FDA Clarifies Role of Manipulation in Determining HCT/P Regulation

January 2, 2015

The U.S. Food and Drug Administration released draft guidance late last month clarifying when human cellular and tissue-based products may be regulated solely under section 361 of the Public Health Service Act and 21 CFR 1271 and when they are regulated as medical devices, drugs or biologics.

For HCT/Ps to qualify under Sec. 361 PHS and 21 CFR 1271, they must be “minimally manipulated” and meant to homologous use only. Their manufacture can’t involve the combination of cells or tissues with articles such as water, crystalloids or a preserving or storage agent, and there can be no new safety concerns raised, the guidance says.

The draft defines minimal manipulation of structural tissue and of cells or nonstructural tissue. In the case of structural tissue, minimal manipulation means processing that doesn’t alter the “relevant characteristics” of the tissue vis à vis its use in reconstruction, repair or replacement. For cells or nonstructural tissues, it refers to processing that leaves intact the relevant biological characteristics.

Under the proposed guidance, processing includes any activity other than recovery, donor screening, donor testing, storage, labeling, packaging, or distribution, the guidance explains. Examples include testing for microorganisms, preparation, sterilization, steps to inactivate or remove adventitious agents, preservation for storage and removal from storage. Other activities common during processing include cutting, grinding, shaping, culturing, enzymatic digestion and decellularization, the guidance says.

Processing of HCT/Ps may employ mechanical methods to change the size or shape of the structural tissue. To determine if this alters the original characteristics, firms must assess whether the changes affect the product’s use in reconstruction, repair or replacement. Grinding and fragmentation, for example, can qualify as minimal or more than minimal manipulation, depending on the assessment, the FDA says.

Guidance Addresses Modifications

The agency points out that other types of processing — such as chemical modification — can also alter the physical state of a structural tissue.

The draft also gives advice on how to tell whether an HCT/P comprises structural or nonstructural tissue. For instance, a structural tissue characteristic is relevant if it “could have a meaningful bearing on the tissue’s utility for reconstruction, repair, or replacement.” Examples of relevant characteristics include strength, flexibility, cushioning, covering, compressibility and response to friction and shear.

The guidance, which updates a 2006 document, features an extensive question-and-answer section, including examples of HCT/Ps that are and are not minimally manipulated. PHS Section 361 authorizes the FDA to take steps to prevent the spread of communicable diseases, while 21 CFR 1271 deal with regulation of HCT/Ps.

Comments on the draft guidance are due Feb. 23. View it at www.fdanews.com/12-23-14-HCT-PsGuidance.pdf. — April Hollis