The Food and Drug Administration (FDA) classifies drug products as a biological product, device, drug or combination product, and assigns the product to the FDA Center that regulates that type of product. This scheme, called the FDA’s product jurisdiction, has remained largely unchanged since 1991. The FDA published its proposed updates to the regulations “to enhance regulatory clarity and efficiency” in the Federal Register on May 15, 2018. The proposed updates clarify the scope of the regulations, streamline the appeals process, harmonize the regulations with recent legislative changes, and clarify certain policies and practices without making any significant change in the FDA’s overall framework. The FDA has invited comments by July 16, 2018.
First, the proposed amendments clarify that the regulation applies to product sponsors (aka applicants) when the product classification or assignment is unclear or in dispute.
Second, the proposed changes streamline and clarify the appeals process for product classifications and assignments. Previously, the procedure required sponsors to file a request under 21 C.F.R. § 3.8(c) for reconsideration of the product jurisdiction made by the Office of Combination Products (OCP) before filing an appeal. The amendments propose to eliminate the requests for reconsideration. As justification for this change, the FDA points out that since the determination of a sponsor’s Request for Designation (RFD) is made “through a robust process” by OCP, the reconsideration requests, based on the same evidence, are rarely successful and lead to inefficiency and confusion. Therefore, if the proposed rule is approved, a sponsor may now submit a supervisory appeal under 21 C.F.R. § 10.75 in the first instance. Accordingly, other than saving time by eliminating an unnecessary step, the RFD process and the appeal process is unlikely to change substantively.
Third, the FDA has clarified that it plans to classify products, including combination products, based on the primary mode of action (PMOA); the proposed rule amends 21 C.F.R. §3.4(a) to clarify that the constituent part providing the PMOA will govern classification of a combination product. The FDA states that such determinations are generally necessary for assigning the product to the Center in the FDA that is responsible for regulating that kind of product. Accordingly, if a combination product has a PMOA consistent with the statutory definition for a biological product, the combination product would be assigned to either the Center for Biologics Evaluation and Research (CBER) or the Center for Drug Evaluation and Research (CDER) based upon which Center regulates that the type of the biological product.
The proposed rule also updates several definitions at 21 C.F.R. § 3.2 and provides a cross-reference to certain other sections to enhance clarity and completeness. Further, the proposed rule removes redundant, confusing or unnecessary advisory content from 21 C.F.R. §§ 3.2, 3.5 and 3.7. Specifically, 21 C.F.R. § 3.2 updates the previously confusing definition for “mode of action” to include simply a statement that each constituent part of a combination product contributes one mode of action. The proposed rule also removes the description of inter-Center agreements, currently present at 21 C.F.R. § 3.5, and removes 21 C.F.R. § 3.7(a)-(b), which discusses when and who should file a RFD, in favor of more clear and complete recommendations present elsewhere (such as in the FDA’s various guidances).
Finally, the proposed amendments attempt to harmonize the rules with legislative changes and recent regulatory updates. For example, The Food and Drug Administration Modernization Act of 1997 (FDAMA) amended the Federal Food, Drug and Cosmetic Act (FD&C Act) to require the FDA to classify products as biological products, devices, drugs, or combination products in response to requests by product sponsors and to assign them to an FDA appropriate Center for regulation. The FDA had previously amended 21 C.F.R. § 3.2 to include those definitions. The Biologics Price Competition and Innovation Act of 2009 amended the Public Health Service Act to include proteins in the definition for biological products. Consistently, the proposals further amend 21 C.F.R. § 3.2 to harmonize with the statutory definition for biological product. The 21st Century Cures Act of 2016 amended the FD&C Act to require provisions relating to coordination between the FDA Centers involved with regulation of various classes of drugs. The proposed amendments incorporate this change by amending 21 C.F.R. § 3.4(c) to make clear that consultations with other agency components will occur as the FDA deems appropriate. The Cures Act further required that combination products be reviewed under a single application whenever appropriate and that sponsors may submit separate applications for the constituent parts of a combination product unless FDA determines a single application is necessary. To comply with these requirements, the proposed amendments delete the part of 21 C.F.R. § 3.4(c) that allows the FDA to require in that constituent parts of a combination product be reviewed under separate applications when appropriate. The proposed amendments also allow for the submission of RFD communications electronically.
In summary, the proposed changes to provide clarification on the FDA’s jurisdiction over a product, the removal of a futile step in the appeals process, and the deletion of excessive advisory content are welcome changes, but they fall short of industry expectation. The FDA’s basic procedures for product classification and designation decisions remains unchanged. The proposal does not include potentially desirable changes, such as relaxing the constraints on the RFD process that will benefit the industry.
The FDA is accepting comments on the new proposed rule until July 16, 2018—and now is the time to act.