FDA BRIEF: Week on May 9, 2016
- Clinical development of direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C (CHC)
- Each marketing application must contain at least one active-controlled comparative trial
General Drug Development Considerations:
- Nonclinical Virology Development Considerations (Mechanism of action, Antiviral activity in cell culture, Cytotoxicity and mitochondrial toxicity, Antiviral activity in animal models, Combination antiviral activity, Resistance and cross-resistance
- General Considerations for Phase 1 and Phase 2 Development (Phase 1a/first-in-human trials, Phase 1b (proof-of-concept), Phase 2 trials with combination DAA regimens
- Drug Development Population
- Efficacy Considerations
- Safety Considerations
Phase 3 Efficacy Trial Considerations:
- Trial Design (Treatment-naïve, non-DAA treatment-experienced,DAA treatment-experienced)
- Trial Population
- Entry Criteria (Assessment of cirrhosis, HCV genotype considerations, DAA treatment experience)
- Randomization, Stratification, and Blinding
- Specific Populations (HIV-1/HCV co-infected, decompensated cirrhosis and pre- or post-transplants, pediatric, advanced chronic kidney disease)
- Dose Selection
- Efficacy Endpoints
- Trial Procedures and Timing of Assessments
- Statistical Considerations (Analysis populations, Efficacy analyses, Noninferiority margin, Handling of missing data, Interim analyses and data monitoring committees, Statistical analysis plan)
- Accelerated Approval (Subpart H) Considerations
Other Considerations: Nonclinical Safety, PK/PD, Clinical Virology, Expanded Access considerations
- Leapfrog guidance on 3-dimensional (3D) printing to share initial thoughts on emerging technologies
- Additive manufacturing (AM) builds an object by iteratively building 2-dimensional (2D) layers and joining each to the layer below, allowing device manufacturers to rapidly alter designs without the need for retooling and to create complex devices built as a single piece
- Guidance outlines considerations for testing and characterization for devices that include at least one AM fabrication step.
Design and Manufacturing Considerations
- Software Workflow
- Material controls
- Post processing
- Process validation and Acceptance Activities
- Quality Data
Device Testing Considerations
- Device Description
- Mechanical Testing Dimensional Measurements
- Material Characterization
- Cleaning and Sterilization
- Biocompatibility
- Labeling considerations
DEADLINE for comments: Aug 8, 2016
FDA has launched 3D Printing Web Content
- Infectious Disease Next Generation Sequencing Based Diagnostic Devices – Infectious Disease NGS Dx devices employimg employing targeted or agnostic sequencing approaches
- Use: Diagnostic aid for microbial infection and in selecting appropriate therapies
- NGS technology: Rapid, actionable detection of clinically important pathogenic organisms in human specimens e.g., urine, blood, cerebrospinal fluid, stool, sputum
- Systems Approach: Use a “one system” approach for evaluation – from sample collection through the output of clinically actionable data using methods from the systems science discipline
- FDA-ARGOS database: Validated regulatory-grade microbial genomic sequence entries
- Guidance summarizes
- BENEFIT-RISK ASSESSMENT
- DEVICE DESCRIPTION
- DEVICE VALIDATION
- DEVICE MODIFICATION
- COMPARATOR DATABASE QUAITY CRITERIA
- Special Protocol Assessment (SPA) provides for protocol evaluation trials prior to initiation
- Process for sponsors and FDA to reach agreement on key design elements of clinical/animal studies
- Sponsors: Submit specific questions about protocol design, scientific, regulatory requirements
- FDA : Issues SPA Letter including assessment of protocol, agreement or nonagreement, abnd responses to questions
- SPA agreement : FDA Concurrence with adequacy and acceptability of specific critical protocol design elements that meet regulatory 33 requirements for approval
- However, existence of SPA agreement does not guarantee FDA filing and approval of NDA
- Guidance summarizes
- ELIGIBLE PROTOCOLS AND GENERAL INFORMATION
- PROCEDURES FOR SUBMISSION OF A REQUEST
- CONTENT OF A REQUEST AND SUBMISSION MATERIALS
- FDA ASSESSMENT PROCESS
- SPONSOR OPTIONS AFTER RECEIPT OF NONAGREEMENT SPA LETTER
- DOCUMENTATION
- CHANGES IN OR RESCISSION OF SPECIAL PROTOCOL ASSESSMENT AGREEMENTS
- DISPUTE RESOLUTION