Off-Label Speech Among Potential Questions for FDA Nominee

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By Bronwyn Mixter

Nov. 13 — Potential issues that Robert Califf, President Barack Obama's nominee to lead the FDA, may get asked about during his Senate confirmation hearing include what drug and device companies can say about unapproved uses of their products, how to accelerate the development and approval of new drugs and the regulation of laboratory-developed tests, an FDA law expert told Bloomberg BNA Nov. 13.

Daniel Kracov, head of the health-care practice at Arnold & Porter LLP in Washington, discussed the potential trial questions the FDA nominee could be asked at his Nov. 17 confirmation hearing before the Senate Health, Education, Labor and Pensions Committee. Califf, currently the deputy commissioner for medical products and tobacco at the Food and Drug Administration and a former Duke University researcher, was nominated for the position in September (179 HCDR, 9/16/15).

Meanwhile, a watchdog group voiced objections to Califf because of how he handled a clinical trial for the blood thinner Xarelto.

On Nov. 10, the HELP Committee said in a statement that the hearing “will be an opportunity for HELP Committee members to hear from the nominee on a range of issues relevant to the FDA—an agency that affects the lives of nearly every American.” The committee added that, “Following next week’s hearing, an executive session will be scheduled for committee members to vote on Dr. Califf’s nomination.”

Califf would succeed former FDA Commissioner Margaret Hamburg, who stepped down at the end of March. Stephen Ostroff, the agency’s former chief scientist, has served as acting commissioner since then.

Potential Questions 

Kracov told Bloomberg BNA that one area that the committee could ask about is what Califf's “views are and what his plans are with regards to the developing case law around the First Amendment and off-label speech by pharmaceutical and medical device manufacturers.”

Off-label refers to uses that aren't approved or cleared by the FDA. Under long-standing policy at the FDA, companies can be subject to criminal prosecution and civil liability if they promote their products for uses for which the FDA hasn’t specifically approved them.

“I think that's got to be something that's on the agenda in terms of how the agency's going to deal with that,” Kracov said. “I think they'll want to get his views on the record.”

In May, Amarin Pharma and a group of doctors sued the FDA in a federal court in New York, challenging the constitutionality of FDA regulations that prohibit Amarin from making completely truthful and nonmisleading statements about its high-triglyceride treatment Vascepa, a pure omega-3 fatty acid known as EPA (90 HCDR, 5/11/15). Amarin wants to be able to tell doctors about how Vascepa can be used safely and effectively off-label without fear of prosecution or liability.

In August, the district court granted preliminary relief to Amarin and said the company may engage in the truthful and nonmisleading promotion of its cardiovascular treatment Vascepa for an off-label use (153 HCDR, 8/10/15).

Since then, the proceedings in the Amarin case have been stayed, to give the parties time to engage in settlement discussions.

Limited Time?

Another FDA law expert, attorney Linda Bentley with Mintz, Levin, Cohn, Ferris, Glovsky and Popeo PC in Boston, told Bloomberg BNA Nov. 13 that 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, Califf’s tenure may be short, Bentley noted.

Bentley also said the committee members’ questioning “will likely be guided by political and ideological considerations.”

Accelerating Drug Development 

Kracov said another area that ties into the 21st Century Cures legislation (H.R. 6) and the Prescription Drug User Fee Act (PDUFA) are Califf's views “on what can be done to accelerate the development and approval of drugs” and particularly, the qualification of biomarkers.

In July, the House voted overwhelmingly (344-77) to pass the 21st Century Cures bill (133 HCDR, 7/13/15), which now moves to the Senate for consideration. The House Energy and Commerce Committee describes H.R. 6 as an effort to speed the discovery, development and delivery of life-saving and -improving therapies.

The qualification of biomarkers “is really a very central theme in 21st Century Cures and something that a lot of companies are worried about just because the drug development process has become so difficult and costly,” Kracov said. Califf is “a drug development guy and I think they'll want to get views on the record,” he said.

A biomarker is an objective characteristic that is measured and evaluated as an indicator of normal biologic processes, pathogenic processes or pharmacologic responses to treatment, according to the FDA. Biomarkers can serve many purposes in clinical drug development, including defining the appropriate patient populations for study.

Another area to ask about is Califf's views on the regulation of lab-developed tests, Kracov said. “I think that's really going to be a central issue on the device side,” he said.

The Centers for Medicare & Medicaid Services regulates laboratory-developed tests (LDTs), while the FDA's Center for Devices and Radiological Health (CDRH) regulates certain in vitro diagnostic (IVDs) tests, or those tests manufactured by device companies.

In the fall of 2014, the FDA issued two controversial draft guidance documents to exert more authority over the LDTs, a move that clinical labs and some other medical groups oppose, but that device manufacturers have supported (190 HCDR, 10/1/14).

Criticism for Califf 

The Project on Government Oversight (POGO) Nov. 12 voiced objections to Califf, saying he led a clinical trial that was sharply criticized as biased in favor of the experimental blood thinner Xarelto.

Califf cochaired the executive committee of the Xarelto clinical trial, POGO said. The FDA approved Johnson & Johnson's Xarelto in 2011 over the objections of the primary FDA scientists assigned to study its safety and effectiveness, the group said. Their review argued that patients could be “at greater risk of harm from stroke and/or bleeding” if they took Xarelto than if they were treated skillfully with warfarin, a blood thinner that has been on the market since the 1950s, POGO said.

POGO said that as FDA commissioner, Califf will hold considerable sway over decisions that affect the interests of the drug industry and the health and safety of the public.

“Dr. Califf’s handling of the Xarelto trial raises concerns about his judgment in overseeing the pharmaceutical industry,” Danielle Brian, executive director of POGO said. “As senators consider Dr. Califf's confirmation to run the FDA, they should ask tough questions about the Xarelto clinical trial.”

Founded in 1981, POGO is a nonpartisan independent watchdog that champions government reforms.

To contact the reporter on this story: Bronwyn Mixter in Washington at

To contact the editor responsible for this story: Brian Broderick at


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