Plan C? The Plan B Decision and Calls for a Third Class of Drugs

HHS Secretary Sebelius’ decision to overturn FDA’s approval of Plan B for widespread over-the-counter use was disappointing to many drug reviewers inside the agency. But FDA’s Office of New Drugs Director John Jenkins says the move should be used to reopen the debate over whether to create a third class of drugs. And Plan B, he says, might be a perfect place to start.

FDA’s Office of New Drug Director John Jenkins is thinking positive on Plan B.

HHS Secretary Kathleen Sebelius’ December 7 decision to over-rule FDA’s review team and reject Teva Pharmaceutical Industries Ltd.’s emergency contraceptive Plan B One Step for widespread over-the-counter use was “disappointing” to many at the agency, Jenkins acknowledged during The RPM Report’s FDA/CMS Summit for Biopharmaceutical Executives in Washington, D.C. on December 8-9.

But while Jenkins said it was “unusual”—and in fact, unprecedented—for an HHS secretary to overturn a FDA review decision, he acknowledged it is within Secretary Sebelius’ legal rights to do so. “The Secretary does have the legal authority…and she chose yesterday to disagree with the agency and instructed us not to approve Plan B for that full over-the-counter access,” he said. “The process was followed.”

As the top drug reviewer at FDA, Jenkins manages the review group that made the decision to remove the age restrictions on Plan B (levonorgestrel) for OTC use, before that decision was overruled by HHS and the Obama Administration. But he hopes that the debate over the emergency contraceptive will have at least one constructive outcome: reopening the discussion on a third class of prescription drugs.

Call it “plan C”: making emergency contraceptives—and other drugs that don’t fit the traditional Rx or OTC mold—available behind the pharmacy counter after consultation with a pharmacist, but without the need for a prescription. In many ways, it’s the best of both worlds: limiting inappropriate use of prescription drugs that may come with adverse side effects, while increasing access to those products by eliminating the need for a separate vist to the doctor’s office.

“There are a lot of products that maybe potentially could be available without a prescription, but it’s really hard to fit them into the model we have today,” Jenkins told the FDA/CMS Summit. “This may be an impetus to move towards an intermediate place in the system.” Plan B, he said, “is just one of the potential products that could be made more readily available if we look at [changing] the system.”

It’s not a new idea: Plan B sparked debate over a third class of drugs when it first went over-the-counter. (Also see "Why Plan B Matters" - Pink Sheet, 1 Jan, 2006.) And there would be significant hurdles to such a change, not the least of which is the need for new legislation granting FDA the authority to establish a third class of drugs. There’s also the reimbursement question: what would coverage of those pharmacy-only drugs look like?

But it’s a model that is already used extensively outside the U.S., and has long had the support of pharmacists as a way to offer more services to patients (and receive greater reimbursement dollars from insurers). Top FDA officials, including Jenkins, are on board as well. All that’s left is the political will on Capitol Hill to do something about it.

Transparency Goes a Long Way

There’s no question that the FDA reviewers involved in approving the Plan B switch to full over-the-counter status were disappointed in HHS Secretary Sebelius’ decision to over-rule those conclusions and reject the application. But, as least publicly, FDA’s head drug reviewer is trying to take a measured approach.

“She chose to disagree with the agency and instructed us not to approve Plan B for that full over-the-counter access. It’s a different model than what we’ve seen, because usually the Secretary isn’t involved with the decisions we’re making,” Jenkins said. “I think we all have to understand that Plan B…is a very controversial issue, and I think people feel very strongly about it on both sides.”

Indeed, the availability of Plan B as an over-the-counter medication has been mired in controversy since the switch application was first submitted to FDA in 2003 by Women’s Capital Corporation. (WWC subsequently sold the rights to Barr Pharmaceuticals Inc.; Barr was later acquired by Teva.)

The OTC switch was rejected twice, in 2004 and 2005, by then-FDA Commissioner Lester Crawford, sparking a firestorm of criticism that the agency and the Bush Administration were putting politics over science—and leading to the high-profile resignation of Susan Wood as head of FDA’s Office of Women’s Health. (Also see "Plan B Delay Draws Criticism From Congress, Academia, FDA Official" - Pink Sheet, 5 Sep, 2005.) Later, it took a court order for FDA to lower the OTC age limit by one year from the originally approved 18 years to 17 years.

That criticism is still there, but there are a few differences this time around.

One is transparency. “We appreciate the fact that the Secretary, in making her decision, has owned the decision, so it was very transparent,” FDA’s Jenkins told the FDA/CMS Summit. HHS posted Sebelius’ memo to FDA Commissioner Hamburg that instructed the agency not to drop the OTC age restrictions on Plan B, and the Commissioner made public her own statement that she disagreed with that decision.

“The transparency goes a long way to understanding that the Secretary has the legal authority to make that decision, she made it, she put her reasons in writing, and made that public,” Jenkins said. “I think that goes a long way to helping the staff feel good about the work they did. The fact that Dr. Hamburg supported the review conclusion from the staff was also very well received.”

