2005N-0345 Drug Approvals: Circumstances under which an active ingredient may be simultaneously marketed in both a prescription drug product and an over-the-counter drug product
FDA Comment Number : EC1121
Submitter : Dr. V. Alan White Date & Time: 10/27/2005 02:10:14
Organization : University of Wisconsin
Category : Academia
Issue Areas/Comments
A. Should FDA initiate a rulemaking to codify its interpretation of section 503(b) of the action regarding when an active ingredient can be simultaneously marketed in both prescription drug product and an OTC drug product?
There is no sufficient reason to distinguish the issue of legalizing OTC Plan B over and above that of OTC Loperamide on the basis of 503(b). Since the same general issues apply in both cases, and OTC Loperamide was approved without raising these issues, it is unclear why these issues should be pertinent to this case except for irrelevant moral/social/theological/political reasons.

B. Is there significant confusion regarding FDA's interpretation of section 503(b) of the act?
If there is confusion about what constitutes a safe and effective OTC drug in some circumstances, a ruling in this particular case (Plan B) is not one that could dispel the confusion in any significant way. Studies show that Plan B is safe and effective for the suggested target OTC population (17+ year-old females), and thus poses no significant risk to that population (except, perhaps, in the estimation of those commentators who import questionable and possibly unconstitutional moral or religious assumptions about danger to embryos, as suggested above, and clearly the FDA may not seriously entertain such concerns in its decision-making).

C. If so, would a rulemaking on this issue help dispet that confusion?
Since there is no reason to believe that the FDA has heretofore interpreted section 503(b) in a confused way, and the case of Plan B introduces no novel issues of safety and efficacy for the target OTC population, then there is no reason to use this case to further refine interpretation of that section. In fact, any ruling on Plan B that further restricts the interpretation of 503(b) may well lead by parity of law to further unintended consequences, such as rescinding the current practice of allowing equivalent-dosage OTC drugs such as Loperamide.

A. If FDA limited sale of an OTC product to a particular subpopulation, e.g., by making the product available to the subpopulation by prescription only, would FDA be able to enforce such a limitation as a matter of law?
2. A./B. Since the FDA has previously ruled on OTC drugs that cannot be vended to minors (e.g., nicotine patches), and entrusted the enforcement of said rulings to local authorities without major incident, it is reasonable to conclude that similar enforcement of the availability of OTC Plan B is
equally feasible.
A. Assuming it is legal to market the same active ingredient in both a prescription and OTC product, may the different products be legally sold in the same package?
3. A./B. Similarity of packaging for prescription and OTC Plan B is purely a practical matter with regard to issues of distribution of the drug, including inventory of the two modes of dispensing the drug and the potential for illegal marketing. Some of these same problems currently are involved in the case of OTC pseudoephedrine, and are being resolved by local and state legislative action to regulate that drug appropriately. Since the FDA has not seen fit to involve itself in this kind of regulation directly, and the case of Plan B does not raise many of the serious issues of public policy that pseudoephedrine does, there is no reason, again except for irrelevant moral/social/theological/political reasons, that the FDA should view this case differently.
It is significant that the commentary on this case is solicited only in terms of the above general questions that cover the specific issue of whether Plan B contraception should be acceptable as an OTC drug. That implies that this case is the first such case considered by the FDA that brings these questions forward. However, for example, the case of Loperamide, which the agency has approved for treatment of diarrhea and is cited in the FDA?s list of dual prescription/OTC-dispensable drugs, completely undercuts this implication. Though the FDA very finely distinguishes the prescription/OTC indication for diarrhea in these two uses as respectively chronic/acute, each occurrence of that condition is in fact an individual medical event, and the prescribed/OTC medication is in fact dispensed in equivalent dosage to prevent a recurrent episode of that condition, whether diagnostically chronic or acute. Logically and medically the use of prescription/OTC Plan B to prevent pregnancy, interpreted merely as an undesirable episodic biological condition, is not different. Should the FDA care to challenge this claim on the basis that potential pregnancy cannot be a medical condition comparable to diarrhea, it should equally consider more carefully the current medical acceptability of procedures such as breast augmentation and rhinoplasty, which are often pursued wholly on the patient?s subjective assessment of somatic undesirability. Clearly both potential pregnancy and potential diarrhea are equivalently undesirable for some patients, and the relevant medications are indicated chiefly for these reasons. Furthermore, if the prevention of possible pregnancy is interpreted by the FDA as something other than an issue of patient-assessed undesirability of a somatic condition, then the FDA would import moral, social, religious, or political assumptions about possible early pregnancy that are of dubious scientific or logical merit to this argument, and might well constitute an unconstitutional basis for any ruling issued by the FDA.