Califf Nomination Suffers 'Pile On': What Can FDA Do To Break Logjam?

The push to make Robert Califf the next FDA commissioner is becoming increasingly muddled in a growing list of political and public health fights that threaten to overwhelm the confirmation, increasing the pressure for a timely Senate vote.

Sens. Ed Markey, D-Mass., and Bernie Sanders, I-Vt., added to the list of holds placed on the Califf nomination Jan. 25 and 26, bringing the total to three.

And Sen. Joe Manchin, D-W.V., promised on Jan. 27 to filibuster the nomination.

The holds and filibuster warning further slow the process of getting Califf to a floor vote and threaten the viability of the nomination, especially with the Obama Administration's days near their end.

Califf still could address all of the issues and get the holds lifted and filibuster removed, but there also is a danger that these troubles will spur even more opposition, which could make a floor vote impossible.

Robert Califf

Markey and Manchin added opioid abuse to the list of issues that Califf will need to address before his nomination can go forward.

Presidential candidate Sanders is holding Califf because of a lack of commitment to lowering drug prices and his ties to the pharmaceutical industry.

Sanders came out against the nomination shortly after it was announced. He does not believe Califf will stand up to the pharmaceutical industry and support patients (Also see "Califf Nomination Hearing Expected Before Holiday Season" - Pink Sheet, 9 Oct, 2015.).

The third hold comes from Sen. Lisa Murkowski, R-Alaska, who was angered over FDA approval of a genetically modified salmon product. She announced the hold just before the Health, Education, Labor and Pensions Committee sent Califf's nomination to the floor (Also see "Califf Nomination Swimming Upstream With Multiple Holds Now Possible" - Pink Sheet, 12 Jan, 2016.).

The Pile-On Effect

The holds still are manageable, Marc Scheineson – head of the food and drug law practice and Alston and Bird, who also was an associate commissioner for legislative affairs and worked on former Commissioner David Kessler's confirmation in 1990 – said in an interview with "The Pink Sheet."

Scheineson said the issues are resolvable, but the number of holds could quickly grow much larger, meaning there is increasing pressure to placate concerns quickly and move to a floor vote.

As holds are announced, they can become a signal for others to pile on, one lobbyist told "The Pink Sheet."

Manchin's filibuster threat may be a product of that effect and could attract more senators concerned about opioids or other FDA issues to join the hold list.

Senate leadership still could schedule floor time for the nomination if Califf is a high priority, but the question remains as to whether it would be worth the effort, the lobbyist said.

Scheineson said he did not believe President Obama will walk away from Califf at this stage.

FDA likely is not ready to give up either, he said, especially after all the effort staff have put into the confirmation process already.

Califf received bipartisan support almost from the outset.

Sen. Lamar Alexander, R-Tenn., who chairs the HELP Committee, along with Ranking Member Patty Murray, D-Wash., both strongly supported Califf before the full committee unanimously supported sending his name to the floor.

Alexander reiterated support for Califf Jan. 28, saying he was hopeful that after a short time his name would come up to the floor.

There also is the possibility that if a Democrat succeeds Obama, that administration could choose to retain Califf, which could provide more motivation to push for a vote (Also see "Califf Nomination May Show Confidence In His Bipartisan Appeal" - Pink Sheet, 15 Sep, 2015.).

Getting Sanders' Attention

FDA officials likely are working with HELP Committee members to try and come up with ways to entice Markey, Manchin, Sanders and Murkowski to end their opposition to a floor vote.

"These holds disappear as magically as they appear," Scheineson said. "It's a matter of getting in front of them with some ideas."

Sanders' presidential aspirations likely make dealing with his hold more difficult.

FDA could commit to continue working on the generic drug backlog as a way of dealing with drug pricing concerns, but Sanders' critique of FDA and Califf doesn't really focus on the regulatory levers the agency could pull and instead seems part of the presidential candidate's broader rhetoric on health care economics.

Indeed, the longer the Sanders campaign runs, the less likely he may be to pull the hold, for fear of hurting his chances in upcoming primaries.

Obama may already be working on the problem. Sanders met with him at the White House Jan. 27.

White House spokesman Josh Earnest said during a Jan. 27 press briefing that he did not know whether Califf came up during the meeting, but said the White House and administration still have full confidence in Califf.

"The president would not have nominated him to the job if he didn't think that he would be able to effectively look out for the interests of middle class families in that role," Earnest said.

Opioid REMS Program Could Be Modified

In contrast with Sanders, Manchin's concerns seem to be ones the agency might actually be able to address with policy changes, if it desired.

Manchin's tactics are more dramatic, though: He called for a new nominee during a floor speech where he announced that he intended to filibuster Califf. It's a bolder way of opposing the nomination, but would essentially accomplish the same goal of delaying consideration.

