Roche’s Flu MedKit Seeks “Alternate Pathway” For OTC Drugs

The antiviral drug home stockpiling MedKit being shepherded by the Department of Health and Human Services could be the first product to test FDA's stated interest in "creative paths to access" that straddle or depart from the traditional choice of Rx or OTC status.

An FDA joint advisory panel of antiviral drug and nonprescription drug committee members convened in October to discuss preliminary proposals for a prescription-based home stockpiling plan for Roche's Tamiflu and GlaxoSmithKline's Relenza (¹ (Also see "FDA Panel To Influenza Home MedKit Sponsors: Get Real" - Pink Sheet, 3 Nov, 2008.) p. 3).

However, the meeting also revived discussion at FDA of drug access models beyond the traditional over-the-counter and prescription routes, including behind-the counter sale.

Commissioner Andrew von Eschenbach announced FDA's interest in a third class of BTC drugs and other regulatory alternatives in March 2007 and the agency held a part 15 hearing on the topic in November that year (² (Also see "BTC Proponents Cite Pharmacists’ Role; Opponents Question Need" - Pink Sheet, 19 Nov, 2007.), p. 4).

FDA lacks the authority to establish a BTC class, despite the regulatory maneuvers that allow Barr's emergency contraceptive Plan B to be sold BTC. However, discussion of "alternative routes" to drug access, including BTC, continues at the agency.

FDA's recent approach has been to welcome sponsors to present applications for nonprescription drugs that may have some risk management element, without a formal policy on BTC or other restrictions (³ (Also see "Behind-The-Counter Guidance Stalled, But Interest Grows To Expand Access" - Pink Sheet, 30 Jun, 2008.), p. 5).

But comments that Office of Nonprescription Products staff made at the meeting suggest FDA so far has not found any creative applications it can approve.

Driving A Hybrid

Roche VP of Anti-Infectives Michael McGuire is keen on the idea of nonprescription availability for Tamiflu, but the firm will have a steep hill to climb to sell FDA - and MedKit shadow-sponsor HHS - on the idea.

Agency staff and advisors have expressed concerns about a scenario in which diagnosis and use happen outside a physician's influence, and full OTC availability compounds those concerns.

Roche's goal, McGuire says, is providing access for people to stockpile prior to a pandemic. In the event of a pandemic, "there'll be such a run on product, on all products, there will be nothing there," he says. "So how do you make the process as simple as possible now to build a stockpile?"

The prescription route as currently proposed "has some barriers," McGuire notes in an interview.

For example, each member of a family would need a separate prescription. "My kids have to see a pediatrician, I have to see an internal medicine" practitioner, he says.

Over-the-counter sale potentially breaks down those barriers and "provides you that pathway that you can go in and purchase" more easily, he says.

During his presentation to the joint panel, McGuire suggested "some nonprescription, OTC-like mechanism that would maximize the access to the MedKit."

A nonprescription mechanism would be "extremely important for individuals who could not or would not be able to see a health care professional," he stressed. This argument may sway officials concerned about the equity of distribution of antiviral drugs.

McGuire says he hopes to work with FDA and learn from advisory panelists about their ideas for balancing widespread access and safety.

"There are two pathways," he says. "We've got to be able to figure out something in between if that's a better way."

A third path "could be a hybrid of what we are seeing here today, or a creation of an alternative regulatory approval mechanism," McGuire told the joint panel. "This is a new path we are all going down."

The HHS Position

At this point, Roche's HHS partners are not sold on the idea of OTC access, according to a spokeswoman for the assistant secretary for preparedness and response, whose office includes the Biomedical Advanced Research and Development Authority, which is driving development of the MedKit concept.

"BARDA is not in accord with the Roche OTC model," she said. "BARDA follows FDA's lead for physicians to provide input and guidance to patients on the usage of these pharmaceutical products, which is the current practice for these licensed drugs."

"Strange Product"

Panelists voted that new consumer studies are needed to make even the prescription MedKit plan viable. However, at FDA's request, the advisors also discussed the possibility of an OTC framework for MedKit.

Panelists were asked to comment on the "type of availability that would best be suited to provide MedKits to the American public." They were instructed to provide any reasons behind those opinions, and to outline any studies they felt should be done to support other types of access.

Ian McGowan, chairman of the joint panel and of the antiviral drugs committee, asked if FDA would "entertain a proposal from a sponsor to consider a third pathway, given the unusual context of pandemic flu and the need for various options." McGowan is a professor of medicine at the University of Pittsburgh.

Andrea Leonard-Segal, director of FDA's Division of Nonprescription Clinical Evaluation within the Office of Nonprescription Products, was cautious, acknowledging the proposed MedKit is a "strange product," in terms of falling outside traditional Rx and OTC frameworks in its intended use.

While acknowledging that sponsors of other drugs recently have "expressed interest in alternative marketing venues of one variety or another," Leonard-Segal noted neither MedKit sponsor has made such a proposal so far.

John Bradley, director of the division of infectious diseases, Children's Hospital and Health Center, San Diego, stressed the importance of the physician interaction in dispensing antiviral medications.

The interaction is an important opportunity to provide information on side effects and communicate to patients how to access and interpret information in order to know if a pandemic is occurring, Bradley said.

Some panelists said self-selection would be critical in an OTC setting, to prevent people with a respiratory infection from using the antiviral treatment in lieu of appropriate care.

Other panelists said there is a strong public health benefit to the much wider access of some form of OTC sale could provide.

Pandemic Not "Business As Usual"

Peter Havens, a pediatric infectious diseases expert from the Medical College of Wisconsin, Milwaukee, said that OTC access in fact "answers many of the problems that I have with the current MedKit concept."

For example, OTC sale would allow consumers to more easily keep MedKit supplies for their children up-to-date as their appropriate doses change over time.

Havens also posed OTC availability as a way to learn about consumers' use of the antiviral drugs. Having data on consumers "potentially using it in ways that we might not know [are] appropriate or not, would allow us to measure the appropriateness, the relationship to resistance and would ... put full control with the consumer," he said.

Havens characterized OTC availability as a "completely libertarian approach," which overcomes many of the problems of the "mixed federal approach" that combines prescription distribution with unsupervised home use and diagnosis, he said.

OTC development "would allow us to gain a lot of information that would speak to the potential utility of the strategy of consumers buying the drugs themselves," Havens said. For example, the agency could learn "how many people would buy it, if use would be appropriate," and measure MedKit use and the program's impact on resistance.

McGowan said in a pandemic context, the drugs' safety is important but less of a concern due to the "enormous" potential benefit. In a pandemic, it would not be "business as usual, as far as the availability of the usual public health structures," he said.

Temporary voting member Richard Neill, a family medicine and community health professor at the University of Pennsylvania, noted that the kits could be beneficial in an actual pandemic scenario because "speed is of the essence."

Marc Lipsitch, a professor in the epidemiology department at Harvard's School of Public Health, countered that OTC availability could lead to undesirable outcomes in an actual pandemic.

Widespread availability "might be a very good thing," but could lead to profiteering, he said. "There are all sorts of weird scenarios in a pandemic with OTC where ... there's no control over who needs it being the ones who get it."

- Christopher Walker ([email protected])