FDA BRIEF: Week of Nov. 21, 2016
PURPOSE: Assist in clinical development of drugs, biologics, for the treatment of patients who have bacillus Calmette-Guerin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC
DEVELOPMENT PROGRAM
- Early Phase
- Late Phase
GENERAL CONSIDERATIONS
- Trial Population and Entry Criteria
- Randomization, Stratification, and Blinding
- Dose Selection
- Single-Arm vs. Randomized, Controlled Trial Design
- Efficacy Endpoints
- Trial Procedures and Timing of Assessments
- Endpoint Adjudication
- Statistical Considerations
- Accelerated Approval (Subpart H and Subpart E) Considerations
- Risk-Benefit Considerations
OTHER CONSIDERATONS
- Risk Management Considerations
- Nonclinical Safety Considerations
PURPOSE: Current regulatory perspective on topics in pediatric drug development
ETHICAL CONSIDERATIONS & SCIENTIFIC APPROACH
AGE CLASSIFICATION
- Subgorups
- Neonates
OPTIMIZATION
- Use of Existing Knowledge in Pediatric Drug Development
- Use of Extrapolation in Pediatric Drug Development
- Use of Modelling and Simulation in Pediatric Drug Development
PRACTICALITIES
- Feasibility
- Outcome Assessments.
- Long-term Clinical Aspects, including safety
PEDIATRIC FORMULATIONS
- Dosage and Administration
- Excipients.
- Palatability and Acceptability
- Neonates
PURPOSE: When and how to identify and characterize drug metabolites whose nonclinical toxicity needs to be evaluated
GENERAL CONCEPTS
- Approaches for Assessing Metabolite Safety
- Identification of Metabolites
- General Considerations for Nonclinical Study Design
RECOMMENDED STUDIES
- General Toxicity Studies
- Genotoxicity Studies
- Embryo-Fetal Development Toxicity Studies
- Carcinogenicity Studies
TIMING
DECISION TREE FLOW DIAGRAM
CASE EXAMPLES
PURPOSE: Defining, establishing, and documenting manufacturing activities for contract drug manufacturing and Current Good Manufacturing Practice (CGMP) requirements
DEFINING : Who, What
RESPONSIBILITIES
DOCUMENTING CGMP ACTIVITIES
- Quality Agreemen
- Manufacturing Activities.
- Change Control
ILLUSTRATIVE SCENARIOS
- Owners and Contract Facilities Are Both Responsible for CGMP
- CGMPs Apply to all Contract Facilities, Including Analytical Testing Laboratories
- Owners and Contract Facilities Perform Change Control Activities
SCOPE: Assist applicants in preparing CLINICAL PHARMACOLOGY section of prescription drug labeling
- to meet regulatory requirements
- ensure appropriate consistency in the format and content
GENERAL PRINCIPLES
- Content and Organization
- Cross-Referencing
SUBSECTIONS
- Mechanism of Action
- Pharmacodynamics
- Pharmacokinetics: Absorption, Distribution, Elimination, Specific Populations, Drug Interaction, Microbiology, Pharmacogenomics
PRESENTATION
- Central Tendency and Variation
- Presentation Format
PROCEDURAL