August 31, 2021: Pharmaceutical Interview Questions and Answers
#ContaminationDuringSterilityTesting #SamplesForSterilityTesting #InvalidationOfSterilityTestFailureResults #SterilityFailureInvestigation
1. What is the probability of detection of contamination during sterility testing?
Sterility tests are limited in their ability to detect contamination because of the small sample size typically used. For example, as described by USP, statistical evaluations indicate that the sterility test sampling plan “only enables the detection of contamination in a lot in which 10% of the units are contaminated about nine times out of ten in making the test” (Ref. 13). To further illustrate, if a 10,000-unit lot with a 0.1 percent contamination level was sterility tested using 20 units, there is a 98 percent chance that the batch would pass the test.
2. How to collect the samples for sterility testing?
It is important that the samples represent the entire batch and processing conditions. Samples should be taken:
• At the beginning, middle, and end of the aseptic processing operation
• In conjunction with processing interventions or excursions
3. When sterility test failure results can be invalidated?
An initial positive test would be invalid only in an instance in which microbial growth can be unequivocally ascribed to laboratory error.
Only if conclusive and documented evidence clearly shows that the contamination occurred as part of testing should a new test be performed.
4. In case of inconclusive investigation, what should be the batch disposition decision?
When available evidence is inconclusive, batches should be rejected as not conforming to sterility requirements.
5. What parameters should be considered while performing sterility failure investigation?
The investigation’s persuasive evidence of the origin of the contamination should be based on at least the following:
1. Identification (speciation) of the organism in the sterility test
2. Record of laboratory tests and deviations
3. Monitoring of production area environment
4. Monitoring Personnel
5. Product Presterilization Bioburden
6. Production record review 7. Manufacturing history
Reference: FDA Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice – September 2004