FDA is seeking to overhaul its OTC drug monograph process to be “more agile and responsive,” noting the current system faces “significant challenges.”

The agency will conduct a public hearing on March 25 and 26 at the agency’s headquarters in Silver Spring, Md., for comments about improving the OTC Drug Review, or OTC monograph process, according to a Federal Register notice released Feb. 21.

FDA’s Center for Drug Evaluation and Research proposed several potential changes and seeks public input on:

expanding the process for allowing deviations from drug formulations approved through new drug applications
issuing monographs by administrative order
identifying a streamlined process that would allow prompt resolution of existing tentative final monographs
issuing regulations to require product specific information
expanding the use of guidances.

In addition to those proposals, FDA asks for comments on the strengths and weaknesses of the OTC Drug Review and possible modifications or alternatives to the program.

Monograph products account for the majority of OTC drugs currently available in the U.S., and stakeholders contend that updating and streamlining FDA’s process for changing or creating new monographs would facilitate making even more drugs available OTC Also see "OTC Monographs Face Obsolescence In Shadow Of NDA Products" - Pink Sheet, 10 December, 2012..

Changing the monograph process could affect the OTC drug marketplace more than FDA’s ongoing consideration of allowing Rx-to-OTC switches under conditions of safe use and potentially incorporating uses of technology Also see "FDA Encourages Novel Switch Ideas, Though NSURE Remains Unsure" - Pink Sheet, 7 November, 2013..

Public Hearing Only A Start

Food and drug attorneys commend the agency for initiating a look at updating the monograph process, but they say improving the system could take more drastic changes than the agency is proposing.

FDA Commissioner Margaret Hamburg, CDER Director Janet Woodcock and other agency executives are “receptive to understanding that it’s not a workable system right now,” said Scott Bass, a partner at Sidley Austin.

Gary Yingling, a partner at Morgan, Lewis & Bockius LLP in Washington, worked on FDA’s initial OTC drug review for establishing monographs in 1972 and 1973 during his services as an assistant counsel at the agency. He said it was apparent then that the monograph process would be slow and cumbersome, and FDA’s proposals do not go far enough to help.

“You look at this and say, ‘You created this and you’re not walking away from it significantly. What you want to do is sort of bend it a little bit.’ I’m not sure that’s going to get them anywhere,” Yingling said.

“I’m just not sure that this is not more show than anything else,” he added.

The Consumer Healthcare Products Association noted that the monograph system has provided a regulatory structure for FDA to evaluate the safety and efficacy of “thousands of OTC products by category rather than face a review of tens of thousands of individual new drug applications.”

But adoption of final rules to create or update monographs and allow additional OTCs to reach the market outside the NDA process “has slowed in recent years, and we’re hopeful FDA will share its perspective on why that is the case at the public hearing,” the trade group said.

Costs Stymie Firms

FDA notes that use of the NDA-deviation process, in particular, has slowed. The process allows a sponsor to apply for a deviation by submitting an NDA showing that the product complies with the conditions of the monograph except for the deviation and providing the necessary data to demonstrate the safety and effectiveness of the product.

“Industry has not utilized the NDA deviation process as a pathway to marketing very often,” according to the notice. FDA “is interested in learning why this is and whether there are changes that could be made to the existing NDA deviation process that would make it a more attractive alternative for industry and that could allow marketing of additional drug products without having to submit a full NDA.”

Yingling said costs are the reason firms rarely ask FDA to approve a deviation from an NDA. Like the process of asking FDA to change a monograph or an actual NDA submission, an NDA deviation represents excessive investments of time and money for firms, and their chances for success are not high.

He said changes such as different delivery formats or coatings for monograph products often require NDA-deviation approvals from FDA.

“That’s not worth a million and a half dollars for filing a new drug application and you’re never going to be able to recoup that money. Those kinds of innovations are basically getting lost,” Yingling said.

Bass said some firms risk incurring enforcement by launching products that are not compliant with a monograph because they cannot afford to go through the process of asking for an NDA deviation or for a monograph change.

“There are ingredients sitting for decades on shelves without FDA action on a monograph or that are going out on the market in violation. It’s not an even playing field and it’s just a system that doesn’t work,” Bass said.

Guidance On Combination Products

In the notice FDA addresses the potential for combining ingredients that are non-monograph, but generally regarded as safe and effective, with monograph ingredients.

The agency proposes issuing regulations on the supporting information sponsors should submit for such combination products then publishing guidances for submitting proposals. Requirements could be for labeling, and quality and pharmacokinetic information, similar to but less detailed than what is required for an NDA, the agency says.

The “use of guidances under this framework could increase [FDA’s] flexibility to address specific product issues as they arise,” according to the notice.

Bass pointed out potential products combining monograph and non-monograph ingredients likely are numerous already.

FDA is “well aware that there are anomalies that exist, that people are trying to figure out how they can market products with combinations,” he said.

And the agency acknowledges the current OTC monograph process’s constraint on innovations. “When manufacturers develop new combinations of ingredients or new dosage forms … the OTC Drug Review is not facile in accommodating these types of changes. Due to these changes, products that are not eligible for consideration under the OTC Drug Review would otherwise require an NDA prior to marketing,” according to the notice.

Noting Changes In Rx, Device Evaluations

One of FDA’s proposals, issuing monographs by administrative order, likely would require enabling legislation from Congress.

The agency says in the notice that the change would involve establishing a process similar to that enacted by the Food and Drug Administration Safety and Innovation Act for device reclassifications. FDASIA changed the device reclassification process from notice and comment rulemaking to an administrative order process.

Changes to the agency’s evaluation of Rx drug ingredients since the OTC Drug Review began also warranted mention in the notice as a sign that the OTC ingredient evaluation process should be improved.

The OTC Drug Review’s “multistep rulemaking strategy was thought to be an effective and efficient approach to reviewing large categories of active ingredients in drug products,” but advancements in drug safety and drug development prompt questions about its efficiency, CDER officials wrote in the notice.

Changes in the regulation of Rx drugs to account for scientific advances “give FDA the ability to quickly obtain new information and take administrative action as needed efficiently and effectively,” the officials said.

FDA will accept requests through March 12 to make presentations during the public hearing.

FDA Floats OTC Monograph Overhaul To Be “More Agile And Responsive”

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