
21 C.F.R. 211.137 (b)
10
must have written procedures designed to assure that correct labels, labeling and packaging materials are used for drug products; such written procedures shall be followed. mix ups have been a major reason for drug product recalls.
21 C.F.R. 211.130
11
Label
For each batch of drug product, there shall be laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient prior to release.
There shall be appropriate laboratory testing, as necessary, of each batch required to be free of objectionable microorganisms.
21 C.F.R. 211.165 (a) & (b)
12
Production and control records shall be reviewed and approved by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed.
Trend Analysis
Distributed Product
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21 C.F.R. 211.192
Any unexplained discrepancy or the failure of a batch or any of its components to meet any of its specifications must be investigated whether or not the batch has already been distributed.
Investigate other batches of same drug product Investigate other drug products that may have been associated with the specific failure or discrepancy Written record of investigation
15
Hypotheses should be scientifically based Subject matter experts should be consulted throughout the investigation, including the initial identification of hypotheses Once a hypothesis is identified, it must be investigated All hypotheses should be validated or invalidated
16
As part of deviation investigations... Root cause identification and definitive corrective actions
Company Program / System should audit:
Timeliness of corrective / preventative actions Effectiveness of actions Documentation
Example:
Environmental monitoring/Cleaning
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After an FDA inspection... Establish scientifically sound corrective and preventative actions
Realistic timeframes
Quality control unit shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. The quality control unit shall be responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company.
21 CFR 211.22(a)
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cGMP: Complaints
Written
Review
Documentation
21 C.F.R. 211.198
Data Integrity
External review: FDA inspections, business deals (due diligence), and products liability cases
21
cGMP: Auditing
Resources Authority
GMPs EXPLAINED
Presented by
The Fourth Annual Pharmaceutical Regulatory and Compliance Congress and Best Practices Forum November 13, 2003