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FDA Reconsidering How it Regulates (Most) OTC Drugs

Last Friday, FDA announced a public meeting to obtain input on reworking the system through which it regulates most* over-the-counter (OTC) drugs, known as the “OTC monograph system.”  This is big, and important, news.

OTC drugs are widely and routinely used, and are big business (in 2012, we spent 29.3 billion dollars on OTC drugs in the U.S.).  Yet most OTC drugs are not “approved” by FDA.  Instead, FDA publishes regulations, known as monographs, that set out what are, essentially, lists of permissible ingredients and labeling claims for therapeutic categories of OTC drugs (e.g., laxatives, antacids).  If a drug meets the standards published in the relevant monograph, a company may sell the drug without pre-market approval from FDA.  Sounds reasonable enough.  But the problem is, as anyone who has any experience with notice-and-comment rulemaking will know, publishing regulations has become a very slow endeavor.  Thus, although the monograph process started in 1972, many of the monographs are not yet final, and, more troublesome, FDA has not been able to respond quickly to safety concerns as new information about OTC drugs is learned. (See, e.g., Jake’s blog post from last year about the monograph covering antibacterial soap, and my discussion of the risk of liver injury associated with acetaminophen, the active agreement in Tylenol, in our Oct. 2013 podcast).

So how did we get where we are today?

I think the monograph system was, at the time it was devised, a clever solution to a difficult regulatory situation.  In 1962, amendments to the Federal Food, Drug, and Cosmetic Act (FDCA) added a requirement that drugs be shown to be effective, as well as safe, before marketing.  Because of this new requirement, FDA had to figure out how to handle all of the prescription and OTC drugs that were already on the market and were not approved under a new drug application (NDA) that demonstrated both safety and effectiveness. For OTC drugs, FDA decided in 1972 to establish the monograph system to review the safety and effectiveness of OTC drugs by therapeutic category rather than reviewing the safety and effectiveness of each OTC drug that was then on the market—of which there were approximately 100,000-500,000 (see FDA’s rule proposing the monograph system at 37 Fed. Reg. 85).  Because of the sheer number of OTC drugs on the market, one can understand why FDA needed to come up with a solution for OTC drugs that did not involve reviewing the safety and effectiveness of each OTC drug.

The legal authority for the OTC monograph system stems from the definition of a “new drug” in the FDCA.  A “new drug,” as defined at section 201(p) of the FDCA, is any drug that is not generally recognized as safe and effective, or has not been used for a material time and to a material extent.  Under section 505 of the FDCA, all new drugs (including generic new drugs) must be approved by FDA before they can be legally marketed.  But if a drug is not a “new drug,” pre-market approval is not required.  And this is how the monograph system operates—if an OTC drug meets the standards set out in a monograph, FDA does not consider that drug to be a new drug, i.e., the drug is considered to be “generally recognized as safe and effective” (and not misbranded), and thus pre-market approval is not required.

All of which is to say that I think FDA’s decision to initiate the OTC monograph process in the 1970s was both understandable and legally supported.  But now that we’ve seen that the current monograph system is simply too slow to adjust to the pace of modern science (or even not-so-modern science), what comes next?

That is the 64,000  — or 29.3 billion — dollar question.

FDA suggested a few possibilities for modernizing the monograph system in its meeting notice – a streamlined approach to finalizing those monographs that are still not final,  issuing monographs by administrative order, instituting a pre-market submission process that is less burdensome than the NDA process, or expanding the use of NDA deviations — but explicitly encouraged meeting attendees to propose additional ideas.

It’s not clear what position the Consumer Health Products Association – the industry group for OTC drug manufacturers – is going to take.  Its statement in response to FDA’s meeting announcement was fairly agnostic.  Which, perhaps, isn’t surprising.  OTC drug manufactures have been operating under the monograph system for 40+ years, and, for all of the monograph system’s problems, they may be reluctant to trade the devil they know for the devil they don’t.

Because of the Administrative Procedure Act’s requirements and the amount of review regulations receive within the executive branch, it may be difficult for FDA to come up with a legally sound system that both continues to involve issuing regulations and is significantly faster than the current system, without statutory change.  To the extent the agency cannot fix all of the problems with the OTC monograph system, the most important public health issue to address is probably the agency’s inability to quickly respond to new safety concerns.  On that issue, it would be helpful for the agency to have clear statutory authority to quickly require safety-related changes when it learns new information about a particular drug or class of drugs—something similar to FDA’s authority to require postmarket studies and safety labeling changes for approved prescription drugs (see sections 505(o)(3) and (4) of the FDCA).  Enabling FDA to respond to new safety concerns, alone, might go a long way toward modernizing the monograph system.

At any rate, I’m glad to see FDA tackling this challenging issue.  Even if (as is likely) FDA cannot solve all of the problems with the OTC monograph system, hopefully it will be able to improve the system within the confines of its statutory authority and maybe even prod Congress into making some statutory changes.

One final note: for those who would like to share their thoughts with FDA, the notice announcing the meeting provides instructions for requesting time to present at the meeting, and for providing written comments to the agency.

*Most OTC drugs are marketed pursuant to a monograph.  There are, however, some OTC drugs that are approved under new drug applications (for example, Colgate Total).

2 Responses to “FDA Reconsidering How it Regulates (Most) OTC Drugs”

  1. Hank Greely says:

    Is it plausible that FDA could define a drug as GRAS (generally regarded as safe) without having to issue a regulation to that effect? As you explain it, a monograph is really a regulation . . . could the FDA just announce, after advice from an advisory committee, that a certain molecule was GRAS? Because otherwise the problem, as you describe it, sounds quite daunting.

  2. Patti Zettler says:

    That is an interesting question. I think the answer is “maybe, but I doubt it will.” There isn’t anything in the FDCA that requires FDA to issue regulations to deem a drug generally recognized as safe and effective (GRASE). But, because FDA has already started down the regulation path, and because of FDA’s Good Guidance Practice regulation (which specifies a process the agency must follow to describe its interpretation or policy on a regulatory issue), I think it would at least need to issue one regulation to announce its new “website policy.” That said, I imagine there might be reluctance to adopt that process—both because companies with products that are NOT deemed GRASE might challenge it, and because I think it would still leave FDA without a good hook to require safety-related changes to marketed drugs. But maybe I’m wrong and there certainly would be value in a quick website policy—it would go a long way toward addressing the slowness of the monograph system, which is, of course, a major problem too.

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