Findings citing 21 CFR 211.167

Your firm failed to conduct laboratory testing to determine whether each batch of drug product purporting to be sterile conforms to such requirements (21 CFR 211.167(a)).

Your firm failed to conduct appropriate laboratory testing to determine whether each batch of drug product purporting to be sterile and pyrogen-free conforms to such requirements (21 CFR 211.167(a)). You manufactured and distributed an (b)(4) product labeled as "sterile." However, you failed to perform sterility testing. It is essential that you conduct sterility testing on these and other purportedly sterile drugs prior to batch disposition decisions. In response to this letter, provide a list of chemical and microbial test methods and specifications used to analyze each batch of your drug product before making a batch disposition decision, and the associated written procedures.

Your firm failed to have, for each batch of controlled-release dosage form, appropriate laboratory determination of satisfactory conformance to the specifications for the rate of release of each active ingredient (21 CFR 211.167(c)). You failed to provide adequate data demonstrating your drug products, (b)(4) , have a (b)(4) of the active ingredient. For example, you claim your (b)(4) lasts for up to (b)(4) and that your (b)(4) products have (b)(4) effect for (b)(4) . Your…

Each batch of drug product purporting to be sterile and/or pyrogen-free is not laboratory tested to determine conformance to such requirements [21 CFR 211.167(a)]. For example: a. Sterility samples of Amnio2x® are frozen prior to sterility testing. Freezing product has the potential to destroy any microbial content in the samples before testing; therefore, contamination, if present, may not be detected. b. Your written procedure for Amnio2x® specifies testing of (b)(4) vials for sterility regardless of lot size, which may consist of as many as (b)(4) vials. This does not ensure that sterility samples are representative of the lot size.

Each of batch of drug product purporting to be pyrogen-free is not laboratory tested to determine conformance to such requirements [21 CFR 211.167(a)]. For example, your firm failed to perform endotoxin testing as a release criterion on (b)(4) units of Signature Cord™ product manufactured and distributed by your firm since November 2018. By the nature of the route of administration, your product is purported to be pyrogen-free and is expected to be pyrogen-free.

Your firm failed to conduct laboratory testing to determine whether each batch of drug product purporting to be sterile and pyrogen-free conforms to such requirements (21 CFR 211.167(a)).