Regulatory affairs and biotechnology in Europe: III. Introduction into good regulatory practice — Validation of virus removal and inactivation

This paper provides for an overview on the practical consequences of the EC guideline (III/8115/89): Validation of Virus Removal and Inactivation. This guideline can only be used as a blueprint in combination with other specific guidelines, especially those concerned with EC recommendations during production and quality control for various biotech products. A potential risk associated with the production and use of biological products is viral contamination. This contamination may be present in the source material, eg. human blood, human or animal tissues, cell banks, or introduced in the manufacturing process through the use of animal sera (eg. foetal calf serum or trypsin) in cell culture supernatant. The objectives of validation are to establish — ideally both qualitatively as well as quantitatively — the overall level of virus clearance. Evidence of viral clearance must be obtained in all stages of purification and adequate viral removal and/or inactivation must be proven. The method used when validating viral removal and /or inactivation is by challenging the system through the deliberate addition (“spiking”) of significant amounts of virus into the crude material to be purified and to different fractions obtained during the various purification stages. Removal or inactivation of the virus during the subsequent stages of purification and /or inactivation is thereafter determined. Such a quality system is by no means a simple one: it is estimated that in some production lines around 600 Standard Operating Procedures are necessary to guarantee the quality and the safety of the desired biotechnological product. Small companies will probably not be able to perform all procedures needed for obtaining the desired quality of the product. Then, external laboratories may take over a part of the Part II development requirements, which may not be representative for the total of internal Quality Assurance. New developments in the production and quality control of biotechnological products may require that companies should introduce novel, sophisticated methods such as: polymerase chain reaction (PCR), as yet not recommended by the CPMP in detail.