EN ISO 22442 compliance for Virus Inactivation studies on Medical Devices using animal tissues and their derivatives

Alessandro Radici, Eurofins Medical Device Testing

The scope of these studies is to show in a lab scale reproducible system whether specific steps of the Sponsor's manufacturing process of a medical device incorporating biological tissue are capable of irreversibly inactivating viruses, according to EN ISO 22442 Part 3 Requirements.

As a preliminary phase, it's necessary to characterise the risk of viral contamination of the biologic material to be incorporated in the device by means of an expert assessment (literature review) of the biological material itself, the manufacturing process of both raw material and finished product as well as the potential viral inactivation steps performance.

After risk characterisation, the choice of test viruses (at least four viruses, including RNA and DNA viruses as well as enveloped and non-enveloped viruses) has to be defined; this choice is based on the following:

• Viral risk characterisation;
• Capability of viruses to grow to high titre in vitro;
• Detection techniques relatively easy and reproducible.

The use of model test viruses is accepted and widely used if robust official scientific literature (i.e. including relevant scientific articles, norms and regulatory guidelines) stating their equivalence in terms of taxonomy and resistance to physicalchemical stress is available.

The virus inactivation may include the validation of different types of steps, such as chemical inactivation, such as immersion in high-level disinfectant solutions, or physical inactivation, such as γ rays irradiation or moist heat treatment.

The experimental design is made typically of three phases:

• Setup phase where virus stable titre is reached; potential residual cytotoxicity is reduced; LOQ of the method is defined and cell susceptibility to virus after exposure to treatment is assessed.
• Inactivation kinetics are defined in terms of exposure time and/or increasing temperatures or dosage depending on the type of inactivation step.
• Actual inactivation step in two independent replicas is simulated in lab scale, considering always a worst-case scenario (e.g. in terms of test specimen size and shape, exposure time, temperature or dosage of the treatment).

Eurofins is able to support medical device manufacturers assessing literature review and running studies under GLP certification as well.

For more information, contact: medical-device@eurofins.com.