On-Again Off-Again Third Category of Drugs is On Again at FDA; Simultaneous Rx and OTC Marketing Also Up for Debate

February 29, 2012

By Kurt R. Karst –      

Every few years, interest in the creation of a third category of drug products – something other than prescription or Over-the-Counter (“OTC”) status – is piqued by FDA, Congress, or by some other entity.  The most recent attempt to explore the creation of a new drug category is FDA’s announcement earlier this week of a March 22-23, 2012 public hearing for FDA to obtain input on a “new paradigm” the Agency is considering.  But before we get into FDA’s “new paradigm,” first some background and history . . . .

The FDC Act was amended in 1951 by the Durham-Humphrey Amendment, Pub. L. No. 82-215, 65 Stat. 648 (1951), to give FDA the authority to require that drugs be limited to prescription status when they cannot be used safely OTC.  The underlying presumption then and now is that prescription restrictions are the exception.  In other words, if a drug can be used safely and effectively OTC it should be.  FDA stated this principle clearly in the Agency’s overview of issues for a May 11, 2001 advisory committee meeting that considered whether three prescription antihistamines should be switched to OTC status.  According to FDA, the FDC Act “restricts drugs to prescription-only status if a learned intermediary is required for the proper use of the drug.  As written, the default assumption of the [FDC Act] is for drugs to be marketed OTC without a prescription unless a decision is made that consumers are not able to appropriately diagnose their condition nor able to correctly choose the remedy and safely use it based on OTC labeling.”

The FDC Act defines a prescription drug at FDC Act § 503(b)(1) as:

A drug intended for use by man which – 

(A) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug; or

(B) is limited by an approved application under section 505 to use under the professional supervision of a practitioner licensed by law to administer such drug . . . .

(As enacted in 1951, FDC Act § 503(b)(1) included three categories of Rx drugs: (1) habit-forming drugs under § 502(d); (2) drugs that are unsafe for use except with a doctor’s supervision; and (3) drugs limited to Rx use under an NDA.  The FDA Modernization Act of 1997 amended FDC Act § 503(b)(1) to repeal subparagraph (A) (habit-forming drugs) and redesignated former subparagraphs (B) and (C) as (A) and (B), respectively.)  The FDC Act does not define the term “OTC drug;” however, it does define a “nonprescription drug” at FDC Act § 760(a)(2) to mean a drug that is “(A) not subject to [FDC Act § 503(b)]; and (B) not subject to approval in an application submitted under [FDC Act § 505].”

Very few drugs straddle the line between prescription and OTC status.  The contraceptive drug PLAN B, which has been in the news as of late (see here), is one example – available without a prescription to women 17 years of age and older, but only with a prescription to younger women.  Another example is cold medicine containing pseudoephedrine, which, under the Combat Methamphetamine Epidemic Act of 2005, is limited to Behind-the-Counter (“BTC”) sales.

Previous explorations to create a third category of drugs have petered out.  In October 2007, FDA announced a November 14, 2007 public meeting to discuss the creation of a BTC class of drugs – i.e., a class of drugs available behind the counter at a pharmacy without a prescription but that require the intervention of a pharmacist before dispensing (see our previous post here).  Previously, FDA declined to create BTC drug status when the Agency denied, in April 2004, a citizen petition requesting that FDA “switch Nicotrol Inhaler (Nicotine Inhalation System) from prescription only to over-the-counter status TO BE SOLD ONLY UNDER A PHARMACIST’S SUPERVISION as a third class of drugs” (Docket No. FDA-2003-P-0289). 

FDA’s November 2007 public meeting was followed by a March 2009 report by the U.S. Government Accountability Office (“GAO”) discussing, among other things, arguments supporting and opposing the creation of a BTC drug category (see our previous posts here and here).  The report also updated a 1995 GAO report on the topic.  

Discussion of the creation of a third drug class then apparently went into hibernation until April 2011, when Center for Drug Evaluation and Research Director Dr. Janet Woodcock floated a trial balloon for reviving the idea at the Food and Drug Law Institute’s annual conference, according to trade press reports.  And that brings us to FDA’s latest action on the topic. 

FDA’s February 28, 2012 Federal Register notice announcing the March 22-23, 2012 public hearing restyles the third drug class not as a BTC class, but rather as a “new paradigm” under which FDA “would approve certain drugs that would otherwise require a prescription for nonprescription use . . . under conditions of safe use.”  These “conditions of safe use,” says FDA, “would be specific to the drug product and might require sale in certain pre-defined health care settings, such as a pharmacy.”  Why now?  FDA points to undertreatment of diseases and other effects on the health care system and suggests that a new system could address these issues:

The requirement to obtain a prescription for appropriate medication (and to make one or more visits to a practitioner) may contribute to undertreatment of certain common medical conditions including hyperlipidemia (high cholesterol), hypertension (high blood pressure), migraine headaches, and asthma.  For instance, some consumers do not seek necessary medical care, which may include prescription drug therapy, because of the cost and time required to visit a health care practitioner for an initial diagnosis and an initial prescription.  Some patients who obtain an initial prescription do not continue on necessary medication because they would need to make additional visits to a health care practitioner for a prescription refill after any refills authorized by the initial prescription have been used or the time during which they can be filled has expired.  Some prescription medications require routine monitoring through the prescribing practitioner such as blood tests to assist in the diagnosis of a condition, or to determine whether or how well the medication is working, or to adjust the dose.  FDA believes that some of these visits could be eliminated by making certain prescription medications available without a prescription but with certain other conditions of safe use that would ensure they could be used safely and effectively without the initial involvement of a health care practitioner.  In some cases, a visit to a practitioner would be required for the initial prescription, but a certain number of refills could be authorized beyond those that would normally be authorized without a return visit under specialized conditions of safe use.

