1Laboratory and QC controls
Failure to make, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to the final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. [21 CFR § 211.165(a)]. Specifically, there are no written specifications or procedures that define all analytical or documentation criteria for release for distribution of (b)(4) batches of stem cells derived from adipose tissue, umbilical cord, and bone marrow.
2Complaint and recall handling
Failure to establish and follow written procedures describing the handling of all written and oral complaints regarding a drug product [21 CFR 211.198(a)] (see also 21 CFR 211.180(e)(2)). Our investigation found that you do not have written procedures for handling or investigating complaints.
3Cleaning validation
Failure to establish and follow written procedures for cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing, or holding of a drug product [21 CFR 211.67(b)]. You do not have written cleaning procedures for the manufacturing of your culture expanded allogeneic adipose-derived animal cell product. Furthermore, your firm does not keep cleaning records, as required by 21 CFR 211.67(c).
4Aseptic 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 appropriate laboratory testing, including sterility testing, on at least (b)(4) batches of the stem cell products derived from adipose tissue, umbilical cord, and bone marrow which are administered intravenously or intrathecally.
5Process 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 that they purport or are represented to possess [21 CFR 211.100(a)]. You have not established written procedures that describe the manufacture of stem cells from umbilical cord and bone marrow.
6Deviation, CAPA, and investigation
Failure to establish and follow written procedures that describe the in-process controls, and tests, or examinations to be conducted on appropriate samples of in-process materials of each batch [21 CFR 211.110(a)]. You are required to establish such control procedures to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. Our investigation found that you do not validate the manufacturing processes for isolating the stem cells derived from culture expanded adipose tissue, umbilical cord, and bone marrow.
7Aseptic processing and sterility assurance
Failure to have a system for monitoring environmental conditions in an aseptic processing area [21 CFR 211.42(c)(10)(iv)]. Specifically, your firm has not established a system for environmental monitoring in the aseptic processing area where stem cell products derived from adipose tissue, umbilical cord, and bone marrow are manufactured.
8Documentation and records
Failure to prepare batch production and control records for each batch of drug product produced that include complete information relating to the production and control of each batch, including documentation that each significant step in the manufacture, processing, packing, or holding of the batch was accomplished [21 CFR 211.188(b)]. Specifically, your batch production records do not include documentation of the accomplishment of each significant step in the manufacture…
