Extra-Label Communication Could Foster Novel Switch NDAs – Industry Attorney

FDA has several avenues to foster more novel Rx-to-OTC switches, including allowing extra-label communications beyond the packaging, similar to dispensing labeling used by a pharmacist, to be part of an approval.

FDA should redefine over-the-counter product labeling to extend beyond point-of-sale packaging in its consideration of a “new paradigm” for Rx-to-OTC switches, which would allow OTC drugs to be marketed with conditions of safe use, a food and drug lawyer suggests.

At a recent American Conference Institute OTC drugs regulatory and compliance forum in New York, David Adams, a partner at Venable LLP in Washington and a former associate chief counsel for drugs at FDA, discussed the potential for new paradigm switches – OTC products marketed under more complex conditions of safe use. Nicholas Beshara, associate chief counsel at the FDA Office of the Chief Counsel, also participated in the panel.

In discussing how FDA could enable novel switches without enhanced authority, Adams proposed that FDA allow additional labeling for switched nonprescription drugs, analogous to dispensing labeling – the drug information material provided when pharmacists dispense some Rx products.

For OTCs, this auxiliary information would not be part of the product label, but, for example, could be attached to a product package to instruct pharmacists on determining whether a consumer should be allowed to purchase the product. For products available away from pharmacy counters, the dispensing labeling could guide consumers through self-diagnosis for the pertinent condition.

Beshara noted that some conditions of safe use could include information accessed online or at an in-store kiosk. “The idea with the kiosk would be that consumers would walk through a decision tree to determine whether or not the product is appropriate for them. There could be a mechanism restricting access to the product based on the answers to the questions,” Beshara said.

FDA Commissioner Margaret Hamburg has said FDA is considering whether it can expand the definition of nonprescription drug labeling to include extra-label information on conditions of safe use. Some stakeholders say the agency can make the change through rule-making, without congressional action.

Some manufacturers are concerned that under existing regulations, generic competitors would be able to skirt any voluntary restrictions that brand drugs switched under unique conditions are subject to (Also see "FDA To Tackle Critical Generics Issue In Switch Paradigm Debate" - Pink Sheet, 12 Mar, 2012.). But the voluntary restrictions hurdle could be cleared via the dispensing labeling approach, Adams says.

Adams said FDA simply could deem generic products are misbranded and, therefore, unapproved new drugs if they fail to follow the same restrictions or to convey the same extra-label information to which the original switch sponsor agreed.

Another key to getting sponsors onboard with novel switches is clear communication of expectations, Adams said.

He suggested FDA issue a guidance covering what manufacturers should expect when submitting a switch NDA, the types of studies that would be needed and the conditions for which FDA would consider allowing firms to move Rx drugs to OTC.

“It’d be important for FDA to state publically that this new paradigm is something that is doable under current law and provide advice on how you might actually do it,” he said.

Exclusivity And Clinical Trials

In comments to FDA, sponsors have expressed concerns about market exclusivity for novel switches, Beshara said at the opening of the two-day conference. “There’s fear that if they didn’t get some amount of exclusivity, it would inhibit the adoption of the new paradigm,” he said.

Existing FDA regulations allow three-year exclusivity periods for switches with clinical trials included in the application, a provision of the 1984 Hatch-Waxman Act to promote generics while leaving intact a financial incentive for research and development.

Under current interpretation of Hatch-Waxman as applied to switches, the only consumer behavior studies used for switches that are considered clinical trials currently are actual use trials (Also see "Market Exclusivity Needed For Special Condition Switches – Expert" - Pink Sheet, 2 Apr, 2012.).

“If you don’t have to conduct a clinical trial, then you wouldn’t get exclusivity because there’s no provision for that,” Brian Malkin, a drug and medical device law attorney with Frommer Lawrence & Haug LLP in Washington said in an interview.

“Self-selection studies, where no actual drug is administered/taken, or label comprehension studies are important parts of an Rx-to-OTC switch application, but they don’t trigger exclusivity, unlike an actual use trial, which can and has triggered exclusivity,” David Spangler, senior VP of policy and general counsel at the Consumer Healthcare Products Association, said in an email.

In recent switch attempts for chronic condition drugs, self-diagnosis and appropriate self-selection were sticking points for advisory panels and the agency. A clinical trial that shows consumers appropriately can select and use a drug marketed under conditions of safe use could potentially help sell FDA on a novel switch (Also see "FDA Advisors Say Greater Insight Needed On Self-Selection Of OTC Statins" - Pink Sheet, 17 Dec, 2007.).

Beshara and Adams noted that extending the period of exclusivity allowed for switches can come only through Congress amending the Food, Drug and Cosmetic Act, not FDA rulemaking. But Adams has no expectation that Congress would make the change. “The earth will stop rotating before Congress goes back and adds more exclusivity,” he said.

Alternatively, Congress could pass legislation allowing an “add-on” exclusivity, which would be up to two-years additional on top of the exclusivity already granted through a NDA.

REMS Avenue Explored

Asked Risk Evaluation and Mitigation Strategies could be applied for OTC switches approved under conditions of safe use, Adams said REMS would be a last resort used only after FDA determined that other mechanisms for limiting consumer access would not be sufficient.

REMS programs can impose a variety of requirements including requiring training or certification for health care providers, patient monitoring, restricted use to particular health care settings, medical tests as a condition for dispensing, enrollment in a patient registry and physicians and pharmacists to follow “Elements To Assure Safe Use,” guidelines measured through a sometimes costly study (Also see "FDA Toots Its Own Horn On Safety Of Marketed Drugs, Imports" - Pink Sheet, 14 May, 2012.).

The REMS process is specific to a drug and, while FDA could impose the same REMS requirements on all OTC drugs within a class, the agency still would have to make a switch determination for each drug.

Adams said FDA likely will shape its approach to novel switches based on comments submitted since the new paradigm Federal Register notice in February. He does not expect major movement by FDA until next year.

Beshara did not estimate when FDA would implement a guideline for novel switches, but said the agency received 160 comments after a public hearing on the topic in March this year. The comment period closed in May.

[Editor’s note: This story was contributed by “The Tan Sheet,” a publication focused on the consumer pharmaceutical and dietary supplements industries that includes in-depth coverage of Rx-to-OTC switches.]