Know Your Nonprescription Drugs Advisory Committee: Anticipating the Common Questions during an RX-to-OTC Switch
Since 1976, more than 700 products have switched from prescription to over-the-counter status (RX-to-OTC switch). Even though medicines to be switched are already available by prescription, FDA often convenes an Advisory Committee meeting – usually to ensure that consumers can use the OTC product safely without the guidance of a physician. As the name implies, the Nonprescription Drugs Advisory Committee (NDAC) is the panel charged with advising FDA on the appropriateness of the RX-to-OTC switch. Therefore, it is essential to understand the common concerns across members of the NDAC and anticipate the questions they will ask at an Advisory Committee meeting to achieve success.
We reviewed the 66 verbatim questions asked at four Nonprescription Drugs Advisory Committee meetings: 2014 Singulair (Merck – 17 questions), 2013 Nasacort (Sanofi/Chattem – 20 questions), 2012 Oxytrol (Merck – 14 questions), 2007 Mevacor (Merck – 15 questions). In our evaluation, we grouped the questions into topics and provided a summary of the most commonly asked question areas.
- Label Elements. 24%* of the questions asked over the four NDAC meetings were centered on particular aspects of the Drug Facts Label (DFL) or the Consumer Information Leaflet (CIL), where applicable.
- The committee asked questions concerning specific data, whether clinical or from consumer trials, that support DFL claims made or the indication itself. Not only is accuracy of the DFL statements important, but also the level of transparency for the consumer.
- Several NDAC members asked to see the actual packaging to examine the DFL and CIL for size and location of label text and figures. Panel members also asked for the actual DFL that was tested during the consumer study.
- Because the panel is so diverse in their experience and professional expertise, it is not uncommon for panel members to be unclear about the regulations set forth for the DFL or CIL. Be prepared to hear remarks on how the label can be improved or questions regarding decision making on placement and size of text.
- Label Comprehension. 18% of the questions centered on comprehension of the proposed DFL. 42% of these label comprehension questions were specific to the low literacy population.
- Many panel members were unfamiliar with a typical label comprehension protocol and asked for details of the process.
- Not all DFL statements are tested or require testing, especially if they are common to existing OTC labels. In addition, statements often change after the label comprehension study because a statement is modified based on study feedback. Many of these statements are not necessarily retested. However, questions were asked on both tested and untested portions of the label.
- Questions regarding results stratified by race or gender were asked. Some OTCs are gender specific, and the panel wanted to understand the likelihood of a consumer of the opposite sex selecting to use a product.
- The committee seemed especially interested in the low literacy (low lit) population.
- Questions often centered on the definition of low lit and the details regarding the REALM (Rapid Estimate of Adult Literacy in Medicine) screening instrument used to define the low lit population.
- Safety and efficacy. Just because a drug is over-the-counter does not mean there are more lenient requirements for safety or efficacy. Actually, the opposite is true. Taking a safe and efficacious prescription medication and gaining approval to market it as an OTC requires that the safety and efficacy be extrapolated to a much larger population without evidence of incremental risk.
- Underlying Safety of Rx. 14% of the questions asked focused on understanding the Rx safety profile.
- Panel members wanted to fully understand the safety risks associated with the product before voting. Therefore, even after the briefing materials were reviewed and the presentations were completed, questions were asked regarding the nature and timing of adverse events from the original Rx trials.
- Safety in special populations were of interest due to the chance for accidental or intentional misuse of the product once OTC. Understanding the risks in children and in the elderly was a concern even if the population in question was included in the indication.
- Underlying Efficacy of Rx Product. Although efficacy has already been established during the approval process for the prescription product proposed to be switched, committee members still wanted to know specific details beyond the information in briefing materials in order to make a benefit-to-risk conclusion. 11% of questions asked focused on the underlying efficacy profile of the Rx product.
- This includes details of the mechanism of action.
- Efficacy is usually represented by a statistical analysis of the primary efficacy endpoint as well as supportive secondary endpoints. Panel members often wanted to know the clinically meaningfulness of such results.
- Sponsors were asked to compare efficacy of the product to be switched to the efficacy of other products on the market, even if there had not been a direct head-to-head trial.
The remaining questions fell into the following categories: off-label use (6%), cost (6%), Actual Use Trial (5%), self-selection (5%), unintended consequences or safety in the OTC environment (3%), Rx patterns of use (3%), dosing (2%), education (2%), benefits of having OTC status (2%), and compliance (2%).
In the end, going before the Non-Prescription Drugs Advisory Committee to get a positive recommendation for an RX-to-OTC switch raises a very specific set of challenges not seen with approval of prescription products. As a result, understanding the committee and being able to anticipate NDAC members’ questions are often the difference between success and failure at an ADCOM.
Most often, if Sponsors prepare diligently and with the appropriate steps, the questions and discussions at the Advisory Committee have been anticipated and are therefore well-thought-out and practiced.
* Percentages have been rounded to the nearest whole number
ABOUT THE AUTHOR
Rachael Carlisle Roehrig, PhD, uses her extensive scientific and regulatory experience to prepare clients for successful regulatory interactions and FDA Advisory Committee meetings. Rachael is also Chair of the Steering Committee and member of the Board for the Product Quality Research Institute. Prior to joining 3D, Rachael was the director of technical & scientific affairs at the Consumer Healthcare Products Association (CHPA) as well as its liaison to the FDA. Connect with Rachael on LinkedIn.