Such activities fit the framework of FDA's Critical Path report, issued in March 2004, which describes the high cost and disappointing results of the current biomedical development process. New drug approvals have flattened out in recent years, particularly for new molecular entities. This trend is even more troubling at a time when the public and private sectors combined are spending more than $100 billion on biomedical research.
Now, a number of occurrences may be creating a "perfect storm" for public-private collaboration on biomedical R&D. First, recent scientific discoveries provide unprecedented opportunities to use biomarkers, computer models, genomics, and other new technologies to develop more informative research methods. At the same time, the pharmaceutical industry faces a crisis. With pipelines drying up, revenues falling, and drug safety issues generating public hostility, manufacturers are under pressure to find more efficient ways to develop and produce safe and effective medical products. Although companies are concerned about protecting intellectual property, they realize that it is too costly to develop biomarkers and genomic tests on their own and that more cooperative efforts make sense.Even the heightened focus on drug safety, which has pushed innovation out of the limelight for the past two years, may bolster efforts to reduce toxic side effects and limit patient exposure to inappropriate therapies. Tests able to identify patients who respond more positively to a product can lead to safer medicines; more targeted clinical studies can help avoid exposing non-responders to an experimental product.
Manufacturers are also recognizing the importance of improving the industrial model for drug manufacturing, notes FDA deputy commissioner Janet Woodcock, who heads up FDA Critical Path efforts. Talk of more industry collaboration "would have fallen on deaf ears" ten years ago, she acknowledges, because manufacturers did not realize until recently how much outdated manufacturing processes were costing them.
Industry now recognizes the need to work with FDA in addressing these problems. FDA's experience with complex biological products gives it "unique insight into the gaps in scientific knowledge and tools needed for more efficient product review," comments Kathryn Carbone, associate director of research at the Center for Biologics Evaluation and Review (CBER). Too many products fail in development, she explained at the September PDA conference, because there is no assay for adequate product characterization or the manufacturer cannot scale up sufficiently.
Because FDA lacks resources to support research on these issues, the agency seeks to spur examination of Critical Path opportunities through joint projects with industry and research organizations, either individually or through group collaborations. In response to increased FDA urging, companies now are "stepping up to the plate," Woodcock says. For example, Novartis announced in September that it is working on three research collaborations with FDA. One examines how to apply process analytical technology (PAT) to new methods for assuring quality manufacturing. FDA and Novartis are negotiating a Cooperative Research and Development Agreement (CRADA) that calls for joint evaluation of research findings and will give FDA experience in implementing and validating proposals under its PAT guidance. Another project involves the development of preclinical biomarkers to evaluate renal toxicity. A third collaboration will assess hurdles related to developing a diagnostic kit utilizing a drug product. Novartis plans to conduct an observational study involving several compounds in its pipeline where a genomic diagnostic may prove to be of value.
Biomarkers and diagnostics are key in the Critical Path program and are particularly important to ensure the safety and efficacy of complex biologics, notes Carbone.
Most manufacturers use their own biomarker development programs to predict animal toxicity and select drugs for development, but FDA seeks collaborative arrangements to validate biomarkers that can be used industry-wide.