CHPA, GSK Advise Against Plan B Rulemaking As 44,000 Comments Pour In

"Sufficient precedent" exists to allow even "narrow distinctions" to differentiate Rx and OTC versions of a dual-status drug and FDA does not need to initiate a rulemaking on the matter, the Consumer Healthcare Products Association maintains.

Precedent demonstrates that different labeling requirements lead "to a drug active ingredient in two or more settings not being the 'same,' even if an outside observer less familiar with the nuances involved would not immediately see the distinctions," CHPA says in an Oct. 31 submission to the agency.

The comments address an advance notice of proposed rulemaking announced by FDA Aug. 26 seeking feedback on the circumstances in which a drug may be simultaneously marketed in both Rx and OTC versions.

The ANPR was announced the same day the agency was "unable" to decide whether Barr Labs' Plan B emergency contraceptive can be sold as an OTC drug for women over the age of 16 and Rx for those 16 and under (¹ (Also see "FDA “Unable” To Decide On Plan B, Seeks Comment On Dual-Status Drugs" - Pink Sheet, 29 Aug, 2005.), p. 4).

At least 44,000 comments have been submitted on the ANPR, according to FDA. The number is expected to increase "dramatically" as the counting continues and late comments are sent in, the agency added.

Under existing law, a drug cannot be marketed both Rx and OTC at the same dose and indication. However, CHPA points out that in the past FDA "has needed to draw fine distinctions among dosage forms, methods of administration or uses to regulate an ingredient differently in different settings."

The group provides several examples of cases in which the difference between a drug's OTC and Rx version is nominal. For example, children's ibuprofen is available OTC in a suspension dose of 100mg/5mL to "temporarily reduce fever." However, the same dose is available only by prescription for "reduction of fever."

The similarity between the two indications illustrates "the fine line between two products distinguished as not being the 'same,'" CHPA states.

The group cites cases of dosage strength variations. Directions for OTC ibuprofen start at 200 mg and go up to 400 mg, while prescription strength doses of the drug start in between the two OTC doses at 300 mg.

Certain OTC drugs carry warnings against use for consumers under a certain age, CHPA adds.

For example, minoxidil ( Rogaine ) labeling warns against use for those under the age of 18, while certain H2 antagonists are indicated for use only in those 12 and over. Rogaine also is indicated in different strengths for men and women. Packaging for the men's version, which is a higher strength product, carries a warning against use by women.

"The commonality in drawing these distinctions, and the very reason for drawing them, balances on whether or not an ingredient is the same thing in two related settings," the trade group states.

In response to the question of whether FDA can limit sale of an OTC product to a particular subpopulation, CHPA says the agency "cannot control the behavior of individual citizens, and that is true whether an active ingredient is OTC, prescription, or both."

"FDA's question as to practicality of enforcing a limitation on prescription versus OTC status misses the mark. Whether one likes to admit it or not, the Food, Drug & Cosmetic Act does not and cannot apply to every setting in which any FDA-regulated product is ultimately used," the group adds.

Comments from GlaxoSmithKline address the question of enforceability by pointing to the firm's experience switching nicotine replacement therapies such as Nicorette over-the-counter. The products are available as OTC drugs only to those over the age of 18.

The firm was required to to demonstrate "that the age limitation was understood at both a label and practical level" prior to approval, GSK notes. Additionally, restricting sale of NRTs in vending machines, creating marketing plans that included training to encourage age verification and a post-market monitoring program were conditions of approval.

"It was the sponsor's responsibility to comply with the restrictions as well as monitor and report on their effectiveness," GSK states. "Monitoring included a program of retailer re-training to correct deficiencies and help ensure ongoing compliance. If the sponsor's efforts proved unsuccessful, a practical, regulatory consequence was a withdrawal of NDA approval."

A rulemaking is not necessary, according to GSK, because there is "no confusion" regarding FDA's interpretation of section 503(b) of the FD&C Act, which discusses when an active ingredient can be marketed Rx and OTC simultaneously.

"If the FDA determines that the data and labeling submitted fulfill the requirement of exemption from section 503(b), then the product is a nonprescription drug," GSK says. "If the FDA determines that the data and labeling do not fulfill exemption from section 503(b), then the product is a prescription drug."

For example, ibuprofen, H2 antagonists and omeprazole are products for which FDA "evaluated the data and determined that for some elements of the drug, section 503(b) exemption does not apply....those elements have remained prescription status."

Conversely, no Rx version of loratadine (Schering-Plough's Claritin ) existed following the product's OTC switch because the drug was considered "exempt in [its] totality" from section 503(b), GSK states.

Many comments submitted on the ANPR asserted the rulemaking was a delay tactic intended to stall approval of the product. A letter urging FDA to abandon the rulemaking was signed by 45 women's health groups and six individuals and calls the rulemaking "an ill-advised and unnecessary attempt to restrict access to Plan B emergency contraception."

According to the letter, "a dual status product will force Plan B behind the counter in most pharmacies, needlessly increasing the cost and burden to pharmacists and to women, and likely, to discourage use."

The individual signatories include Nonprescription Drugs Advisory Committee consultant James Trussell and Carolyn Westhoff, who authored a November 2003 New England Journal of Medicine article about the suitability of emergency contraceptives for OTC use.

Among the groups that signed the letter are the American College of Obstetricians & Gynecologists, the Association of Reproductive Health Professionals, the Guttmacher Institute, NARAL, the National Women's Health Network, the National Women's Law Center, Pharmacy Access Partnership and the Republican Majority for Choice. Many of the groups submitted individual comments in addition to the letter.

Sens. Hillary Clinton (D-N.Y.) and Patty Murray (D-N.Y.) announced that their petition urging an "expeditious" decision on the Plan B application was signed by nearly 10,000 people before being submitted to the ANPR docket.

Murray also had bipartisan language seeking an expeditious rulemaking process added to the conference report on the Agriculture Appropriations bill.

- Bridget Behling