Based on the common medical conditions FDA identifies, one can guess the types of drugs that might be considered under a new paradigm.  FDA also says that the paradigm laid out in the notice might be useful for certain rescue medicines, such asthma inhalers and drugs for allergic reactions (e.g., epinephrine).

FDA’s public hearing notice contains a series of questions grouped into three categories that the Agency hopes will define the scope of the hearing, including: (1) “Types of Technology and Conditions of Safe Use” (e.g., “What types of technologies (e.g., kiosks, computer algorithms) are currently in development that could assist in allowing drugs to be used safely and effectively in the nonprescription setting?”); (2) “Pharmacy, Consumer, and Health Care Provider Issues” (e.g., “How might various types of conditions of safe use on nonprescription drug products affect pharmacy business operations?”); and (3) “Other Related Issues” (e.g., “How would insurance coverage of pharmaceuticals be affected by approving nonprescription products with conditions of safe use for widely prescribed prescription drugs under this paradigm?”).

Interestingly, as part of FDA’s discussion of its “new paradigm,” the Agency indicates that it might be open to considering permitting the simultaneous prescription and OTC marketing of the same drug.  “FDA is also considering whether the same drug product could be simultaneously available as both a prescription and nonprescription product with conditions of safe use.  Dual availability could help ensure greater access to needed medications by making obtaining them more flexible,” says FDA in the public hearing notice.

FDA has relied on FDC Act § 503(b), generally, for the assertion that, absent a “meaningful difference,” the FDC Act does not permit the simultaneous prescription and OTC marketing of the same drug for the same indications, in the same dosage forms and at the same strength, and on FDC Act § 503(b)(4) specifically to contend that a product whose labeling contains the “Rx-only” symbol (legend) where the same drug is approved for OTC use is misbranded and may not be legally marketed.  (FDC Act § 503(b)(4) renders a prescription drug misbranded if it fails to bear the “Rx-only” symbol and an OTC drug misbranded if it does.)  FDA discussed its interpretation of what constitutes a “meaningful difference” in a September 2005 Advance Notice of Proposed Rulemaking concerning the approval of PLAN B for OTC use in certain women.  Historically, a “meaningful difference” exists if the Rx and OTC drug products differ in: (1) active ingredient; (2) indication; (3) strength; (4) route of administration; or (5) dosage form.  FDA’s approval of PLAN B added age as a sixth difference. 

To this day, FDA is grappling with simultaneous prescription and OTC marketing issues.  Following the Rx-to-OTC switch of PEG 3350 (MIRALAX), FDA objected to the continued marketing of approved generic prescription versions of the same drug.  FDA approved prescription MIRALAX on February 18, 1999 under NDA No. 020698 for the treatment of occasional constipation.  FDA subsequently approved several ANDAs for generic versions of prescription MIRALAX.  On October 6, 2006, FDA approved NDA No. 022015 for OTC MIRALAX for the relief of occasional constipation.  After the approval of OTC MIRALAX, FDA removed all Orange Book references to NDA No. 020698 (prescription MIRALAX), and in April 2007, FDA’s Office of Generic Drugs sent letters to ANDA sponsors of prescription PEG 3350 stating that the FDC Act “does not permit both Rx and OTC versions of the same drug product to be marketed at the same time.”  The letters clearly rely on FDC Act § 503(b)(4) to contend that prescription PEG 3350 products are “misbranded and may not be legally marketed.”  The letters also cite FDC Act § 503(b), generally, for the assertion that the FDC Act does not permit the simultaneous Rx and OTC marketing of the same drug. 

On October 24, 2008, FDA issued a Notice for an Opportunity for Hearing (Docket No. FDA-2008-N-0549) on a proposal to withdraw approval of prescription PEG 3350 ANDAs on the basis that the Durham-Humphrey Amendment prohibits the simultaneous marketing of the same drug as Rx and OTC.  Moreover, FDA determined “that there is no meaningful difference between the Rx and OTC PEG 3350 drug products.”  Several ANDA sponsors requested a hearing and submitted comments to FDA challenging both the Agency’s interpretation of the statute to preclude simultaneous prescription and OTC marketing of the same drug, and FDA’s determination that no meaningful difference exists between the Rx and OTC versions of PEG 3350.  FDA has not yet scheduled a hearing.  Whether FDA’s “new paradigm” will resolve the issue, or perhaps result in a new “meaningful difference” (e.g., conditions of safe use) remains to be seen.


  • CDER Director Dr. Janet Woodcock suggested during a February 29th speech at the International Conference on Drug Development (Austin, Texas) that the “new paradigm” discussed in FDA's Federal Register notice might be taken up by Congress and included as part of a PDUFA bill, instead of by FDA as a proposed rulemaking.  No specifics were provided by Dr. Woodcock.