Doom and gloom have settled on the pharmaceutical industry. Pfizer recently announced it is closing manufacturing sites and research centers and cutting 10,000 jobs because of declining profits, stagnant sales, and a dry pipeline. Lower revenues and profits at Bristol-Myers Squibb have fueled talk of a merger or takeover. AstraZeneca is eliminating 3000 jobs and restructuring manufacturing and research and development (R&D) operations to offset losses from looming generic competition. At the same time, Democratic leaders in Congress are increasing the rhetoric about too-high drug prices, drug safety problems, excessive drug advertising, and the need to expand access to more generic products, particularly for biotechnology therapies.
These developments have raised hurdles for bringing new medicines to market. A December 2006 report from the Government Accountability Office describes the declining productivity of the pharmaceutical research enterprise. Industry increased R&D spending from $16 billion in 1993 to $40 billion in 2004, and estimates put the number at $60 billion last year. Yet, the number of new drugs being tested by manufacturers has declined, resulting in fewer important new molecular entities (NMEs) coming to market. The US Food and Drug Administration approved only 22 NMEs in 2006, including new biologics. The total has been flat in the past few years, but is "way off the historic highs of the mid-1990s," commented Steven Galson, director of the Center for Drug Evaluation and Research (CDER) at the January Well Characterized Biotechnology Pharmaceutical meeting in Washington, DC.
What is most distressing is that drug pipelines have dried up at a time of rapid biomedical discovery. Breakthroughs in genomic and molecular research and in bioinformatics were supposed to usher in a period of unprecedented progress in drug development. FDA has been working hard to harmonize regulations, streamline the approval process, and provide more guidance for industry. And, manufacturers have moved to modernize quality-testing and production systems, to streamline research processes, and to reduce wasteful production methods. While these efforts have drawn applause, they have been offset by a focus on drug safety that has prompted both regulators and manufacturers to expand the scope of clinical trials and new-product testing. Some important new drugs and vaccines did come to market last year, but the average cost of developing a new drug now hovers at the $1-billion mark.
Spotlight on safety
In an effort to deal with these issues, FDA Commissioner Andrew von Eschenbach unveiled a plan that addresses many of the drug-safety issues raised in last year's scathing Institute of Medicine (IOM) publication demanding major changes to better balance FDA's assessment of risks and benefits. The FDA report on The Future of Drug Safety outlines proposals to develop safety "report cards" on important new drugs, to post an online drug-safety newsletter, and to expand its access to health-system databanks to detect safety signals more quickly. Galson also promised a "true culture change" to address the tension between pre-and postapproval staffs.
The unstated goal is to head off legislation requiring more significant organizational changes and added mandates for manufacturers and regulators alike. Senators Charles Grassley (R-IA) and Chris Dodd (D-CT) recently reintroduced legislation to establish a separate drug-safety office at FDA. And, Senators Edward Kennedy (D-MA) and Mike Enzi (R-WY) proposed their drug-safety bill that requires risk-mitigation strategies for all new drugs and mandates clinical-trial registration.
The FDA announcement covered activities that the agency can implement on its own, provided it receives added resources from user fees and appropriated funds. If FDA and industry want Congress to reauthorize the Prescription Drug User Fee Act (PDUFA) by fall, however, they probably will have to accept some new requirements for ensuring drug safety.
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