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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.

  1. Develop a risk-based approach for animal study protocol development
  2. Define clear study objectives and acceptance criteria
  3. Select appropriate animal model with scientific justification
  4. Design protocol considering all three phases (procurement, preservation, reperfusion)
  5. Implement contamination control measures
  6. Evaluate device transportability if applicable
  7. Consider both ex vivo and in vivo models based on study objectives
  8. Establish appropriate biomarker panel for organ assessment
  9. Implement proper histopathological evaluation procedures
  10. Submit Pre-Submission to FDA for feedback on proposed animal studies
  11. Follow GLP requirements
  12. 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

  • 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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