Sen. Johnny Isakson (R-Ga.) introduced a bi-partisan bill (S. 1767) on July 15, 2015, to help streamline and clarify the FDA regulatory process for combination products.  Co-sponsored by Sens. Robert Casey (D-Pa.) and Pat Roberts (R-Kan.), the “Combination Product Regulatory Fairness Act of 2015” is, according to Roberts, intended to “clarify the regulatory process for innovative treatments that do not easily fit into the current categories of FDA approval.”

The following are some of the highlights from S. 1767:

“Device” and “Combination Product” Designations—Under current section 503(g)(1) of the FDCA, a combination product is assigned to a FDA center based on a determination of the “primary mode of action” (PMOA) of the combination product.  While the definitions of “drug” and a “device” in the FDCA are similar, the statute provides that a device does not “achieve its primary intended purposes through chemical action within or on the body of man” and “is not dependent upon being metabolized for the achievement of its primary intended purposes.”  Thus, whether a product achieves its primary intended purposes through chemical action determines whether the product will be primarily regulated as a drug or a medical device, which can be a critical factor in the amount and type of testing required for premarket review (as well as other regulatory requirements).  As we previously reported, companies often disagree with FDA’s determination as to which product center has primary jurisdiction over a combination product.

Under the bill, if FDA disagrees with the sponsor’s conclusion that the product is a device, FDA would be required to provide the sponsor with a “competent and reliable scientific rationale” that “cites any scientific evidence relied upon” to support the agency’s decision.  A sponsor would then be able to propose a study to establish the significance, if any, of the product’s chemical action in achieving its primary intended purpose and FDA would be required to collaborate with the sponsor to reach agreement on the study design.

The bill would also require FDA to provide a rationale when it disagrees with the sponsor’s conclusion about the PMOA of a combination product and would prohibit FDA from determining that the PMOA of a combination product is that of a drug or biological product “solely” because the combination product has any chemical action within or on the human body.

Number of Marketing Applications—The bill would require FDA to conduct the premarket review of a combination product, whenever possible, under a single premarket application.

Data Requirements—The bill would limit the data that FDA can require to support a marketing application for a combination product containing an “approved constituent product” that was previously approved, cleared, or licensed by FDA and for which the information from such approved constituent product is available for use or for which the sponsor has a right of reference.

Combination Product Review Plan—The legislation would create a process through which a sponsor may submit to FDA a “Combination Product Review Plan” (CPRP) to obtain clarity on the applicable review standards and requirements for a combination product, postmarket modifications to the product, or good manufacturing practices for the product.

Coordination Across Agency Centers—The bill includes numerous provisions aimed at improving consistency and agency center coordination in the review of combination products, including:

• The Office of Combination Products (OCP) would be required to coordinate and oversee the timeliness and alignment of premarket reviews of combination products; ensure that the lead center is the primary point of contact for the sponsor; ensure that consulting centers attend any meetings with the sponsor during premarket review, if applicable, and that each consulting center complies with the guidance described below and other relevant guidance, regulations, and policies; and coordinate communications to and from the consulting centers.

• OCP would be required to ensure that all consulting centers complete their premarket reviews within timeframes that allow the lead center to meet its performance goal in connection with applicable user fee legislation.

• The lead center’s communications and commitments would be binding on the consulting center “to the extent consistent with other provisions of law and the requirements of all affected agency centers.”

• OCP would be required to resolve disputes that arise during the review of a combination product within 90 days of receipt of written notice of such conflicts.

• Within 2 years of enactment, FDA would be required to issue final guidance describing the responsibilities of each center in the review of combination products, including each center’s role in evaluating evidence development and review.

Some of these provisions echo language in section 2141 of the first discussion draft of the 21st Century Cures Act.  The 21st Century Cures  bill  approved by the House on July 10 (H.R. 6) omitted these provisions and includes only a requirement in that FDA issue and periodically update final guidance describing the responsibilities of each agency center regarding its review of combination products.