Viral Clearance Validation Services
The inherent risk of viral contamination is a commonly known and understood principle among scientists and researchers. Such contaminations can arise from the source cell line (cell substrate) itself or from adventitious viruses exogenously introduced during the production process.
Although biopharmaceuticals derived from cell lines have never been implicated in the transmission of viruses, past instances of contamination have occurred with agents whose presence was not known or even suspected. Therefore, it is critically important, and federally required, that comprehensive measures are applied to such programs to ensure, above all else, patient safety.
Products requiring viral clearance testing:
- Gene therapies
- Monoclonal antibodies
- Recombinant proteins
- Blood products
- Animal/human tissues/fluids products
- Medical devices containing animal or human blood-derived components
- Therapeutic vectors
- Vaccines
Global Viral Clearance Testing Facilities and Regulatory Support
Our facilities in Wayne, Pennsylvania, and Cologne, Germany offer dedicated client labs and private client offices to support maximal productivity during on-site visits.
These sites have an array of fully qualified and validated, state-of-the-art chromatography systems along with a suite of virus filtration equipment. In addition to the dedicated client labs, we are one of the few CROs to offer access to a dedicated lab for blood product viral clearance studies.
Our laboratories in the United States and Europe have the technical and regulatory expertise to ensure viral clearance studies comply with the relevant guidelines in your market:
- US Food and Drug Administration (FDA)
- European Medicines Agency (EMA)
- Paul Ehrlich Institute of Germany (PEI)
- Ministry of Health, Labour, and Welfare of Japan (WHLW)
- Korean Ministry of Health and Welfare (MOHW)
- World Health Organization (WHO)
Your Regulatory Submission, Backed by Three Decades of Experience
Leverage a database of thousands of studies performed by previous clients to guide the development, execution, and evaluation of your next viral clearance study. From downscale assistance to report generation, you can expect a study design, execution, and report that will support your regulatory submission without delay.
Virus Availability
We have a wide selection of both enveloped and non-enveloped viruses available for your viral clearance studies. If you do not see the virus you need to conduct your study, please submit a Contact Us request and let us know what your project requirements are. We can source new viruses from our approved vendor list or coordinate a transfer from one of our many laboratories around the world.
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RNA Enveloped Viruses:
Viruses Family Size (nm) Physicochemical Resistance Human immunodeficiency virus-1 Retroviridae 80-110 Low Xenotropic murine retroviruses Retroviridae 80-110 Low Amphotropic murine retrovirus Retroviridae 80-110 Low Ecotropic murine retrovirus Retroviridae 80-110 Low Bovine viral diarrhea virus Flaviviridae 40-60 Low - Medium Vesicular stomatitis virus Rhabdoviridae 45-100 x 100-430 nm Low Parainfluenza type 3 Paramyxoviridae 100-200 Low Sindbis virus Togaviridae 70-80 Low Porcine Hemagglutinating Encephalitis virus Coronaviridae 60-160 Low Murine Endogenous Retrovirus Retroviridae 80-110 Low -
RNA Non-Enveloped Viruses:
Viruses Family Size (nm) Physicochemical Resistance Reovirus type 3 Reoviridae 60-80 Medium Poliovirus type 1 Picornaviridae 23-30 Medium - High Encephalomyocarditis virus Picornaviridae 25-30 Low - Medium Hepatitis A virus Picornaviridae 25-30 Medium - High Feline Calicivirus Caliciviridae 35-39 Medium -
DNA Enveloped Viruses:
Viruses Family Size (nm) Physicochemical Resistance Pseudorabies virus Herpesviridae 120-200 Low Herpes simplex virus-1 Herpesviridae 120-300 Low Herpes simplex virus-2 Herpesviridae 120-300 Low Infectious bovine rhinotracheitis virus Herpesviridae 120-200 Low Autographa californica nucleopolyhedrovirus Baculoviridae 21 x 260 Low Baculovirus Baculoviridae 200-450 (length),
30-100 (capsid)Low -
DNA Non-Enveloped Viruses:
Viruses Family Size (nm) Physicochemical Resistance Human adenovirus type 5 Adenoviridae 80-100 Medium Simian virus 40 Polyomaviridae 40-50 High Porcine parvovirus Parvoviridae 20-26 High Murine minute virus Parvoviridae 20-26 High Bovine parvovirus Parvoviridae 20-26 High
ClearancePlus℠ Platform
Extensive experience with multiple product types enables us to provide support and advice tailored to each product and its requirements, including downscale assistance, execution of process steps, as well as interpretation and troubleshooting of results.
Features and Benefits
- Risk-based assessments – Comprehensive review of a client’s viral safety testing program, production processes and raw material quality in order to minimize required viral clearance and ensure an economic study design
- Holistic study design – Review of required pretesting, virus spikes, sampling modes, detection methods and assay sensitivities to define the most effective virus clearance study approach
- Optimized sensitivity – Standard inclusion of large volume plating for all product-relevant samples to improve LRV claims and demonstrate effective and robust virus reduction
- Customized service – Extensive experience with multiple product types and purification steps, allowing us to provide support and advice tailored to each product and its requirements, including downscale assistance, execution of process steps and interpretation and troubleshooting of results
- Industry leadership – Application of best practices as determined by performance of internal studies and as presented in multiple viral safety conferences, symposia, publications and technical reports in order to define the most scientifically sound study design
Frequently Asked Questions (FAQs) About Viral Clearance Studies
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What are clearance studies?
Clearance is a measure of the capacity of the dedicated manufacturing process steps to primarily inactivate or remove viruses and transmissible spongiform encephalopathy (TSE) agents.
Viral clearance studies involve deliberate spiking of viruses or TSE agents into process intermediates and then demonstrating their inactivation or removal during the subsequent processing steps.
This is usually done on a scaled-down version – a laboratory version – of the selected process steps.
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What are some examples of viral inactivation methods?
Examples of viral inactivation methods are:
- Low pH inactivation is effective against enveloped viruses
- Solvent/detergent inactivation is effective against enveloped viruses
- Pasteurization, which inactivates both enveloped and some non-enveloped viruses
- Terminal dry heat, which inactivates both enveloped and some non-enveloped viruses
- Irradiation and high-energy light
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Can viruses be filtered?
Viruses can be filtered through the process of nanofiltration, which removes viruses according to their size, while permitting flow through of the desired proteins. A model virus of a specific size will represent all viruses of the same or greater size.
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At what temperature can a virus be inactivated?
The inactivation of a virus requires temperatures of 60°C and above and is highly dependent on the remaining moisture in the sample and the duration of incubation.