November 5, 2004 CDER Critical Path Opportunities 1 CDER Critical Path Opportunities Douglas C. Throckmorton, M.D. November 5, 2004
Dec 31, 2015
November 5, 2004 CDER Critical Path Opportunities 1
CDER Critical PathOpportunities
Douglas C. Throckmorton, M.D.November 5, 2004
November 5, 2004 CDER Critical Path Opportunities 2
OutlineCritical Path in CDER
Identified Critical Path opportunities in CDER
Examples of proposed opportunities
November 5, 2004 CDER Critical Path Opportunities 3
CDER Goals for 2005
HHS Strategic
Goals
CDERInitiatives
FDAStrategic
Goals
Achieve Excellence
in Management Practices
Increase Science
Enterprise Research
Improve Quality of
Health Care Services
Enhance health care system to
respond to bioterrorism
and other public health challenges
StrongFDA
RiskManagement/
Innovation
PatientSafety
BetterInformed
Consumers
ProtectingAgainst
Terrorism
QualitySystem
StrategicObjectives
CGMPsCritical
Path
StructuredProductLabeling
CounterTerrorism
Efforts
Follow-on
Biologics
November 5, 2004 CDER Critical Path Opportunities 4
Identified Critical Path Opportunities in CDER
November 5, 2004 CDER Critical Path Opportunities 5
CDER Critical Path OpportunitiesCDER received around 60 written proposals with variable levels of detail. Two types of proposals:(1) Issues Addressable with FDA Data & Resources
Goals: Data review and analysis to facilitate guidance and standards-setting
(2) Longer-Term Projects Related to new, complex issues in drug developmentRely more on external sources of expertise and dataGoals: Identify sources of expertise, work towards guidance and standards-setting
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Proposals from All 3 Key Dimensions on 'Critical Path' of Development
November 5, 2004 CDER Critical Path Opportunities 7
CDER Critical Path OpportunitiesData Review and Analysis to Facilitate Guidance and Standards-Setting
November 5, 2004 CDER Critical Path Opportunities 8
Assessing SafetyDevelopment of Safety Biomarkers/Surrogates
Database on pre-clinical and clinical evaluation of arrhythmic risk; Search for pre-clinical markers to reduce/eliminate need for clinical studies
Data warehouse of electronic electro-cardiograms (ECGs) accessible by Industry and FDA
Databases to facilitate rodent models of carcinogenicity, genotoxicity, and reproductive/ developmental toxicology
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Assessing Safety (continued)
Develop database of existing Controlled Substances Staff recommendations on product abuse liability
Develop a centralized approach to monitor outcomes of exposure to drug products during pregnancy
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Demonstrating Medical Utility(Proof of Efficacy)
Development of Efficacy Biomarkers/Surrogates Development and evaluation of new rapid diagnostic tests for infectious diseaseDevelopment of vascular imaging techniques in development of drugs for neuro-cognitive disorders, cardiovascular disease, and depression Assessment of imaging techniques (e.g., MRI) in development of drugs for rheumatoid arthritis and osteoarthritis Assessment of novel biomarkers and clinical surrogates for Systemic Lupus Erythematosus, Inflammatory Bowel Disease, and Sepsis. Evaluate degree of correlation of Hepatitis C viral load in blood with histologic findings of the liver in Hepatitis C disease to assess potential utility of Hepatitis C as a surrogate marker in clinical trials.
