Same Surgical Procedure Exception under 21 CFR 1271.15(b): FDA Raises More Questions Than it Answers Regarding the Scope of the Exception

Nov 12, 2014   

November 12th, 2014

The FDA has released a new draft guidance document for industry entitled “Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception” (the Guidance Document), which can be read here. This Guidance Document is FDA’s attempt at clarifying the “same surgical procedure” exception set forth at 21 C.F.R. 1271.15. That exception allows for the use of autologous stem cell treatments without submitting to regulation under FDA’s drug or biologic regulations. As always, “FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities.”

As background, FDA regulates human cells and tissues intended for use in transplantations, implantation, or transfer into human recipients as human cells, tissues, or cellular or tissue-based products. FDA defines “human cells, tissues, or cellular or tissue-based products” (HCT/Ps) to mean:

[A]rticles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. Examples of HCT/Ps include, but are not limited to, bone, ligament, skin, dura mater, heart valve, cornea, hematopoietic stem/progenitor cells derived from peripheral and cord blood, manipulated autologous chondrocytes, epithelial cells on a synthetic matrix, and semen or other reproductive tissue. 21 CFR 1271.3(d).

FDA has set forth its regulations for HCT/Ps in 21 C.F.R. part 1271. In this part of the Code of Federal Regulations, FDA has divided HCT/Ps into two categories: (1) HCT/Ps regulated solely under part 1271 and section 361 of the Public Health Service Act (PHSA) (42 USC 264), and (2) HCT/Ps regulated under part 1271 and FDA’s regulations governing medical devices or drugs under the FDCA or biological products under section 351 of the PHSA (42 USC 262). However, practitioners can avoid regulation under Part 1271 if their treatment modalities fall within the “same surgical procedure” exception under 1271.15(b), which states “you are not required to comply with the requirements of this part if you are an establishment that removes HCT/Ps from an individual and implants such HCT/Ps into the same individual during the same surgical procedure.”

FDA’s new Guidance Document gives a brief overview of the history of the exception. In 1997, the FDA issued a document called “Proposed Approach to Regulation of Cellular and Tissue-Based Products” in which it stated “[t]he agency would not assert any regulatory control over cells or tissues that are removed form a patient and transplanted back into that patient during a single surgical procedure. The communicable disease risks, as well as the safety and effectiveness risks, would generally be no different than those typically associated with surgery.” After that, in 1998, FDA published a proposed rule in the Federal Register, 63 Fed Reg 26744, regulating the registration of HCT/P establishments followed by a final rule in 2001, 66 Fed Reg 5447. In the proposed rule, FDA stated that it received a comment assuming that a hospital retaining autologous tissue to be used in a subsequent application on the same patient, even if the use would occur in a future, not-yet-scheduled surgical procedure, would not be subject to registration and listing. In its final rule, FDA agreed that “so long as the hospital does not engage in any other activity encompassed with in [sic] the definition of “manufacture,” the hospital would not be required to register or comply with the other provisions to be codified in part 1271. For example, if the hospital expanded the cells or tissues, it would not meet the terms of the exception.”

After describing that historical background, FDA concludes in the new Guidance Document that “autologous cells or tissues that are removed from an individual and implanted into the same individual without intervening processing steps beyond rinsing, cleansing, or sizing, or certain manufacturing steps, raise no additional risks of contamination and communicable disease transmission beyond that typically associated with surgery.” FDA does not explain the leap from its 2001 explanation regarding hospital activities to its new decision that anyintervening steps outside of “rinsing, cleansing, or sizing” would bring a procedure outside of the “same surgical procedure” exception. What has happened between 2001 and now that has led FDA to determine that rinsing, cleansing, and sizing fit within the 1271.15 exception? This is only the first of many questions this new Guidance Document raises but does not answer. While attempting to provide some clarity to the regenerative medicine industry, FDA has, as it often does, raised additional questions and confusion as to how certain treatments and procedures will be regulated.

For instance, in addressing “[w]hen does the exception in 1271.15(b) apply?” (see Q4. of the Guidance Document), FDA states there are three criteria that must be met to fall under the exception. These criteria are that (1) the HCT/Ps must be removed and implanted into the same individual (autologous use), (2) the HCT/Ps must be implanted within the same surgical procedure, and (3) the HCT/Ps remain “‘such HCT/Ps;’ they are in their original form.” FDA has included a footnote to the third criterion stating:

Note that the criteria of “minimal manipulation” expressed in 21 CFR 1271.10 (a) is not the standard for establishing whether an HCT/P is “such HCT/P” under § 1271.15. Accordingly, even manufacturing steps considered minimal manipulation within § 1271.10(a), will typically cause the HCT/P to no longer be “such HCT/P” under §1271.15(b), unless the HCT/P is only rinsed, cleaned, sized, or shaped. (Emphasis added.)

This new narrower 1271.15 same surgical procedure exception leads to numerous other questions that our clients are asking in their medical practices. This footnote makes clear that the 1271 same surgical procedure exception is actually narrower than the “more than minimal manipulation” standard, which FDA has previously interpreted in guidance documents and regulatory preambles as being incredibly narrow. Would FDA consider centrifugation to be “rinsing, cleansing, sizing or shaping?” How does this Guidance Document affect the physicians in the United States who are utilizing centrifugation to work with stromal vascular fraction (SVF), many of whom using SVF in their practices under the auspices of the same surgical procedure exception? How does this interpretation affect cell separation procedures?

In attempting to clarify the types of procedures that fall within the same surgical procedure exception, FDA provides the following insights: “[P]rocedures 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, are considered to be the same surgical procedures. Examples include autologous skin grafting and coronary artery bypass surgery involving autologous vein or artery grafting.” (See Q3 of the Guidance Document.) As this statement seems to encompass a fairly broad range of procedures, it will be interesting to see exactly which procedures, other than those specifically mentioned, FDA will consider “surgical.”

FDA also attempts to address whether procedures that involve more than a single operation could fall under the same surgical procedure exception and whether autologous tissue can be shipped within the exception. In the Guidance Document, FDA writes that, in most situations, more than one procedure would not qualify under this exception. However, neither time nor the number of “procedures” involved is dispositive. Instead, there may be circumstances in which “removal and future implantation may be a number of days apart” and still fall within the exception (see A4 of the Guidance Document). HCT/Ps may only be rinsed, cleansed, and/or stored during the intervening time, according to FDA, and no other “manufacturing steps beyond labeling and storage may be performed.” Accordingly, it seems that procedures performed days apart can still be deemed to be the same surgical procedure. FDA also states that shipping of HCT/Ps cannot be done at any time during the procedure to fall under this exception, no matter what the purpose of the shipment (even for storage).

Despite the new questions raised, one of the few clear conclusions that can be drawn from this new draft Guidance Document is that FDA has decided to apply the same surgical procedure exception of part 1271 very narrowly. Practitioners and professionals in the regenerative medicine industry who believe that they are currently practicing within the same surgical procedure exception should closely scrutinize their practices in light of this Guidance Document to prepare and insulate themselves from potential enforcement action that may stem from violation of FDA’s newest interpretations. As this Guidance Document is a draft, FDA has chosen to accept comments, and comments must be submitted in writing by December 22, 2014. Fuerst, Ittleman, David, and Joseph, PL will continue to monitor this policy document and all other issues relating to FDA’s regulation of the regenerative medicine industry.