As 2015 comes to a close for the FDA, it remains an agency in transition. The agency should soon see a new commissioner and may be the subject of legislative overhauls. We have recently reported on the FDA’s new patient engagement advisory committee, anticipated biosimilars naming guidance, PDUFA reauthorization, and continued issuance of warning letters.
FDA funding, drug approvals: key concerns
RAPS reported FDA Acting Commissioner Ostroff’s recent comments, describing the importance of biomarkers in drug development, inspection policies, and patient-centric approaches. With so much talk of FDA reform, his comments on the agency’s role as a regulator may be of importance to industry. “We have to preserve FDA’s role as the protector of the American public […] We must not shortchange the standards that have provided safe and effective medical products.”
This comes as a coalition of universities, businesses and nonprofits that encourages funding for medical research is pushing for at least $2.8 billion in funding for the FDA next year, an increase of roughly $200 million. Research America published its November 11 letter to Congress, stating it expects “the FDA to assure that these products meet the high standards Americans deserve, and, because lives may hang in the balance, to do so as quickly as possible. The FDA needs adequate resources to meet those expectations.”
The Hill also notes that Congress is looking at options to speed up FDA drug approval. In particular, the 21st Century Cures Act encourages using “real world” observations effects of drugs which is less rigorous than clinical trials, and promotes the use of preliminary measures known as biomarkers instead of waiting for the definitive results of a trial. The Senate continues working on its own version of the legislation, but there remains a debate about the appropriate levels to fund the NIH and FDA in the bill. Reports indicate it is struggling to gain traction in the Senate and any potential legislative language might be narrower in terms of FDA reforms than what passed in the House.
Next Commissioner?
FDA’s next commissioner and the agency’s leadership face a number of new responsibilities and potentially major changes. The FDA continues to implement the Food Safety Modernization Act, the regulation of e-cigarettes, and the emerging biosimilars market. These challenges will certainly be the focus of Dr. Robert Califf, a cardiologist from Duke, if confirmed as the agency’s next top official.
On Tuesday, November 17, Dr. Califf received bipartisan support at his hearing despite questions on drug pricing and industry ties. Senator Elizabeth Warren (D-MA) and Democratic presidential candidate Bernie Sanders (I-VT) pressed Dr. Califf on compensation received during his time at Duke. Dr. Califf responded that the central repository of data for any given trial “is the really critical factor here. All of our contracts require that we have access to the database. Seventy percent of the studies we wanted to do we couldn’t because companies were unwilling to grant that right. We had to walk away.” He added that Duke agreed to make public the contracts it had concluded with companies. Warren insisted she get to read the fine print on his Duke contracts before deciding whether to support him.
In an interesting moment, Warren pressed Dr. Califf as to how much influence drug companies had on Duke trials, to which Dr. Califf replied that “industry has a right to make suggestions, but no right to censor or make changes unless the authors agree.” Lamar Alexander (R-TN) disagreed with any assertion there would be conflicts of interest for Dr. Califf. Alexander added that FDA and industry can improve their collaboration. This echoes Dr. Califf’s 2014 comments in which he said government regulations can be a “barrier” to medical innovation.
On medical devices, Dr. Califf called for a system to collect reports of side effects similar to one that already exists for drugs. He said that might have helped detect earlier problems with medical scopes that were linked to “superbug” bacteria outbreaks at hospitals around the country.
Dr. Califf also addressed the agency’s use of guidance documents. When asked why FDA weighs in using guidance instead of regulations that must go through a cost-benefit analysis and comment period, Dr. Califf stressed the need for transparency. Although guidances do not have the full force of a regulation, he contends it helps stakeholders better understand FDA’s thinking on a subject.
While Sanders has routinely stated his intention to vote against Dr. Califf, it has been reported that the nominee has broad support and will likely be confirmed in the near future. He has medical society and academic support, evidenced by Jeffrey M. Drazen, a Harvard Medical School professor and editor of the New England Journal of Medicine, writing that lawmakers should confirm Dr. Califf “as soon as possible.”
Food and drug lawyer Linda Bentley is cited in Bloomberg BNA noting while there are lots of challenges for the next commissioner, “the other reality is that even if Califf is able to get through the hearing process and is appointed Commissioner, he may have little time to implement his plans before Obama is out of office.” While there is no fixed term for the FDA’s leader, if a new president with a different agenda is elected next year, Dr. Califf’s tenure may be short, she said.
Other FDA Updates
Also in FDA-related news, it has been reported the agency’s Centers for Devices and Radiological Health (CDER) has approved almost every Premarket Approval Application (PMA) it received for devices in 2015. This has been tied to FDA’s improved assessment of PMA deficiencies at earlier stages in the review process. However, 510(k) applications, FDA’s determination of substantial equivalence, is similar to previous years.
Additionally, on November 2, 2015, the U.S. Department of Health and Human Services Office of Inspector General (OIG) published its Work Plan for fiscal year 2016. The OIG stated its intention to continue to audit FDA’s monitoring of food recalls and in 2016 the OIG will also look at domestic food recalls. The goal is to determine if the FDA has successfully implemented Food Safety Modernization Act requirements and whether the agency has an effective recall process in place for the nation’s food supply. The OIG will also examine the FDA’s oversight of networked medical devices used at hospitals. The OIG will be determining if the devices used at hospitals effectively protect patients’ electronic protected health information.
Finally, FDA released a paper discussing methods to identify and implement standards that will ensure next-generation sequencing (NGS) tests produce accurate and reliable results. NGS in research and clinical practice has led to the identification of genomic variants. Due to the novelty of the variant, it is often difficult to obtain evidence linking it to a particular disease or to a specific and timely clinical action. FDA writes that publicly accessible databases, where data on genetic variants from various sources is aggregated and curated, should enable the collective development of evidence for clinical interpretation of a greater portion of the human genome.