Switch Paradigm Change Sees Long Road, Breeds Questions

Industry has opposed establishing an intermediate class of drugs between Rx and OTC, and FDA has held it does not have authority to require firms to allow products to be approved for behind-the-counter access or some other alternative distribution. But the creation of some form of third route to access appears likely.

FDA already has a comprehensive set of questions on a “new paradigm” for nonprescription drug approvals “under conditions of safe use,” but myriad additional questions will emerge on issues ranging from approval standards and enforcement of potential restrictions to how the products are accessed by consumers.

Industry stakeholders, pharmacy experts and consumer health advocates will present on and discuss innovative routes to nonprescription status at FDA’s March 22-23 hearing at its White Oak headquarters in Silver Spring, Md. (Also see "FDA Digs Deeper On “New Paradigm” To Expand Rx Switches" - Pink Sheet, 5 Mar, 2012.).

The industry historically has opposed establishing an intermediate class of drugs between Rx and OTC, and FDA has held it does not have authority to require firms to allow their products to be approved for behind-the-counter access or some other alternative distribution.

But the creation of some form of third route to access appears likely.

“If industry were to devise one, I think that FDA has always been willing to consider it,” said Peter Barton Hutt, of Washington firm Covington & Burling and a former FDA chief counsel.

“I think it is more likely, as people come to think about it, to actually become a reality,” he added.

FDA drug center director Janet Woodcock repeatedly has supported facilitating more switches, and commented recently that the alternative routes to nonprescription approvals the agency is considering could be included as part of the bill to reauthorize the Prescription Drug User Fee Act. The timing now makes that unlikely for the currently pending bill. Stakeholders noted in the past that a third class of drugs or voluntary restrictions likely would require legislative changes, in part to help protect sponsors from unfair competition.

Smorgasbord Of Ideas

Interest from industry is growing and unlikely to fade if FDA does not start approving novel switches this year.

“There’s still a few switches out there that are a little harder to find and come by under the old system, and there are companies that have been pushing FDA to be thinking about different, novel ways to do this,” said Bill Soller, a professor and executive director of the Center for Consumer Self Care at the University of California, San Francisco, School of Pharmacy.

What’s more, FDA’s 2010 reorganization of Center for Drug Evaluation and Research divisions positions the center strongly for looking at the many questions about this topic, both those known and yet-to-surface, added Soller, a longtime advocate for expanding drugs and medical devices available for consumers’ self-care (Also see "FDA's ONP Reorganization Challenges Industry To Prioritize OTCs" - Pink Sheet, 15 Mar, 2010.).

In 2010, FDA reorganized the Office of Nonprescription Products as the Office of Drug Evaluation IV, with responsibility for the then-new Division of Medical Imaging Products in addition to the Division of Nonprescription Clinical Evaluation and the Division of Nonprescription Regulation Development. Charles Ganley moved from heading DNP to ODE IV.

With both diagnostics and OTCs under his purview, Ganley is well positioned to look at a new paradigm, Soller said

And FDA will not have a shortage of ideas to consider, beginning with presentations at the public hearing.

“I think it’s going to be a real smorgasbord, and some of the food’s going to be tasty and some of it’s going to be tainted,” Soller said.

A Shot In The Arm?

While FDA and consumer health care advocates look to a public health benefit in innovative switches, sponsors likely consider the change foremost a method of boosting revenue from Rx drugs that have lost exclusivity and increasingly lose market share to generics but are not candidates for actual OTC status.

“The OTC industry has needed a shot in the arm for drug development,” said Soller.

Eric Brass, a physician and a former chairman of FDA’s Nonprescription Drugs Advisory Committee, also noted the potential boost for the pharma industry from an intermediate class of drugs.

“I think that reasonable, enforceable restricted access regulations would be of great interest to the industry because of its potential to lead to new classes of drugs and new OTC indications, with the potential to improve individual and public health,” he said.

However, restricted access to nonprescription drugs for the purpose of enhancing consumers’ self-care might not serve as a driver of replacement revenue.

