A large number of quality control related 483s and warning letters in recent years demonstrate that regulated companies are having problems with the implementation of regulations for quality control laboratories.
FDA and other agencies have held inspections of QC laboratories in the highest emphasis because the drug products and APIs (Active Pharmaceutical Ingredient) are released to the market after testing and approval without any further check.
General Requirements
- Scientifically sound and appropriate specifications
- Establish written specifications, sampling, procedures
- Conformity to written specifications
- Calibration of instruments
- Test results documented at the time of performance
- Appropriate procedures for the acceptance of components, in-process materials, and drug products
- Methods must be documented and approved
Testing and Approval or Rejection of Components
- The Representative sample consists of a number of units that are drawn based on rational criteria such as random sampling and intended to assure that the sample accurately portrays the material being sampled.
- At least one specific identity test is conducted on the component by the manufacturer at the time of receipt.
- The manufacturer establishes the reliability of the supplier's analysis by validating the supplier's test results at appropriate intervals.
Sampling and Testing of In-process Materials and DrugProducts
- Written procedures shall be established and followed for inprocess testing
- In-process materials shall be tested for identity, strength, quality, and purity, and approved or rejected by the QU
- Testing of samples shall assure that the drug product and in process material conform to specifications
Testing and Release for Distribution
- Documented accuracy, sensitivity, specificity, and reproducibility of test methods
- Test each batch for conformance to specifications
- Follow written sampling and testing plans
- Document testing methods and number of units/batch
Drug Product StabilityTesting
- Written stability testing program
- Full shelf-life studies for determining the expiration date
- Combination of accelerated studies and basic stability
- Conducted on samples from representative batches
- Sample size and test intervals based on statistical criteria
Reserve Samples
- Reserve samples from representative sample lots or batches
- Stored under conditions consistent with product labeling
- Results of the examination shall be recorded and maintained with other stability data on the drug product
- Investigate any evidence of reserve sample deterioration
Laboratory Records
- A description of the sample
- The location of the method validation data
- A description of the suitability of the method
- Record of the sample weight including all test data obtained
- A statement that test methods are accurate, reliable, and followed' (21CFR part 58).
Related: Tips for Regulated Laboratories
Inspectors will check following points during pharmaceutical quality control laboratory inspections:
- Test activities
- Contract testing
- Ensuring suppliers quality
- Self inspection
- Trending
- Change control
- Risk management
- Laboratory documentation
- Personnel
- Training
- Facility
- Equipment validation
- Cleaning
- Materials
- Sampling
- Starting/packagin gmaterials
- Testing
- Stability testing
- Validation of test methods
- Handling of test results
- Out of Specification (OOS)
- Failures
- Retesting and Resampling
- Process release of test results
- Batch release
FDA inspection and oversight of quality control (QC) laboratories are essential elements of the agency’s evaluation of the compliance status of regulated companies representing multiple industries - pharmaceuticals, biologics, medical devices, as well as foods and cosmetics - as well as the contract QC laboratories which service these industries.
Lack of compliance can result in severe regulatory actions, criminal liability, fines, and the inability to obtain product approvals.
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