For each drug product, there should be a laboratory determination that the product meets final specifications prior to release. According to the Code of Federal Regulations, 21 CFR 211.165, there should be written procedures describing the sampling, testing and acceptance criteria for the testing. Therefore, analytical test methods should be written with sufficient detail to allow another analyst to reproduce the conditions and obtain results. The test method should include:
- Scope of the method
- Equipment needed
- Operating parameters
- Reagents or standards needed
- Sample preparation
- Standard preparation
- Step-by-step description of the method
- System suitability requirements
- Calculations needed
- Data Reporting
A company recently received the following observation:
…. Laboratory controls do not include the establishment of scientifically sound and appropriate specifications, standards, sampling plans and test procedures designed to assure that in-process materials and drug products conform to appropriate standards of identity, strength, quality and purity.
Specifically, the following laboratory control deficiencies were observed when reviewing laboratory test methods and testing records for … drug products:
a. Test methods for active pharmaceutical ingredients (APIs) are deficient in that they do not contain adequate system suitability (SST) parameters and other controls for … assays before sample analyses. For example,
i. There are no pre-defined SST parameters for repeatability
ii. Instructions for standard and sample preparations, including weigh amounts and solution stability, are not included in test methods
b. Standard and sample preparatory information is not recorded onto ‘batch submission forms’ or laboratory notebooks.
c. Test results are not second-person checked.
For more information regarding analytical test method validation, development and content, refer to the following: FDA Guidance for Industry: Analytical Procedures and Methods Validation for Drugs and Biologics, FDA Guidance for Industry: Q2(R1) Validation of Analytical Procedures: Text and Methodology, draft Guidance for Industry: Q2(R2) Validation of Analytical Procedures and draft Guidance for Industry: Q14 Analytical Procedure Development.
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