Many references describe airborne microbial challenge test to evaluate the possible contamination of pharmaceutical packages due to improper filling or sealing.
This Application Note intends to present the general Guide Lines as suggested by PDA.
Material and Equipments
– Challenge Micro-organisms: Bacillus subtilis spores
– Basic bacteriological laboratory equipment
– Microbiological media
– Airtight test chamber
– Microbiological spore nebulization unit with impinger, motor and fan
– Termometer, pressure tester, moisture tester
– Chamber sterilization equipment
– Microbiological air sampler.
This test is applicable to sterile pharmaceutical packages that cannot tolerate liquid immersion and rely on tortuous path or barrier seal to ensure package integrity.
Microbial challenge test by aerosolized micro-organisms involves placing product-filled or media-filled package units into a specially designed aerosolization chamber and charging the atmosphere within the chamber with a nebulized cloud or aerosol of micro-organisms for a specified period of time. During the challenge test the package may be subjected to differential pressure challenges.
The atmosphere within the chamber must be kept within definites humidity and temperature ranges and well circulated. At the end of the challenge the units are removed from the chamber.
If media-filled product is used, the units are then incubated and examined for microbial growth. Otherwise, the package contents are removed and exposed to media which is subsequently incubated and examined for growth.
Microbial aerosolization challenge tests determine the presence of micro-organisms that have penetrated a package exposed to aerosolized micro-organisms.
The sensitivity of the test is based on the incidence of ingress of aerosolized micro-organisms into positive control package defects and the ability to detect such ingress.
Ackers, M.A., “Package Integrity Testing” Parenteral Quality Control: Sterility, Pyrogen, Particulate & Package Integrity Testing, M.J. Akers ed., Marcel Dekker, N.Y., copy 1985
American Society for Testing and Materials, F1585-95 Integrity Testing for porous barrier medical devices
Americal Society for Testing and Materials, F1608-95 Microbial Ranking of porous packaging materials (exposure chamber method)
Blakistone, B. Harper, C. “New developments in seal integrity testing”, Plastic Package Integrity Testing, Assuring Seal Quality, Institute of Packaging, copy 1995
Hansen,J, “In quest of sterile packaging: Part I. Approaches to package testing. Medical Device & Diagnos, p.56-61, ug 1995
Korczynski, M., “Evaluation of closure integrity” Aseptical Pharmaceutical Manufacturing: Technology for the 1990’s, Interpharm Press, Buffalo Grove, IL, copy 1987
Reich, R. “A Method for evaluating the microbial barrier properties of intact packages”, Medical Devices Diagnos. Ind. p. 80-88, Mar 1985
Pharmaceutical Package Integrity, Technical Report No.27, PDA Journal of Pharmaceutical Science and Technology, pg 9, 25, 26, 1998.