That transparency, however, may be small comfort for women’s groups and others that feel that emergency contraception should be more easily available to all females of child-bearing potential, and fear that once again, politics (and, in particular, the 2012 elections) came into play on Plan B. (Also see "Plan B Decision May Offer FDA Best Political Protection Available" - Pink Sheet, 19 Dec, 2011.)

They point both to Sebelius’ testimony during her HHS confirmation process that “doctors and science” should guide “who can safely and appropriately use Plan B,” and that the decision seems to contradict President Obama’s 2009 executive order which pledged that “science and the scientific process must inform and guide decisions of my Administration on a wide range of issues, including improvement of public health.”

Obama insisted during a press briefing the day following the HHS decision that he supported the decision, but that it was the Secretary’s alone to make. As a father of two young daughters, Obama said, the government needs to “apply some common sense” in deciding whether drugs with potential adverse side effects should be available “alongside bubble gum or batteries.” Most parents, he added, “would probably feel the same way.”

Those statements go a long way towards underscoring the potential dynamics of Plan B on the campaign trail: Obama clearly would be less comfortable espousing the contrary view.

Moving Drugs Behind the Counter

However it plays on the campaign trail, the decision, FDA’s Jenkins says, leaves open an opportunity for stakeholders to advocate for the creation a third class of drugs that could be sold behind the pharmacy counter, but without the need for a prescription. “One of the things I think the Plan B review and debate has emphasized is that our system in the United States probably could use some tweaking,” he said.

“We have a black-and-white system. You’re either prescription or you’re non-prescription. Most other countries in the world have an intermediate step in there where, it’s a pharmacy access program where you don’t have to have a prescription, but you can get it from the pharmacists. Not on the shelf at 7-Eleven, which is the model we have.”

Plan B already straddles the line between prescription and OTC. The drug has had a “dual use” structure since first going over-the-counter, with OTC access available to women 18 and older (later lowered by one year in response to a court order), and a prescription required for patients under that age limit. And in a handful of states (Alaska, California, Hawaii, Maine, Massachusetts, New Hampshire, New Mexico, Vermont and Washington), pharmacists can be certified to provide Plan B directly to patients under 17.

Jenkins thinks expanding the behind the counter model on a national level would address some of the uneasiness about making emergency contraception more widely available. “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 an emergency contraceptive without their parents’ knowledge, etc?”

“We have to acknowledge it’s a very controversial area,” he said. “We’ve now been through this multiple times. The science tells us one thing, but science informs public policy, and I think we’ll have to see what the path forward is. We have not had a chance to hear from [HHS]...what they see as the path forward; and we haven’t had a chance to talk to the company about the path forward.”

“But I think a lot of this comes down to, we have an on/off system. We have prescription and non-prescription, and maybe that model doesn’t work very well in our society for some drugs.”

Jenkins isn’t alone in his thinking. Center for Drug Evaluation & Research Director Janet Woodcock floated the idea of a third class of drugs at the Food & Drug Law Institute’s annual meeting last April.”Most of the easier [OTC] switches have already happened,” Woodcock said, adding that a behind-the-counter, or pharmacy-only model for certain prescription drugs “would be extremely beneficial.” (Also see "CDER Director Sees Behind-The-Counter Switches As Best Bet" - Pink Sheet, 11 Apr, 2011.)

Implications for OTC Statins

In addition to Plan B, FDA’s Jenkins says statins would be ideal candidates for behind-the-counter use. Merck & Co. Inc.has tried multiple times to allow drugstore sales of Mevacor (lovastatin), but failed to convince FDA advisory committees (on three occasions) that patients could self-diagnose their high cholesterol and use the drug appropriately without a the advice of a physician.

“Companies have brought forward statins for over-the-counter approval, and I think they fail to show that a consumer, just looking at the box, can understand whether they’re an appropriate candidate to take a statin over the counter and then use it properly,” Jenkins said. “So again, this may be an impetus to move towards an intermediate place in the system, where maybe there can be some restrictions to engage the pharmacist in some of these access programs.”

Another statin manufacturer, Pfizer Inc., appears ready for that change. The company has expressed an interest in eventually moving newly off-patent Lipitor (atorvastatin) over-the-counter—once it has squeezed out all the potential prescription revenue. Pfizer VP-Worldwide Regulatory Strategy Robert Clark, who was participating in a panel discussion with Jenkins at the FDA/CMS Summit, reiterated that interest: “We’d be happy to work with you on that middle ground, on certain product categories anyway.”

Conventional oral contraceptives may also be potential candidates for a third class of drugs; FDA has considered switching OCs to over-the-counter status in the past, but backed off due to concerns from the medical community. Roche/GlaxoSmithKline PLC’s Rx weight loss drug orlistat (Xenical) had also been mentioned as a pharmacy-only candidate before FDA approved it in half the prescription dose under the brand name Alli in 2007.

Has the time come for a serious discussion about a third class of drugs? FDA officials see the public health benefit of a pharmacy-only model, and some key stakeholders are on board as well. But the push to a behind-the-counter model will depend in part on to what extent outside stakeholders use the Plan B decision to advocate for change—and whether Congress can be persuaded to act.