FDA publishes Draft Guidance for Minimal Manipulation of Human Cells, Tissues, and Cellular- and Tissue-Based Products

Recommendation

9/10 May 2023
Heidelberg, Germany

Annex 2 & Co. - GMP Compliance for Biopharmaceuticals
Regulatory Requirements and Practical Implementation

On 22 December, the FDA published a Draft Guidance for Industry and Food and Drug Administration Staff as assistance for human cells, tissues, and cellular and tissue-based product (HCT/P) manufacturers, healthcare providers, and FDA staff. The document is supposed to give recommendations for meeting the criterion under Title 21 of the Code of Federal Regulations (CFR) Part 1271, specifically the 21 CFR 1271.10(a)(1) criterion of minimal manipulation. It is anticipated that this guidance will improve stakeholders’ understanding of the definitions of minimal manipulation and how to apply the regulatory criterion to their HCT/Ps. This guidance is open for comments now, and, when finalized, it will supersede the guidance entitled “Guidance for Industry and FDA Staff: Minimal Manipulation of Structural Tissue Jurisdictional Update” dated September 2006.

HCT/Ps are defined in § 1271.3(d) as articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. The FDA has implemented a risk-based approach to the regulation of HCT/Ps. Under the authority of section 361 of the PHS Act, the authority established regulations for all HCT/Ps to prevent the introduction, transmission, and spread of communicable diseases. An HCT/P is regulated solely under section 361 of the PHS Act and 21 CFR Part 1271 if it meets all of the following criteria (21 CFR 1271.10(a)):

• The HCT/P is minimally manipulated;
• The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent;
• The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P; and either: 
    1. The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or
    2. The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:
         a.Is for autologous use;
         b.Is for allogeneic use in a first-degree or second-degree blood relative; or
         c.Is for reproductive use.

Amongst the background information, the guidance document includes questions and answers to the following topics:

• General Concepts
• Structural Tissue
• Cells or Nonstructural Tissues

For more details pelase also see the complete draft of the Guidance "Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products".