FDA WARNING_LETTER - Signature Biologics, LLC - December 16, 2021

The FDA issued a Warning Letter to Signature Biologics, LLC, following a December 2021 inspection, for manufacturing and distributing "Signature Cord™," a human umbilical cord-derived product for allogeneic use. The FDA determined this product is a drug and biological product under the FD&C Act and PHS Act, not solely an HCT/P, because it fails to meet minimal manipulation criteria (21 CFR 1271.10(a)(1)).

Consequently, Signature Cord™ requires an approved Biologics License Application (BLA) or an Investigational New Drug (IND) application, neither of which is in effect. This constitutes violations of the FD&C Act and PHS Act.

The inspection also revealed significant Current Good Manufacturing Practice (CGMP) deviations (21 U.S.C. 351(a)(2)(B) and 21 CFR Parts 210 and 211), affecting over (b)(4) vials manufactured between November 2018 and December 2021. Deficiencies include: 1. Failure to validate aseptic processes for maximum commercial batch sizes (21 CFR 211.113(b)). 2. Inadequate environmental monitoring in aseptic processing areas, including insufficient viable air monitoring and excessively high acceptable microbial limits (21 CFR 211.42(c)(10)(iv)).