Microbiological Monitoring of the Environment
The microbiological monitoring program shall be performed during routine production and media fills and procedure for microbiological monitoring program are clearly defined in SOP.
Microbiological monitoring – frequency of monitoring, type of monitoring, sites monitored, alert and action level specifications, and clearly defined procedure for actions taken when specifications are exceeded should be included.
- Microbiological Methods
The microbiological materials and methods used in the environmental monitoring program should be defined and mentioned in SOP. Methods may include sample collection, transport, and neutralization of sanitizers, incubation, and calculation of results.
The following are sources of microbial contamination and their monitoring that should be addressed, including specifications:
- Airborne microorganisms
- Microorganisms on inanimate surfaces
- Microorganisms on personnel
- Water systems
- Product component bioburden
- Yeasts, Molds, and Anaerobic Microorganisms
Procedure for of periodic or routine monitoring methods for yeasts, molds, and anaerobes should be defined and mentioned in SOP.
- Exceeded Limits
Define the procedure for actions required when specifications are exceeded the predefined limit.
Container-Closure and Package Integrity
The procedures and results of demonstrating the integrity test of the microbiological barrier of the container-closure system should be mentioned.
Also consider and describe the procedure of container-closure integrity testing in initial validation and stability studies.
In initial validation of microbiological integrity of container-closure systems, product sterility testing is not normally considered sufficient.
The effectiveness and sensitivity of the experimental method applicable for container-closure integrity testing should be specified, defined and evaluated.
Sterility Testing Methods and Release Criteria
Procedure for Sterility test should be described in SOP and the protocol for the selection of representative units during production should be mentions with rationales.
For a drug product represented to be a drug recognized in an official compendium, when test methods differ significantly from official compendial test methods, a demonstration of the equivalency to the official compendial method should be provided.
Testing performed within barrier systems should be defined and information concerning validation of the barrier system may be necessary.
Bacterial Endotoxins Test and Method
Procedure for the bacterial endotoxins test used for the product test should be mentioned (if applicable) and should include qualification of the laboratory, inhibition and enhancement testing and results, determination of non-inhibitory concentration and maximum valid dilution.
For Reference and more information “Guidance on Validation of the Limulus Amebocyte Lysate Test As An End-Product Endotoxin Test for Human And Animal Parenteral Drugs, Biological Products, and Medical Devices.”
Evidence of Formal Written Procedures
Evidence should be available in the formal, written procedures describing the above elements and that these procedures are followed. Such evidence may consist of SOP’s or a listing of SOP’s or protocols submitted