The Food and Drug Administration’s Center for Biologics Evaluation and Research and Center for Devices and Radiological Health has issued a draft guidance (available at http://1.usa.gov/1nEBjUq). It describes the statutory and regulatory foundations permitting the agency to approve “Premarket Approval” (PMA) applications for medical devices even when all of the data that FDA requires are not available at the time of approval. The lynchpin is that “FDA believes that applying postmarket controls in order to reduce premarket data collection, when appropriate, improves patient access to safe and effective medical devices that are important to the public health.” The Food, Drug and Cosmetics Act requires that FDA use the “least burdensome” data requests to establish the effectiveness of a device and that “probable benefits” be weighed against “probable risks.”
There is no new regulatory ground broken in this guidance, but it emphasizes the ability of the agency to be flexible. Current events in blood banking may provide an important example of that flexibility. I have argued that advisory committee discussion of the path to approval of pathogen reduction (PR) technologies was “hijacked” by attempts to apply rigid pharmaceutical principles to the evaluation of an extraordinarily complex biological product and its use – platelets and platelet transfusion. The agency has chosen to eschew the approach recommended by its Blood Products Advisory Committee that would have required large new clinical trials at great expense, entailing long delays, to evaluate what were – at best – controversial risks. Instead, FDA is considering using, in part, the postmarket experience in the European Union (EU) with a sponsor’s pathogen-reduced platelets to evaluate a PMA. Assuming approval, FDA will require the sponsor to execute a substantial postmarket surveillance program to confirm what appears to be acceptable safety and effectiveness across the pond. The availability of PR holds promise to eliminate platelet-associated bacterial sepsis (the most common cause of infectious mortality from transfusion in the US), as well as the contortions we are considering for its mitigation. PR could alleviate our need to identify and provide to appropriate recipients with irradiated platelets and provide a layer of protection against a broad array of emerging pathogens.
The postmarket surveillance requirements under consideration will need an unprecedented level of cooperation from the sponsor, us, and our colleagues in hospitals to provide what I think the agency will request. Postmarket requirements will likely increase the cost of the technology to the collection facilities that will apply PR to blood products and to the providers that will use them- so we need to understand the cost-benefit proposition being considered. In the least, the approaches explained in this guidance and being applied in this example offer you an understanding what it will take to move forward.
Louis Katz, MD, Executive Vice President, Scientific, Medical, and Technical; LKatz@americasblood.org