Akan Biosciences, Inc. — FDA Warning Letter Findings

Failure to test using appropriate FDA-licensed, approved or cleared donor screening tests, in accordance with the manufacturer’s instructions, to adequately and appropriately reduce the risk of transmission of relevant communicable disease agents or diseases [21 CFR 1271.80(c)] . For example, the specimens for communicable disease testing, collected from donors (b)(6), (b)(7)(C) and (b)(6), (b)(7)(C) , were tested for the antibody to human immunodeficiency virus, types 1 and 2 (anti-HIV-1/2), hepatitis B surface antigen (HBsAg), the antibody to hepatitis C virus (anti-HCV), and Treponema pallidum using test kits that were not FDA-licensed, approved, or cleared for donor screening. Donor (b)(6), (b)(7)(C) was determined eligible on 3/30/2022. Donor (b)(6), (b)(7)(C) was determined eligible on 3/31/2022.

Failure to clearly identify an HCT/P that is in quarantine pending completion of a donor-eligibility determination and failure to ship HCT/Ps with the required accompanying records for which the donor eligibility determination has not been completed [21 CFR 1271.60(b) and (c)] . For example, your firm distributed (b)(4) vials of Ayama™ to (b)(4) physician/clinic locations in (b)(4) shipments between 4/6/2022 and 7/5/2022. The (b)(4) vials were part of (b)(4) batch vials of Ayama™ manufactured from 5/27-28/2021 ( (b)(4) batches, (b)(4) batch vials total) from adipose tissue recovered from donor (b)(6), (b)(7)(C) . Donor screening and donor testing had not been completed for donor (b)(6), (b)(7)(C) ; therefore, a donor-eligibility determination had not been documented. The (b)(4) vials of Ayama were not clearly identified as quarantined and were not accompanied by records stating that the product must not be implanted, transplanted, infused, or transferred until completion of donor eligibility determination.

Failure to screen a donor of cells or tissue by reviewing the donor’s relevant medical records for risk factors for, and clinical evidence of, relevant communicable disease agents and diseases [21 CFR 1271.75(a)(1)] . For example: a) Your Form, DS-01-02 (Version 1.0) "Donor Screening Questionnaire,” is used as a relevant medical record to determine donor eligibility and was used to screen donors (b)(6), (b)(7)(C) and (b)(6), (b)(7)(C) . However, the form does not address…

Failure to test a specimen from a donor of cells or tissue, whether viable or non-viable, for evidence of infection due to relevant communicable disease agents [21 CFR 1271.85(a)] . For example, FDA has identified human immunodeficiency virus, type 1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) as relevant communicable disease agents [21 CFR 1271.3(r)], and donors of HCT/Ps must be tested for such agents to adequately and appropriately reduce the risk of transmission of relevant communicable disease. The donor specimens collected from donors (b)(6), (b)(7)(C) and (b)(6), (b)(7)(C) were not tested for the antibody to hepatitis B core antigen (anti-HBc) and HIV-1, HCV, and HBV by the nucleic acid test (NAT) method. Such donors were not tested to adequately and appropriately reduce the risk of transmission of these diseases because NAT testing can detect evidence of infection at a significantly earlier stage than is possible under other tests. These donors were determined eligible on 3/30/2022 and 3/31/2022, respectively.

Failure to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess [21 CFR 211.100(a)] . For example, your firm has not validated the manufacturing process for the adipose tissue product, Ayama™, with respect to identity, strength, quality and purity.

Failure to collect a donor specimen for testing for relevant communicable diseases at the time of recovery of cells or tissue from the donor or up to seven days before or after recovery [21 CFR 1271.80(b)] . For example, HCT/Ps were recovered from donor (b)(6), (b)(7)(C) on (b)(6), (b)(7)(C) , however a donor specimen for testing was collected from the donor on (b)(6), (b)(7)(C) , which is not within the required timeframe for collection of a specimen for testing.

Failure to ship in quarantine a pre-distribution shipment of HCT/Ps between establishments for which the pre-established criteria designed to prevent communicable disease transmission have not been documented as being met [21 CFR 1271.265(b)] . For example, your firm delivered (b)(4) vials of Ayama™ (part of (b)(4) batch vials manufactured between 3/31/2022 and 4/4/2022 from adipose tissue recovered from donors (b)(6), (b)(7)(C) and (b)(6), (b)(7)(C) ) to your distributor on 5/11/2022 that were not shipped in quarantine to prevent improper release. The products had not been determined to be available for distribution, as described in 21 CFR 1271.265(c), as there was no documentation that the pre-established criteria designed to prevent communicable disease transmission had been met.

Failure to have an adequate system for monitoring environmental conditions in an aseptic processing area necessary to prevent contamination or mixups [21 CFR 211.42(c)(10)(iv)] . For example, a) You have not performed environmental monitoring of the aseptic processing area in association with each production run. You process batches on (b)(4) basis. However, SOP (b)(4) (Version 3, Effective date: August 8, 2020) indicates that “ (b)(4) plates” sampling (i.e., contact plates…