Sage Products Inc – FDA Warning Letter, Sep 1, 2016

The FDA inspected Sage Products Inc.'s drug manufacturing facility from June 2 to September 1, 2016, revealing CGMP violations, rendering their drug products adulterated.

Key violations include: 1. **Failure to validate test methods (21 CFR 211.165(e)):** Sage's (b)(4) microbiological screening method for liquid drug products was inadequate. It failed to reliably detect objectionable microorganisms like *Burkholderia cepacia*, leading to product recalls since 2006. The method's validation deficiencies include an insufficient dilution factor, lack of enrichment and scraping steps, and inadequate recovery of stressed organisms. The FDA advised using a verified compendial method. 2. **Insufficient sampling plans and test procedures (21 CFR 211.160(b)):** Procedures for microbial enumeration were inadequate. A positive (b)(4) test result was not sufficiently investigated, with a small, unrepresentative sample used for "confirmatory" testing, potentially invalidating initial positive findings. 3. **Failure to clean and maintain equipment (21 CFR 211.67(a)):** Bioburden analysis acceptance criteria for the Clean-in-Place (CIP) system failed to include *B. cepacia*, despite a history of contamination and a biofilm identified in the system.

Additionally, products manufactured by ChemRite CoPac, Inc. for