1Aseptic processing and sterility assurance
Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)). Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a…
2Deviation, CAPA, and investigation
Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
3Laboratory and QC controls
Your firm failed to establish the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).
4Deviation, CAPA, and investigation
In response to Observation 1 of the Form FDA 483, you state that your investigation was extended to other batches and bulk drug samples were submitted to the manufacturer. However, you did not provide: a. Copies of completed investigation reports. b. Documentation showing visual inspections were performed for other potentially impacted batches. c. Documentation of examination and/or testing of the bulk drug products.
5Training and personnel
In response to Observation 3 of the Form FDA 483, you acknowledge that (b)(4) sampling was missing and that you will improve microbiological (b)(4) sampling. However, you did not provide an updated copy of your firm’s environmental and personnel monitoring procedures including microbial sampling, alert/action limits, and routine monitoring activities. In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and…
6Validation and qualification
In response to Observation 2 of the Form FDA 483, you state that the “accuracy, specificity, and reproducibility of titration assay method has been initiated and established for ascorbic acid 500mg/mL injection.” However, you did not provide a completed method validation report for the titration assay of ascorbic acid.
