No. 21 CFR 211.113(a) requires appropriate written procedures to be established and followed during manufacturing to prevent objectionable microorganisms in drug products not required to be sterile.
Additionally, the second paragraph of USP General Chapter <51> Antimicrobial Effectiveness Testing reads:
- Antimicrobial preservatives should not be used as a substitute for good manufacturing practices, solely to reduce the viable microbial population of a nonsterile product, or control the pre sterilization bioburden of a multidose formulation during manufacturing.
- Drug manufacturers should not rely on antimicrobial preservatives to reduce initial out-of-specification plate counts to within-specification levels and then market the product. Section 211.165(f) mandates that drug products failing to meet established standards or specifications be rejected. The initial test results exhibiting out-of specification levels of microbes are not disqualified even if subsequent test results are within specifications. In such cases, FDA still expects the manufacturer to reject the drug product based on the initial results.
- It is also not acceptable for manufacturers to allow an inappropriately long time (e.g., weeks) to pass before testing the product, which might permit the preservative to reduce levels of microbes possibly introduced during manufacture and thus avoid out-of-specification test results.
- Finally, drug manufacturers should review their manufacturing process to determine procedures or equipment that might introduce contaminating microorganisms into the process or product.
