Non-Clinical Testing Recommendations for Machine Perfusion Devices Used to Preserve Vascularized Human Organs for Transplant
This guidance applies to devices intended to preserve human vascularized organs through machine perfusion (hypothermic or normothermic) from procurement until transplant. It excludes devices for cold static storage and HCT/Ps preservation devices.
Recommended Actions
- Develop a risk-based approach for animal study protocol development
- Define clear study objectives and acceptance criteria
- Select appropriate animal model with scientific justification
- Design protocol considering all three phases (procurement, preservation, reperfusion)
- Implement contamination control measures
- Evaluate device transportability if applicable
- Consider both ex vivo and in vivo models based on study objectives
- Establish appropriate biomarker panel for organ assessment
- Implement proper histopathological evaluation procedures
- Submit Pre-Submission to FDA for feedback on proposed animal studies
- Follow GLP requirements
- Document all procedures and results thoroughly
Key Considerations
Non-clinical testing
- Risk-based approach for developing animal study protocols
- Protocol should have focused objectives and a priori acceptance criteria
- Provide rationale for animal model selection considering anatomical, physiological, and immunological factors
- Evaluate three phases: organ procurement, preservation, and reperfusion
- Specify warm and cold ischemia times reflecting intended use
- Total preservation time should consider expected maximum transportation time
- Assess device transportability if applicable
Biocompatibility
- Perform bacterial cultures on perfusate samples at end of perfusion session
- Evaluate perfusate composition and additives
- Assess organ edema through weight measurements before and after reperfusion
Safety
- Evaluate strategies to mitigate organ injury from mechanical trauma during transport
- Assess reperfusion injury through ex vivo or in vivo models
- Collect tissue biopsies from multiple organ regions before and after reperfusion
- Independent pathologist evaluation focusing on endothelial cell integrity
Other considerations
- Consider using both ex vivo and in vivo models to verify findings
- Follow GLP requirements (21 CFR Part 58)
- Balance ethical principles of The Three R’s with regulatory least burdensome principles
- Submit Pre-Submission to obtain FDA feedback on proposed animal studies
Relevant Guidances
- Animal Testing for Medical Device Safety and Performance Evaluation
- Jurisdictional Determinations for HCT/P Processing Devices: CBER vs CDRH Assignment
- Good Laboratory Practice (GLP) Requirements for Non-Clinical Laboratory Studies
Related references and norms
- 21 CFR Part 58: Good Laboratory Practice for Nonclinical Laboratory Studies
Original guidance
- Non-Clinical Testing Recommendations for Machine Perfusion Devices Used to Preserve Vascularized Human Organs for Transplant
- HTML / PDF
- Issue date: 2019-05-08
- Last changed date: 2019-05-07
- Status: FINAL
- Official FDA topics: Medical Devices, Gastroenterology-Urology, 510(k), Premarket
- ReguVirta summary file ID: 7c3a981bf8d471a3a4be9e07e9c6cf29
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