Combo Product Safety: US FDA Rule On Postmarket Reporting Nears Finalization

Industry is eagerly awaiting guidance on combination products, and after seven years the postmarketing reg may be at top of the agency’s queue.

FDA's proposed rule on postmarket safety reporting for combination products appears to finally be making its way to the top of the queue, with the agency acknowledging that it is among the next steps in modernizing the combination products review program.

The rule – which was first proposed in 2009 – aims to clarify postmarketing safety reporting requirements for such products by spelling out the types of alerts that should be reported to FDA. For example, a company "must submit to FDA a report of an adverse experience associated with the use of a drug or biological product that is both serious and unexpected, whether foreign or domestic, as soon as possible but in no case later than 15 days of initial receipt of the information," the proposed rule states.

Industry, however, has been eagerly for the proposed rule to become finalized, as developments in combination products have grown significantly in recent years. Brad Thompson, a Member of the Firm at Epstein Becker & Green and general counsel to the Combination Products Coalition, tells the Pink Sheet that the final rule has been "languishing for quite some time." Industry is awaiting guidance on the topic, Thompson says, FDA has to finish the rule before it gets to a guidance.

"The guidance is really indispensable because there’s a level of detail that we need that just isn’t [in the rule]. … The final rule isn’t out and hasn’t been out for quite some time. It’s just very frustrating, the pace at which things go. Again, good intentions on the part of FDA; just they’re not executing it," Thompson said

Thompson added that the delay to finalizing the rule was related to retooling the IT systems at the agency, but now it is a matter of inattention on the part of FDA.

"It’s just FDA has go so many rules and so few resources, that it’s just been sitting in the queue," Thompson said. My understanding is it’s as simple as that. It just hasn’t been moved forward."

Thompson previously described the recent policy spotlight on the combo-products space, including in a recent user-fee deal, as a welcome development after a period of neglect. (Also see "Putting The Pieces Together For Combo Products Oversight" - Pink Sheet, 27 Oct, 2016.)

FDA did not provide a specific time frame for when the rule is expected to become finalized, but did the reg was first on the list of “next steps” in a brief progress report that was announced by FDA commissioner Robert Califf and Associate Director for Science Policy in the Office of Medical Products and Tobacco Nina Hunter in a Dec. 2 blog post. The agency did not immediately return a request for comment regarding the time frame for the postmarketing reg. (See table below for the complete list of updates.)

FDA's Office of Planning first launched an internal assessment of the agency's inter-center consultations for combination products in 2014, following complaints from industry that the product centers within FDA were not effectively coordinating and communicating, leading to confusion and delays in the review of combination products. (Also see "FDA's Combo Product Consultations To Be Streamlined" - Pink Sheet, 15 Oct, 2015.)

Also among the agency's next steps in the modernization of the combination products review program are an update of a June 2011 draft guidance on the classification of medical products as drugs and devices, the issuance of guidance on the Pre-Request for Designation process for requesting early feedback on combination products and the provision of key points of contact in Office of Combination Products and medical product centers for combination product review.

Combination Products Review Program: Progress and Potential
Commitment	Progress	Next Steps
Issuing more guidance for review of combination products (e.g., our pending draft guidance document on human factors)	Publication of Draft Guidance “Human Factors Studies and Related Clinical Study Considerations in Combination Product Design and Development” Publication of Final Guidance “Applying Human Factors and Usability Engineering to Medical Devices	Finalize Guidance on Human Factors, cGMP, Postapproval Modifications and Final Rule on Postmarket Safety Reporting Update guidance on classification of medical products Issue guidance on Pre-RFD process for requesting early feedback on combination products
Enhancing and simplifying data access and sharing for internal staff	Established process for each medical product center to request and maintain access to databases Access now granted within 48 hours in most cases (as opposed to several weeks)	As databases evolve, continue gathering requirements for future enhancements
Facilitating staff in requesting and monitoring inter-center consults	Leveraged lean tools and concepts to improve intercenter consult request (ICCR) process for combination products review Currently executing a pilot for the new process using a phased approach across medical product centers	Pilot completion expected by mid-2017, with final process established and implemented across the Agency. All staff involved with combination products review will be trained on the same process and use the same request form for monitoring submissions and consult requests
Updating and maintaining internal contact directory for experts to review combination products	Through ICCR pilot, we have begun to clarify roles, establish subject matter experts & identify key points of contact for various disciplines across medical product centers	Once established internally, we will provide key points of contact in Office of Combination Products and medical product centers for combination product review, and will maintain and update this information
Improving our internal standard operating procedures and policies (SOPPs) for premarket reviews and compliance activities	Through ICCR pilot, we have initiated a new process for requesting consults for combination products review	Through ICCR pilot, we have begun to clarify roles, establish subject matter experts & identify key points of contact for various disciplines across medical product centers
Source: FDA progress report posted Dec. 2, 2016