1Stability and storage
Failure to establish and follow a 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, as required by 21 CFR 211.166(a). Specifically, you assigned a (b)(4) expiration date to your products without supporting data. Response to the Form FDA-483 We have reviewed your response, dated March 28, 2024, to FDA’s Form FDA-483 in detail…
2Aseptic processing and sterility assurance
Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions, as required by 21 CFR 211.42(c)(10)(v). For example, you have not validated your process for cleaning and disinfecting the ISO (b)(4) cleanrooms where your products are manufactured.
3Aseptic processing and sterility assurance
Aseptic processing areas are deficient regarding the system for environmental monitoring to prevent contamination, as required by 21 CFR 211.42(c)(10)(iv). For example, you have not performed non-viable particulate monitoring, personnel monitoring, active or passive viable air sampling, or sampling of critical surfaces for microorganisms in the aseptic processing area in association with each production batch.
4Aseptic processing and sterility assurance
Failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes, as required by 21 CFR 211.113(b). For example, you failed to adequately validate (i.e., by performing media fill simulations) the aseptic process used to manufacture your Purified Fluid Allograft product. Your product purports to be sterile and is expected to be sterile.
5Aseptic processing and sterility assurance
Written records are not always made of investigations into unexplained discrepancies or the failure of a batch or any of its components to meet specifications whether or not the batch has already been distributed , as required by 21 CFR 211.192. For example, from March 2023 and June 2023, your firm had two sterility failures during finished product testing of your Purified Fluid Allograft product. Although you identified the contaminating organisms, you failed to conduct an investigation to determine the root cause of the failures.
6Aseptic processing and sterility assurance
Failure to establish written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess, as required by 21 CFR 211.100(a). Specifically, a. The manufacturing process for your Purified Fluid Allograft product has not been adequately validated with respect to identity, strength, quality, and purity. During the inspection, you provided a validation study for your amniotic fluid product, which only tested for sterility. However, this is not sufficient to assure the identity, strength, quality, and purity of your product. b. The manufacturing process for your Allograft Matrix product has not been validated with respect to identity, strength, quality, and purity.
