A tiger with teeth. These developments set the stage for a tougher regulatory stance when David Kessler became FDA commissioner in late 1990.
Determined to erase FDA's "paper tiger" image, he beefed up agency compliance staffs and launched a campaign to halt industry
promotion of off-label drug uses through educational programs and the fast-growing Internet.
The enforcement crackdown also extended to vitamins and dietary supplements: Congress approved legislation giving FDA authority
to halt unsubstantiated health claims and to establish GMPs for these products. Here again, agreement on an implementation
plan has been delayed by debate and legal battles.
Commissioner Kessler also launched a campaign in 1994 to extend FDA regulation to tobacco products. The effort was halted
by a 2000 Supreme Court ruling that FDA lacked authority in this area, but the initial attack led to hefty industry payments
to state governments and curbs on tobacco marketing and sales.
Industry antes up
All these new programs greatly increased FDA's responsibilities and made it difficult for the staff to keep up with assignments,
including timely review of NDAs and inspection of drug manufacturing facilities. The delays generated support for the Prescription
Drug User Fee Act of 1992, which required pharmaceutical companies to pay fees to support a more efficient application review
process, among other services. The program's five-year "sunset" provision has required reauthorization of user fees in 1997
and 2002. It is up for renewal again in 2007, and negotiations between FDA, industry, and interest groups are well underway.
A global initiative to accelerate drug development and streamline registration also was launched at this time. In 1992, FDA
joined with regulators and manufacturers from Europe and Japan to establish the International Conference on Harmonization.
The program has produced common standards in all three regions for testing and registering new drugs and biologics, with a
focus on assessing drug quality through stability testing, and for conducting preclinical animal tests and clinical studies.
In reauthorizing the user-fee program in 1997, Congress enacted the FDA Modernization Act, which revised many agency practices.
Its numerous provisions clarify and streamline clinical research and application-review policies and revise marketing rules
and postmarketing surveillance requirements. A key section of the bill provides six months of added exclusivity on a drug
if the manufacturer conducts additional studies to add pediatric information to the product's label.
New challenges for the new century
Efforts to support biomedical innovation and to streamline FDA regulatory processes have become even more visible in recent
years. In the wake of the Sept. 11, 2001 terrorist attacks, Congress approved the Project BioShield Act of 2004, which encourages
the development of drugs and vaccines to prevent or treat bioterrorist threats.
In 2002, FDA launched a major initiative to update the regulation of GMPs for drugs and biologics. It advocates a more risk-based
regulatory approach for inspecting manufacturing facilities and ensuring product quality. The GMP modernization plan also
encourages manufacturers to adopt more innovative approaches to monitoring production processes and includes efforts to revise
policies governing electronic data submissions to the agency.
Critical initiatives. Another major initiative champions new approaches and tools likely to encourage pharmaceutical innovation. FDA's Critical
Path report of March 2004 urges more agency collaboration with industry to spur research and development, including innovation
in drug manufacturing and quality assessment. A subsequent Opportunities List describes a wide range of research and regulatory
initiatives with the potential to spur biomedical discovery.
Drug safety also has emerged as a major public concern. In 2004, evidence linking Cox-2 inhibitor painkillers to cardiovascular
events spurred major protests that lax FDA policies were exposing patients to unsafe drugs. Manufacturers pulled several products
off the market, and FDA launched several initiatives to make drug safety oversight more open and effective. This movement
included establishing a Drug Safety Board in 2005 and reorganizing drug safety offices. More changes are still to come.
An important milestone this year was the publication of a long-debated final rule revising the content and format of drug
labeling. The new format includes a highlights section at the beginning of the label that aims to make it easier for healthcare
professionals to access, read, and use information in approved labeling.