A new guidance document issued by the US Food and Drug Administration (FDA) is trying to clarify the differences between tissue products and procedures which fall under the agency's regulations, and those products and procedures which do not.
FDA regulates tissue products—otherwise known as human cell, tissue or cellular or tissue-based products (HCT/Ps)—under Chapter 21, Section 1271 of the Code of Federal Regulations (21 CFR 1271). Specifically, FDA regulates all HCT/Ps "intended for implantation, transplantation, infusion or transfer into a human recipient."
Regulatory oversight in this area is intended to ensure products subject to more than "minimal" manipulation (21 CFR 1271.3(f)) are safe for use, effective, not contaminated and free from transmissible diseases (similar to requirements for blood and plasma products).
Per FDA, "minimal manipulation" is taken to mean:
- For structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue's utility for reconstruction, repair, or replacement; and
- (2) For cells or nonstructural tissues, processing that does not alter the relevant biological characteristics of cells or tissues.
As a result of this section, some products are therefore exempt from FDA regulation under the general theory that simple procedures that don't alter the substance of the HCT/P are, in essence, a medical procedure. While FDA has regulatory authority over medical products, it has no authority over the practice of medicine.
This section has been contentious at FDA in recent years, with FDA sending out at least two Warning Letters (1) (2) challenging companies' attempts to fall under the exemption, and prevailing in a lawsuit against another.
Other Exemptions Under 21 CFR 1271
In addition to the minimal manipulation section of 21 CFR 1271, FDA is also directed to offer exemptions to certain entities under 21 CFR 1271.15.
The section outlines five types of entities which FDA considers exempt from its registration and listing regulations:
- establishments that use HCT/Ps solely for nonclinical scientific or educational purposes
- establishments that remove HCT/Ps from an individual and implants such HCT/P's into the same individual during the same surgical procedure
- carriers who accept, receive, carry, or deliver HCT/Ps in the usual course of business as a carrier
- establishments that do not recover, screen, test, process, label, package, or distribute, but only receive or store HCT/Ps solely for implantation, transplantation, infusion, or transfer within their facility
- establishments that only recover reproductive cells or tissue and immediately transfer them into a sexually intimate partner of the cell or tissue donor
The Surgical Exemption
The second of those exemption criteria—that FDA will not regulate establishments removing an HCT/Ps from an individual and re-implanting it into the patient during the same surgical procedure—was seen as being particularly important. As FDA explains in its new guidance document, Same Surgical Procedure Exception Questions and Answers Regarding the Scope of the Exception, the agency came to this conclusion after considering that "the communicable disease risks, as well as the safety and effectiveness risks, would generally be no different than those typically associated with surgery."
However, FDA has also broadened that exemption somewhat in non-binding comments. Responding to a comment on its then-proposed rule, FDA said that hospitals—so long as they don't conduct any activities which could be construed as "manufacturing" under the law—would be allowed to retain autologous tissue "not used in a scheduled surgical procedure to be used in a subsequent application on the same patient."
The hospitals argued this procedure, despite not being conducted at the same time, was nonetheless "essentially a single continuous procedure."
FDA's latest guidance further defines and elaborates upon this concept. For example, it clarifies that any surgical procedure—"procedures that involve an incision or instrumentation (e.g., incision or surgical technique) during which an HCT/P is removed from and implanted into the same patient within a single operation performed at the same establishment"—falls under the guidance.
In addition, FDA notes that "under limited circumstances" it may consider as a "continuous procedure" surgeries conducted as long as "days" apart so long as they do not undergo any substantial manipulation.
"During this time, the HCT/P may be rinsed or cleansed and temporarily stored after being labeled pending implantation, and still be considered same surgical procedure, provided no other processing steps, and no other manufacturing steps beyond being labeled and stored are performed," FDA explained.
Surgeries that would take place at two different locations would not qualify for the exemption, and neither would a facility which ships a product to another establishment for temporary storage, FDA added.
As of now, only two procedures "may qualify" for this exemption, though FDA did not rule out other procedures:
- Craniotomy with subsequent implantation of the bone flap to reverse the cranial defect.
- Parathyroidectomy with subsequent implantation of a portion of the tissue to preserve parathyroid function.
Comments on the guidance will be accepted until 22 December 2014.
Same Surgical Procedure Exception Questions and Answers Regarding the Scope of the Exception (FR)