Virus Clearance Validation Services - Confidence®
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.
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.
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.
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 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, ... |
*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, ... |
*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, ... |