November 5, 2004 CDER Critical Path Opportunities 11
Demonstrating Medical Utility (cont) (Proof of Efficacy)
Develop data driven model for prediction of bioavailability/ bioequivalence from data on drug dissolution
Facilitate or conduct investigations to better define the benefit and risk components and to improve trial designs of clinical investigations for menopausal symptom therapy
Develop library of pharmacogenomic variation to enrich clinical studies of antidepressant drugs in the pediatric population
November 5, 2004 CDER Critical Path Opportunities 12
IndustrializationDevelop methods to assess comparability of biologic products, including following manufacturing changes (e.g., changes in cell culture conditions):
Use of Gene arrays to assess impact of changes
‘Follow-on Biologics’
November 5, 2004 CDER Critical Path Opportunities 13
CDER Critical Path Opportunities
Guidance and Standards-Setting in New Areas of Drug Development
November 5, 2004 CDER Critical Path Opportunities 14
New Areas of Drug Development
Develop Statistical guidance applicable to multiple therapeutic areas
Non-inferiority testing, Bayesian methods, Missing data, and Adaptive trial designs
Create a new framework for understanding product manufacturing and assessment within the ‘Context of Complexity of Products and Manufacturing Processes’
Develop instrument calibration standards
Evaluate statistical methods to supplement pre-clinical safety data: bootstrap methodologies and re-sampling
November 5, 2004 CDER Critical Path Opportunities 15
New Areas of Drug Development (continued)
Develop guidance pertaining to patient-reported outcomes (PRO) endpoints in phase III studies
Develop adequate analytical methods to fully characterize novel dosage forms
e.g., liposomes, patches, topicals, inhalants
Determine bioequivalence of locally-acting drug products
November 5, 2004 CDER Critical Path Opportunities 16
CDER Critical PathNear-Term Opportunities
Examples…
November 5, 2004 CDER Critical Path Opportunities 17
ECG Research Database and Toolkit (Assessing Safety)
Needs: To improve FDA’s ability to evaluate drugs for cardiac safety To enhance efficiency of ECG data collection and submission
Goals:Develop standard for electronic exchange of ECGsDevelop ECG research database and web-based toolSupport development of clear standards, guidance, and tools to test and guide development of product safety
November 5, 2004 CDER Critical Path Opportunities 18
ECG Research Database and Toolkit (continued)
Contributes to:A more efficient assessment of cardiac risk
Increases ability of sponsors to predict success and failure in earlier stages of product development
identification of novel ECG markers to predict clinical toxicity
Lower costs for new product developmentmore efficient ECG data collection and submission
Increases ability of sponsors to produce high quality products and applications
November 5, 2004 CDER Critical Path Opportunities 19
ECG Research Database and Toolkit (continued)
Target timeline:Completion of database tool and database: <12 months
November 5, 2004 CDER Critical Path Opportunities 20
Pediatrics Trial Database Development and Analysis (Demonstrating Medical Utility)
Needs: To evaluate the assumptions used to design pediatric drug studies
Goals:Develop analytic database of pediatric trials conducted since initiation of pediatric exclusivity and Best Pharmaceuticals for Children Act (BPCA)Assess appropriateness for extrapolation of safety and efficacy data from adults to childrenDetermine best practices for novel trial designsDevelop guidance for future pediatric trials based on this review
November 5, 2004 CDER Critical Path Opportunities 21
Pediatrics Trial Database(continued)
Contributes to:Increased interest in and feasibility of product development for unmet public health needs
Increased sponsor ability to produce high quality products and applications
Target Timeline:Develop analytical database (12-24 months)
Determine best practices (24-36 months)
Discuss and publish guidance on best practices (36-48 months)
November 5, 2004 CDER Critical Path Opportunities 22
Instrument Calibration Guidance (Industrialization)
Needs: Expand concept of product quality by designFacilitate more efficiently produced and consistently formulated drug productsProactively support the use of new instrumental methods for drug manufacture as described in CGMP initiative
November 5, 2004 CDER Critical Path Opportunities 23
Instrument Calibration Guidance (continued)
Goals:Develop methods for defining and validating calibration standards
Develop instrument calibration standards
Publish guidance describing standards
Provide training to CDER staff on new instrumentation and standards
November 5, 2004 CDER Critical Path Opportunities 24
Instrument Calibration Guidance(continued)
Contributes to:Increase FDA Utilization of Quality by Design and Risk-Based Assessment in Product Quality Review by promoting the use of novel analytic methods to assess manufacturing quality and consistency
Reduce Likelihood of Production of Low Quality Products by promoting consistent use of new technology in ensuring quality of products
Maintain Low Risk of Defective and Contaminated Products Reaching Market
November 5, 2004 CDER Critical Path Opportunities 25
Instrument Calibration Guidance(continued)
Target Timeline:Research and identify candidate instrument reference standards (12 months)
Conduct studies on instrumentation (12-24 months)
Discuss and publish guidance (36 months)
November 5, 2004 CDER Critical Path Opportunities 26
CDER Critical Path SummaryPresent state of health product development is not sustainable
FDA must lead effort to question any assumptions that limit or slow new product development:
Are they justified?
Are there more efficient alternatives?
If so, why are the alternatives not being utilized?
November 5, 2004 CDER Critical Path Opportunities 27
CDER Critical Path Summary
Critical Path is integrated into the CDER goals
CDER has identified a preliminary list of Critical Path opportunities that will have substantial impact if funded