On July 15, 2016, the Food and Drug Administration (FDA) released a forty-six page document outlining how the FDA will use the user fees from industry, breaking down both the planned deadlines for new guidance documents and pilot projects, as well as themes of importance (i.e., patient input to the regulatory process, use of real-world evidence, biomarker qualification, and increased pharmacovigilance).
August FDA Meeting
A month later, in mid-August, the FDA and industry stakeholders met to discuss performance and procedural goals for PDUFA VI, focusing on what is to come on pre-market reviews, postmarket safety, regulatory decision tools, and other ways the FDA is working to prepare for the future of drug development.
At the meeting, Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research (CDER), highlighted the importance of encouraging patient input and really integrating it into regulatory decision making, particularly on how to make their needs known and ensure they are met during the regulatory process. Woodcock also noted that tools to collect meaningful patient input needs to be addressed, in addition to what the burden of disease means to patients and what different adverse events mean to them.
Woodcock also highlighted ways to enhance the use of real world evidence (RWE) in regulatory decision making. The FDA, in part, proposes to: conduct a public workshop to gather input into topics related to the use of RWE for regulatory decision-making; initiate activities to address key issues in the use of RWE for regulatory decision-making; and publish draft guidance on how RWE can contribute to the assessment of safety and effectiveness in regulatory submissions.
Theresa Mullen, director of CDER’s Office of Strategic Programs, responded to concerns raised about the slow process by which FDA guidance documents are finalized. She noted that the FDA only has a “handful of employees who have the expertise to write such documents.”
What is to Come?
One area that is expected to explode in the coming year is innovative clinical trial designs (particularly with regard to computerized simulations). Sponsors who have previously submitted unique ideas (or previously hesitant to do so) should now expect to receive feedback from the FDA on such ideas. The FDA presently proposes to conduct a pilot program for highly innovative trial designs for which simulations are necessary to determine trial operating characteristics, including a limited number of investigational new drug (IND) applications.
Another hot topic is “Advancing Model-Informed Drug Development (MIDD),” particularly as a new pilot program aims to gauge industry interest. The FDA proposes the Agency convene a series of workshops to identify best practices for MIDD; conduct a pilot program for MIDD approaches; develop guidance on MIDD; and strengthen staff capacity to support MIDD strategies.
When it comes to postmarket safety, FDA is hoping to improve processes and IT systems that track such data, as well as looking to integrate new sources of data into its Sentinel Initiative. The FDA is hoping to update its policies and procedures to include consistent and timely notification of sponsors: when a serious safety signal is identified, and not less than seventy-two hours before public posting of a quarterly FDAAA 921 safety notice (to the extent practicable).
Industry Reaction
AstraZeneca, for one, is asking for the ability for industry to gain better access to Sentinel data as sponsors “have an obligation to conduct robust safety surveillance on their products.” Additionally, AstraZeneca feels that sponsors “should be informed if the FDA plans to use Sentinel for routine signal detection, as this will likely generate more signals that will require investigation by sponsors and more company resources devoted to this activity.”
PhRMA, however, is not asking for any additions or revisions to the proposed performance goals, noting that “Implementation of the proposed PDUFA VI performance goals will enhance FDA’s access to the tools, processes, and expertise necessary to keep pace with the latest scientific advances in drug development and regulation, potentially accelerating clinical development and reducing the time needed to bring new medicines to patients.”
BIO, a biotech trade group, also praised the FDA for PDUFA VI, especially for agreeing to evaluate the use of new trial designs and for the FDA’s “receptiveness to the use of biomarkers as surrogate endpoints,” exemplifying “the combination of communication and flexibility that is a hallmark of the PDUFA VI goals.”