Viral clearance studies

What are viral clearance studies?

Viral clearance studies are conducted for viral safety evaluation of biopharmaceuticals. It is required to demonstrate the capability of inactivation and removal of potential viral contaminants for the process development and submission to the Regulatory Authorities.

The objective of viral clearance studies is to assess process steps that can be considered to be effective in inactivating/removing viruses and to estimate quantitatively the overall level of virus reduction obtained by the process.

This should be achieved by the deliberate addition ("spiking") of significant amounts of a virus to the crude material and/or to different fractions obtained during the various process steps and demonstrating its removal or inactivation during the subsequent steps.

It is not necessary to evaluate or characterize every step of a manufacturing process if adequate clearance is demonstrated by the use of fewer steps.

Viruses for clearance evaluation and process characterization studies should be chosen to resemble viruses which may contaminate the product and to represent a wide range of
physico-chemical properties in order to test the ability of the system to eliminate viruses in general.

The manufacturer should justify the choice of viruses in accordance with the aims of the evaluation and characterization study and the guidance provided in the guideline.

Viruses can be used in a viral clearance fall into three categories "relevant" viruses, specific "model" viruses and non-specific "model" viruses.

"Relevant" viruses are viruses used in process evaluation of viral clearance studies which are either the identified viruses, or of the same species as the viruses that are known, or likely to contaminate the cell substrate or any other reagents or materials used in the production process.

When a "relevant" virus is not available or when it is not well adapted to process evaluation of viral clearance studies, a specific "model” virus should be used as a substitute.

A specific "model" virus may be a virus which is closely related to the known or suspected virus (same genus or family), having similar physical and chemical properties to the
observed or suspected virus.

A non-specific "model" virus is a virus used for characterization of viral clearance of the
process when the purpose is to characterize the capacity of the manufacturing process to remove and/or inactivate viruses in general, i.e., to characterize the robustness of the
purification process.

Examples of viruses which have been used in viral clearance evaluation studies, introduced in ICH-Q5A "Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin".

• Vesicular stomatitis virus
• Parainfluenza virus
• MuLV
• Sindbis virus
• Bovine viral diarrhea viruses (BVDV)
• Pseudorabies virus
• Poliovirus Sabin Type 1
• Encephalomyocarditis virus (EMC)
• Reovirus 3
• SV40
• Parvoviruses

Viral clearance studies are conducted by scaling down the manufacturing process.

Each factor reflects the actual manufacturing process.

Examples include flow velocity, buffer, column, pH, temperature, protein concentration, salinity etc., if using a chromatography.

It is recommended to evaluate two or more manufacturing processes to verify virus inactivation and capability of removal.

Biomanufacturers need to clarify their approaches and to incorporate viral clearance methods into their processes for validation.

Our approaches to viral clearance studies

For all stages throughout the development, manufacturing and release of your biological product, Eurofins BioPharma Product Testing (Eurofins BPT) network of companies offers comprehensive, fully cGMP-compliant viral clearance services and all of our assays are fully validated to meet regulatory requirements.

Eurofins BPT network of companies offer four service models to fulfill the client's needs.

Level 1- Basic Service:

The client provides all materials and down-scale procedures and performs the study in our viral clearance suites.

Level 2 - Enhanced Service:

The client provides all materials and down-scale procedures and performs all column chromatography steps. Our personnel perform inactivation and virus removal filtration steps.

Level 3 - Full Service:

The client provides all materials and down-scale procedures for transfer to our personnel, who perform all clearance steps.

Level 4 - Turnkey Service:

The client provides a description of the full-scale manufacturing process. Our personnel develop and validate the down-scale procedures and perform all clearance steps.

*Please contact us for the latest availability of Level- 4 services (Noted on 20-Jan, 2022).

For our several study options, the following table shows the client's requirements for each model.

Eurofins BPT network of companies can use all 15 viruses listed below in viral clearance studies.

*: HT Supplement is a mixture of sodium hypoxanthine and thymidine, which is used in media.

**: Hydrolyzed Protein

We have six dedicated viral clearance suites for extensive capacity and timely execution and reporting of study results.

We have multiple HEPA-filtered viral clearance lab and also we are equipped with multiple HEPA chromatography systems. We have other basic lab equipment for viral clearance studies.

We are so confident in our viral clearance technical expertise. We will work with you to design your viral clearance study. Please contact us anytime.

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