FDA takes steps to automate drug registration; Plan B OTC availability still an area of contention

FDA issued a proposed rule late last month that would allow pharmaceutical manufacturers to register and list products electronically in an effort to minimize the paper-based element of the process, allowing the agency to host a comprehensive national database of medications and to be more flexible in its role of monitoring the safety of medications for sale, according to officials.

"Having drug makers submit drug information electronically will help to keep an accurate, up-to-date inventory of drugs on the market," said Department of Health and Human Services (HHS) Secretary Mike Leavitt. "This will help us maintain more accurate information and make it easier for us to respond to drug emergencies such as recalls and drug shortages."

The rule would establish an electronic Drug Registration and Listing System (DRLS) and also would alter the existing procedures surrounding FDA's assignment of National Drug Codes (NDCs), requiring that NDC codes be displayed on a medication's label.

"FDA has neither finalized guidance documents for listing procedures nor established adequate avenues of communication, according to drug firms," the report stated.

HHS also cited FDA's methods of collecting information from pharmaceutical manufacturers as a primary cause of the inaccuracies. Interviews with FDA personnel revealed that the agency does not actively pursue information for the more than 9,000 products on the market not listed in the directory. The substantial volume of NDCs that have all required documentation from pharmaceutical companies, yet are pending FDA examination, also represents a procedural breakdown by the agency, according to HHS.

One recent step taken by FDA to resolve some of the problems cited by the HHS study included the establishment of the electronic DRLS. FDA also announced the availability of an electronic regulatory submissions gateway for its Center for Drug Evaluation and Research (CDER) to process biological license applications (BLAs), new drug applications (NDAs), drug master files (DMFs), and investigational new drug applications (INDs).

PLAN B APPROVED, ISSUES REMAIN

Despite FDA's making the emergency contraceptive known as Plan B, or the "morning after" pill, available OTC to women aged 18 and older, the fallout may continue. Lawsuits involving FDA's handling of Plan B will likely continue in the courts for the foreseeable future.

Acting FDA Commissioner Andrew von Eschenbach, MD, has been named in a lawsuit filed in 2005 by the Center for Reproductive Rights. The organization's lawsuit, which alleges that political appointees of the agency bypassed scientific evidence in the Plan B approval process, will continue, according to Nancy Northup, president of the Center for Reproductive Rights.

Meanwhile, the Family Research Council, a conservative Judeo-Christian-based advocacy group, also said it is exploring some form of legal action against FDA because of the dual status granted to Plan B as both an OTC and a prescription product. In a statement, the organization said that the agency overstepped its bounds as a rule-making entity and is displaying "a deliberate disregard for women's health and the law."

Representatives from Barr Pharmaceuticals, the parent company of Plan B marketer Duramed, said they plan to ask FDA to reconsider the age limitation set for the contraceptive's OTC availability sometime in the future. Barr had sought OTC availability for Plan B for women aged 16 years and older in an initial sNDA submitted in 2003, but FDA's decision requires that women aged 17 years and younger have a prescription for the contraceptive.

"While we still feel that Plan B should be available to a broader age group without a prescription, we are pleased that the agency has determined that Plan B is safe and effective for use by those 18 years of age and older as an over-the-counter product," said Bruce Downey, Barr's chairman and CEO. "We will also continue our efforts to work with the FDA to reduce the age restriction of the OTC use of Plan B."

In conjunction with the approval, Barr (Duramed) has committed to:

Criticism about FDA's handling of Plan B's OTC availability dogged the agency since it issued a nonapprovable letter in May 2004 for the initial sNDA. A joint meeting of FDA's Nonprescription Drugs Advisory Committee and the Reproductive Health Drugs Advisory Committee in December 2003 had recommended that the sNDA be accepted, but Steven Galson, MD, MPH, then acting director of CDER, wrote in the nonapprovable letter that "adequate data" had not been provided that young adolescent women could use Plan B safely without a prescription.

The debate over OTC availability of Plan B continued through the tenure of former acting FDA Commissioner Lester Crawford, DVM, PhD, whose appointment to the post was blocked in the Senate. Dr Crawford resigned in September 2005, and the approval of Dr von Eschenbach as the FDA commissioner has been delayed in the Senate, with the controversy over Plan B also being an issue.

FDA'S CONSIDERATION OF ADAPTIVE TRIALS GAINS MOMENTUM

FDA's exploration of "adaptive" clinical trials will be the focus at a 2-day workshop that the agency and the Society of Clinical Research Associates (SoCRA) have scheduled for November.

As part of its ongoing Critical Path initiative, FDA is considering allowing adaptive trials of new medications as alternatives to the standard double-blind, placebo-controlled clinical trials. FDA leaders have said they believe the adaptive study designs would allow medications to come to the marketplace more quickly and efficiently. Information gathered at the workshop will be considered as FDA continues to craft guidances that could lead to the use of adaptive clinical trial designs in drug development.

The workshop is scheduled November 15 and November 16 in Indianapolis, Ind.

SOURCES Food and Drug Administration. FDA proposes new rule to automate drug registration and listing [press release]. Washington, DC: US Food and Drug Administration: August 23, 2006. Available at: http:// http://www.fda.gov/bbs/topics/NEWS/2006/NEW01435.html. Accessed August 28, 2006.

Department of Health and Human Services Office of Inspector General. The Food and Drug Administration's national drug code directory. Washington, DC: Department of Health and Human Services; August 2006. Available at: http:// http://www.oig.hhs.gov/oei/reports/oei-06-05-00060.pdf. Accessed August 28, 2006.

Food and Drug Administration. Food and Drug Administration electronic submissions gateway. Federal Register. 2006;71:45057–45058. Available at: http:// http://www.fda.gov/OHRMS/DOCKETS/98fr/E6-12808.pdf. Accessed August 17, 2006.

Food and Drug Administration. FDA approves over-the-counter access for Plan B for women 18 and older; prescription remains required for those 17 and under. Available at: http:// http://www.fda.gov/bbs/topics/NEWS/2006/NEW01436.html. Accessed August 25, 2006.

Barr Pharmaceuticals, Inc. FDA grants OTC status to Barr's Plan B emergency contraceptive. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=60908&p=irol-newsArticle&ID=899120. Accessed August 25, 2006.

Food and Drug Administration. Industry exchange workshop on Food and Drug Administration clinical trial requirements; public workshop. Federal Register. 2006; 71:46231. Available at: http:// http://www.fda.gov/OHRMS/DOCKETS/98fr/E6-13114.pdf. Accessed August 17, 2006.