Safeguarding Your Products with Comprehensive Viral Safety Testing

The viral safety testing strategy for biologics is crucial in ensuring the safety of these products before they are advanced into clinical studies and released onto the market.

According to current regulations, viral safety testing is mandatory for:

  • Starting materials used in biomanufacturing, e.g., cell banks, viral vectors, virus seeds
  • Process intermediates, e.g., bulk harvests
  • Biological raw materials
  • Biological products, e.g., vaccines, cell and gene therapy products

Charles River offers a portfolio of state-of-the-art virus detection methods. Methods can be chosen and customized to address your specific concerns and needs, ensuring that an appropriate testing strategy is designed for your product. Fast Track Testing is also available for a quick delivery of urgently needed results.

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A Guide to Viral Assays

Viral safety testing assays detect and, if necessary, quantify unwanted viral contamination in biological products, utilizing methods such as in vitro cell-based assays, molecular assays, and in vivo animal assays. A comprehensive strategy combines these assays to assess cell banks, raw materials, and manufacturing processes, employing both broad-spectrum and specific detection, alongside robust viral clearance studies to demonstrate that processes effectively remove or inactivate potential viruses.

Laboratory technician performing biologics testing

Risk-Based Strategies for Viral Safety Assurance
A CMC expert team developed a risk assessment template focusing on prevention and detection, particularly for CAR-T products, due to limited guidance and unique product characteristics.
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General Virus Detection Assays

  • In vitro Adventitious Agent Testing (14- and 28-day adventitious virus assays) - Our adventitious virus assays allow for the detection of low-level viral contaminants. We have a wide range of cell line and virus combinations available for use based on the nature of your sample.
  • In vivo Adventitious Agent Testing - In vivo assays for the detection of inapparent viruses using adult and suckling mice, eggs, and guinea pigs.
  • Transmission Electron Microscopy (TEM) - GMP-compliant, validated state-of-the-art digital TEM analyses for cell substrates and bulk harvests are performed by our partner ATEM Structural Discovery. TEM is used to characterize and quantify specifically the retroviral burden in cell substrates and bulk harvest samples. It also detects adventitious viruses and other microbial contaminants.
  • Next Generation Sequencing (NGS) – Use our NGS services for adventitious virus detection and genetic characterization of cell lines under GMP conditions, with comprehensive data analysis so you can make critical decisions. Our advanced services set new standards, replacing conventional methods with faster, safer, and animal-free alternatives in biologics testing.
two Charles River scientists working on next-generation sequencing

Next level viral safety testing
Biologics are vulnerable to viral contamination, posing a risk to patient safety. This whitepaper discusses traditional detection methods and their limitations and demonstrates how validated NGS technology can enhance viral safety testing, ensuring reduced risk and expedited market access.
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Specific Virus Detection Assays

  • Bovine and porcine viruses (9 CFR tests) - Our porcine and bovine adventitious agent assays follow for 9 CFR-compliant detection of viral agents in fetal bovine serum, porcine trypsin, porcine pepsin, cell-free supernatants, cell lysates, and other bovine and porcine products.
  • Mouse, hamster, and rat antibody production (MAP, HAP, RAP) tests for rodent viruses
  • NAT-based methods (PCR, RT-PCR) - We offer standard qPCR and ddPCR based methods for detection and, if needed, quantification of RNA and DNA viruses. Rapid, sensitive, and specific broad-range PCR assays for adenoviruses, herpesviruses, papillomaviruses, and polyomaviruses are also available. Please contact us for customized method development.

Retrovirus Detection Assays

  • XC plaque assay - Our assays for extended and direct XC plaque assays allow for the detection and quantification of ecotropic murine leukemia viruses.
  • S+L- focus assays - S+L- assays are available for either direct detection or as an endpoint for other assays to allow for the detection of xenotropic, amphotropic, and mink cell focus-forming murine leukemia viruses.
  • Co-cultivation assays - Our assays co-cultivate test cells with susceptible cell substrates for the amplification of potential infectious retrovirus that would otherwise not be detected by direct infectivity studies. A variety of endpoint assays, including PBRT, and S+L- focus assays, are available for detection.
  • Detection of retroviruses using PCR-based reverse transcriptase (PBRT) assay.
3d illustration of bacteria

Adventitious Agent Testing For MMV: How Much Do We Really Know?
Experts discuss the current state of viral safety testing and the emergence of broad molecular methods, such as Next-Generation Sequencing (NGS), that address some of the gaps in traditional viral safety testing of biologics.
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Frequently Asked Questions (FAQs) About Adventitious Agents

  • What are adventitious viruses?

    Adventitious viruses are contaminating agents that have been unintentionally introduced into the manufacturing process of a biological product. These viral contaminants represent a safety risk and may originate from:

    • Cell substrates used in biomanufacturing (e.g., CHO cells, Vero cells)
    • Raw materials of biological origin (e.g., fetal bovine serum, trypsin)
    • Human handling or environmental exposure

    According to the World Health Organization, adventitious agents (including viruses) are, "Contaminating microorganisms of the cell culture or source materials that have been unintentionally introduced into the manufacturing process of a biological product."

  • Why is adventitious virus testing important?

    For any vaccine, medicine, or therapy produced using biological materials, there is the possibility that those materials may be contaminated with viruses and other infectious agents. If those contaminants are given to animals or humans, there is the risk that they could cause serious disease. To ensure the safety of biologics, regulatory agencies worldwide have developed guidelines for adventitious agent testing, including viruses.

  • What are the regulatory requirements for viral safety testing?

    Regulatory bodies like the FDA and EMA have specific guidelines and expectations for viral safety testing in the development and manufacturing of biological products. These regulations are centered around risk-based principles and mitigation strategies, with a particular focus on the ICH Q5A(R2) guideline on viral safety evaluation. These guidelines also emphasize the reduction, refinement, and replacement of animal testing where possible, promoting the use of NGS and other in vitro methods.

  • What types of products require viral safety testing?

    Viral safety testing is mandatory for medicinal products derived from human or animal cells such as recombinant proteins, monoclonal antibodies, vaccines, and cell and gene therapy products. It is also required for blood products and medical devices that contain a biological component.

  • What is Next Generation Sequencing?

    Next Generation Sequencing (NGS), also known as high-throughput sequencing, is a molecular technique that allows for the comprehensive sequencing of nucleic acids in biological samples. NGS is increasingly being adopted in viral safety testing for biopharmaceuticals due to its broad, sensitive, and rapid detection capabilities. ICH Q5A (R2) guideline recognizes the potential of NGS to supplement or replace current viral safety tests.

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