Virus clearance validation services

Virus Clearance Services

Confidence® Virus Clearance Validation Services

Supporting Biopharma Companies in Successful Virus Clearance

Virus safety is one of the greatest concerns of biopharma and pharma manufacturers. It requires the selection of clean raw materials, testing at various production steps and the clearance of viruses. Clearance is the only means to prevent contamination caused by unexpected viruses, so a reliable clearance process, with proper validation, is essential to guarantee patient safety. Confidence® Virus Clearance Services from Sartorius provide virus spiking studies for purification technologies, as well as expert consultation on process design and optimization. This enables biopharma manufacturers to optimize their processes and increase the potential of successful GLP study completion.
 

  • Short turnaround times as fast as 6 weeks
  • Highly purified virus stocks 
  • LRV determination for all virus clearance steps 
  • Optimized use of Sartorius virus clearance products
  • Joint team experience of over 50 years and 700 completed studies


The Fundamentals of Virus Clearance Studies

In this video, you will learn more about the basic principles of virus clearance studies. In addition, we introduce you to the most important aspects of conducting these studies at Sartorius and give you more details about our virus clearance service offering.

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Why Are Virus Clearance Studies So Important?

Every virus safety strategy is based on three pillars: selection of appropriate raw materials, testing of intermediate samples during production and removal/inactivation of viral contaminants. The latter is validated through virus clearance studies, which are an essential part of a manufacturer’s strategy to ensure product safety. 

Failed Virus Clearance Poses Significant Risk to Patient Safety

The ultimate goal of virus clearance is patient safety. Consequences of Viral contamination can, in the worst–case. cause harm to the patient’s health or cause drug shortage. The table below shows information about frequency and occurrence of viral contamination.

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Source: Nature Biotechnology, 2020 “Viral contamination in biologic manufacture and implications for emerging therapies”. https://doi.org/10.1038/s41587-020-0507-2 

Virus Clearance Validation is a Regulatory Requirement

Virus clearance is a regulatory requirement to ensure patient safety. To ensure that a manufacturer’s purification processes can deal with the unexpected, regulatory bodies implement the three basics of virus safety: Selection, Testing and Reduction.

FDA:

“Retrovirus clearance studies should be performed prior to Phase 1 trials”  

“Clearance studies for other viruses and/or other contaminants should be carried out prior to production for Phase 2/3 trials and may need to be repeated if the final manufacturing process has changed. “

Source: Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use, 1997  (FDA-1994-D-0318)

ICH Q5A:

“Careful design of viral clearance studies using different methods (orthogonal) of virus inactivation or removal in the same production process in order to achieve maximum viral clearance”  

“Viral clearance evaluation studies are performed to demonstrate the clearance of a virus known to be present in the MCB and/or to provide some level of assurance that adventitious viruses which could not be detected, or might gain access to the production process, would be cleared.”

Source: Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin, 1997

EMEA/CHMP/BWP:

“prior to Phase I studies, ...,, the process should be evaluated for the inactivation/removal of an enveloped virus and a small non-enveloped virus, unless otherwise justified. Two orthogonal steps should be assessed, if possible.”  

“Whenever significant changes... in the manufacturing process are made... additional virus studies may be needed.”

Source: Guideline On Virus Safety Evaluation Of Biotechnological Investigational Medicinal Products, 2008 EMEA/CHMP/BWP/398498/2005 (2008)

How Reduction is Done: Exemplary mAb Purification Process

Virus clearance approaches for the biopharmaceutical industry require individual, scalable and flexible process solutions based on different technology platforms. Sartorius’ unique and orthogonal virus clearance technologies features virus removal by virus retentive filtration and membrane chromatography, as well as low pH virus inactivation. 

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How Is a Virus Clearance Validation Study Structured?

Virus clearance studies can be subdivided into three phases: the pre-study, the main study and reporting. During clearance studies, purified virus stocks are deliberately spiked into the unit operation start material. A scaled-down model of the manufacturing environment, adhering to the customer process conditions, must be chosen.

The Five Basic Steps of a Virus Clearance Validation Study

Step 1

Customer-Specific
Study Design

Depended on customer's requirements the study will be planned & designed

Step 2

Spiking & Determination
of Initial Virus Load

Spiking of customer product determination of total virus load in start material

Step 3

Execution of
Virus Clearance Step(s)

Execute down-scaled virus clearance step(s) - samples assayed

Step 4

Calculation of LRV

Determination of total virus load in product-containing fraction and consequently calculation of the log reduction value

Step 5

Assessment / Report

Result captured in assessment and creation of validation report

How We Help You to Succeed

The Confidence® Virus Clearance Services Packages

Confidence® Virus Clearance Services are unique to the industry. Sartorius expertise spans both virus clearance services and our specific clearance technologies, making it possible to provide a holistic solution to the customer. Our services are commonly combined with Sartorius' Virosart® virus filters and Sartobind® membrane adsorbers, though products from other suppliers or other technologies, such as resins and low pH, can also be available. 

Package

Basic

Advanced

Customized

Cytotoxicity test

Viral interference test

Virus titration (per run)

4x

MVM: 8x / MuLV: 5x

Flexible

Large-volume plating

5x

5x

Flexible

Supply of virus

Variable*

Variable*

Variable*

Documentation and flux data

Viruses available

MVM & MuLV

MVM & MuLV

MVM & MuLV, Reo-3, PRV, ...

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*Depending on filter size and spike ratio

Package

Basic

Advanced

Customized

Cytotoxicity test

3x 

3x 

3x 

Viral interference test

Virus titration (per run)

4x 

8x

Flexible

Large-volume plating

5x

5x

Flexible

Supply of virus

Variable*

Variable*

Variable*

Documentation and flux data

Viruses available

MVM & MuLV

MVM & MuLV

MVM & MuLV, Reo-3, PRV, ...

Request a Quote

Request a Quote

Request a Quote


*Depending on membrane size and spike ratio

In addition to virus filters and membrane adsorbers, our services also support resins and low pH purification steps. These latter processes can be highly variable, so we recommend that you contact us for a quote.


Package

Customized

Cytotoxicity test

Viral interference test

Virus titration (per run)

Flexible

Large-volume plating

Flexible

Documentation and flux data

Viruses available

MVM & MuLV, Reo-3, PRV, ...

Request a Quote

Preventing Unexpected Results in a GLP Study

Learn how Virus Clearance Feasibility Studies can help you avoid development delays and cost overruns.

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Downloads

Flyer: Confidence® Virus Clearance Services

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