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CDER 2007 Update
Critical Path Initiative
Our role in the Agency’s Critical Path Initiative is to stimulate and facilitate a national effort to modernize the scientific processes through which a potential human drug or therapeutic biologic is transformed from a discovery or proof of concept into a medical product.
Despite recent innovations, many serious and life-threatening diseases still lack effective treatments. In our view, the scientific tools needed to develop medical products have not kept pace with the rapid advances in product discovery. As a result, fewer of the sound ideas spawned in medical laboratories are producing safe and effective treatments.
Because of our unique vantage point, we can work with companies, patient groups, academic researchers and other stakeholders to coordinate, develop and help disseminate solutions to scientific hurdles that are impairing the efficiency of medical product development.
Critical Path progress in 2007
Developing Critical Path Opportunities Document for Generic Drugs
In May of 2007, we released Critical Path Opportunities for Generic Drugs. This document identifies key opportunities to improve standards and methods to evaluate bioequivalence for locally acting drugs. It also helps increase understanding of the manufacturing controls needed to produce complex pharmaceutical formulations with consistently high quality.
Improving warfarin dosing
Because there is wide variation in patient response to this blood thinning drug that may lead to severe consequences of under- or over-dosing, we are involved in two projects.
- We relabeled warfarin in August 2007 to recommend that prescribers consider testing for genetic variants of enzymes that alter the body’s ability to metabolize or respond to warfarin. In parallel, we approved the first warfarin sensitivity test, which detects these genetic variants.
- We are developing dosing models that may lead to safer initial dosing for warfarin.
Examining the genetic basis of adverse events
In 2007, the Serious Adverse Events Consortium, a nonprofit partnership among several leading pharmaceutical companies, the FDA and academic institutions, launched initial research programs designed to identify genetic markers that may help predict which individuals are at risk for serious drug-related adverse events. Two areas of initial focus will address drug-related liver toxicity and a rare but serious drug-related skin condition called Stevens-Johnson Syndrome.
Advancing biomarker qualification
The Predictive Safety Testing Consortium is a collaboration of the CPath Institute, 17 pharmaceutical industry partners and FDA. One goal of this consortium is to validate the predictive value of new preclinical biomarkers of toxicity and qualify their use in specific regulatory contexts. In 2007, a set of biomarkers of nephrotoxicity were submitted to FDA for qualification through a pilot process. They were evaluated at the agency to understand evidentiary standards and metrics associated with the qualification of novel biomarkers.
In addition, we are collaborating with a public-private research partnership tasked with discovering, developing and qualifying new biological markers to support new drug development, preventive medicine and medical diagnostics. The Biomarker Consortium includes representation from the Foundation for the National Institutes of Health, FDA, Centers for Medicaid and Medicare Services, NIH and the pharmaceutical, biotechnology, diagnostics and medical device industries.
Identifying indicators of cardiac toxicity
FDA and Mortara Instruments, a manufacturer of electrocardiographic equipment, are working to create a repository for digital ECGs and a suite of tools to enable their efficient review. FDA invited sponsors to upload digital ECGs directly to the repository, where they are made immediately available to the reviewers. Currently, the warehouse contains more than one million ECGs. In addition to supporting our mission to evaluate the effects of drugs on the heart, the repository is an important research resource for future studies to identify improved predictors of cardiovascular risks related to use of medications.
In a second phase of this effort, FDA and an academic research center founded the Cardiovascular Safety and Research Consortium to coordinate and support research projects involving the warehouse.
Developing guidances on advanced clinical trial design
We began developing guidance to facilitate innovations in study design and analysis related to end of Phase 2a meetings, adaptive trial designs and non-inferiority trial designs.
Developing tools for product characterization and manufacturing understanding
The industrialization challenges posed by the demands of physical product design, characterization, scale-up and manufacturing are often little understood outside of FDA and the pharmaceutical manufacturing communities. Many product failures during development are ultimately attributable to problems relating to the transition from laboratory prototype to industrial product. To improve predictability in this area, it is crucial that FDA has both improved technical standards—tests, procedures and reference materials—and improved methods for design, characterization and product manufacture. A number of studies in these areas were initiated to respond to critical manufacturing science questions.
Pharmacogenomics, personalized medicine
The Critical Path recognizes the importance of pharmacogenomics and encourages its use in drug development. Pharmacogenomics allows health-care providers to identify differences in people’s drug-risk-response profiles and predict the best possible treatment options for them.
In 2007, FDA continued laying the groundwork for incorporating pharmacogenomics in our regulatory reviews and into clinical practice. Our activities included:
- Issuing a Draft Companion Guidance to the Pharmacogenomics Guidance on Recommendation for the Generation and Submission of Genomic Data.
- Publishing Guiding Principles for Joint FDA EMEA Voluntary Genomic Data Submission Briefing Meetings.
- Posting on our genomics Web site Valid Genomic Biomarkers in Drug Labels.
- Co-authoring Guidelines and Recommendations for Laboratory Analysis and Application of Pharmacogenetics to Clinical Practice.
- Initiation of Part 2 of the Microarray Quality Control initiative to identify sources of variability in genomic classifiers derived from microarray gene expression and genome-wide association study data.
- Receiving 12 additional voluntary genomic data submissions from industry.
More information is at http://www.fda.gov/cder/genomics.
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Date created: July 31, 2008 |
