Addressing challenges in mRNA manufacturing: Methods of purification

August 22, 2023 by Staff Writer (10 minute read)

Category | Advanced therapy

mRNA skyrocketed to fame during the COVID-19 pandemic thanks to the pivotal role it played in the development of Pfizer-BioNTech’s and Moderna’s vaccines. But beyond its performance in the fight against SARS-CoV-2, today mRNA is also being considered for a variety of groundbreaking applications, including the treatment of conditions such as influenza, HIV, cancer, and genetic diseases. That said, there are several challenges and improvement opportunities when it comes to mRNA process development, one of which includes how to obtain highly pure and concentrated mRNA material for downstream applications. This can be accomplished by both optimizing the IVT reaction, as well as through purification methodologies.

Insufficient purification methods can negatively impact translational efficiency and create risk for developing a product with impurities — such as dsRNA and residual host cell DNA — that may cause an undesired immune response or other adverse effects in the human population. Unfortunately, given RNA’s large molecule size (30 to 50 nanometers), it’s less compatible with traditional chromatography methods used for other types of materials. Adding to the complexity, the impurity profile of mRNAs varies widely from molecule to molecule, so the corresponding purification methods must vary, as well. Commonly used chromatography methods of mRNA purification include reversed phase, ion exchange (IEX), size exclusion (SEC), hydrophobic interaction (HIC), and affinity.

With so many factors to consider, many biotechnology and pharmaceutical companies choose to partner with a CDMO with end-to-end mRNA development and manufacturing experience, including purification. By doing so, they can take advantage of the CDMO’s industry-leading experience with similar types of projects, as well as their advanced equipment and facilities. In Thermo Fisher Scientific’s mRNA process development lab in Monza, Italy, we’re working to optimize the IVT reaction by adjusting buffer components and conditions, which can significantly reduce the number of impurities that need to be removed. Beyond IVT, we’re also working to optimize the purification process leveraging both standard and emerging techniques, and we’re collaborating with customers to develop project-specific strategies to meet their unique needs.

Learn more about our mRNA service offerings, as well as the advantages and disadvantages of different purification methods, by watching our full webinar here.