Overview
EN ISO 22442-3:2007 (ISO 22442-3:2007) defines requirements for the validation of elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents during manufacture of medical devices that utilize animal tissues or derivatives. It applies to non‑viable animal‑derived materials used in devices (excluding in vitro diagnostic devices) and is intended to be used where the risk management process (see ISO 22442‑1) identifies a need for validation. The standard supports demonstrated product safety by documenting scientifically sound validation studies, reporting, and routine process control.
Key Topics
- Scope and applicability - Focus on animal‑derived medical devices and processes that require viral/TSE control; excludes other transmissible or non‑transmissible agents and IVDs.
- Risk management linkage - Applies when the risk assessment (ISO 22442‑1) indicates potential viral/TSE transmission risk.
- Literature review - Systematic review of published data to identify known risks and prior evidence of inactivation or removal for specific agents and processes.
- Validation study design - Requirements for protocols, scaled‑down models, inoculation and challenge studies, controls, and acceptance criteria.
- Conduct and interpretation - Guidance on executing studies, calculating reduction factors, statistical evaluation of virus titres, and assessing the validity of results.
- Reporting and review - Requirements for a comprehensive final validation report and independent review.
- Routine monitoring - Ongoing control of critical process parameters and maintenance of validated conditions in production.
- Informative annexes - Practical guidance on viruses vs. TSE agents, scaling‑down, statistical methods, reduction factor calculations, and detection probabilities.
Applications
EN ISO 22442-3 is used to validate manufacturing steps that claim to remove or inactivate viral and TSE agents, for example:
- Processing steps for bovine/porcine heart valves, collagen coatings, bone substitutes, haemostatic products.
- Use of animal‑derived reagents or process aids (e.g., foetal calf serum, tallow derivatives) where residual risk must be controlled.
- Demonstrating efficacy of sterilization, chemical inactivation, filtration, or process washing steps in removing infectious agents.
Who should use this standard
- Medical device manufacturers using animal‑origin materials
- Validation scientists and process engineers
- Quality and regulatory teams preparing technical documentation
- Notified Bodies and auditors assessing conformity with EU Medical Device Directive requirements
- Laboratories planning viral inactivation/removal studies
Related standards
- ISO 22442‑1 - Application of risk management (precedes validation need)
- ISO 22442‑2 - Controls on sourcing, collection and handling of animal tissues
- ISO 13485 - Quality management system for medical device manufacture
- EU Medical Device Directive 93/42/EEC (as referenced for conformity)
Keywords: EN ISO 22442-3:2007, validation of inactivation, virus elimination, TSE agents, medical devices utilizing animal tissues, risk management, viral reduction factors, validation protocol.
