Using Readily Biodegradable Detergents for Viral Inactivation
Viral inactivation is an essential step in the biological manufacturing process. It helps ensure that products are free of viral contamination and safe for human use. Several methods exist to achieve viral inactivation, including using biodegradable detergents. This article will cover how biodegradable detergents can be effectively used for viral inactivation. Biodegradable detergents break down naturally, reducing their environmental impact and minimizing chemical residue, so they are safer for humans and ecosystems.
As global concern for environmental sustainability grows, there is an increasing need to explore eco-friendly alternatives in biomanufacturing. Adopting biodegradable detergents in biomanufacturing processes presents a sustainable and effective solution for viral inactivation, contributing to public health and environmental conservation efforts.
An overview of biodegradable detergents
Viruses can contaminate products during biological manufacturing in several ways, including through raw materials or contaminated cell lines. But no matter how viruses are introduced, viral inactivation is a safety measure that helps mitigate risks and ensures products meet regulatory standards and are safe for human use. Detergents are one of the most commonly used methods of viral inactivation.
Viruses contain a lipid/protein coat called the virus envelope. This envelope comprises a lipid bilayer derived from the host cell membrane, interspersed with various viral proteins. The lipid bilayer is a crucial structural component, providing stability and protection to the virus's genetic material against environmental factors such as enzymes and chemicals that could degrade it. The proteins embedded in this lipid bilayer also play essential roles in the virus's ability to recognize, attach to and enter host cells.
These viral proteins interact with specific receptors on the surface of target cells to facilitate the fusion of the viral envelope with the host cell membrane, allowing viral genomes to enter the host cell and initiate infection. Detergent treatments disrupt the lipid bilayer of an enveloped virus, leading to inactivation.
One challenge with detergent inactivation is environmental concerns about certain detergents. Triton X-100, for example, has been an industry standard for detergent-mediated viral inactivation. However, it has been linked to adverse effects, including acute oral toxicity, eye damage, skin irritation and chronic aquatic toxicity. The European Chemicals Agency (ECHA) added detergent to the list of substances of very high concern (SVHC) under REACH regulations in December 2016. Manufacturers who want to use such detergents in the EU must obtain authorization or an exemption.
Avantor has developed a biodegradable detergent free of alkylphenols that meets environmental, health, and safety (EHS) regulations.
Scientific techniques for viral inactivation
Other techniques for viral inactivation do not use detergents and are commonly used in the biopharmaceutical and biologics industries. Each has benefits and challenges. Some of the most common techniques:
- Low pH treatment involves lowering the pH of the biologic products to acidic levels. That can alter the viral structure or induce aggregation or precipitation of the viral particles.
- Solvent/detergent treatments, such as tri-n-butyl phosphate (TnBP), can disrupt viral envelopes and inactivate viruses. However, this method introduces solvents into the process, which can complicate purification steps and require phosphates to neutralize the solvent's effects.
- Heat treatment applies temperatures of 60°C or higher to inactivate a wide range of viruses. However, heat treatment can damage other molecules, such as proteins or nucleic acids, reducing their activity or stability.
Evaluating the effectiveness of biodegradable detergent in viral inactivation
The effectiveness of one readily biodegradable detergent — JT.Baker® viral inactivation solutions (VIS) — was measured with three different virus models. XMuLV is the most used model enveloped virus in mAb manufacturing. HSV-1 represents herpes viruses and BVDV represents Hepatitis C, a potential contaminant of human plasma-derived products.
The tests measured the efficacy of the detergent at different time points and temperatures. Results showed that J.T.Baker VIS was highly effective at inactivating viruses within one minute and was consistent across all time points. The temperature had little impact on the effectiveness of the biodegradable detergent, even at low temperatures at which viruses are typically more resistant.
These results are important for manufacturers that want to shorten incubation times or operate at low temperatures, as well as in clinical diagnostic applications.
Environmental considerations
Biodegradable detergents can be more efficient than traditional detergents. According to Guideline 301F by the Organisation for Economic Cooperation and Development (OECD), the active detergent present in J.T.Baker VIS is readily biodegradable. Avantor’s biodegradable detergent is not listed on the European Chemicals Agency list of substances of high concern (SVHC).
In addition to inactivating viruses across various operating temperatures (from 4⁰C to room temperature), these detergents exhibit no environmental toxicity for minimal ecological impact. Their use does not compromise product stability or process performance. Any remaining detergent presence can be detected through simple analytical assays and removed in subsequent manufacturing steps. These qualities illustrate why biodegradable detergents are an attractive, eco-friendly, and efficient means of neutralizing enveloped viruses in biologics production.
To learn more about biodegradable detergents and get detailed explanations of the studies described above, read Enhancing Virus Clearance Process Capability Using a Biodegradable Detergent from Avantor. Technical specifications and compatibility reports for J.T.Baker® viral inactivation solutions can be found here.