President Obama's nominee for FDA commissioner was grilled Tuesday by members of the Senate committee on Health, Education, Labor and Pensions on issues ranging from the controversy over drug pricing to his previous ties to the pharmaceutical industry. And while committee members were largely respectful of of the experience and credentials of Dr. Robert Califf, a renowned cardiologist, there was plenty of controversy.
Here are the most important issues that the HELP Committee addressed during Tuesday's hearing—and how the would-be successor to Dr. Margaret Hamburg fielded lawmakers' inquiries.
1) Integrity and independence from the pharmaceutical industry
One of the biggest points of contention surrounding Califf's nomination has been his past involvement with the pharmaceutical industry, including during his tenure at the Duke University School of Medicine.
Critics have asserted that Califf has uncomfortably close ties to the very sector he may eventually oversee. For example, he's received more than $200,000 in consulting fees from pharma giants including Johnson & Johnson, GlaxoSmithKline and Merck. But one big reason for this was Califf's role as an investigator who oversaw major clinical trials, including one for J&J's Xarelto (rivoroxaban) that landed him nearly $50,000 in remuneration.
Democratic Sen. Elizabeth Warren (MA) and Sen. Bernie Sanders (I-VT), who is challenging Hillary Clinton for the Democratic presidential nomination, pressed Califf on these issues. Warren requested access to clinical trial contracts between his team at Duke and pharma companies. Later on in the hearing, Califf revisited this point and noted that Duke already had agreed to provide the contracts to the Senate.
"I would say 70% of the studies I wanted to do we couldn’t do because the companies didn’t want to give up control of the databases," he said.
Califf remained adamant about his record of independence from the pharmaceutical industry over the course of the hearing. He pointed to Duke's policy of retaining control of the databases associated with clinical trials, as well as the retention of the right to publish studies without edits from pharma companies.
The Obama administration has also noted that Califf has fully divested any stakes he may have had in pharma companies, and that the consulting fees that he's received were all donated to nonprofits.
But it's important to recognize that there is also another bit of potential controversy surrounding Califf's past as a clinical investigator. Shortly after the president nominated him for FDA chief, Califf requested that his name be removed from a number of papers that he co-authored for the journal Clinical Trials—an unusual move that could raise ethics questions.
His stated reason for this was to avoid a conflict of interest as some sections of the papers criticized certain FDA practices in clinical trial oversight, and recommended changes that could prove to be controversial.
2) Drug pricing and the role of the Food and Drug Administration
Warren may have been discerning about Califf's record, but Sanders approached open hostility toward the nomination, even launching his questioning by stating that he would not be supporting Califf's confirmation (he had made his intention on this clear well before the hearing).
Sanders shared Warren's concerns about Califf's industry ties. But the Vermont senator levied this criticism into doubts regarding Califf's willingness to tackle the red-hot issue of high drug prices.
"I told you I would not support your nomination because I didn’t believe you were strong enough on pricing of prescription drugs," said Sanders.
"About one out of five Americans can’t afford to fill the prescription that their doctors are writing for them... The prices in Canada are far, far less expensive than they are in the U.S...Last year, the top four drug companies in this country, Pfizer, Johnson & Johnson, Novartis, and Hoffmann La-Roche made $57 billion in profit in one year...They are doing quite well."
"We need an FDA commissioner who is going to be aggressive. I don’t think you get that."
As Califf noted on several occasions in response to this line of criticism, controlling drug prices is largely beyond the FDA's purview. The agency is mainly tasked with assessing the safety and efficacy of drug candidates.
But the nominee did take exception to Sanders' proposition that the U.S. should be able to import drugs from other countries—a position that was also held by former Commissioner Margaret Hamburg. "We have major concerns with re-importation, the system it would take to ensure [safety and quality]," said Califf.
He also responded with apprehension at the thought of expanding the availability and use of compounded drugs in order to lower prices, noting that there have been high-profile cases of quality control issues at compounding pharmacies.
