Plan B Restrictions Set “Unique Example” Experts Say, But What May Follow?

Barr's postmarketing commitment for Plan B 's newly approved behind-the-counter (BTC) sale status may be the most innovative and closely-watched element of the switch and the drug's planned dual-marketing campaign.

While FDA has stressed that the approval of the emergency contraceptive for pharmacy-restricted sale does not set a precedent for future switch opportunities, the decision reflects the agency's comfort level in terms of switch innovation.

FDA announced the approval of Plan B for sale from behind pharmacy counters to consumers ages 18 and older Aug. 24 (¹ (Also see "Plan B Pioneers OTC “Pharmacy Counter” Approval, Dual-Status Marketing" - Pink Sheet, 28 Aug, 2006.), p. 3).

The drug still is available by prescription for women under 18 years old. The age split originally raised questions about the regulatory feasibility of selling the drug in both Rx and OTC settings at the same dose and indication.

The agency requested public comment in August 2005 on whether the proposed dual Rx and OTC status of Plan B necessitated a rulemaking to resolve labeling issues and other concerns.

However, FDA announced July 31 a rulemaking was not necessary after a review of the comments.

"Fudged"?

Former Nonprescription Drugs Advisory Committee Chair Alastair Wood, MD, explained the rulemaking issues raised by the agency.

"There were two rulemaking problems as I see it. One was the need for discussion of a behind-the-counter option, which doesn't exist right now, and the other was the simultaneous sale of the same dosage form by prescription and OTC for the same indication," he stated.

"So there were two issues, both of which appear to have just been fudged. It sounds like a criticism, but it's not. I think [Plan B] should have been approved cleanly," he stated.

"I think the story is that we can't base predictions on what the FDA will do in the future based on this" approval, Wood said.

Current NDAC Acting Chair Eric Brass, MD, PhD, Harbor-UCLA Center for Clinical Pharmacology, concurred with Wood, stating, "This is not a precedent and represents a unique public health issue....It's just too difficult to answer how it relates to other situations."

"I think the critical issue of this is the continued willingness of the agency to evaluate each new switch on its own merits within the context of public health and to work within its regulatory framework and with sponsors to try to find innovative solutions where the public health will be benefited," he stated.

However, some experts feel that the atypical approval may have some impact on future switch candidates, particularly in regard to the robust postmarking commitments that accompany Barr's switch package.

FDA "always say[s] it's not precedent-setting, but you can't help but set examples, and each one is an example and you can't help but build on that. So whether it's called a precedent or not, it certainly will have an important impact on OTC drug development," stated Bill Soller, PhD, executive director, Center for Consumer Self Care, UCSF School of Pharmacy.

Intense Surveillance

"I think there is a strong interest in looking at this for the entire OTC industry to want to see Barr and Duramed be successful in developing an effective postmarketing surveillance effort that would be able to demonstrate and, if need be, refine what has been approved by FDA in order to continue this kind of distribution and maybe even expand" distribution to younger populations, eventually, Soller said.

Barr has outlined its plans to monitor how Plan B will be distributed and used in its Convenient Access Responsible Education (CARE) postmarketing program submitted with its switch NDA for the drug (² (Also see "Barr Takes CARE To Monitor Plan B Consumer Behavior Trends" - Pink Sheet, 4 Sep, 2006.), p. 5).

CARE includes programs that would gather data on pharmacy distribution and consumer behavior patterns to address concerns expressed by the agency and advocacy groups about enforcement of the age restriction and unsafe use of the drug.

The program includes plans for intense advertising and educational campaigns aimed at healthcare professionals and consumers, random checks for pharmacists' compliance with the age restriction via secret shoppers, and market research surveys to track consumer behaviors and any changes to STI contraction rates and use of other contraceptive methods.

Soller suggested NDAC schedule a meeting with Barr in the future to assess the data gathered through the company's postmarketing and possibly reevaluate Plan B's status.

"I think importantly, and I haven't seen this, that the OTC drug advisory committee should request of FDA that whatever Barr decides to do, that they come back in a specified period of time and report to the advisory committee as to their success," Soller said.

One of the primary questions that should be answered through the gathering of postmarketing data will be the enforceability of the FDA-imposed age restriction.

