FDA revises drug labels to clarify information for health professionals

FDA began 2006 by unveiling a long-anticipated final rule that significantly overhauls approved labeling for drugs and biologics. This new rule has been in the works for years, delayed by manufacturer concerns that the revisions will expose companies to more liability suits. Although the new labeling's basic framework came as no surprise, compliance will require significant investments by manufacturers to meet the new design and content requirements, which will double the length of many package inserts (PIs).

HIGHLIGHTING SAFETY

The most significant change in the PI requirements is the new "Highlights" section. This presents a summary of a product's most important prescribing information, including boxed warnings (if applicable), approved uses, recommended dosages, warnings, and adverse events. Links to the rule and guidances are available at http:// http://www.fda.gov/cder/regulatory/physlabel/default.htm.

At the end of the new PI will be a "Patient Counseling Information" section that reiterates the most important uses and limitations of the medication to help physicians discuss risks with patients. Any FDA-approved patient information or MedGuide has to accompany the full label or be added on at the end.

FDA is phasing in compliance with these requirements, starting with new drugs and eventually covering all products approved within the last 5 years or those making significant label changes. Although older drugs are not required to adopt the new format, FDA hopes that many will do so, and legal concerns may encourage updating.

PRE-EMPTING STATES

While the Highlights section will be useful to prescribers and patients, pharmaceutical companies voiced concerns that this structure could expose them to liability suits from individuals who suffer adverse events that are not highlighted, but "hidden" in the full prescribing information. Some manufacturers also said they are concerned that a dual-label system will generate charges that products with old labels fail to adequately warn of safety issues.

To address these concerns, FDA added to the preamble of the final rule (published in the January 24, 2006, Federal Register) a discussion of how FDA-approved drug labeling-both old and new formats-pre-empts conflicting or contrasting state consumer protection laws that add warnings and other information to drug labels. FDA stated that it has primary responsibility for determining the content and scope of drug labeling and that states may dilute important safety information by requiring extraneous or unscientific material.

Some patient advocates and plaintiffs' lawyers criticized these statements, charging that FDA had overstepped its authority in asserting such broad pre-emptive powers. Some members of Congress have called for legislation to remove the controversial pre-emption language. Although legislative change is not likely, the situation puts pressure on manufacturers to keep label information up-to-date, as any omission in safety information submitted to FDA could expose a company to charges of hiding important prescribing information.

NEW OPPORTUNITIES

Establishing the format and content of professional labeling sets the stage for FDA to move forward with other initiatives. Agency officials have been discussing the need to simplify the "Brief Summary" that accompanies print advertising, and the new Highlights section at the beginning of the PI provides a model for developing much briefer and more consumer-friendly prescribing information.

The final rule also supports the expansion of FDA's e-labeling program, designed to transmit approved labeling to the DailyMed online health information clearinghouse operated by the National Library of Medicine. Electronic tags on label data will allow physicians to search for information by indication and by product, and eventually this data will populate a section of the FDA's website (facts@fda) offering comprehensive information on all FDA-regulated products. The e-labeling system makes it easier for manufacturers to revise labeling as new information emerges on a drug: sections of approved labeling can be updated without changing the entire document. E-labeling also will support a paperless labeling initiative that manufacturers have been developing for the past decade, as well as broader e-prescribing activities focused on reducing prescribing errors and inappropriate drug use.

REIMBURSEMENT FOR TRIALS

While CMS officials praised the CED policy as a way to extend Medicare coverage to additional services and products, some patients and pharmaceutical manufacturers expressed concerns that the agency could deny reimbursement of innovative treatments unless sponsors support post-approval studies. CMS senior advisor Peter Bach, MD, explained that the policy will apply only to limited situations, such as a new drug that appears to be "incredibly promising" for an extended population.

In response to initial criticism, Dr Bach said that the CMS will issue a revised draft guidance describing a narrower focus for the CED program. Meanwhile, only a few of the NCI trials have begun to enroll patients, making it difficult for Medicare beneficiaries to participate.

INFLUENCING DRUG APPROVALS

Increased information about appropriate drug use aims to help CMS steer providers and health plans to more cost-effective products and pharmaceuticals. These developments will shape coverage decisions by Medicare prescription drug plans (PDPs) and also may have a significant impact on the development and marketing of new drugs and medical products. As public and private payors increasingly seek information about product effectiveness, pharmaceutical and medical device companies are designing clinical trials to support product coverage decisions. Researchers are consulting more often with CMS and other payors early in the development process to avoid surprise information requests later.

These developments raise questions about how coverage decisions by Medicare and health plans will affect the FDA approval system. As CMS limits reimbursement to products with documented clinical advantages or cost benefits over available medications, FDA market approval may appear more "provisional" in the future. There has been talk of CMS playing a more specific role in FDA regulatory activities. One aim is to help sponsors generate research information that could support Medicare coverage decisions.

Two years ago, FDA and CMS conducted a coordinated review of new drug-eluting stents to speed availability of the product to patients. FDA is considering a pilot test of a more formal, parallel review process for medical devices to be used in rare instances for products offering important clinical benefits, but this approach could extend to drugs in the future.

Less controversial are plans for more FDA-CMS collaboration in post-marketing surveillance. Once a drug comes to market, both FDA and CMS will be involved in efforts to evaluate safety and appropriate use. One early initiative is to coordinate policies for establishing patient registries to answer outstanding questions not resolved in clinical trials.

Closer collaboration between CMS and FDA has the potential to build tension between the different missions of the 2 agencies: FDA's task is to promote public access to safe and effective drugs and medical products, while CMS aims to ensure that it pays appropriately for reasonable and necessary treatments.

Ms Wechsler is a Washington-based reporter specializing in federal and state healthcare issues.