When asked if he would support direct price negotiations between Medicare and drug companies, Califf demurred to the Obama administration's position that such bargaining should be allowed. And responding to a question from Sen. Al Franken (D-MN) regarding his recommendations for lowering drug prices, Califf said that approving more generics and biosimilars and preventing drug shortages would be critical.
"When someone gets a monopoly, we need to understand who the competitors are and make sure they are doing the right things to get their products on the market," he said.
3) Patient safety and the pace of drug approvals
As BioPharma Dive has previously reported, the pace of drug approvals has spiked significantly over the past several years, largely in response to industry and patient advocate pressure to expand the availability of treatment options (particularly for unmet medical needs).
But this trend has also raised concerns among certain critics who question whether the rapid clip of regulatory blessings is occurring at the expense of patient safety. Some note that the use of post-marketing surveillance and black box warnings has ballooned significantly alongside drug approvals.
In one pointed exchange, Warren asked Califf about the propriety of clearing therapies at such a rapid rate, once again referencing Califf's ties to the industry. "Your relationships also raise concerns about your motivations," said Warren. "Do you agree with arguments to lower standards for FDA approval of drugs and devices?"
"I have never been a proponent of lowering standards for anything," Califf shot back. "I have been in favor of raising standards. In no case would I argue to lower the standard. I think I have been staunch in that regard."
In a related discussion that touched on both drug pricing and approvals, Califf told Sen. Lamar Alexander (R-NC) that the FDA could do more to bring lower-cost generics to the market. "88% of US prescriptions now are generic," said Califf.
"We can do even better. We started with a huge backlog that were waiting for user fees to come in. The easy ones went through quickly. The new ones are put in a fast lane. But we have a backlog that requires a back and forth."
4) Quality control and the woes of international manufacturing
Industry observers are likely aware that manufacturing plants in developing nations such as India and China don't always have a stellar record of quality control. In September, the FDA added the 10th Indian plant to its "do-not-import" list in 2015 alone, and the EU is in a major spat with India over an import ban on hundreds of generic drugs.
This is a critical issue since the vast majority of generics used around the world (and in the U.S.) are manufactured in developing nations. And its importance didn't elude Califf's questioners, including Sen. Bill Cassidy (R-LA).
Califf said the FDA would continue to focus on the issue by promoting more inspections in the relevant regions. "I did a lot of work in India and China over the last decade," he said. "It is going to be a focus and we will have to pay attention to it. A lot [of product] is coming from India and China... We can’t shut [down supply chains] in India and China, but we can shut down importation."
5) Biosimilars, innovation in drug development, and data exclusivity
The debate over biopharma data exclusivity will be central to the upcoming legislative skirmish over Obama's 12-nation Trans-Pacific Partnership (TPP) trade agreement. While biologic drugs have 12 years of data exclusivity in the U.S. (a provision of the Affordable Care Act), the compromise hammered out between TPP nations limits this exclusivity to between five and eight years.
So it's not surprising that several senators, such as Sen. Orrin Hatch (R-UT), emphasized the importance of exclusivity measures for medical innovation.
"I am very concerned about data exclusivity," said Hatch, who has already made his support for Califf's nomination clear. "We made sure in Hatch-Waxman that there was enough time for companies to recoup costs."
"If we reduce data exclusivity time, especially with biologics, you are talking about companies charging a lot more and our industries subsidizing other companies around the world. Can we make it so these companies have a chance to recoup investments?"
"I do understand your concern," Califf responded. "We want to make sure there is a return on investment. As you know, the FDA doesn’t set the length of data exclusivity. But what we can do is we can do trials that are bigger and more representative of patients at much lower cost. I hope you will work with us on this."
Califf also touched on an issue that's been in the industry's crosshairs since the approval of Zarxio, the first biosimilar in the U.S.: the labeling pathway for biosimilar drugs.
"The labels ultimately have to encourage biosimilars and enable patients and providers to understand when there are differences," he said. "I can’t tell you when we will be done but I can tell you it’s a high priority." He also called the process for biologics a "tough, complicated issue."