Viral clearance studies
In order to exclude the risk of viral contamination of a therapeutic product linked to raw materials (contamination by emerging or as yet unknown or undetectable viruses, e.g. from facilities hosting animals used to produce a drug) or production methods (contamination of the bioreactors used to produce recombinant proteins in mammalian cells), one should seek to demonstrate that the product purification process is able to eliminate and/or inactivate viruses.
Virus validation studies involve (i) the intentional addition of a defined viral load at various steps in the manufacturing process and (ii) observation of the reduction in viral load during subsequent steps. To this end, we spike the intermediate products in our labs for each of the scaled-down production steps that theoretically contribute to viral elimination and/or inactivation. Experimental determination of the viral loads found before and after treatment enables calculation of a reduction factor (the log reduction value, LRV) that is specific to the step and the virus used. A production/purification step is considered to be efficient when a LRV of 4 log10 is achieved.
The major difficulty with this type of study is not so much calculation of the LRV but the unambiguous identification and demonstration of the contribution of each parameter of the process involved in viral reduction. Texcell’s experience in this domain enables us to design a virus validation protocol that will be most relevant to your product and the latter's development stage and that will allow you to get the best possible LRV as a function of technical and regulatory constraints.
Guidelines
A number of guidelines (published by regulatory organisations such as the FDA (the US Food and Drug Administration), EMEA (the European Agency for the Evaluation of Medicinal Products), EP (the European Pharmacopoeia), WHO (the World Health Organisation) and ICH (the International Conference on Harmonisation)) describe the viral safety evaluation of biological products. The major guidelines concerning virus validation are as follows:
- Note for Guidance on Virus Validation Studies: the design, contribution and interpretation of studies validating the inactivation and removal of viruses. Date for coming into operation: 14 August 1996. (CPMP/BWP/268/95) Version 2. February 1996.
- Note for Guidance on Quality of Biotechnological Products: viral safety evaluation of biotechnology products derived from cell lines of human or animal origin. (CPMP/ICH/295/95) ICH Topic Q 5 A, Step 4, Consensus Guideline, 4 March 1997. Date for coming into operation: October 1997.
Furthermore, thanks to the relationships that Texcell has established with regulatory agencies worldwide, we are able to provide protocols and study plans that fully comply with regulatory requirements. A Texcell dossier allows you to contact the regulatory authorities directly.
