Appendix XXII A. Viral Safety

(Ph. Eur. general texts 5.1.7)

This chapter provides general requirements concerning the viral safety of medicinal products whose manufacture has involved the use of materials of human or animal origin. Since viral safety is a complex issue, it is important that a risk assessment is carried out. Requirements to be applied to a specific medicinal product are decided by the competent authority.

Where the risk of viral contamination exists, complementary measures are used as appropriate to assure the viral safety of medicinal products, based on:

— selection of source materials and testing for viral contaminants;

— testing the capacity of the production process to remove and/or inactivate viruses;

— testing for viral contamination at appropriate stages of production.

Where appropriate, one or more validated procedures for removal or inactivation of viruses are applied.

Further detailed recommendations on viral safety, including validation studies, are provided, in particular, by the Note for guidance on virus validation studies: the design, contribution and interpretation of studies validating the inactivation and removal of viruses (CPMP/BWP/268/95) of the Committee for Proprietary Medicinal Products, and the ICH guideline Q5A: Viral safety evaluation of biotechnology products derived from cell lines of human or animal origin (including any subsequent revisions of these documents).

Requirements concerning immunological products for veterinary use are dealt with in the monographs Vaccines for veterinary use (0062) and Immunosera for veterinary use (0030) and related general chapters.

Risk assessment

A risk assessment with respect to viral safety is carried out where materials of human or animal origin are used as ingredients of medicinal products or in the manufacture of active substances, excipients or medicinal products.

The principle of the risk assessment is to consider various factors that may influence the potential level of infectious particles in the medicinal product and factors related to the use of the medicinal product that determine or influence the viral risk to the recipients.

The risk assessment takes into consideration relevant factors, for example:

— the species of origin;

— the organ, tissue, fluid of origin;

— the potential contaminants in view of the origin of the raw material and the history of the donor(s), preferably including epidemiological data;

— the potential contaminants from the manufacturing process (for example, from risk materials used during manufacture);

— the infectivity and pathogenicity of the potential contaminants for the intended recipients of the medicinal product, taking account of the route of administration of the medicinal product;

— the amount of material used to produce a dose of medicinal product;

— controls carried out on the donor(s), on the raw material, during production and on the final product;

— the manufacturing process of the product and its capacity to remove and/or inactivate viruses.

The risk assessment can be based mainly on the manufacturing conditions if these include rigorous inactivation steps (for example, for gelatin etc., and products terminally sterilised by steam or dry heat as described in the general texts on sterility (5.1)).