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Virus validation studies of immunoglobulin preparations
1Virological Research Group, Octapharma AG, Frankfurt, Germany.
Objective:
A validation study of the viral safety of a new polyvalent intravenous immunoglobulin (OCTAGAM) according to EU-guideline III/8115/89-EN and the requirements of the Federal Agency for Sera and Vaccines in Germany was undertaken in May 1994. The following processing steps were analyzed: Cohn-Oncley fractionation, solvent/detergent (SD) treatment, pH 4 exposure, storage of the final product at low pH and immune neutralisation.
Methods:
The following virus reduction factors were obtained: Cohn-Oncley fractionation: HIV-1 > 5.50; sindbis virus > 6.36; pseudorabies virus > 7.28; coxsackievirus-B6 2.70; poliovirus-1 > 3.80; SV40 > 5.51. Solvent/Detergent treatment: HIV-1 > 6.03; sindbis virus > 7.80; pseudorabies virus > 8.38. pH 4 exposure: HIV-1 > 8.60; sindbis virus > 8.94; pseudorabies virus > 5.95; coxsackievirus-B6 2.72; SV40 1.15. Immune neutralisation: coxsackievirus-B6 > 4.98, polio-virus-1 > 5.14, HAV > 3.44, HSV-1 > 5.92. The following virus reduction factors were calculated for the final product: HIV-1 > 20.13; sindbis virus > 23.10; pseudorabies virus > 21.61; coxsackievirus-B6 > 10.4; poliovirus-1: > 8.94; HAV > 3.44; SV40 > 6.66.
Conclusion:
The results of our validation studies demonstrated that in addition to Cohn fractionation and immune neutralization, the two additional steps of solvent/detergent treatment and pH 4 exposure, mainly contribute to the safety of OCTAGAM with respect to both enveloped and non-enveloped viruses.
Insights
This study validated the viral safety of OCTAGAM, a new intravenous immunoglobulin. Key steps like solvent/detergent treatment and pH 4 exposure significantly enhance viral clearance for both enveloped and non-enveloped viruses.
Area of Science:
- Immunology
- Virology
- Pharmaceutical Science
Background:
- Intravenous immunoglobulin (IVIG) therapy is crucial for treating various immune deficiencies.
- Ensuring the viral safety of IVIG products is paramount to patient health.
- Regulatory guidelines mandate rigorous viral clearance validation for blood-derived products.
Purpose of the Study:
- To validate the viral safety of a new polyvalent intravenous immunoglobulin (OCTAGAM).
- To assess the efficacy of specific manufacturing steps in reducing viral load.
- To comply with EU guidelines and German regulatory requirements for viral safety.
Main Methods:
- Analysis of viral reduction factors across multiple processing steps: Cohn-Oncley fractionation, solvent/detergent (SD) treatment, pH 4 exposure, and immune neutralization.
- Testing with a panel of enveloped (e.g., HIV-1, Sindbis virus, pseudorabies virus) and non-enveloped viruses (e.g., coxsackievirus-B6, poliovirus-1, SV40, HAV).
- Calculation of overall virus reduction factors for the final OCTAGAM product.
Main Results:
- Cohn-Oncley fractionation demonstrated significant reduction factors for most tested viruses.
- Solvent/Detergent (SD) treatment and pH 4 exposure showed substantial reduction, particularly for enveloped viruses.
- The final OCTAGAM product achieved high overall virus reduction factors, exceeding 20 for HIV-1 and pseudorabies virus.
Conclusions:
- Solvent/Detergent treatment and pH 4 exposure are critical steps in ensuring the viral safety of OCTAGAM.
- These steps, in conjunction with Cohn fractionation and immune neutralization, provide robust protection against both enveloped and non-enveloped viruses.
- The validation studies confirm OCTAGAM's safety profile concerning viral contamination.