1Aseptic processing and sterility assurance
Failure to establish laboratory controls that include scientifically sound and appropriate specifications designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity [21 CFR 211.160(b)]. For example, you have not established scientifically sound and appropriate specifications and test procedures to assure that your products conform to appropriate standards of identity, strength, quality, and purity. Your finished product testing is limited to sterility testing and endotoxin testing as measurements of product attributes.
2Process validation
Failure to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess [21 CFR 211.100(a)]. For example: a. The manufacturing processes for your products have not been validated with respect to identity, strength, quality, and purity. b. Prior to June 2021, you had not established written procedures for manufacturing AmnioAllograft™ or AmnioAMP-WJ™.
3Aseptic processing and sterility assurance
Failure to have an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions [21 CFR 211.42(c)(10)(v)]. For example: a. You have not validated your process for cleaning and disinfecting the cleanrooms, the critical processing areas where your products are manufactured. b. According to your Standard Operating Procedure (SOP) SB-024 titled “Clean Environment Cleaning and Maintenance”, your cleanrooms require cleaning with a (b)(4) only…
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 [21 CFR 211.113(b)]. For example: a. The aseptic processes used to manufacture your products have not been validated (i.e., by performing media fill simulations). By the nature of their routes of administration, your products purport to be…
5Stability and storage
Failure to establish and follow a written testing program designed to assess the stability characteristics of drug products and to use the results of such stability testing to determine appropriate storage conditions and expiration dates [21 CFR 211.166(a)]. Specifically, you assigned a (b)(4) - to (b)(4) -year expiration date to your products without stability testing. We have reviewed your written response, dated December 2, 2021, to FDA’s inspectional observations on the…
6Aseptic processing and sterility assurance
Failure to thoroughly investigate any unexplained discrepancy, or the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed, [21 CFR 211.192]. For example, you failed to thoroughly investigate the following sterility and environmental monitoring failures: a. From January 2021 and November 2021, your firm has had approximately (b)(4) sterility failures and (b)(4) endotoxin failures; however, you did…
