Washington Report

Manufacturers Face New Challenges Battling Global Threats (continued)

Stepping up oversight In the event of a pandemic outbreak, manufacturers and regulators also will be looking to shift production capacity from other therapies to produce vaccine to attack that influenza strain. In anticipation of such a move, FDA's Center for Biologics Evaluation and Research (CBER), which has put vaccine licensing and quality assurance at the top of its priority list, says it will regard a vaccine for a pandemic flu strain from a licensed manufacturer as a product undergoing a routine change and thus require only a supplement application for approval. The agency also may offer accelerated approval to new vaccine sponsors, using antibody levels as surrogate markers for efficacy. Another CBER goal is to be more aware of possible manufacturing problems that could curtail vaccine production, as seen at Chiron's UK facility this past year. The agency now plans to conduct good manufacturing practices inspections of flu vaccine manufacturers annually instead of every two years. This recognizes that complex manufacturing issues may arise when producing new influenza vaccines each year. The hope is that recently inspected manufacturers will be well positioned to quickly develop and produce a vaccine in the event of a pandemic. FDA also has signed information-sharing agreements with British and other regulators from countries where vaccines are produced for US distribution. The aim is to facilitate access to information on problems that arise from manufacturing inspections and to better communicate information on new technologies in manufacturing operations. One sign of progress is that GlaxoSmithKline (GSK) announced in May that it has filed a license application for its Fluarix vaccine, which is produced in Europe. GSK plans to provide 10 million doses of the product for the 2005–2006 flu season once the application is approved. At the same time, Chiron recently acknowledged that it probably will not meet earlier predictions for resuming full production of flu vaccine at its UK facility. The company now expects to produce 18–26 million doses of its Fluvirin vaccine for the 2005–2006 flu season, instead of the 25–30 million doses predicted a few months ago. Chiron attributes the reduction to delays in ramping up production of the third of three prevalent flu vaccine strains. Chiron must retrain more than 100 production workers involved in quality control activities plus integrate hundreds of manufacturing process changes into its newly overhauled production system. FDA was scheduled to inspect the re-engineered facility in July, which will determine the company's ability to begin shipping vaccine in September. Countering bioterrorism Many of the challenges confronting vaccine manufacturers during an influenza pandemic also affect the development of treatments to counter potential bioterrorist attacks. Congress approved Project BioShield legislation in July 2004 after months of debate. That bill provides funding for government purchase of vaccines and therapies for national stockpiles and supports R&D funding for biopharmaceutical companies developing new treatments. It also allows FDA to authorize emergency use of unapproved new products and permits the agency to approve countermeasures on the basis of animal testing. The policy has generated little enthusiasm among pharmaceutical companies, however, primarily because it fails to shield manufacturers from lawsuits related to anti-bioterrorism products. In response, members of Congress who want to spur industry investment in this area have been crafting BioShield II legislation. Senators Orrin Hatch (R-UT), Joe Lieberman (D-CN), and Sam Brownback (R-KS) introduced a bill (S. 975) that aims to assure  the biopharmaceutical industry that the government will be a reliable partner in this high-risk R&D field. Key provisions expand liability protections, boost tax incentives for countermeasure development, and support FDA fast-track approval of such treatments. Manufacturers have called on Congress to remedy the "valley of death"—the gap between funds available for basic research to document scientific proof of principle and actual procurement orders from federal agencies—in financial support for countermeasures. Small biopharmaceutical companies interested in pursuing counter-terrorism projects maintain that they need public funding to move from the lab into commercial production because they cannot raise private capital for such high-risk projects without purchase agreements in hand. New BioShield legislation also aims to be more explicit about offering R&D incentives for dual-use medical products that combat infectious diseases as well as bioterrorist chemicals. Although the proposed bill primarily encourages government funding for medical countermeasures, it recognizes that many new treatments will be appropriate for the civilian market for antibiotics and could be important in combating diseases in the developing nations, where malaria and tuberculosis have become resistant to current drugs. Even though proposals to indemnify pharmaceutical companies have drawn fire, the big fight is over proposals to enhance intellectual property protections. A highly contentious provision would award companies that develop biodefense products "wild card" patents (i.e., up to two years extended exclusivity on another company product). Generic-drug makers as well as pharmacy benefit managers insist that such legislation will delay competition from low-cost generics and raise pharmaceutical costs for public and private healthcare programs. The wild card provision is likely to be dropped as Senate leaders move to combine more acceptable provisions of this and other biodefense measures into a bill with sufficient bipartisan support to gain approval. With six Senate committees evaluating various sections of Bioshield proposals, there will be ample opportunity to debate whether the legislation is a giveaway to pharmaceutical manufacturers or a reasonable approach to spurring new countermeasure development. PT