Since 1976, more than 700 products have switched from prescription to over-the-counter status (Rx-to-OTC switch). Even though such medicines are already available by prescription, the FDA often convenes an Advisory Committee (ADCOM) 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 the FDA on the appropriateness of the Rx-to-OTC switch. To achieve success for your Rx-to-OTC switch, it’s essential to understand the common concerns and anticipate the questions of NDAC members.
We reviewed the 66 verbatim questions asked at four NDAC meetings: 2014 Singulair (Merck, 17 questions), 2013 Nasacort (Sanofi/Chattem, 20 questions), 2012 Oxytrol (Merck, 14 questions), and 2007 Mevacor (Merck, 15 questions). Here are the most common question areas.
- Label elements: 24%* of questions asked were centered on aspects of the Drug Facts label (DFL) or the Consumer Information Leaflet (CIL).
- The committee asked questions concerning specific data, whether clinical or from consumer trials, to support DFL claims made or the indication itself. Accuracy of the DFL statements and transparency for the consumer are both important.
- 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 panels are diverse in their experience and professional expertise, it is not uncommon for them to be unclear about DFL or CIL regulations. 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 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, and 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.
- Questions often centered on the definition of low literacy and details regarding the Rapid Estimate of Adult Literacy in Medicine (REALM) screening instrument used to define the low-literacy population.
- Safety and efficacy: NDAC members noted that just because a drug is OTC doesn’t mean it has more lenient requirements for safety or efficacy
– actually, the opposite is true. Taking a safe and efficacious Rx medication and gaining approval to market it as an OTC requires that safety and efficacy be extrapolated to a much larger population without evidence of incremental risk.
- Underlying safety of Rx:14% of questions focused on understanding the Rx safety profile.
- Panel members wanted to fully understand the safety risks associated with the product before voting. Even after briefing materials were reviewed and presentations were completed, questions were asked regarding the nature and timing of adverse events from the original Rx trials.
- Safety in special populations was of interest due to the chance for accidental or intentional misuse of the product. Understanding the risks for children and seniors was a concern even if the population in question was included in the indication.
- Underlying efficacy of Rx: Although efficacy has already been established during the approval process for the Rx, 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 focused on the underlying efficacy profile of the Rx, including 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 clinical meaningfulness of such results.
- Sponsors were asked to compare efficacy of the product to be switched to 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 OTC status 2%, and compliance 2%.
If sponsors prepare diligently and appropriately, the NDAC’s questions and discussions will be anticipated and your answers will be practiced.
* Percentages have been rounded to the nearest whole number.