Organ Preservation Solutions for Transplantation - Testing and Development Requirements
This guidance addresses solutions designed for flushing, transport, and preservation of whole organs (kidney, liver, pancreas, heart, and lung) for transplantation. It excludes solutions for cornea preservation, tissue preservation, cell preservation, and machines designed for organ perfusion.
What You Need to Know? 👇
What are the key requirements for IDE submissions for organ preservation solutions?
IDE submissions must include complete device description with USP-grade chemical composition, bench and animal testing data, biocompatibility testing for packaging materials, sterility assurance documentation, and a multi-center randomized controlled clinical trial plan with appropriate statistical analysis.
What animal testing is required before clinical trials for organ preservation solutions?
Animal testing must demonstrate safety and establish surrogate endpoints for each organ type. Studies should use relevant animal models (preferably larger animals like pigs), test against control solutions, and evaluate specific organ performance parameters with statistical analysis.
What are the recommended primary endpoints for organ preservation solution clinical trials?
Primary endpoints are 7-day patient survival for heart, lung, and liver preservation solutions (ventilator/ECMO-free survival for lungs), and 7-day graft survival for kidney preservation solutions. Thirty-day follow-up is strongly recommended as secondary endpoint.
Can foreign clinical data be included in organ preservation solution marketing applications?
Yes, foreign clinical data can be included in marketing applications, but FDA recommends including at least one U.S. investigational site due to differences in clinical practice and patient outcomes between U.S. and foreign transplantation centers.
What chemical purity standards apply to organ preservation solution components?
All chemical components must be United States Pharmacopoeia (USP) grade. If non-USP grade chemicals are used, adequate justification must be provided to demonstrate sufficient purity for the intended use in organ preservation applications.
What packaging requirements exist for organ preservation solutions?
Packaging materials must be appropriate for blood or tissue contact and require biocompatibility testing per CDRH Blue Book memorandum G95-1. Alternatively, sponsors may reference legally marketed products using identical materials for similar intended uses.
What You Need to Do 👇
Recommended Actions
- Develop comprehensive device description including chemical composition and manufacturing process
- Conduct bench testing for stability and particulate analysis
- Perform animal studies with appropriate models
- Design and implement multi-center clinical trial with minimum three sites
- Establish appropriate primary and secondary endpoints based on organ type
- Develop statistical analysis plan
- Ensure packaging materials meet biocompatibility requirements
- Conduct sterility testing
- Document preservation times for all organs
- Consider including at least one US site in clinical studies
- Prepare comprehensive documentation of all prior investigations and published literature
Key Considerations
Clinical testing
- Multi-center, prospective, randomized, controlled trial recommended
- Minimum of three investigational sites
- Primary endpoint: 7-day patient survival (heart, lung, liver) or 7-day graft survival (kidney)
- 30-day follow-up strongly recommended
- Secondary endpoints specific to organ function required
Non-clinical testing
- Bench testing for product stability under proper and worst-case conditions
- Analysis of chemical constituents and degradation products
- Particulate measurement meeting USP specifications
- Animal testing required for safety demonstration
- Large animal model recommended for confirmatory studies
Biocompatibility
- Packaging material must be appropriate for blood/tissue contact
- Testing according to ISO 10993-1 required for packaging materials
- Alternative: identification of legally marketed product using same materials
Safety
- Sterility testing required (endotoxin and bacteria)
- Chemical components should be USP grade
- Solutions must meet USP specifications for large volume parenteral solutions
Other considerations
- Complete chemical composition listing required
- Manufacturing process description needed
- Stability testing data required
- Statistical plan must be provided
- Foreign clinical data acceptable but at least one US site recommended
Relevant Guidances 🔗
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Biological Evaluation of Medical Devices Standards in the Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program
- Design Considerations for Medical Device Pivotal Clinical Studies
Related references and norms 📂
- ISO 10993-1: Biological Evaluation of Medical Devices Part-1: Evaluation and Testing
- USP: United States Pharmacopoeia specifications for large volume parenteral solutions