By Riëtte van Laack –
On February 11, FDA issued its response to a December 2009 citizen petition (Docket No. FDA-2009-P-0587-0013) requesting that FDA issue an order confirming that certain prescription prenatal vitamins containing 1-4 mg folic acid, either alone or in combination with other vitamins and mineral, are generally recognized as safe and effective (“GRAS/E”) prescription drug products and therefore may be marketed without an approved new drug application (“NDA”) or abbreviated NDA (“ANDA”) (see our previous post here).
As explained in FDA’s response, in a 2004 report to Congress, FDA had determined that prescription drug products have certain characteristics make them unsuitable for marketing under a monograph system similar to the system used for certain over-the-counter drug products. In a footnote, the Agency clarifies why the one exception to this rule, the Rx monograph for prescription radioactive drugs for basic research, 21 C.F.R. § 361.1, is not an applicable precedent.
Citing case law supporting that the term “new drug” refers to the entire drug product, i.e., the active ingredient (s) and excipients, the Agency concludes that to determine GRAS/E status for the prescription prenatal vitamin products, each product must be shown safe and effective in adequate and well-controlled clinical studies. GRAS/E status of one drug product cannot be used to support GRAS/E status of another drug product with the same active ingredient. Moreover, GRAS/E status must be supported by at least the same quality and quantity of scientific evidence as is required for approval of an NDA.
The impact of this denial likely will be small. FDA on various occasions and in different contexts has affirmed that folic-acid containing prenatal vitamins are safe and effective. Although the Agency has confirmed that prenatal vitamins marketed as prescription drugs are not exempt from its Compliance Policy Guide (see our previous post here), the Agency has not taken action against the marketing of these products as unapproved prescription drugs.
FDA’s denial leaves the regulation of prenatal vitamins essentially where it has been for over 20 years – is a state of confusion. The products are safe and effective, and are essential from a public health standpoint, but should they be marketed as unapproved drugs, medical foods, or dietary supplements? There are examples of prenatal products on the market in each category, and an argument can be made is support of all three. It is likely that this confusion will remain, as this appears to be a very low priority issue for FDA, given the lack of safety concerns and the need for prenatal vitamins. Therefore, with some restrictions as to ingredients and claims, companies marketing these products should be able to continue to choose the category that best fits their marketing strategy.