Stability and Expiration Dating
1. What is the expiration dating on the subject product?
2. Do the stability studies performed on the selected product include preservative effectiveness testing?
3. What is the source of Analytic Method?
4. If sterility testing is performed by an outside laboratory, what is the name and address.
5. Has the firm audited the contract laboratory procedures and test results? What is the date of the last audit?
6. If sterility testing is performed in-house, what are the qualifications off personnel responsible for sterility testing?
7. Does the firm have adequate written procedures for the sampling and testing of products for sterility, potency, pyrogens, particulate matter, and other appropriate tests?
8. Review sampling and testing records for three lots of the selected drug product: were all required tests performed appropriately, and were results within specifications?
9. Review sterility testing results summary data accumulated since the last EIR, or the last six months, whichever is greater. What is the firm’s overall failure rate upon:
a. initial testing
b. first retest
c. second retest
10. How much time routinely elapses between sterilization of a product and when sterility test samples are put on test? What are the holding conditions of lot samples waiting to be tested?
11. What is the average number of lots sterility tested per month?
12. Describe the firm’s procedures for evaluating batches that fail the initial sterility test. How are “false positives” determined? If the cause of a sterility failure cannot be determined as arising from the production environment or laboratory error, what decision is made by the firm concerning the release of the lot in question? (attach retest protocol)
13. Are the “false positive” rates similar for aseptically filled products and terminally sterilized products? If the rate for aseptically filled products is markedly higher than for terminally sterilized products that are manipulated in a similar manner during sterility testing, then this rate indicates truely contaminated rather than “false positive”, and an in-depth review should be made of the sterilization process.
15. What air quality is provided in the laboratory environment?
16. What air quality is specified for sterility testing areas? Is laminar air flow provided?
17. What type of environmental monitoring is performed in the laboratory (e.g., type and location of sampling; sampling equipment; frequency)?
18. Compare the firm’s written environmental specifications for the laboratory with sampling data for the previous three months. Are results within specifications? If not, what action was taken by the firm with reference to: (a) environmental specifications;
(b) product undergoing testing at the time of the out-of-spec results?
19. Have all testing, measuring, monitoring equipment (thermometer, thermocouple systems, pressure gauges, pH meter, etc.) used in production and in laboratory testing been calibrated?
20. Is equipment periodically checked for accuracy and recalibrated?
21. Are there written procedures covering the calibration and periodic checking and recalibration of production and laboratory equipment, including set intervals and specifications?
22.If the firm is using an automated process control system is source code documentation is available at the firm? Aslo see 21 CFR part 11 compliance.
Process Validation guidelines Series
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