The FDA may have intended the draft rule for product jurisdiction for combination products to clarify the agency’s approach to how it will deal with such products, but the draft has proven unpopular so far, suggesting the agency has its work cut out for it.
The draft rule, which was prompted in part by the 21st Century Cures Act, proposed to eliminate a step in the appeals process, a step the agency suggested was superfluous. As previously discussed, the FDA also oddly cited the prospect that the proposed rule would save lives, but stakeholder see a lot of problems in the draft. For instance, the Washington Legal Foundation said stakeholders might have expected the draft to explain how the agency would “place the dividing line between drugs and devices,” but that the draft fails to do so.
WLF’s Richard Samp and Corey Andrews, respectively the organization’s chief counsel and senior litigation counsel, said the draft rule deviates from the statute with regard to determining a product’s primary mode of action. Samp and Andrews said the statute defines PMOA as “the single mode of action of a combination product expected to make the greatest contribution to the overall intended therapeutic effects of the combination product.” In contrast, they said, the draft rule proposed to evalute the primary mode of action for each of the constituent parts rather than determining the PMOA of the product as a whole, an approach they said “improperly skews” those determinations toward a determination that the product should be reviewed as a drug application.
Several organizations recommended that the FDA allow requests for designation to run to 30 pages rather than the current 15-page limit, but attorneys with the D.C.-based law firm Hyman Phelps & McNamara had other critiques of the draft rule as well. HPM’s Jeffrey Gibbs and Jennifer Thomas said the agency’s position appears to be that a combination product “is a drug or biologic rather than a device if it exhibits any chemical action that contributes to the therapeutic effect.” Thomas and Gibbs said FDA regulations pertaining to combo products dictate that any component of a combination product may have only one mode of action, and that the net effect of these two conditions is to “bias FDA’s jurisdictional evaluations significantly in favor of determining that products composed of multiple distinct components should be regulated as drugs or biologics, rather than [as] devices”
Thomas and Gibbs cited the well-known conflict between the FDA and Prevor of Valmondois, France, over the diphoterine application – which led to a lawsuit that twice appeared in the District Court for the District of Columbia – as an example of the FDA’s propensity for determining that a combination product is a drug despite “very minimal chemical action.” They stated also that the agency’s requirement that the applicant prove the combination is primarily a device within 15 pages is further evidence of a bias against a determination that the product operates principally as a medical device.
Another FDA draft document pertaining to medical devices has provoked concerns among those in industry, the multiple function draft guidance released by the agency in mid-April. The intent in developing the draft was to clarify how FDA staff would deal with applications that embody components that meet the regulatory definition of a device along with components that do not meet that definition, but stakeholders expressed concerns over what seems to have come across as a regulatory slippery slope.
Fears of Regulatory Mission Creep
In that draft, the agency coined the term “device-function-under-review” to distinguish between the regulated and non-regulated functions, and the FDA said the term “function” means “a distinct purpose of the product.” Definitional issues aside, some who commented for the docket indicated that the draft could be applied to combination products, possibly leading to regulatory mischief. Another concern is that any function fulfilled by a component that qualifies as a device that is under enforcement discretion might nonetheless fall under premarket scrutiny if the agency determines that the component in question could provoke questions regarding the safety and/or effectiveness of the entire product.
Another point of consideration is how the FDA’s field investigators would handle inspections of a facility when these non-device components are involved in a product, but there are also lingering questions revolving around recalls and field corrections. Those in the field of in vitro diagnostics may be concerned that controls and calibrators might be swept up in a premarket review if the agency fails to make explicit that these components would not be seen as subject to review despite that the agency has explicitly exempted them from such scrutiny.