Surfactants in bioprocessing: Addressing environmental concerns and the call for sustainable alternatives

Triton™ X-100 (tert-octyl phenyl ethoxylate) is a widely and extensively used non-ionic detergent in the biopharmaceutical industry, particularly in the manufacture of biologics, plasma-derived products, and cell and gene therapies (CGTs). It is favoured due to its ability to disrupt biological membranes without harming proteins, making it effective in applications such as cell lysis and the inactivation of adventitious lipid-enveloped viruses that may contaminate biologic manufacturing processes using human and animal cell lines. However, despite its usefulness in these areas, Triton™ X-100 poses significant environmental risks due to the degradation of its by-products.

Triton™ X-100 degrades into 4-tert-octylphenol (4-tert-OP), a persistent, bioaccumulative, and toxic (PBT) substance. The European Chemicals Agency (ECHA) has classified 4-tert-OP as a substance of very high concern due to its serious and probable effects on the environment, particularly as an endocrine disruptor. Once released into the environment, Triton™ X-100 and its degradation products, including 4-tert-OP, do not readily break down and can accumulate in aquatic organisms. This leads to long-term environmental persistence, affecting not only water bodies but also the soil. The accumulation of 4-tert-OP in the tissues of aquatic organisms poses risks to the broader food chain, potentially impacting fish, birds, and mammals by disrupting their endocrine systems. Additionally, photodegradation of Triton™ X-100 in water can lead to changes in its chemical composition, altering its toxic effects on different aquatic organisms. Therefore, both Triton™ X-100 and its photodegradation products must be considered when managing water environments contaminated with this chemical.

As a result of these environmental risks, ECHA added Triton™ X-100 to the Candidate List of Substances of Very High Concern in 2017 and placed it on the Authorisation List (Annex XIV), effectively banning its use in the European Union as of January 4, 2021, except for a small number of publicly listed exemptions. Pharmaceutical manufacturers operating outside the EU, however, continue to use Triton™ X-100. In light of the growing global awareness of the chemical’s harmful environmental impact, regulatory bodies, such as the United States Environmental Protection Agency (EPA), recognize the need for action.

The industry is responding to the rising demand for sustainable alternatives. The recently revised ICH Q5A(R2) “Guidance on Viral Safety Evaluation of Biotechnology Products Derived from Human or Animal Cell Lines,” adopted in November 2023, acknowledges this shift. It encourages the exploration of alternative detergents with similar physicochemical properties and equivalent XMuLV inactivation capabilities as Triton™ X-100, highlighting the industry’s efforts to mitigate its environmental footprint.

While Triton™ X-100 remains an important tool in the biopharmaceutical industry, its significant and long-lasting effects on the environment—especially its endocrine-disrupting degradation products—have led to its regulatory restriction and a growing demand for safer, sustainable alternatives. As these concerns continue to be recognized globally, the pharmaceutical industry is proactively searching for replacements that offer the same effectiveness without the detrimental environmental impact.

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Source: Croda, EXCLUSIVE WHITEPAPER: Next-generation Triton™ X-100 replacements for pharmaceutical bioprocessing.https://www.crodapharma.com/en-gb/news-and-blog/virodex-whitepaper,

Concerns about Triton™ X-100 have been an ongoing discussion across multiple regulatory authorities around the world. https://www.crodapharma.com/en-gb/news-and-blog/triton-x-concerns,

ECHA Chemical Safety Report. b00aa135-eaed-e3fb-4033-87000df37ecb (europa.eu),

LinkedIn article here

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