Has FDA Already Resolved One Critical Issue Concerning Forced Rx-to-OTC Switches?

By Kurt R. Karst –      

FDA’s ability to force a prescription-to-over-the-counter switch (“Rx-to-OTC switch”) has been hotly contested over the past decade.  The crux of the debate concerning forced Rx-to-OTC switches is whether FDA, absent a New Drug Application (“NDA”) sponsor’s consent, has the authority to force an Rx-to-OTC switch; and if so, on what legal basis.  (Although FDA attempted a forced switch once – almost 30 years ago – when the Agency proposed to switch metaproterenol sulfate metered-dose inhaler drugs from Rx to OTC status under the OTC Drug Review, FDA did not carry through with the switch after extensive adverse comment.)  A little-known FDA response to a citizen petition, however, appears to have settled what FDA believes is its legal basis to effect a forced switch.  But first, some background . . . .

The 1951 Durham-Humphrey Amendments to the FDC Act gave FDA the authority to require that drugs be limited to Rx status when they cannot be used safely for OTC use.  Thus, the underlying presumption (then and now) is that Rx restrictions are the exception, and that if a drug can be used safely and effectively OTC it should be.  The Durham-Humphrey Amendments also amended the FDC Act (§ 503(b)(3)) to state that FDA “may by regulation remove drugs subject to [FDC Act § 505 [(i.e., new drugs)] from the requirements of [FDC Act § 503(b)(1)] when such requirements are not necessary for the protection of the public health.”  FDA’s regulation implementing § 503(b)(3) is codified at 21 C.F.R. § 310.200(b), and states that FDA may approve an Rx-to-OTC switch when Rx dispensing is:

not necessary for the protection of the public health by reason of the drug’s toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, and . . . [t]he drug is safe and effective for use in self-medication as directed in proposed labeling. 

There are two different mechanisms under the FDC Act for FDA to make an Rx-to-OTC switch: (1) FDC Act § 503(b)(3) explicitly provides FDA with the authority to issue a regulation changing the status of an Rx drug to an OTC drug; and (2) the FDC Act grants FDA the authority to approve and reject NDAs. 

FDA’s regulation at 21 C.F.R. § 310.200(b), which implements FDC Act § 503(b)(3), identifies processes for initiating consideration of an Rx-to-OTC switch.  Specifically, a proposal to exempt a drug from Rx-only requirements may be initiated by the FDA Commissioner or by “any interested person” in the form of a sponsor submitting an NDA or by a third party petitioning FDA.  Regardless of who initiates a request for an Rx-to-OTC switch, however, the evidence must demonstrate that the statutory Rx-only dispensing requirements are no longer necessary to protect the public health, and that the drug is safe and effective for use in self-medication as directed in proposed labeling. 

Those opposed to forced switches have argued that FDA can only authorize a switch over the NDA sponsor’s objections following a formal, trial-like administrative process known as an adjudication, and that FDA lacks the authority to force an Rx-to-OTC switch through rulemaking.  (The distinction between rulemaking and adjudication is based on the nature of the decision facing an agency.  Actions pursuant to generalized facts do not require an individual hearing and can be taken according to procedures applicable to rulemaking – either formal rulemaking, informal notice-and-comment rulemaking, or the rarely used negotiated rulemaking.  Actions pursuant to individualized facts require some level of hearing and are classified as an adjudication.)  Moreover, forced switch opponents have argued, among other things, that even if rulemaking is appropriate, FDA cannot use informal notice-and-comment rulemaking, but instead must use formal, hearing-based rulemaking.  

Forced switch proponents have argued, among other things, that the FDC Act expressly authorizes FDA to force a switch following rulemaking – not adjudication – and that FDA is free to undertake any type of rulemaking the Agency deems appropriate, such as informal notice-and-comment rulemaking. 

Over the past decade, FDA has been asked on at least three separate occasions to make a forced switch.  First, in July 1998, WellPoint (Blue Cross of California) submitted a citizen petition to FDA (Docket No. FDA-1998-P-0254) requesting that the Agency convert from Rx to OTC status several antihistamine drugs.  (The WellPoint petition was the subject of a joint meeting of the Nonprescription Drugs Advisory Committee & the Pulmonary – Allergy Drugs Advisory Committee in May 2001.)  Second, in March 2007, FDA was petitioned (Docket No. FDA-2007-P-0056) to force a switch of fexofenadine HCl and cetirizine HCl.  FDA has not substantively responded to either petition.   

Finally, in February 2001, the Center for Reproductive Rights petitioned FDA (Docket No. FDA-2001-P-0123) to force a switch of PLAN B (levonorgestrel) Tablets.  FDA denied the petition in June 2006 “because it did not contain sufficient data to satisfy the statutory and regulatory requirements for an Rx-only to OTC switch for Plan B.”  Moreover,  given the then-pending NDA supplement for OTC PLAN B, FDA refused to allow the petition to “circumvent the [NDA supplement] process to which the sponsor of the drug is entitled.”  Importantly, however, FDA noted in its response that:

Although your petition does not explicitly state that you are requesting FDA initiate notice-and-comment rulemaking, the Act . . . authorizes only two mechanisms for FDA to make an Rx to OTC switch: [informal] notice-and-comment rulemaking and approval of a drug application . . . . You are not yourselves applicants for drug approval, and you are not permitted to submit a supplement to another company’s application.  21 CFR 314.71(a).  Accordingly, your petition can only be construed as a request that we initiate notice-and-comment rulemaking proceedings pursuant to which a rule would be promulgated allowing Plan B and other emergency contraceptives to be made available OTC. [(emphasis added)]

In other words, FDA in its petition decision appears to have determined that informal notice-and-comment rulemaking is the appropriate route to effect a forced switch over an NDA sponsor’s objections, and that administrative adjudication is not necessary.