OTC Regulatory Pathway Needs NDA Flexibility, Monograph Scope – Sharfstein

Former FDA deputy commissioner Joshua Sharfstein, noting public health advocates’ disappointment with results from Sunscreen Innovation Act requirements, proposes an OTC drug review pathway that combines elements of the NDA and monograph systems and would require legislation to create.

Former FDA deputy commissioner Joshua Sharfstein suggests an alternative pathway for OTC monograph changes could succeed where rules for sunscreen ingredients Congress approved in 2014 so far have failed to accelerate approvals.

Sharfstein, who left FDA in January 2011 after two years as principal deputy commissioner, offered his views in the New England Journal of Medicine as results from the Sunscreen Innovation Act disappoint many industry and public health advocates. His comments, though, address improving the efficiency of FDA’s evaluation for all proposed additions to its monograph for OTC drug ingredients.

In a July 9 perspective piece – "A Spotlight on Sunscreen Regulation" – he discussed efforts under SIA to facilitate introducing next-generation sunscreen drug ingredients by imposing deadlines for FDA decisions on time and extent applications.

The problem, according to Sharfstein, is the current OTC drug monograph system is not designed to work as efficiently as FDA’s evaluation and regulation processes for Rx and OTC ingredients approved through new drug applications.

Instead, he recommends Congress enact legislation "establishing an alternative approval pathway that combines the flexibility of the new drug pathway with the ability to simultaneously approve multiple formulations and concentrations" as FDA does in OTC monograph rulemaking.

Joshua Sharfstein, former FDA deputy commissioner, says OTC product regulation proceeds in slow motion compared to the rest of the agency’s regulatory processes.

"FDA should be able to negotiate with sponsors to get the right data without years of rulemaking, establish post-marketing data requirements, consult with other countries' regulators to establish consistent standards where possible, and move quickly in the event that safety concerns emerge," he said.

Legislation establishing this pathway also should provide FDA with additional revenue to facilitate timely analyses and reviews, noted Sharfstein, who headed Maryland’s public health agency after leaving FDA and in January moved to an associate dean post at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

“Between procedural requirements and inadequate resources, over-the-counter product regulation proceeds in slow motion as compared with the rest of the agency. Rulemaking typically consumes many years, or even decades review or approve innovative products that could pose novel safety concerns,” he said.

While FDA conducts deadline-constrained evaluations of NDAs, including for Rx-to-OTC switches and other new OTC ingredients, the monograph is changed after the agency agrees with clinical trial and other data that firms submit to show ingredients are generally recognized as safe and effective.

So, GRASE typically is reserved for "products that have been out there for a long, long, long, long time," Sharfstein said in an audio interview accompanying the article.

The agency has acknowledged the monograph system is ineffective and since February 2014 has been considering options recommended by industry stakeholders and other parties on improving the process. The agency also has said a lack of user-fee support relegates the monograph process to a low priority (Also see "Without User Fees, OTC Monograph Changes Are Low Priority At FDA" - Pink Sheet, 14 Aug, 2014.).

The Consumer Healthcare Products Association said Sharfstein’s recommendations add to the ideas already floated for improving FDA’s OTC ingredient approval process.

“CHPA is intrigued by his ideas, and we have had a number of conversations with FDA about where we might align on monograph reform concepts,” the trade group said in a statement.

FDA did not argue against SIA but told Congress additional rules were not the solution to the difficulty in adding ingredients to the OTC monograph. Should Sharfstein’s recommendations prompt legislation, the agency likely would remind lawmakers that without targeted funding, additional regulations will not accelerate ingredient evaluations (Also see "Sunscreen Safety Framework Is FDA’s First Step, With More Tests Needed – NDAC" - Pink Sheet, 8 Sep, 2014.).

Criticism 'Missed The Mark'

Sharfstein noted in the article that FDA's proposed decisions in early 2015 – within three months of SIA’s enactment – to reject the pending eight sunscreen ingredient TEAs spurred a fierce backlash from some in the industry, public health groups and media.

However, "these attacks missed their mark," he said.

"It's no surprise that the FDA would act cautiously given the scientific advice it's received [from its Nonprescription Drugs Advisory Committee] and a legal structure that essentially provides it with just one tool: authorizing extensive marketing of multiple products and formulations," he added.

