FDA Gets Into The Weeds On HCT/P Rules In Warning Letter To Human Tissue Firm
June 19th, 2024 // 12:21 pm @ jmpickett
In May 2024, CBER at FDA issued a warning letter to Akan Biosciences for unresolved FDA audit observations after several months of back and forth discussions between the agency and Akan. The FDA 483 highlighted several issues regarding 585 vials of a human tissue product. Also, the warning letter spent a lot of time covering the reasons that Akan’s product failed to meet the requirements of 21 CFR 1271, which states that certain human cells or tissues – HCT/Ps – for exemptions from certain FDA requirements, one of which is premarket review. Akan’s human tissue product is an adipose derived, stromal vascular fraction cell product made for allogenic use under the name Ayama.
The FDA warning letter is a good example of the agency’s enforcement priorities for these human tissue products. It also highlights the regular scrutiny that HCT/P manufacturers receive. The warning letter is also a good example for HCT/P manufacturers of the agency’s core enforcement priorities regarding all tissue and cell products. FDA has issued many guidances over the years to better explain 21 CFR Part 1271, also called the tissue rules, but the major goal has always been this: to prevent the introduction, transmission, and spread of all communicable disease. To achieve this aim, the tissue rules by FDA focus on these areas:
- Prevent the unintended use of contaminated tissues that could transmit infectious diseases, including AIDS and hepatitis.
- Prevent inappropriate handling or processing that could damage or contaminate human tissues.
- Ensure that clinical effectiveness and safety is shown for tissues that have been highly processed, are used for something other than their normal function and are mixed with non-tissue components, or are used for various metabolic uses.
It is probably not a surprise that FDA focuses on these concepts in its warning letter to Akan. The opening warning letter discussion regarding minimal manipulation and homologous use addresses the third point above, and it shows the agency’s belief that Akan’s products should have more oversight. Also, when it addresses the tissue company’s subpar donor screening and testing, the agency focuses on point 1 above and preventing the unintended use of possibly contaminated tissue. The warning letter also discusses the company’s GMP deficiencies stresses point 3 above, which is preventing improper processing and handling.
The warning letter also shows context for the sort of operations that will trigger a warning letter rather than an untitled letter. Regarding the enforcement of HCT/Ps, CBER has always kept a careful eye on them. In 2024, CBER has sent six letters to HCT/P companies. In a review of CBER letters recently, it can be seen that FDA often issues warning letters when GMP or donor screening and testing inadequacies are seen during an FDA inspection. On the other hand, untitled letters usually focus more on the product characteristics as found in publicly available marketing information, such as on company social media and websites.
Overall, this warning letter shows the continuing relevance of adhering to the agency’s tissue rules. If your tissue company gets a 483, you should carefully think about the corrective actions you take and deal with FDA’s concerns. The agency’s tissue rules are supposed to balance innovation in the field of regenerative medicine, while preventing communicable diseases from being transmitted. But CBER makes it clear that it will take aggressive action when there are clear signs that a tissue company is out of compliance.
