BS EN ISO 22442-3:2007 Medical devices utilizing animal tissues and their derivatives. Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents
For the safety of medical devices there are two complementary approaches (see BS EN ISO 22442-1) that can be adopted to control the potential contamination of tissues. These typically are:
• Selecting source material for minimal contamination with viruses and/or TSE agents (see BS EN ISO 22442-1 and BS EN ISO 22442-2)
• Providing valid scientific evidence to demonstrate the ability of the production processes to eliminate or inactivate viruses and/or TSE agents (BS EN ISO 22442-3).
Requirements for a quality system for medical devices for regulatory use are specified in BS EN ISO 13485:2003 Medical devices. Quality management systems. Requirements for regulatory purposes. The standards for quality management systems recognize that, for certain processes used in manufacturing, the effectiveness of that process cannot be fully verified by subsequent inspection and testing of the product. The elimination and/or inactivation of viruses and TSE agents is an example of a special process because process efficacy cannot be verified by inspection and testing of the product. For this reason, the following need to be considered in particular:
- Definition of the process(es) and materials to be used
- Adequate inactivation validation before routine use
- Performance monitoring of the process during manufacture
- Appropriate equipment maintenance
- Staff training.
Historically there have been many instances of unknown or unsuspected viral contamination during manufacture. For this reason, evaluation of the manufacturing process can provide a measure of confidence that a wide number of viruses, including unknown pathogenic viruses are eliminated. Similar principles may apply to TSE agents.
To show compliance with this part of BS EN ISO 22442, its specified requirements should be fulfilled. The guidance given in this standard is not normative and is not provided as a checklist for auditors.
BS EN ISO 22442-3 specifies requirements for the validation of the elimination and/or inactivation of viruses and TSE agents during the manufacture of medical devices (excluding in vitro diagnostic medical devices) utilizing animal tissue or products derived from animal tissue, which are non-viable or have been rendered non-viable. It applies where required by the risk management process as described in BS EN ISO 22442-1. It does not cover other transmissible and non-transmissible agents.
Analysis and management of risk is described in BS EN ISO 22442-1. Conventional processes used for sterilization, when used for the treatment of animal tissues for medical devices, have not been shown to be completely effective in inactivating the causative agents of transmissible spongiform encephalopathy. Selective sourcing is extremely important (see BS EN ISO 22442-1 and BS EN ISO 22442-2).
This part of BS EN ISO 22442 does not cover the utilization of human tissues in medical devices, nor does it specify a quality management system for the control of all stages of production of medical devices.
It is not a requirement of this part of BS EN ISO 22442 to have a full quality management system during manufacture, but it does specify requirements for some of the elements of a quality management system. Attention is drawn to the standards for quality management systems (see BS EN ISO 13485) that control all stages of production or reprocessing of medical devices. The quality management system elements that are required by this part of BS EN ISO 22442 can form part of a quality management system conforming to BS EN ISO 13485.
Part 3 of BS EN ISO 22442 does not consider the effect of any method of elimination and/or inactivation on the suitability of the medical device for its intended use.
Contents include:
- Introduction
- Normative references
- Terms and definitions
- General requirements
- Risk management
- Sourcing and manufacturing process
- General requirements related to validation
- Literature review
- Conduct of the literature review
- Application of literature review output
- Viruses
- TSE agents
- Elimination and/or inactivation study of viruses and TSE agents
- Protocol
- Conduct of the study
- Interpretation of data
- Final report
- Review of final report
- Routine monitoring and control of critical process parameters
- Requirements related to literature review
- Guidance on the elimination and/or inactivation study for viruses
- Guidance on the elimination and/or inactivation study for TSE agents
- Guidance on scaling down
- Statistical evaluation of virus titres and reduction factors and assessment of their validity
- Calculation of reduction factors
- Probability of detection of agents at low concentrations
- Relationship between this European Standard and the Essential Requirements of Directive 93/42/EEC as amended by Commission Directive 2003/32/EC
- Bibliography
BS EN ISO 22442-3:2007 replaces BS EN 12442-3:2000 which has been withdrawn.
