The week of November 17, 2014 two new compounding pharmacy warning letters were posted by FDA. The first warning letter issued October 29, 2014 the firm was cited sterility issues when repacking Acastin and/or Lucentis medications. The inspection originated as a result of notification of FDA by the Florida Department of Business and Professional Regulation of 37 adverse events linked to these products. As cited in the warning letter, the facility failed to use a functional laminar flow hood and to separate the sterile drug processing area from the common pharmacy area, and completely removed the rubber stoppers from the sterile, preservative free vials, thus exposing the content to an uncontrolled environment during repackaging. The firm signed an affidavit describing the practices and methods used in preparing syringes containing Avastin (bevacizumab) or Lucentis (ranibizumab). In this affidavit, the firm stated that syringes were prepared in a laminar flow hood; however, the firm also stated that the hood was “not turned on” or “functional” and was only used because it was a flat surface. In addition, the firm stated that the routine practice for preparing the syringes consisted of opening vials by removing the rubber stopper, then using syringes to produce approximately [redacted] doses from one vial of Avastin (bevacizumab). Both Avestin and Lucentis are provided preservative free from the manufacturer.
The second warning letter, issued November 10, 2014 the firm was cited for manufacturing versus compounding. Section 503 of the Food Drug and Cosmetic Act requires a valid prescription for individually-identified patients; because you manufacture and distribute drugs without valid prescriptions for individually-identified patients, the manufacture of those drugs is also subject to FDA’s Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (CFR), Parts 210 and 211. The following CGMP deficiencies were identified during the inspection:
1. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).
2. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a))
3. Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).
4. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv))
5. Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).