Virus Inactivation
Manufacturing
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Plasma Pool Testing
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Partitioning/Fractionation
- Virus Inactivation
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Virus Elimination
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Virus Validation
After fractionation the intermediate product is submitted to processes that destroy viral structure. These virus inactivation processes include:
- Pasteurization
- Low pH treatment
- Solvent/detergent treatment
- Sodium thiocyanate treatment
Pasteurization
Pasteurization is the process of using heat treatment to inactivate a wide range of viruses of differing physico-chemical properties. Both enveloped and non-enveloped viruses are inactivated while an aqueous solution facilitates efficacy. Although stabilizers are needed for protection of fragile proteins; nevertheless, no residual stabilizers remain in the final product. Pasteurization has an excellent safety record for virus inactivation.
In 1979, CSL Behring (at that time Behringwerke) introduced pasteurization to inactivate pathogens. CSL Behring was the first company to use heat treatment in aqueous stabilized solution at 60°C for 10 hours of labile factors (e.g. factor VIII).
Low pH Treatment (Acidic pH Inactivation)
Some viruses, when exposed to a low pH, will denature spontaneously. Similar to pasteurization, this technique for viral inactivation is useful if the target protein is more resistant to low pHs than the viral impurity. This technique is effective against enveloped viruses.
Solvent/Detergent (S/D) Viral Inactivation
S/D treatments effectively inactivate enveloped viruses by destroying the lipid envelope. The detergents used in this method interrupt the interactions between the molecules in the virus's lipid coating. Most enveloped viruses cannot live without their lipid coating, so they die when exposed to these detergents. This process does not denature proteins, because the detergents only affect lipids and lipid derivatives.
Sodium Thiocyanate Treatment
Sodium thiocyanate inactivates certain viruses as factor FIX is eluted from the affinity column [monoclonal antibody (MAb) column]. It may also be used to regenerate (i.e. sanitize) the MAb column during the production process.