OTC/Supplement Co-Packaging Policy In The Works At FDA

Any future FDA guidance or regulation on co-packaging OTCs with dietary supplements would have to reflect the agency's resolution of concerns related to duration of use, dual-labeling and multiple claims for such products.

In a Feb. 1 letter to House Government Reform Committee Chairman Dan Burton (R-Ind.), the agency says it is "working to develop a policy that optimizes consumer health but does not unnecessarily restrict access to dietary supplements or OTC drugs."

"In formulating our approach, we are carefully considering the complex issues associated with co-packaging: multiple claims, dual labeling, conditions of use, the risk of overdose and the agency's historical regulation of combination drug products," FDA says. "We may ultimately determine that it is appropriate to issue guidance or regulations on co-packaging."

OTCs "are developed to address some type of acute medical problem that is expected to be of short duration," FDA notes, adding that supplements are intended for daily, longer-term consumption.

"Thus, an apparent conflict can be created when OTC drug labels and dietary supplement labels appear on the same product or package," the agency tells Burton. "Even though the labels may identify the supplement and drug uses in separate places, FDA is concerned about consumer confusion."

In addition, adverse consequences can result when OTC label directions for use are not followed properly, the agency asserts. Labeling approved as part of an NDA or ANDA "may not be consistent with co-packaged labeling," FDA also asserts.

FDA's statement responds to Burton's Jan. 22 letter requesting the agency clarify its enforcement position with regard to OTC/supplement combinations sold as two separate dosage forms in a single package (¹ (Also see "OTC/Supplement Combo Guidance, Sale Urged By Rep. Burton" - Pink Sheet, 28 Jan, 2002.), p. 13). Burton also inquired as to conditions under which an OTC/supplement combo may be sold in a single-dosage form.

While FDA leaves the door open for a possible guidance or reg on co-packaged products, the agency reiterates it has no immediate plans to develop a guidance on single-dosage form OTC/supplement combinations, saying "the law on this question is relatively clear."

When an ingredient is added to an OTC drug, the resulting combination is a drug, even if the ingredient can be separately regulated as a supplement, FDA asserts. The agency made similar arguments in October warning letters to Omni Nutraceuticals and B.F. Ascher for products that combined acetaminophen with one or more supplement ingredients (² (Also see "OTC/Dietary Supplement Combos Cited In FDA Warning Letters" - Pink Sheet, 22 Oct, 2001.), p. 3).

Burton also inquired whether the agency would permit marketing of red yeast rice-containing supplements.

FDA notes the Pharmanex v. Shalala case, which upheld an agency finding that Pharmanex was marketing the drug lovastatin (Merck's Mevacor ) in its Cholestin red yeast rice supplement, does not "prohibit the marketing of all red yeast rice-containing products as dietary supplements."

"The agency has not objected to the marketing of dietary supplements containing red yeast rice if they do not contain lovastatin or other substances that are approved drugs," the letter states.

In the Pharmanex proceedings, FDA acknowledged not all strains of red yeast rice can produce lovastatin but asserted the supplement company designed a manufacturing process intended to maximize and standardize lovastatin levels in Cholestin.

Following a Salt Lake City federal judge's decision in March affirming FDA's determination on Cholestin, the agency issued warning letters advising supplement firms that "red yeast rice products that contain lovastatin are subject to regulation as drugs."

"It should be noted that there are health and safety reasons why products such as Cholestin should continue to be regulated as drugs," the agency contends, referring to the July 2000 vote by a joint panel of FDA's Nonprescription and Endocrinologic & Metabolic Drugs Advisory Committees against switching Mevacor and Bristol-Myers Squibb's Pravachol OTC.

"The concerns raised by the FDA and its consultants about the safe and effective use of statins in the OTC drug arena have not been adequately addressed by pharmaceutical sponsors," the letter notes.

Moreover, the agency says it plans to publish a proposed rule on supplement GMPs "near the middle of FY 2002," to be followed by a 90-day comment period; a final rule could be issued by mid-FY 2003. FDA withdrew the proposed rule from the Office of Management & Budget in December.