He said FDA can “move quickly with a range of actions to protect the public” when problems emerge with any Rx or OTC ingredient approved through the NDA pathway. While this regulatory tool “is well suited to individual new therapeutics, it is cumbersome for many products intended to be sold over the counter in a wide variety of formulations and concentrations.”

In the interview, Sharfstein elaborated: "The agency's stuck right now with this over-the-counter process where if they make [a sunscreen ingredient] available, it's very widely available, and there's not a lot of flexibility for the agency to undo what an approval would look like."

The result, he said, is a standoff between the agency and parties pushing for approval of additional sunscreen ingredients to combat rising rates of skin cancer.

Sharfstein paraphrased FDA’s position as: "Look, these are products that will be worn by millions of people who are not sick, who don't have melanoma, and we want to have some degree of assurance of safety [but] we're stuck with this approval process that is very rigid and doesn't give us a lot of flexibility to change our mind later."

FDA leadership underscored the challenges inherent in the OTC drug monograph system in follow-up meetings with sunscreen ingredient TEA applicants and at recent industry conferences, suggesting GRASE actually is a higher bar than NDA approvals in terms of the burden of proof it imposes on sponsors.

For that reason and other bureaucratic complexities, attaining a GRASE designation can be more a demanding process and considerably more time-consuming, agency officials and industry stakeholders say.

Janet Woodcock, director of FDA's Center for Drug Evaluation and Research, in May said that neither the TEA pathway nor SIA regulations require FDA to award GRASE status to a sunscreen drug ingredient only because of its marketing history in other countries. She highlighted shortcomings in the current framework that Sharfstein identified, and similarly suggested that "a more flexible and … agile system" is needed (Also see "‘Confusion’ Clogs Sunscreen TEA Proposals, ‘Radio Silence’ On NSURE Progress – Woodcock" - Pink Sheet, 18 May, 2015.).

Public Health Benefit Needs Proof

While sunscreen ingredient innovators would stand to gain from improvements to the OTC drug review system, public health advocates consistently argue that an updated, wider ingredient selection would help address the skin cancer epidemic in the U.S.

In the NEJM interview, Sharfstein tackled whether availability of additional sunscreen active ingredients, some available in Europe for more than a decade, would make a difference for public health.

"I think it is very much a hope among people who advocate for fewer cases of melanoma that more flexibility around the ingredients, long-lasting ingredients, would have an effect on reducing melanoma, [but] I don't think that that has been firmly established," he said.

Sharfstein acknowledged it is "plausible" the sunscreen ingredients FDA tentatively rejected this year could have properties that allow for longer-lasting application or superior water resistance among other potential performance enhancements. "But again, I have not seen in this discussion a very clear explanation of the public health benefits that would be gained," he said.

He suggested escalating skin cancer rates could be linked more to use of indoor tanning beds, particularly by young people, and under-use of sunscreen in general than to outdated UV filters that are markedly less effective than their potential successors.

While acknowledging challenges in pushing legislative proposals through Congress, he characterized the Public Access to Sunscreens Coalition as "a pretty savvy group" that proved worthy of the task through its leading role in SIA being passed in 2014 (Also see "Sunscreen Innovation Act Starts Clock Ticking On FDA Review Of TEAs" - HBW Insight, 14 Nov, 2014.).

"My goal for them," he told NEJM Managing Editor Stephen Morrissey, is “take a look at the FDA's authority and say, 'Let's make this easier for the FDA to do what we're hoping they will do.' And the way to do that is to give the agency more flexibility in handling products like this – not just to pressure FDA to use a process that really is not intended for this kind of innovation."

Among comments on Sharfstein's article NEJM accepted through July 15, PASS policy advisor Michael Werner emphasized prompt action to address soaring skin-cancer rates, citing data from the Surgeon General indicating that 5 million people will be treated for skin cancer in 2015 in the U.S. at a cost of more than $8 billion.

"The broader reforms identified by Dr. Sharfstein may take years to enact. Given the epidemic of skin cancer in this country, additional delays have a cost in human suffering we can ill afford," Werner said.

[Editor's note: “The Rose Sheet” also published this article. "The Pink Sheet" DAILY brings selected complementary coverage from our sister publications to our subscribers.]