Manchin argued Califf is not the person to change FDA's culture and make a serious attempt at addressing the opioid epidemic.

"That will not happen if the person at the helm is not a strong advocate who is committed to pushing back against the pressure to continually approve new opioid medications, given the significant risks to public health," Manchin said.

"I believe that the FDA must break its cozy relationship with the pharmaceutical industry and instead start a relationship with the millions of Americans impacted by prescription drug abuse."

Manchin's concerns dovetail with Markey's, who wants "immediate reforms to the agency's approval process for opioid painkillers," according to a written statement.

In addition, Markey urged FDA to conduct advisory committee meetings for any upcoming opioid approval questions, consider addiction, abuse and dependence as part of its determination of whether an opioid is safe, and rescind its 2015 approval of Purdue Pharma LP's OxyContin (oxycodone) for use in children.

"FDA continues to operate as if safety just means the right dose when it should include all the dangers of these painkillers," Markey said in the statement. "FDA needs to commit to shift the way it approaches and evaluates addiction before I can support Dr. Califf's nomination."

The agency could agree to look at strengthening its Risk Evaluation and Mitigation Strategy on extended-release and long-acting opioids, Scheineson said.

Center for Drug Evaluation and Research Director Janet Woodcock also said Jan. 28 that the agency is planning an extensive series of opioid-related activities, but would not give more details on what exactly was coming.

Califf said in answers to written questions from Sen. Elizabeth Warren, D-Mass., that the agency is currently evaluating the opioid REMS and whether changes are needed. He also said there are ongoing studies to quantify opioids' long-term risk of abuse and misuse.

FDA likely will not rescind OxyContin's indication in children, which stemmed from an agency request to Purdue under the Best Pharmaceuticals for Children Act (BPCA) (Also see "Keeping Track: Neurology And Pain Products Keep FDA Occupied" - Pink Sheet, 17 Aug, 2015.).

Califf wrote in answers to Warren's questions that efforts to curb misuse and abuse must be balanced with "legitimate and safe use of pain medicine by patients who need them."

FDA also continues to push for abuse-deterrent formulation development and research into alternative pain treatments, he wrote.

"Our hope is that there will be alternative treatment options for pain management using non-opioid pain medications," Califf said in the written response. "We are actively encouraging and supporting the development of such products."

FDA has approved abuse-deterrent labeling claims, but they have been difficult to obtain (Also see "Opioid Market Snapshot: No Pain, No Gain For Abuse-Deterrence Claims" - Pink Sheet, 24 Mar, 2014.).

Let's Talk About Fish

Murkowski also reiterated that her concerns about Califf during a floor speech the same day as Manchin's filibuster threat.

Murkowski said in the floor speech that it has been difficult to get FDA to talk with her about her problems with genetically engineered fish and its labeling.

"The FDA is an agency that has considerable authorities, and we here in the Congress need to know that we can have this level of dialogue and discussion going back and forth, and I think we have seen a real lack or a shortfall," Murkowski said in a Jan. 27 floor speech.

Murkowski was angered she did not receive advance notice that the product was being approved, which prompted talk of holding Califf (Also see "Califf Nomination Gets Fishy" - Pink Sheet, 1 Dec, 2015.).

FDA was directed to prevent import of genetically modified salmon until labeling guidelines were finalized in the fiscal year 2016 omnibus appropriations bill. An import alert was released Jan. 29 to that effect (Also see "Priority Review Vouchers, FDA Funding Win In Omnibus Budget Deal" - Pink Sheet, 16 Dec, 2015.).

No Playbook For Success

There is no set formula to push a commissioner across the finish line, Scheineson said.

The one trump card supporters can use is that FDA is an important public health agency that runs better with a confirmed commissioner and that senators should not stand in the way of the protection of public health, Scheineson said.

So far that has been Alexander's strategy. He said Jan. 28 that he expected senators would want a strong FDA chief because the agency touches almost every American.

It does not seem to predict a quick confirmation, however.

Califf's confirmation has now been in process more than four months, following his September nomination.

Scheineson said it took six months for Kessler to become commissioner (Also see "FDA COMMISSIONER KESSLER EXPECTED ON THE JOB EARLY IN DECEMBER" - Pink Sheet, 5 Nov, 1990.).

Margaret Hamburg, whom Califf would replace, was nominated for the post in March 2009 shortly after Obama took office. She was sworn in on May 22 that year (Also see "The Hamburg Era Begins At FDA: NEJM Editorial Faces Critics Head-On, May Buy Breathing Room" - Pink Sheet, 1 Jun, 2009.).