Draft Proposal Aimed at modernizing the OTC monograph process

More than 300,000 OTC drug products marketed for use by consumers without the intervention of a health care professional, are currently on the U.S. market. There are two regulatory pathways for the legal marketing of OTC drugs: marketing in compliance with an OTC monograph and marketing through an approved new drug application (NDA) that is later switched to OTC designation.

For those manufacturers that seek to market a drug product that is not covered under the OTC monograph process and are not interested in pursuing the NDA route, the route of updating a monograph is a cumbersome and lengthy process, involving a three-phase legislative rule making process. In an effort to advance and innovate OTC regulations, an OTC user fee solution was recently submitted as part of a bipartisan house bill -- the Over-the-Counter Monograph Safety, Innovation, and Reform Act of 2017. Under this proposal, OTC drug manufacturers would pay an annual fee for their facilities and an extra fee each time they submit a request to review proposed changes related to their product. It would also introduce a fixed time limit requiring FDA to take action within 15 and 18 months to approve and finalize proposed monograph changes. It would also allow FDA to send out interim orders, for example in the case of an urgent safety issue, while changes to monograph are being discussed. The funds obtained from the user fees would allow FDA to increase personnel for overseeing OTC products from 33 to 100 within five years.

Prior discussion on establishment of OTC user fees took place at a June 2016 FDA meeting that sought to obtain public and industry input. Overall, consumers and the OTC drug industry look forward to this and other legislation to advance and modernize the legacy OTC process and to better serve and protect consumers. However, there was caution expressed about how the fees will be applied e.g. to those marketing the finished OTC product only or to all manufacturing OTC active ingredients (where some substances predominantly sold as excipients can be used as active ingredients in a few OTC monographs at concentrations exceeding their use as excipients). The latter may cause inactive ingredient manufacturers to withdraw from supplying to OTC drug manufacturers if subjected to products fees, which would result in products no longer being available to consumers. In addition, there is concern of the fairness of the fee structure, in that a fee for review of amendments to a monograph would only target the initial innovator while benefiting others seeking to market the same OTC product. Some have suggested that there should be incentives for innovators who bring a new OTC product to market, such as a period of exclusivity. Needless to say, the draft OTC Over-the- User Fee proposal will need more FDA, public and industry input to balance out the fee burden.

Why Was This Bill Introduced?

Under the monograph route, products are marketed in accordance with a previously approved monograph. The monograph is like a recipe that describes the accepted active ingredient(s), dose, formulation and specific uses to treat symptoms or conditions without a prescription. A drug product containing the accepted active ingredient with accepted labeling for the treatment of a specific symptom or condition does not need FDA approval before being marketed to consumers. In addition, there are no user fees associated with this marketing route, unlike seeking approval through a formal FDA NDA/BLA approval process.

The monograph drug review process began in 1972 from a mandate in the Kefauver-Harris Amendment of 1962 for FDA to review pre-1962 drugs for both safety and efficacy in order for them to stay on market; it resulted in defining 80 therapeutic classes of drugs for review. To be covered by this review, a product’s formulation (including the concentration of its active ingredients, labeling, and indications for use and dosage form) must either have:

  • Existed in the U.S. marketplace on or before the inception of the OTC Drug Review
  • Been included by FDA in the review in accordance with existing regulations (e.g. 21 CFR 330.14 and 330.10(a)(12) and 21 CFR 10.30)

If either of these provisions is not met, the OTC drug is not eligible for evaluation under the OTC Drug Review.

This legacy OTC monograph drug review process as stated above is a lengthy process where it involved rulemaking in a three phase legislative process. The FDA assigned a panel to review the active ingredients and asked for safety and efficacy data to support the claim(s). Based on a favorable review of the data, FDA would then publish a tentative monograph open for public comment. Based on the strength of the subsequent data, FDA would then either publish a final regulation or decide to leave open the comment period, thus leaving the tentative monograph in place. Unlike the defined NDAs review cycles under PDUFA, there is no time requirement for this process to be completed and therefore the issuance of a final monograph can take many years. As of date, the monograph drug review process is still incomplete, with approximately 88 monographs pending finalization. However in the meantime, those products containing active substances at the identified concentrations for specified uses defined in the tentative monographs are allowed in the marketplace as long as they are manufactured under GMP conditions.

The alternative process to a U.S. OTC drug is to pursue an initial NDA approval and then petition FDA to convert the drug and its usage to OTC status. The general drug characteristics required for an OTC conversion include benefits outweighing risks, a low potential for misuse and abuse, consumer can use them for self-diagnosed conditions; ability to be adequately labeled and health practitioners not being needed for product’s safe and effective use (i.e. no prescription is required). Although an alternative to the legacy OTC pathway this regulatory pathway is subject to all NDA regulatory compliance requirements that exceed those of legacy OTC drugs.

Do you have any questions? Please reach out to Marinka Tellier, NSF International’s Director of Regulatory Affairs for Pharma Biotech, at mtellier@nsf.org or Andy Papas, NSF International’s VP of Regulatory Affairs for Pharma Biotech, at apapas@nsf.org, or visit our website to learn more about NSF's pharma biotech services.

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