Biological and biotechnological products, such as monoclonal antibodies, recombinant proteins, glycoproteins, and vaccines, which are produced from cell lines, organs, tissues, blood or other body fluids are at risk of viral contamination. Viral contamination has the potential for viral diseases transmission by affecting raw materials, bioreactor, and downstream processing during manufacturing. Therefore, pharmaceutical organizations need to ensure viral safety and incorporate viral clearance into the manufacturing process. Viral clearance studies are not only an essential part of a manufacturing program to ensure product safety, but also required by regulatory authorities for investigational new drug (IND) applications. Both Food and Drug Administration (FDA) and European Medicines Agency (EMA) have put in place requirements for viral safety in relation to biologics, and a degree of harmonization has been achieved through International Conference on Harmonization (ICH).
Viral Clearance Services at Creative Animodel
Creative Animodel provides a variety of viral clearance services which can be divided into viral inactivation and viral removal. The selection of the methods to be employed for viral clearance depends on the size and stability of the biologics, the methods of purification, and the nature and titer of the viruses. Each method of inactivation and removal has special characteristics that need to be taken into account. Our services include but are not limited to:Viral inactivation
Viral inactivation methods are generally effective against enveloped viruses while have limited effect on non-enveloped viruses.
|Pasteurization||Inactivates both enveloped and some non-enveloped virusesRelatively simple equipment||Protein stabilizers may also protect virusesProcess validation is required|
|Terminal dry heat||Inactivates both enveloped and some non-enveloped virusesTreatment applied on the final container||Extensive validation is required in freezing and lyophilization conditionsStrict control of moisture content is required|
|Vapor heat||Inactivates both enveloped and some non-enveloped viruses||Extensive validation is required in freezing and lyophilization conditionsRelatively complex to implement|
|Solvent/detergent||Efficient against enveloped virusesDoes not denature proteinsRelatively simple equipment||Non-enveloped viruses are unaffectedNot generally affected by buffers usedSolvent/detergent reagents must be removed|
|Acid pH||Efficient against enveloped virusesRelatively simple equipment||Process validation is required Limited efficacy against non-enveloped virusesElevated temperatures is required at pH4|
Viral removal methods are effective with both enveloped and non-enveloped viruses.
|Services||Advantages||Points to consider|
|Precipitation||Purifies proteinEffective against both enveloped and non-enveloped viruses||Virus removal is usually modestDifficult to model|
|Chromatography||Purifies proteinEffective against both enveloped and non-enveloped viruses||Highly variable from one virus to anotherVirus removal depends on the choices of resin, protein solution and buffersResin must be sanitized between lots|
|Nanofiltration||Effective against both enveloped and non-enveloped virusesDoes not denature proteinsHigh recovery of small proteinsRisk of downstream contamination limited when performed just prior to aseptic filling||Virus removal depends on the pore size of filter usedFilter defects may not be detectedElimination of small viruses may be incomplete|
Scientists from Creative Animodel have decades of experience in the design and performance of viral clearance. We have both technical and regulatory expertise to ensure studies comply with the relevant guidelines in clients’ target markets. If you have any requirements, please feel free to contact us.
1. Horowitz, B.; et al. Guidelines on Viral Inactivation and Removal Procedures Intended to Assure the Viral Safety of Human Blood Plasma Products. Technical Report, 2004, 924(924):1-232.