On Tuesday, May 15, 2018, the U.S. Food and Drug Administration (FDA) published a proposed rule to amend its regulations concerning how medical products are classified and assigned to agency components for premarket review and regulation.1 In most respects, the rule is intended to provide greater clarity, streamline administrative processes and align the regulations with more recent legislative and regulatory measures as well as with current agency practice. Nonetheless, certain modifications may have an impact by cabining the role of the Office of Combination Products (OCP) and increasing the discretion of product sponsors.

Clarify Scope of Part 3

If finalized, the proposed rule would amend 21 C.F.R. § 3.3 to clarify that the procedures in Part 3 apply when the classification of a product as a biological product, drug, device, or combination product is unclear or in dispute. The proposed rule reflects a change in terminology by referring to the classification of products, whereas the current rule refers to a dispute with respect to the identity of the agency component with primary jurisdiction.

As a practical matter, this amendment does not depart from agency practice because product classification is a pre-requisite to determining the agency component with primary jurisdiction. The proposed rule explains that FDA has long accepted sponsor requests for product classifications under Part 3 but clarifies that a request for classification or assignment designation is only available to sponsors and is not required. The amendment makes clear that a sponsor can choose whether to engage OCP, or make the call concerning product jurisdiction on its own and file its premarket submission directly with one of the medical product centers.

Streamline Appeals Process

The proposed rule would remove the procedure outlined in 21 C.F.R. § 3.8(c) that allows sponsors to request a reconsideration of a classification or agency component designation by the product jurisdiction officer. FDA explained that this procedure was inefficient for sponsors, because further evaluation of the same data and information by OCP is unlikely to lead to a different determination. Although the proposed rule would eliminate the reconsideration procedure, the supervisory appeal procedure under 21 C.F.R. § 10.75 would still be available to sponsors that disagree with the classification or designation, allowing review at the next supervisory level. Additionally, an interested person’s ability to file a petition for an administrative reconsideration in accordance with the criteria and timelines in 21 C.F.R. § 10.33 is not affected by the proposed rule.

FDA also has not taken the opportunity to revise 21 C.F.R. § 3.9(b), which authorizes a product jurisdiction officer to change the designated agency component upon consent of the sponsor or otherwise if necessary to protect the public health or for other compelling reasons. FDA has been reluctant to invoke § 3.9(b) out of concern that doing so would suggest that one of its components lacks the requisite authorities or resources to take appropriate action concerning a product to protect the public health.

Align With Recent Statutory and Regulatory Measures

A stated goal of the proposed rule is to align the Part 3 regulations with statutory and other regulatory changes that have occurred since the regulations were promulgated in 1991. Thus, the proposed rule would amend the definition of “biological product mode of action” in 21 C.F.R. § 3.2 to align with the statutory definition of “biological product” in section 351(i) of the Public Health Service Act (PHS Act). Notably, the definition under the proposed rule would classify proteins as biological products. The proposed rule does not, however, address proteins currently regulated as devices, such as collagen, or how other proteins with similar modes of action will be classified in the future.

Other proposed changes to align the regulations with recent statutory measures and administrative practices include:

  • Clarifying that intercenter consultation and coordination may occur as appropriate, consistent with current practice;
  • Expanding the definition of “application” in 21 C.F.R. § 3.2 to encompass De Novo classification requests and pre-submission engagements;
  • Providing a cross-reference to the definition of “constituent part” regarding current good manufacturing practices for combination products;

The proposed rule also clarifies, consistent with recent legislative changes, that sponsors are not prohibited from submitting separate applications for the constituent parts of a combination product unless FDA determines that a single application is required. The new language does not state any circumstances under which FDA can require separate applications, as FDA has done for companion diagnostics. According to the preamble, FDA will issue guidance on this topic.

Update Advisory Content and Other Clarifications

The proposed rule would remove certain content in 21 C.F.R. §§ 3.2, 3.5 and 3.7 that FDA categorizes as “advisory content”—including recommendations regarding who should file a Request for Designation (RFD) and when the RFD should be filed—in favor of providing recommendations in guidance documents, policy statements or on the agency’s website. Finally, the rule proposes a number of additional changes in an effort to provide greater clarity. The proposed rule better addresses situations where a product (e.g. certain biologics) could be assigned to more than one center (e.g. either the Center for Biologics Evaluation and Research (CBER) or to the Center for Drug Evaluation and Research (CDER)). The proposed rule would modify 21 C.F.R. § 3.4 to specify that FDA will assign a combination product to the agency component that regulates the constituent part that provides the primary mode of action for that type of product so that the agency component with the most institutional knowledge about that particular constituent part would have jurisdiction.

FDA estimates that the rule will impose an upfront cost in the first year, as the industry reads and understands the regulations, but that the rule will result in a net cost savings over time due to the reduction in uncertainty about the RFD process. FDA anticipates that the enhanced clarity provided by the proposed rule will allow sponsors to make decisions that are better informed while redirecting resources to activities that advance product development and marketing applications. Electronic or written comments on the proposed rule may be submitted until July 16, 2016.