Enforceability concerns in particular "speak to the need for some sort of postmarketing surveillance study in order to really define what is happening once this - I won't call it a precedent - 'unique example' has now played out in the marketplace," Soller stated.

Enforcement Concerns

FDA has communicated that one of the primary reasons Plan B's switch dictates that product will be sold from the pharmacy is to enforce the 18 and older age restriction.

This pharmacy-only sales format could also apply to future switch candidates that may require restrictions for specific populations, experts suggested.

Products that may not make strong candidates for a pharmacy access status include those bearing indications that are difficult to self-diagnose because pharmacists traditionally do not perform diagnostic tasks or interpret test results.

NDAC's January 2005 recommendation not to switch Merck's cholesterol-lowering drug, Mevacor (lovastatin), from an Rx to an OTC product was based in part on the lack of data demonstrating consumers could correctly self-select the drug in a nonprescription setting (³ (Also see "Mevacor Daily Regimen Compliance Questioned By FDA Committees" - Pink Sheet, 17 Jan, 2005.), p. 5).

However, products that may present safety issues when taken in excess or inappropriately possibly could find a place behind the pharmacy counter.

BTC access could apply to "any product that might carry a little higher risk of accidental overdose or not taking it in the correct way, like Plan B. It just creates a kind of hurdle to getting the drug," said Adams Laboratories' Bill Howard, PhD.

The recent move of cough/cold product ingredient pseudoephedrine from OTC to behind-the-pharmacy counter as a result of the passage of the Combat Meth provisions of the Patriot Act was due to concerns about the ingredient's use in the manufacture of the illegal drug, methamphetamine (⁴ (Also see "Pseudoephedrine Will Be Behind The Counter Across The Country By October" - Pink Sheet, 6 Mar, 2006.), p. 5).

Some experts noted experience of acetaminophen products, such as McNeil Consumer Healthcare's Tylenol in the UK where the product is restricted due to potentially fatal liver damage associated with overdose.

Acetaminophen restrictions implemented in the UK, such as smaller package sizes and purchase amount limits, have been shown to reduce the number of acetaminophen-related deaths since the measures' 1998 inception (⁵ (Also see "Acetaminophen-Related Overdose Deaths Down In UK Due To Law – BMJ" - Pink Sheet, 8 Nov, 2004.), p. 9).

However, some experts question the benefit of creating barriers to access for drugs currently available over-the-counter.

"Trying to be highly-protective over existing products because of potential safety issues is really not the consumer-centered type of perspective that really is warranted in this current emphasis on drug safety," Soller opined.

"Looking more broadly, a satisfied consumer, a safe consumer, is one that is going to be better from the standpoint of overall healthcare needs for the United States, but also better from the standpoint of business practice. That's the kind of perspective that allows us to think in more innovative ways in making products more accessible," he continued.

BTC Limits Access...And Possibly Sales

Experts agree that the applicability of the Plan B switch process to potential switches in the future is limited as well as uncertain.

Bernard Schachtel, MD, Medical Director of Jupiter, Fla.-based Schachtel Research Company does not advise that the Plan B approach should be accepted blindly "because it is a quite limited approach of behind-the-counter."

"This is actually a rather tepid approach and it's quite limiting for women for whom time might be an issue to require them to purchase this only from a drug store, especially if they live in a rural area," he stated.

Howard believes that companies looking to switch drugs from Rx-to-OTC would choose a behind-the-counter distribution model "only if they were desperate, because it inherently limits sales."

BTC access "is not going to the be the panacea that people think it might be in the sense that, for one thing, there's only a limited amount of space back there, so you couldn't have a lot of products" stored behind the pharmacy counter, he stated.

Another potential concern for manufacturers of behind-the-pharmacy counter products is the loss of brand interaction between the consumer and the product due to pharmacists acting as the gatekeeper to BTC products.

For example, in countries that have a third drug class for pharmacy access products such as Canada, once a BTC product loses exclusivity, pharmacists are able to automatically substitute private-label versions of BTC drugs and distribute the name brand only at a customer's request.

"The main issue is how can consumers in the 21st century who are very, very aware of their healthcare needs and of different medications for them, how can we reduce barriers to accessibility, not how can we introduce them," according to Schachtel.

- Jessica Lake