Resorbable Adhesion Barrier Devices for Abdominal and Pelvic Use - Development and Testing Requirements
This guidance discusses the development of preclinical and clinical information required for Investigational Device Exemption (IDE), Premarket Approval (PMA), or Product Development Protocol (PDP) applications for resorbable adhesion barrier products used in abdominal and/or pelvic cavity. It specifically applies to adhesion barriers that are resorbed within 30 days of placement.
What You Need to Know? 👇
What are the key regulatory requirements for resorbable adhesion barrier devices?
Resorbable adhesion barriers are Class III significant risk devices requiring FDA premarket approval (PMA). They need approved Investigational Device Exemption (IDE) for clinical studies, comprehensive preclinical testing including biocompatibility and animal studies, and must demonstrate safety and effectiveness through controlled clinical trials with proper statistical analysis.
How long should biocompatibility testing continue for resorbable adhesion barriers?
Biocompatibility testing should extend beyond the point where the material is no longer detectable in the body. For devices resorbed within 30 days, subchronic implantation studies should monitor animals until after complete resorption, including systemic toxicity assessment, macroscopic pathology, and histopathology evaluations.
What are the essential preclinical studies required before human testing?
Essential preclinical studies include cytotoxicity, sensitization, irritation, systemic toxicity, genotoxicity, and subchronic implantation testing. Additional studies for adhesion barriers include testing for delayed healing, infectivity enhancement with bacterial challenge, pharmacokinetics (ADME), and animal effectiveness studies demonstrating proof of concept.
What clinical trial design is recommended for adhesion barrier effectiveness studies?
FDA recommends randomized, concurrently-controlled pivotal trials with proper masking to minimize bias. Studies should include clear endpoints, intent-to-treat analysis, second-look procedures for adhesion assessment, video recording for independent review, and statistical methods addressing poolability across multiple sites.
What manufacturing information must be included in regulatory submissions?
Manufacturing submissions must include complete device description, step-by-step manufacturing process, final product specifications with test methods, stability data supporting expiration dating, sterilization validation achieving 10^-6 sterility assurance level, pyrogenicity testing, and residual chemical analysis of the sterilized product.
What special considerations apply to adhesion barriers used in cancer patients?
For adhesion barriers intended for cancer patients, additional preclinical testing is required focusing on tumor growth acceleration and metastasis effects. Clinical trials may need oncology-specific protocols. Otherwise, the device should be contraindicated for patients with known or suspected malignancies.
What You Need to Do 👇
Recommended Actions
- Develop comprehensive preclinical testing plan including biocompatibility, animal studies, and bench testing
- Design randomized controlled clinical trial with clear endpoints and assessment methods
- Establish detailed manufacturing controls and specifications
- Create comprehensive labeling addressing all required elements
- Prepare complete risk/benefit analysis based on all available data
- Consider need for post-approval studies
- Engage early with FDA for feedback on development plans
- Document all testing and manufacturing processes thoroughly
- Develop training program for proper device use
- Plan for separate evaluation if both laparoscopic and laparotomy use intended
Key Considerations
Clinical testing
- Randomized, concurrently-controlled pivotal trials are recommended
- Second-look surgery is primary modality for assessment
- Clear inclusion/exclusion criteria needed for patient selection
- Follow-up period and evaluations must be defined prospectively
- Comprehensive statistical analysis plan required
- Post-approval studies may be required for unresolved safety issues
Non-clinical testing
- Animal studies needed for proof of concept and effectiveness
- Studies should represent surgical approach, sites, and types of adhesions
- Pharmacokinetics studies required to determine absorption, distribution, metabolism and excretion
- Physical/mechanical bench testing required
Human Factors
- Training requirements for device applicators must be described
- Instructions for use must be detailed and reflect study experience
- Patient informed consent requirements specified
Labeling
- Must include device description, indications, contraindications, warnings/precautions
- Adverse events must be clearly presented
- Clinical studies summary required
- Detailed instructions for use needed
Biocompatibility
- Must follow ISO 10993-1 guidelines
- Six standard tests required for implanted devices
- Special testing needed for delay/prevention of healing
- Reproductive/developmental toxicity studies required in two species
Safety
- Infectivity testing required
- Sterility assurance level of 10^-6 needed
- Pyrogenicity testing required
- Complete safety analysis needed for risk/benefit assessment
Other considerations
- Manufacturing process and controls must be described
- Product stability and shelf life data required
- Device applicator information needed if used
- Separate evaluation needed for laparoscopic vs laparotomy use
Relevant Guidances 🔗
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Design Considerations for Medical Device Pivotal Clinical Studies
- Informed Consent in Clinical Investigations: Requirements, Documentation, and Procedures
- Applying Human Factors Engineering and Usability Engineering to Medical Devices
- Reprocessing Instructions for Reusable Medical Devices and Non-Sterile Single-Use Devices - Development and Validation
Related references and norms 📂
- ISO 10993-1:1992: Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing
- ANSI/AAMI/ISO 10993-7:1995: Biological Evaluation of Medical Devices - Part 7: Ethylene Oxide Sterilization Residuals