You Can’t Put That Tissue There: FDA Clarifies Important HCT/P Regulatory Criteria

One of the first warning letters of 2018 was issued to a manufacturer of a human cell, tissue, and cellular and tissue-based product (HCT/P) that the Food and Drug Administration said was regulated as a drug, and as a biological product, and required a biologics license because it did not meet the definitions of minimal manipulation and homologous use. The meanings of these two terms are the subject of a new guidance FDA issued in November 2017. The guidance, Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use (Guidance), provides clarification on these two criteria that are used to determine how an HCT/P will be regulated by FDA.

FDA also issued another HCT/P guidance, Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception, which covers another HCT/P regulatory exception, at the same time. We are not covering the Same Surgical Exception guidance in this article. Because both guidances cover various aspects of adipose tissue regulation, the agency withdrew the previous adipose tissue draft guidance titled: Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from Adipose Tissue: Regulatory Considerations. Adipose tissue regulation will be discussed in more detail below.

Background

HCT/Ps are biologic products typically regulated by the Center for Biologics Evaluation and Research (CBER). FDA’s regulatory authority over HCT/Ps stems from both the Federal Food, Drug, and Cosmetic Act (FDCA) and the Public Health Service Act (PHSA). Some HCT/Ps do not require premarket approval and are regulated only under section 361 of the PHSA and 21 CFR Part 1271. In order to avoid regulation as a new drug requiring premarket approval, an HCT/P in this category must meet all of the following criteria:

1. The HCT/P is minimally manipulated (see below for how FDA defines this phrase);
2. The HCT/P is intended only for homologous use;
3. 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
4. Either:

• 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
• The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and: