Driving Innovation in Sustainable mRNA Manufacturing

July 1, 2026 by Marko Schwestka

Performance while reducing environmental risk

In 2023, global demand for mRNA-based treatments surpassed €16 billion as biopharmaceutical companies accelerated efforts in vaccines, oncology, and personalized therapies. This expanding market highlights two key priorities for mRNA manufacturers: technical excellence and sustainability. Enzyme selection for in vitro transcription (IVT) must now align with regulatory expectations and environmental considerations as well as performance.

Many manufacturers now rank environmental impact among their top criteria when sourcing critical raw materials, underscoring a shift in procurement strategies. Codex® HiCap RNA polymerase sets a new standard for high-efficiency mRNA synthesis by integrating sustainable formulation strategies. The removal of Triton X-100 — identified by the European Chemicals Agency (ECHA) as an environmental concern — demonstrates a commitment to reducing ecological impact without compromising performance.

Analytical data from production lots show Codex HiCap analogue incorporation and consistently low double-stranded RNA (dsRNA) impurities, both critical for product quality and patient safety. This approach demonstrates how anticipating regulatory changes and prioritizing environmentally responsible materials can support robust and reproducible mRNA workflows.

Understanding REACH and Its Impact on Biopharmaceutical Manufacturing
The European Union’s Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation governs the use of chemical substances across industries. Triton X-100 has been classified as a Substance of Very High Concern (SVHC) due to its potential endocrine-disrupting effects in aquatic environments.

Although formulations containing less than 0.1 percent Triton X-100 remain within legal limits, the compound can persist in wastewater and accumulate in ecosystems. As a result, biopharmaceutical manufacturers increasingly view eliminating SVHC substances as both an environmental responsibility and a strategic decision for regulatory readiness. For companies targeting European markets or working with EU partners, removing these substances supports compliance, reduces environmental risk, and simplifies regulatory processes.

HiCap Formulation: Sustaining Performance While Reducing Environmental Risk
Aldevron’s reformulation of HiCap RNA polymerase eliminates Triton X-100 while maintaining performance required for mRNA manufacturing. Alternative detergents were selected and validated through systematic testing across multiple production lots.

Analytical data confirms that the reformulated enzyme preserves key performance attributes. Optimization efforts addressed initial stability considerations, resulting in a formulation that matches the original enzyme’s stability profile. Consistency across batches confirms the robustness of the new formulation while supporting sustainability goals.

Dual Advantage: Performance and Environmental Responsibility
HiCap RNA polymerase delivers two essential benefits for mRNA manufacturing:

• Enhanced cap analogue incorporation efficiency
  Improves the percentage of properly capped mRNA molecules and reduces downstream purification needs.
• Reduced dsRNA RNA impurities
  Minimizes byproducts that can trigger unwanted immune responses, improving safety profiles.

Comparative data indicate that while some enzymes optimize either capping efficiency or impurity reduction, Codex HiCap achieves both in a single formulation. Its REACH-aligned composition further strengthens its value by addressing environmental and regulatory priorities.

Strategic Implications for mRNA Drug Substance Manufacturing
HiCap’s formulation supports several long-term priorities:

• Regulatory readiness
  Removing SVHC substances aligns with evolving global requirements.
• Supply chain transparency
  Clear raw material composition reduces regulatory scrutiny.
• Sustainable manufacturing
  Supports increasing demand for environmentally responsible practices.
• Long-term stability
  Batch consistency reduces the likelihood of future process changes or comparability challenges.

Technical Specifications and Availability
The REACH-aligned Codex HiCap RNA polymerase maintains the performance specifications of the original formulation and is available in research and cGMP grades. Performance characteristics include:

• High cap analogue incorporation efficiency
• Reduced double-stranded RNA formation
• Equivalent stability and shelf life
• Compatibility with standard IVT workflows

Aldevron can provide analytical support, including LC-MS characterization of cap structures and impurity assessment.

Advancing Sustainable mRNA Manufacturing
Codex HiCap RNA polymerase integrates technical rigor with environmental responsibility. Its formulation eliminates substances of concern while maintaining high performance, aligning with industry trends toward sustainability and regulatory compliance.

As the mRNA field continues to expand across vaccines, oncology, and rare diseases, demand for high-quality, sustainable raw materials will grow. Codex HiCap supports this evolution by delivering consistent capping efficiency, reduced impurities, and a REACH-aligned composition.

• Have questions on this topic? Contact Us
• Visit Aldevron’s Codex® HiCap RNA T7 Polymerase page
• Download our whitepaper, Enabling mRNA Therapeutic Development Through Enhanced IVT Capping Efficiency
• Download our whitepaper, Enhancing Safety and Efficacy of mRNA-Based Therapeutics
• Have an idea for a topic? Let us know!

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