Findings citing 21 CFR 211.110

Your firm failed to establish and follow adequate 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 (21 CFR 211.110(a)). Your firm also failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the…

Your firm failed to establish and follow adequate 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 (21 CFR 211.110(a)). 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…

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). Your firm failed to conduct adequate manufacturing investigations into out-of-specification (OOS) results obtained by your external laboratory for your (b)(4) , an over-the-counter (OTC) drug product. As such, root cause(s) for the OOS results were not…

Your firm failed to establish and follow adequate 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 (21 CFR 211.110(a)). 100% Manual Visual Inspection Your procedures governing the conduct of 100% manual visual inspection of in-process materials and finished drug products lack action levels for significant…

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.

In-process control procedures are deficient in that your control procedures do not include bioburden testing [21 CFR 211.110(a)(6)]. According to your Process Performance Qualification Report for Placental Collagen Matrix (PCM) (effective 2/20/23), your firm removed (b)(4) bioburden testing from routine commercial production of AXIOFILL™ after completing “validation production.” Your product is (b)(4) sterilized. In-process bioburden testing is critical for assuring that bioburden levels do not exceed the validated sterility assurance level (SAL).