Overview
ISO 22442-3:2007 specifies requirements for the validation of methods used to eliminate and/or inactivate viruses and transmissible spongiform encephalopathy (TSE) agents during the manufacture of medical devices that use animal tissues or derivatives. It applies to materials that are non‑viable or rendered non‑viable and is used where the risk management process (see ISO 22442-1) indicates validation is necessary. The standard excludes in vitro diagnostic devices, human tissues and other transmissible or non‑transmissible agents.
Key topics and requirements
- Risk-based approach: Validation is applied where indicated by ISO 22442-1 risk analysis; selective sourcing (ISO 22442-2) is complementary.
- Literature review: Conduct and document a thorough literature review to inform choice of relevant viruses/TSE agents and validation strategy.
- Validation studies: Define and execute elimination/inactivation studies with documented protocols, including scaled‑down process models when appropriate.
- Reduction factor: Measure and report virus/TSE load reduction as reduction factors (log10 ten‑fold reductions).
- Study design and interpretation: Include protocol, conduct, statistical evaluation, calculation of reduction factors and assessment of validity (informative annexes provide guidance).
- Personnel, equipment and calibration: Assign qualified staff, maintain calibration and planned maintenance for instruments and equipment used in validation.
- Documentation and reporting: Produce a final report and establish procedures for review, revalidation and routine monitoring of critical process parameters.
- Informative guidance: Annexes address viruses, TSE agents, scaling down, statistical methods and probability of detection at low concentrations.
Practical applications and users
Who uses ISO 22442-3:2007:
- Medical device manufacturers using bovine, porcine or other animal‑derived materials (e.g., heart valves, collagen coatings, bone substitutes).
- Quality assurance and regulatory affairs teams implementing validation under a quality system (elements align with ISO 13485).
- Process development and R&D groups designing inactivation/elimination steps and scaled‑down studies.
- Contract testing laboratories performing virus/TSE inactivation validation and statistical analysis.
- Notified bodies and regulators assessing safety documentation for animal‑derived devices.
Practical benefits:
- Demonstrates scientifically based control of viral and TSE contamination risk.
- Supports product safety dossiers and regulatory submissions.
- Provides a documented framework for routine monitoring and revalidation.
Related standards