In an April 6 FDA Voice blog post, the agency announced the formation of a Combination Products Policy Council, which will be able to make decisions on combination products, product classification, and cross-labeled products. This is the latest step in a series of actions FDA has taken recently to adjust the combination products review process.
Combination products are those medical products that merge two or more components from the drug, device, and/or biologic categories. This can lead to confusion over what center--CDRH, CDER, or CBER--should be the lead review center based on a determination of what the product's primary mode of action (PMOA) is. There is also complexity in trying to line up and fulfill the various requirements and timelines of each center. As FDA officials wrote in this week's blog post, "differences in statutory and regulatory requirements for different application types, including evidentiary standards, data requirements, and review limitations, make it challenging to coordinate reviews and ensure alignment and consistency in addressing issues across centers."
A regulatory expert with wide medical product experience agreed with the need for improvement in this arena. Jur Strobos, MD, JD, FACEP, wrote to MD+DI, "From my standpoint, I share the agency's earlier concern that there is inconsistency in decision-making. My own view is that this is because the designation is largely an exparte process between the company and the company's chosen designee--whether CDRH, CBER or CDER. It also appears to me from the outside that communication on a specific product between the potentially designated centers after a preliminary take by the company's preferred center could be improved. Because the process is confidential between the FDA and the company, there is no public oversight over the process and, by the time the public knows of the decision, it is too late for anyone to object."
Strobos is a permanent advisory board member for Claravant Analytics, a company that helps guide medical companies through the regulatory and intellectual property processes.
Learn more about combination product regulation during the MD&M East Conference, June 14-16, in New York City.
FDA's changes follow months of consideration from industry, lawmakers, and the agency itself about the best way to change the combination product premarket review approach. Last fall, the agency scrutinized the process and found issues that included different review and tracking data systems at each center, a need for improved communication between centers, and a lack of resources.
Strobos noted that decisions about which center should be the lead review center for a combination product can sometimes be controversial. He wrote:
"As with any organization that has silos, I think there also must be competition between the Centers and preference for one's own center to take new and exciting products. To that end, CDER (which is the largest and most well-funded Center) is a powerhouse of intellect and experience, and (in my view) has expansively read its jurisdiction. For instance, there is a recent series of court cases in which designation to CDER has been challenged by a company in which there was substantial criticism from the court. Nonetheless, after several years of litigation, CDER has prevailed with its original expansive reading. Another example is that nasal saline sprays are considered primarily drugs based on the argument that it is not the pressure and flow but the interaction of sodium chloride with mucous that produces the intended result. To me, this seems to be over-reaching and how the sprayer works is the primary issue in review and not the application of saline."
While the formal appeal process to challenge a determination of which center is the lead will still be available, the council hopes to head off the need for this by "conven[ing] parties across centers, foster[ing] understanding and consistent application of requirements, and develop[ing] a unified FDA position on issues that arise." Council members will be drawn from different FDA centers and offices and will weigh in on draft guidances and other communications regarding combination product policy.
Nina Hunter, PhD, FDA's associate director for science policy in the office of medical products and tobacco, and Rachel Sherman, MD, MPH, FDA's associate deputy commissioner in the office of medical products and tobacco as well as chairperson of the council, wrote, "We are confident that the Council's efforts will ensure transparency and consistency in our approach to combination product policy development and implementation, ultimately helping to ensure that innovative combination products marketed to the American people are safe, effective, and appropriately labeled."
Last month, FDA announced it was using lean management process mapping to get a better idea of the sources of problems within combination products review now and to form an optimized process for the future. Hunter and Sherman, authors of the March 7 blog post revealing that effort, wrote, "Lean management works. And we're confident that applying lean management principles to combination product review will allow use to enhance communication and coordination among the groups that oversee the development, review, and approval of combination products."
Also last month, AdvaMed applauded the Senate Health, Education, Labor and Pension (HELP) Committee mark up of three pieces of medtech legislation, including the "Combination Product Regulatory Fairness Act" (S. 1767). This bill "will provide needed clarity to the agency's process for reviewing combination products--whether device/drug, device/biologic or drug/biologic--ensuring more timely and predictable reviews of these novel products and again improving patient access in the long run," said JC Scott, senior executive vice president of government affairs at AdvaMed, in a statement.
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