The dust generated by the decision to reject the over-the-counter switch of Teva Pharmaceuticals USA Inc.’s emergency contraceptive Plan B One Step (levonorgestrel 1.5 mg) will take a long time to settle, but the good news for pharmaceutical companies is that process was about as clean as it could be from industry perspective.

To many, the decision by Department of Health and Human Services Secretary Kathleen Sebelius to overrule FDA Commissioner Margaret Hamburg and deny the switch application seems heavy-handed and politically motivated. Sebelius’ Dec. 7 memorandum based her decision on the lack of data for 11-year-old females, 10% of whom have reached reproductive age and would thus be in Plan B’s patient population, but critics see the upcoming elections, not label comprehension studies, as the basis for the decision.

Health and Human Services Secretary Kathleen Sebelius

Photo courtesy of HHS

For the Rx industry, the impact of the decision should be measured not so much in how it could disgruntle President Obama’s fervent supporters or affect independent voters, but what it says about how FDA will continue to review drug applications and oversee development and marketing. Here, the answer is also a little murky, and the results will not become clear even by November 2012. But though there is cause for concern, there are also some hopeful signals.

Sexual politics aren’t going away after the next election, so industry needs to ask itself, assuming a political decision for this kind of application is going to be made, how would they like it made? Have FDA pressured to make the preferred decision itself? An overruling by HHS? Or have the agency structurally independent from the executive branch so that neither kind of pressure was possible?

Industry-Rattling Precedent?

The pessimists’ argument about Sebelius’ decision is that it is a potentially far-reaching precedent that injects considerable uncertainty into the approval process. Food and drug attorney Stephen Mahinka, a partner with Morgan, Lewis & Bockius, noted the HHS hierarchy typically lacks the expertise to weigh in on drug safety and efficacy: “They don’t get into FDA things for good reason.” Sebelius’ rationale for overruling FDA’s Hamburg is “potentially very expansive” and could emerge as a hurdle in other controversial drug areas, such as cancer treatments, he added.

Dan Grossman of Ibis Reproductive Health posited that the specter of HHS interference could become “a little bit of a black box” and stifle innovation in the area of Rx-to-OTC switches.

Harvard professor Daniel Carpenter even suggested the ruling meant that FDA should be separated from HHS in order to insure independent decisions. In a New York Times op-ed entitled “Free the FDA,” Carpenter argued that “the precedent risks placing the real power for drug approval not just with a cabinet secretary, but with the White House itself. The only solution, then, is to make the FDA truly independent. Americans have already done this, through the Federal Reserve, to protect our money supply from political meddling; it’s time to do it for drugs.”

A wholly independent FDA is probably not a character that sponsors would like to meet in a dark drug review alley.

The drug industry has advocated a fixed term for the FDA commissioner to provider management continuity and insulate it from political pressure, but a wholly independent FDA is probably not a character that sponsors would like to meet in a dark drug review alley. Companies have long been concerned about proposals to create an independent safety center within the agency because of fears that it would naturally see its mission as one of finding risks in drugs. A completely independent FDA, freed of any political pressure to show that it was approving drugs quickly, might theoretically go down a similar, worrisome path.

Owning The Decision

The last major dust-up over Plan B, surrounding its initial OTC switch for women over 18, resulted in a high-profile resignation and a lawsuit that unveiled the fact that FDA decision-makers felt intimidated during the review process Also see "Galson Backed Initial Plan B Denial In Fear His Job Was In Jeopardy – Jenkins" - Pink Sheet, 4 September, 2006.. In having Sebelius make the political move, the agency was insulated and its scientific integrity upheld, to some extent avoiding the fallout of the original switch decision during the Bush Administration.

FDA still has some legal mopping up to do this time around Also see "Updated Plan B Lawsuit Could Expand EC Switch Targets" - Pink Sheet, 19 December, 2011., but the difference in how the decision is perceived within the agency seems palpably better for morale.

FDA Center for Drug Evaluation and Research official John Jenkins played down Sebelius’ intrusion into the drug approval process.

Jenkins, director of CDER’s Office of New Drugs, said members of the review team that handled Teva’s application were disappointed that Sebelius overruled them. But he added that they understood the broader political controversy surrounding Plan B, and Hamburg’s support for their conclusion gave the reviewers a boost.

“I think we appreciate the fact that the secretary, in making her decision, has owned the decision, so it was very transparent,” Jenkins said Dec. 8 at the FDA/CMS Summit in Washington.

Jenkins also suggested that the decision could lead to more consideration of creating behind-the-counter products, in addition to the existing Rx and OTC classes ([A#05111212014]).

“Maybe some of the conversation that needs to be had around Plan B is: Does the United States need a system where we can rely more on that pharmacy-access type of program to allay some of the concerns about young girls having access to emergency contraceptives without their parents’ knowledge?” Jenkins said. “I think we have to acknowledge it’s a very controversial area.”

The decision “may be an impetus to move toward an intermediate place within the system where maybe there can be some restrictions to engage the pharmacists in some of these access programs,” Jenkins said. “I think Plan B is just one of the potential products that could be made more readily available if we look at the system.”

And if more approval options are the upshot of this Plan B controversy, that’s the kind of political heat that industry should welcome.

Plan B Decision May Offer FDA Best Political Protection Available

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