14/15 December 2023
End of July, the FDA/CBER published in its newsletter the reference to a new Guideline Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use. This new guideline replaces the previous guideline of the same name dated November 2017.
A comprehensible interpretation of the criteria for minimal manipulation and homologous use and the definitions of related key terms are of great importance for industry stakeholders, but also for all other persons involved. Interest in this issue has been correspondingly high since the criteria and definitions were first proposed. The present document is intended to improve the understanding of the definitions of minimal manipulation in 21 CFR 1271.3(f) and homologous use in 21 CFR 1271.3(c). At the same time, it is intended to contribute to a better understanding of the regulatory criteria for Human Cell and Tissue Products (HCT/Ps) in 21 CFR 1271.10(a)(1) and (2).
The November 2017 version allowed for a transitional period of 36 months during which the new Investigational New Drug (IND) and Biologics License Application (BLA) requirements for certain HCT/Ps had to be enforced only to a limited extent. The new guideline extends this period until May 2021.
21 CFR 1271.3(d) defines HCT/Ps as products containing or consisting of human cells or tissues and intended for implantation, transplantation, infusion or transfer to a human recipient. Because of the unique nature of HCT/Ps, the FDA has proposed a tiered, risk-based approach to regulating HCT/Ps, which was first implemented in 2005. Under this tiered, risk-based approach, certain HCT/Ps that meet the defined criteria or are covered by certain exceptions do not require pre-market review and approval. In developing the tiered, risk-based approach, the agency focused on public health and regulatory concerns, including how to prevent the transmission of communicable diseases; what processing controls are needed to prevent contamination that could ultimately lead to an unsafe or ineffective product. The focus was also on maintaining the integrity and efficacy to ensure that the products deliver the intended effect and clinical safety and efficacy.
The tiered, risk-based approach is contained in a series of regulations, commonly referred to as "tissue rules", that are enacted and published by the FDA through notification and commentary of regulations under the authority of the Communicable Disease Authority under Section 361 of the PHS Act (42 U.S.C. 264).
For further details, please read the Guideline Regulatory Considerations for Human Cells, issues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use.