September 2, 2021: Pharmaceutical Interview Questions and Answers
What should be covered in the autoclave validation document which is essential for submission to the regulatory agency for terminal sterilization cycle?
A. Description of the autoclave process
a. Information such as cycle type (e.g., saturated steam, water immersion, and water spray)
b. Cycle parameters and performance specifications
iv. Minimum and maximum Fo.
c. Autoclave(s) to be used for production sterilization, including manufacturer and model.
B. Autoclave Loading Patterns – description of representative autoclave loading patterns
C. Methods and Controls to Monitor Production Cycles
b. Biological indicators
c. Number and location of each
d. Acceptance and rejection specifications.
D. Requalification of Production Autoclaves – Routine and unscheduled requalification of production autoclaves, including frequency, should be provided.
E. Thermal Qualification of the Cycle
a. Heat Distribution and Penetration Studies that demonstrate the uniformity, reproducibility, and conformance to specifications of the production sterilization cycle should be provided.
b. Results from a minimum of three consecutive, successful cycles should be provided to ensure that the results are consistent and meaningful.
F. Thermal Monitors -The number of thermal monitors used and their location in the chamber should be described. A diagram is helpful.
G. The Effects of Loading on Thermal Input – Data should be generated with minimum and maximum load to demonstrate the effects of loading on thermal input to product.
H. Data summaries should consist of, for example, high and low temperatures (range), average temperature during the dwell period, minimum and maximum F0 values, dwell time, run date and time, and identification of the autoclave(s) used. These data should have been generated from studies carried out in production autoclave(s) that will be used for sterilization of the product that is the subject of the application.
I. Microbiological Efficacy of the Cycle – Validation studies that demonstrate the efficacy (lethality) of the production cycle should be provided. A sterility assurance of 10-6 or better should be demonstrated for any terminal sterilization process.
J. Identification and Characterization of Bioburden Organisms – Describe the methods and results from studies used to identify and characterize bioburden organisms. The amount and type of information supplied may be dependent on the validation strategy chosen. For example, more information may be needed for bioburden-based autoclave processes than for overkill processes. Information concerning the number, type, and resistance of bioburden organisms may be necessary, including those organisms associated with the product solution and the container and closure. It may be necessary to identify the most heatresistant bioburden organisms.
K. Identification, Resistance, and Stability of Biological Indicators – Information and data concerning the identification, resistance (D and Z values), and stability of biological indicators used in the biological validation of the cycle should be provided. If biological indicators are purchased from a commercial source, it may be necessary to corroborate the microbial count and resistance, and provide performance specifications.
L. The Resistance of the Biological Indicator Relative to That of Bioburden Studies characterizing the resistance of the biological indicator relative to that of bioburden may be necessary. Resistance in or on the product (i.e., in the product solution, or on the surface of container or closure parts or interfaces) should be determined as necessary. If spore carriers are used (e.g., spore strips), the resistance of spores on the carrier relative to that of directly inoculated product should be determined, if necessary.
Reference: Guidance for Industry for the Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products