1Aseptic processing and sterility assurance
Failure to have an adequate system for monitoring environmental conditions in an aseptic processing area, 21 CFR 211.42(c)(10)(iv), as well as failure to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile. 21 CFR 211.113(b). Your written procedures for environmental monitoring of your firm’s aseptic processing areas (e.g., laminar flow hoods) are not sufficient to detect…
2Stability 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, your firm has assigned a five-year expiration date for your products without supporting data regarding the stability characteristics of the products. Response to the Form FDA-483 We acknowledge receipt of…
3Aseptic processing and sterility assurance
Failure to perform appropriate laboratory testing, as necessary, of each batch of drug product required to be free of objectionable microorganisms.21 CFR 211.165(b). Specifically, you failed to perform endotoxin testing on final product batches. Such laboratory testing is necessary as your products are purported to be sterile.
4Aseptic 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, from January 2021 to August 2022, you failed to investigate three action-level excursions for environmental monitoring observed in the a septic processing area (e.g., laminar flow hoods).
5Laboratory and QC controls
Failure to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure the components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality and purity. 21 CFR211.160(b). For example, you have not established appropriate specifications to assure that your products conform to appropriate standards of identity, strength, quality, and purity.
6Process validation
Failure to establish adequate written procedures for production and process controls designed to assure that the drug products have the identity, strength, purity, and quality that they are purported or represented to possess. 21 CFR 211.100(a). Specifically, your firm has not validated the manufacturing processes for your products with respect to identity, strength, quality, and purity.
7Documentation and records
Failure to prepare batch production and control records that document each significant step in the manufacture, processing, packing, or holding of your umbilical cord blood products. 21 CFR 211.188(b). Specifically, your batch production records do not include documentation of the accomplishment of each significant step in the manufacture of your products or the person(s) performing each of those steps, for example: a. The weight of, for e.g., umbilical cord tissue used in processing. b. The amount of saline used to formulate the final product. c. Processing of tissue in the (b)(4) machine, including weight of tissue processed, machine operational parameters, run time, and the number of runs completed. d. Identification of equipment, such as laminar flow hoods, used in processing.
