Proceedings of the Tenth International Conference of Drug Regulatory Authorities (ICDRA) - Hong Kong, China, 24 - 27 June 2002
(2002; 166 pages) View the PDF document
Table of Contents
View the documentAbbreviations and acronyms used in this report
Open this folder and view contentsOpening ceremony
Open this folder and view contentsHerbal medicines
Open this folder and view contentsKeynote address
Close this folderSafety of blood-derived products
View the documentQuality and safety of plasma for fractionation
View the documentProcedures for inactivation and removal of viruses
View the documentGMP in blood plasma collection centres
View the documentPlasma fractionation - Brazilian programme of self-sufficiency in blood products
View the documentSafety of blood products in New Zealand
View the documentRegulatory experience in Argentina
View the documentSafety of blood products in the Islamic Republic of Iran
View the documentRecommendations
Open this folder and view contentsAntimicrobial resistance - new initiatives
Open this folder and view contentsHarmonization I
Open this folder and view contentsHarmonization II
Open this folder and view contentsProtection of trial subjects in clinical trials
Open this folder and view contentsRegulating biotechnology products
Open this folder and view contentsRegulatory challenges: health sector reform and drug regulatory capacity
Open this folder and view contentsAccess to drugs and vaccines I
Open this folder and view contentsAccess to drugs and vaccines II
Open this folder and view contentsCounterfeit pharmaceutical products
Open this folder and view contentsHomoeopathy
Open this folder and view contentsSafety monitoring
Open this folder and view contentsE-Commerce
Open this folder and view contentsCurrent topics
Open this folder and view contentsRegulatory challenges of new technologies
View the documentList of participants
View the documentBack cover
 

Procedures for inactivation and removal of viruses

Dr Johannes Löwer, Germany

WHO guidelines on viral inactivation and removal procedures summarize current knowledge on virus inactivation and removal methods. They are intended to assist national control authorities and to provide guidance for manufacturers of blood products.

Human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are commonly tested plasma-borne viruses. Hepatitis A virus (HAV) and parvovirus B19 may be less of a problem in terms of contamination, although B19 can be dangerous in certain groups, such as pregnant women.

In studying viral inactivation, it is important to select the correct viruses for validation experiments. If possible, the virus of interest itself should be studied (this is possible for HIV and HAV, for example). Some viruses, however, such as HBV, cannot be cultured, and other viruses have to be used as a model. It is important to note that some model viruses do not properly reflect the behaviour of the relevant viruses on treatment. For example, porcine parvovirus (PPV) is not destroyed by pasteurization, but human parvovirus B19 is.

In modelling the production process, correct down-scaling is crucial. The robustness of virus inactivation or removal should be considered with respect to critical process parameters. An effective virus removal process should demonstrate more than 4 log10 inactivation/removing capacity. Reduction factors of less than 1 log10 cannot be considered.

There are various methods of inactivation.

• Pasteurization at 60°C for 10 hours. Critical factors affecting the process include temperature and concentration of stabilizer.

• Terminal dry heat (at least 80°C) or vapour heat (typically 60°C). Critical factors include temperature and strict control of residual moisture.

• Solvent detergent treatment. This does not affect nonenveloped viruses. Critical factors include the concentration of the reagents, avoidance of virus aggregates, and temperature.

• Incubation at pH 4 for between 6 hours and 21 days. Critical factors include pH and temperature.

• Cold ethanol fractionation. Critical factors include ethanol concentration, temperature, and filtration and centrifugation conditions.

• Chromatography. Critical factors include column load and height, chromatographic profiles, flow rates and conductivity.

• Nanofiltration. Critical factors include pressure, flow rate, filtration time, filter integrity and load, and composition of the intermediate product.


There is a danger that virus inactivation or removal methods may damage the proteins in the product. Therefore, the consistency and integrity of the product must be demonstrated.

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