The restriction most commonly mentioned is behind-the-counter distribution by pharmacists, which already is used for emergency contraception under an extraordinary and controversial approval by FDA.

But requirements for more extensive consultations with pharmacists or for consumers to complete narrowly focused self-assessments enabled by specially designed diagnostic technologies likely will be needed for restrictions on nonprescription access to be effective.

Brass maintained that behind-the-counter distribution by pharmacists, used for many drugs in other countries, does not appear to benefit public health.

“If it only provides barriers to access without providing an additional incremental safety or benefit margin, then it should not be used and we should have the same general sales category that we currently have and drugs should not need to go through a step-wise fashion of that process,” said Brass, a physician, a professor of medicine at the University of California, Los Angeles, and director of Harbor-UCLA Center for Clinical Pharmacology.

But requirements with “potential to improve the screening of consumers before they’re allowed to purchase the drug, if that kind of restricted access clearly has benefit, then that should be the mechanism used,” he said.

Innovative switch sponsors also will consider their costs. Merck & Co. Inc. for instance, has invested in three applications to switch Mevacor Daily (lovastatin) to OTC status but each time has not been allowed to launch the first-in-class nonprescription product indicated for high cholesterol due to concerns about consumer self-selection (Also see "FDA Advisors Say Greater Insight Needed On Self-Selection Of OTC Statins" - Pink Sheet, 17 Dec, 2007.).

While Merck and other firms with drug ingredients that face high odds for failure in OTC switch applications could have potentially lucrative markets with restricted access approvals, they also realize their attempts would be costly.

“There’s an enormous amount of uncertainty and enormous amounts of opportunity, both positively and negatively that could result from this,” Brass observed.

Soller also observed that access restrictions are intended to ensure a consumer accurately self-assesses for an indication and self-selects a specific drug, and FDA would set as high a standard for approving restrictions as it does on determining the safety and efficacy of a drug.

But the agency will face a challenge in determining how to evaluate and approve the procedures, diagnostic technologies and other components of proposals to affect restrictions on consumers’ access to a nonprescription drug.

“People are now learning new mechanics, a new framework to think about safety, and they’ve got a whole new paradigm to look at. I don’t know what FDA will do with that. It’s not what has been a traditional approach to benefit/risk” evaluation, Soller said.

“You need lots of data to make something like that happen, and it just doesn’t exist in the OTC arena,” he added.

Brass also noted the likely difficulty for industry and FDA in bringing safe, effective and enforceable access restrictions to market. “Each individual proposed solution for each individual proposed drug for each individual proposed indication would have to be looked at individually. My only plea is that evaluations would be evidence-based and in the interest of improving personal and public health.”

In addition to high cholesterol drugs, FDA included treatments for high blood pressure, migraines and asthma as examples of possible categories for innovative switches. But, unlike the potential access restrictions, the number of drugs that actually would be suitable for innovative switches probably is limited.

“I think that the number of areas that would be considered would be pretty large, however, I think the number where it would really make a difference is smaller than people think,” Brass said.

The HHS Wild Card

Another factor to consider in how FDA would approve and regulate drugs in a third class, Hutt pointed out, is the agency’s decisions can be vetoed.

Health and Human Services Secretary Kathleen Sebelius’ veto of FDA’s intended approval of full OTC access for the Plan B One-Step emergency contraceptive is an example of how the agency’s decisions based on scientific evidence can be trumped by public policy (Also see "HHS Overrules FDA On Plan B OTC, Sends Teva Back To Drawing Board" - Pink Sheet, 7 Dec, 2011.).

Rx-to-OTC switches “are not science issues. They are public policy issues,” Hutt said.

And this tension between science and policy will remain, he added. “FDA scientists don’t like to get overruled on their judgments, but that’s why we have other people involved, non-scientists involved who are entitled to have their judgments.”

[Editor’s note: Read more about this topic in “The Tan Sheet,” your source for nonprescription pharmaceutical and nutritional industry news. For more information call 1-800-332-2181. To register for a free trial, click here.]