The last decade has seen enormous growth in the human tissue products industry, following the Food and Drug Administration’s (FDA) establishment, in 2001, of a tiered approach to the regulation of these products (referred to as “human cells, tissues and cell- and tissue-based products,” or “HCT/Ps”). Under this approach, some HCT/Ps are subject only to regulation under Section 361 of the Public Health Service Act (PHSA). Of note, these “Section 361 HCT/Ps” do not require premarket approval. Other HCT/Ps (primarily those that are more than minimally manipulated, are not for homologous use, or are dependent on metabolic activity) are regulated under Section 351 of the PHSA and do require FDA premarket approval in the form of a Biologics License Application (BLA). Judging by a number of recent actions by the FDA’s Center for Biologics Evaluation and Research (CBER), the FDA appears to be focusing its regulatory attention on these Section 361 HCT/Ps.
First, the HCT/P industry should be aware that the FDA’s new draft guidance (issued January 27, 2015) on “Current Good Manufacturing Practice Requirements for Combination Products,”includes a section on “combination products that include biological products and HCT/Ps.” The draft guidance is intended to “describe and explain the final rule on CGMP requirements for combination products... that FDA issued on January 22, 2013.”
This guidance follows the CBER’s announcement, at the end of December, of the availability of two draft guidance documents concerning HCT/Ps. The first, entitled “Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products,” is intended to provide further clarity and recommendations on how manufacturers of HCT/Ps may satisfy the minimal manipulation requirement under 21 C.F.R. § 1271.10(a)(1). Although the FDA previously addressed this criterion in its 2006 guidance document, titled “Minimal Manipulation of Structural Tissue Jurisdictional Update,” the FDA intends for its latest draft guidance to supersede the 2006 document.1 The FDA will be accepting comments on the draft guidance until February 23, 2015. Industry stakeholders who are interested in further discussing the application of this draft document or submitting comments should contact Arent Fox’s FDA Practice (Food & Drug) team.
The second draft guidance that was issued in December, titled “Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from Adipose Tissue: Regulatory Considerations,” is a response to “numerous inquiries” that the FDA has received specifically regarding the regulation of adipose tissues under Section 361 of the PHSA. The guidance addresses a number of important issues, including the parameters of “minimal manipulation” for adipose tissue and what uses of adipose tissue are considered homologous. Comments on this guidance are due by February 23, 2015. It is our understanding that adipose tissue is not the only area in which the FDA is receiving requests for this type of guidance, so it is possible that similar guidance for other types of HCT/Ps will be forthcoming. On a related note, when the FDA’s Tissue Reference Group (TRG)2 provided its Fiscal Year 2014 annual update on December 15, 2014, it announced that ground adipose tissue that is defatted and decellularized is more than minimally manipulated and, therefore, not a 361 HCT/P because the processing alters the original relevant characteristics of the adipose tissue’s utility for reconstruction, repair, or replacement.
In the same update, the TRG also announced that a dehydrated amniotic membrane product for wound covering and healing for dermal ulcers and defects does not meet the criteria for regulation solely under Section 361 of the PHSA because healing of dermal ulcers and defects is a non-homologous use for amniotic membrane. Together, these TRG opinions illustrate that decellularization and dehydration cannot always be assumed to be “minimal manipulation;” rather, the proper characterization of these activities depends upon the purpose for which the HCT/P is offered.
Three other draft guidances concerning HCT/Ps were issued in the fall. On October 23, 2014, the FDA announced the availability of a draft guidance concerning the “Same Surgical Procedure Exception Under 21 CFR 1271.15(b).” The draft guidance addresses the exception from regulation for establishments that remove HCT/Ps from individuals and implant them back into the same individual during the same surgical procedure. The guidance emphasizes the fact the FDA intends the same surgical procedure exception to be narrowly construed, and views the exception as applying only when autologous cells or tissues are removed from an individual and implanted into the same individual without intervening processing steps beyond rinsing, cleansing, or sizing, or certain minor manufacturing steps that do not change them from their original form. The following day, the FDA announced a draft guidance, titled, “Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps).” On November 5, 2014, the FDA announced the availability of a draft guidance on “Use of Donor Screening Tests to Test Donors of Human Cells, Tissues and Cellular and Tissue-Based Products (HCT/Ps) for Infection with Treponema pallidum (Syphilis).”
Going forward, the CBER has announced that, in 2015, it intends to issue two additional draft guidances for the HCT/P industry. Specifically, the Center intends to issue draft guidance both on “Homologous Use of Human Cells, Tissues, and Cellular and Tissue Based Products, “and “Manufacturer Investigation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Adverse Reactions.” Arent Fox will be monitoring the FDA’s activities for any future updates regarding the regulatory framework governing HCT/Ps.