New knowledge of genetic biomarkers for disease is spurring development of pharmacogenomic (PG)-based drugs and biological
products and raising new challenges for FDA and manufacturers. Genomics information promises to spur discovery of more individualized
treatment regimens by identifying patients most likely to respond to certain medicines — as well as individuals more susceptible
to adverse events.
Manufacturers can use this information to select high-response individuals for clinical trials, an approach that promises
to reduce clinical research costs, accelerate drug development, and promote appropriate and safe use of complex new treatments.
FDA is eager to encourage more industry use of pharmacogenomic data in drug development in order to achieve these benefits.
Last November (2003), the agency issued a draft guidance designed to prompt manufacturers to voluntarily share with FDA internally
developed PG information that can help the agency and the research community keep abreast of genomics developments and establish
new genetic biomarkers. Most companies, though, are reluctant to submit this data to FDA for fear of raising questions that
could delay product approval or restrict labels.
The guidance, which FDA plans to finalize by next year, recommends that sponsors send in voluntary genomic data submissions
(VGDSs) for analysis by a special FDA review group, separate from the established new drug review process. Some companies
already are sharing PG data with FDA, and the agency is clarifying procedures to encourage other firms to do the same.
Manufacturers may be reluctant to share PG data with FDA, however, if they fear that information on new biomarkers might prompt
the agency to require a diagnostic test in order to bring a new treatment to market. The discovery of more genomic markers
that can identify high- and low-responding patients is prompting regulators to seek diagnostic tests to determine which patients
should be treated with a therapy, the appropriate dose, and the risks associated with treatment.
FDA acting Deputy Director Janet Woodcock is spearheading an effort to issue guidance clarifying how FDA will regulate diagnostics
and pharmacologic interventions that traditionally are considered separate entities for regulatory, reimbursement, and clinical
practice purposes. Different FDA centers regulate medical devices, drugs, and biologics, but the growing number of medical
products that involve multiple components prompted the establishment of a central Office of Combination Products (OCP) two
years ago. While some FDA staffers would like to require the use of a diagnostic for any therapy with an identifiable biomarker,
manufacturers seek a more flexible approach that recognizes significant differences in the processes and procedures for developing
diagnostics as compared to drugs and biologics.
PATHWAYS FOR PARTNERS
Manufacturers and FDA officials discussed these issues and options for policy development at a July workshop on "Co-Development
of Drug, Biological and Device Products" co-sponsored by FDA and the Drug Information Association (DIA). While Woodcock believes
that codevelopment provides a real opportunity to improve medical outcomes, the overriding concern for manufacturers is that
FDA might require a diagnostic test in order to gain approval of a new therapy.
Industry representatives maintained that PG therapies and diagnostics should not be regarded as combination products, noting
that such products usually are developed and brought to market separately. Lois Hinman, director of regulatory affairs at
Hoffman-LaRoche referred to linked therapies as "partner products" instead of combinations. "Flexibility is key," Hinman said;
she is looking for FDA to develop guidance that describes a range of codevelopment scenarios.
Manufacturers also insist that any codevelopment arrangements involving drug and diagnostic firms must be voluntary. Industry
wants FDA to present substantial evidence of medical need and of a diagnostic's ability to improve safety or efficacy in a
target population before requesting diagnostic codevelopment. And both FDA and manufacturers desire a clear process for undertaking
such codevelopment, including a schedule of critical meetings and clarification of which FDA offices will be involved and
how they will coordinate their work.