OTC Switches Face Tougher FDA Evaluations, Less Predictable Process

OTC switch sponsors bear more responsibility than in previous years to convince FDA a product would be safely used and has a strong risk/benefit profile, say Pinney Associates consultants. FDA currently is more conservative on risk/benefit decisions and the advisory committee process isn't productive, they say.

Facing a more conservative FDA, a less predictable advisory committee process and “evolving” standards for evaluating Rx-to-OTC switches, drug firms have to do more and better work than previously to demonstrate their proposed switches' public health benefits, say drug application consultants.

“The current group at FDA seems a bit more conservative than groups in the past and in particular, more concerned about safety and unintended consequences” of OTC switches, says Christine Sweeney, director of issues management at Pinney Associates, a consumer health consultancy group.

Further, FDA staff do not often “take charge of the [advisory] committee process,” Sweeney said during a recent webinar by Bethesda, Md.-based Pinney.

“This puts significant responsibility on the sponsor to convince them the advisory committee panel that a product” should be switched, she said.

Advisory panels have their own problems, Sweeney suggested, as members get “very little orientation and training” and many are not well informed on OTC drug issues. The advisory committee process overall “has become a bit less functional and less predictable,” she said.

An advisory committee for any switch is made up of members of the Non-Prescription Drug and Advisory Committee (NDAC), which comprises 14 voting members from across medical practice and clinical research areas. Some advisory committees also include a separate reviewing division of experts in the treatment area targeted by a potential switch. However, these experts often are more resistant to switches, Sweeney said.

“The current group at FDA seems a bit more conservative than groups in the past and in particular, more concerned about safety and unintended consequences” of OTC switches. – Christine Sweeney, Pinney Associates

“Opposition by the subject review division is not really unusual as the medical community is their constituency and their regulatory scope is reduced when a product switches from Rx to OTC.”

Sweeney’s comments reflect an assessment by a previous NDAC chairman, Alastair Wood, during an industry conference in 2015. Wood pointed out many NDAC decisions about switches are based on “emotional” reasons that industry should dispel, but sponsors have done a “poor job” countering “quixotic and novel objections” to their switches.
(Also see "‘Emotional’ NDACs Stymie OTC Switches – Former Chairman Wood" - Pink Sheet, 18 Mar, 2015.)

'Log Jam' In Switch Pipeline

The problems with FDA and advisory committees have created a “log jam” in the pipeline of Rx-to-OTC switches, said George Quesnelle, senior strategic advisor for OTC commercialization and optimization at Pinney, during the Feb. 8 webinar, which was the first in a two-part series.

Quesnelle suggested FDA is eager for OTC switch new drug applications (NDAs) incorporating technologies that educate or assist consumers in selecting and using a nonprescription treatment, as proposed in the agency’s Nonprescription Drug Safe Use Regulatory Expansion initiative, particularly in the areas of high cholesterol, hypertension, migraine and asthma.

FDA launched NSURE in 2014 to encourage OTC switch sponsors to develop technology to assist in preventing consumers from under-utilizing or incorrectly taking OTCs that are switched from Rx and no longer used under a doctor’s supervision. (Also see "Chronic Conditions Data Emphasize Need For Additional, Innovative OTCs" - Pink Sheet, 2 Jul, 2014.)

However, “not a lot seems to be happening on FDA’s end to move this forward,” Quesnelle said.

Consumer's Decision: 'Biggest Concern'

Switch application sponsors might very well show strong safety for OTC use of a currently Rx ingredients by consumers who actually need the treatment, but they also face a hard sell in convincing FDA that other consumers won't also use it. "FDA's biggest concern is those who should not be using the drug and whether they make the right decision not to use the drug," Sweeney said.

The agency wants to know what will happen to consumers who take the drug against contraindications, such as certain diseases or current use of certain drugs, or warnings such as for pregnant women.

FDA also wants to know the:

• prevalence of any condition in the OTC target population;
• severity of reactions from contraindications;
• percentage of the population treated for a condition;
• diagnosis and treatment of a condition with Rx drugs.

“In reality, I think the agency is waiting for companies who are proposing a switch to present some sort of NSURE initiative as part of a submission package, to evaluate it. It comes down to the sponsor taking the lead, and engaging in discussions with the agency,” he said.

Quesnelle acknowledged companies are hesitant to prepare switch NDAs as the process is expensive – costing between $20m and $40m over a period of about three to four years. “For switches approved, it is a major source of growth for those OTC companies. If you have a viable switch product, I believe it is worth the effort,” he said.

Sweeney noted less than 35 switches were approved between 2000-2017 in the US, while more than 100,000 OTC drugs are available based on roughly 800 active ingredients in more than 80 therapeutic categories overall.

Some industry consultants speculate the uncertain fate of the Affordable Care Act has companies waiting to invest in switch research until they have a better understanding of how the Rx and OTC landscapes will be shaped.

During a 2017 webinar, a Kline & Co. market consultant said research the firm conducted found many companies are hesitant to prepare an OTC switch application because safety and efficacy data for their Rx product is over a year old and may not support allowing OTC sales. (Also see "OTC Switch Interest Cooled By Study Costs To Update Safety Data" - Pink Sheet, 5 Jul, 2017.)

Switch NDA: Not A 'Check Box’ Exercise

“Rx-to-OTC switch is not a regulatory check-box exercise, it’s a policy change, supported by argument and data,” Sweeney said on the appropriate approach for developing an NDA application. Most switch NDAs contain three studies: self-selection, label-comprehension and actual-use.

A sponsor should be able to demonstrate consumers can self-select based on a condition, OTC label criteria and their own medical history and profile, Sweeney said.

Additionally, FDA wants to see that the consumer can self-treat by following label directions appropriately and stop use or see a doctor as directed. Sponsors may consider presenting studies that demonstrate a consumer can tell when a product is not working and can recognize early signs of adverse events, she added.

In label comprehension studies, companies should ensure about 25% to 30% of their cohort are low-literacy consumers, people with an eighth-grade reading level, Sweeney said.

The agency also wants to know what will happen to consumers who take the drug against contraindications, such as certain diseases or current use of certain drugs, or warnings such as for pregnant women. The agency wants to know the:

In addition to the OTC Drug Facts label for their product, sponsors should submit and information that provides a better picture of how the product is being used as a prescription drug and how it will likely be used as an OTC, she added. The data may include:

• preclinical and clinical information;
• Rx marketing and use;
• non-RX experience;
• consumer behavior studies.

Additionally, sponsors should make a “persuasive case” that the benefits of their switch outweigh the risks, with evidence available from the NDA studies, Sweeney said. "In order for FDA to tolerate any amount of potential risk that might be associated with a switch, there must be potential benefits with which to balance those risks," she said(see box below).

"The argument can generally be made that the requirement to obtain a prescription for an appropriate medication and make one or more visits to practitioners, results in under-treatment. By removing that requirement, many more patients will seek treatment," she said.

 Sponsors in many cases can argue that OTC access encourages consumers to use a treatment sooner. Emergency contraceptives, which became available OTC in some formulations in the US only after protracted litigation against FDA, must "be taken as soon as possible after intercourse to be effective,” Sweeney pointed out. “The prescription served as a barrier for intended use.”

From the editors of the Tan Sheet.