Part of the Solution: How Purification Experts Make Novel Drugs Safe for Use
Before a vaccine or gene therapy can be submitted to patients, it needs to be free from impurities. A group of purification specialists in a small town in western Slovenia develops innovative technologies that separate right from wrong fast and efficiently – making sure patients worldwide receive safe medication.
This article is posted on Sartorius Blog.
Producing a biological drug is a complex process: Long research for the right candidate is followed by a complex upscaling process until the desired drug can finally be produced in large volumes.
And even then, it’s not ready to be given to patients: It’s not only the desired antibodies that grow in the cell broth, but unwanted by-products like metabolic products, residues of cell culture media, endotoxins or viral particles also find ideal growth conditions.
To get a safe drug, these impurities need to be removed in complex and time-consuming separation processes with products like filters or chromatography devices. While filters separate unwanted molecules based on size, chromatography solutions separate molecules based on criteria like charge, hydrophobicity or affinity to specific ligands. In combination, they get the job done.
The challenge: Purifying large biomolecules for the production of cell and gene therapies
However, there is a challenge: What worked well with the first wave of biopharmaceuticals, for example with monoclonal antibodies, became more difficult with the advancement of cell and gene therapies.
These advanced therapies consist of even larger biomolecules, e. g, messenger RNA, viral vectors or CAR T cells, and are hard to separate with established techniques. For example, traditional chromatography solutions have limited binding capacity for such large molecules, leading to lower yields and less efficient separation. Large molecules also diffuse slowly, which can lead to poor resolution and longer processing times. Their large size can cause clogging in the pores of traditional chromatography media, and flow rate can be limited which makes it difficult to process large volumes quickly.
Separating Right From Wrong
That’s where Sartorius BIA Separations comes in: The company in Slovenia, which Sartorius acquired in 2020, invented a breakthrough technology: Convective Interaction Media Monolith Chromatography.
Purification specialist BIA Separations to become part of Sartorius
“What sounds complex, works – simply put – like a super-efficient sponge. The monolith columns have a sponge-like structure with small, interconnected tubes, that separate what we want to have from what we don’t want to have,” says Dr. Jana Krapež Trošt.
She is Co-Managing Director of Sartorius BIA Separations, responsible for sales of Sartorius’ advanced therapy solutions in the EMEA region and has been with the company for more than ten years.
The clue: “Convective flow overcomes the typical challenges with large molecules as pressure is applied instead of relying on the natural diffusion. This makes the process much faster and allows for quick transportation through the monolith. The large interconnected pores lead to higher flow rates and finally, the large surface area of monoliths in convective flow systems provide higher binding capacities, enabling efficient separation of large molecules like plasmid DNA or messenger RNA,” Jana explains.
These nucleic acids both play crucial roles in the development of cell and gene therapies, where they are used to introduce genetic material into cells to correct or compensate for defective genes.
Getting New Gene Therapies to Patients in Need
“Our monoliths were for example used in the production of Zolgensma, the first gene therapy approved by the US Food and Drug Administration (FDA) for the treatment of patients with spinal muscular atrophy under the age of two,” Jana says.
“The manufacturer struggled to achieve the desired purity of the drug. Through the monolith columns, together, we were able to achieve the purity that was needed to get the drug to market and help kids in dire need for treatment.”
Monolithic chromatography is also used in the production process of other innovative therapies that have recently received further or extended approvals from the FDA.
The products also have a strong presence with a range of novel drug candidates in clinical pipelines.
A Young, Ambitious Team Working on New Developments
And the 250-person strong team in Slovenia is working on further solutions for production, purification and analysis of large biomolecules. With an average age of around 35 years the team is quite young. The majority are PhDs or master graduates with higher education and nearly half of the team is occupied with research and development.
Next on their agenda: sterile chromatography columns for cell and gene therapies.
“We see more and more new and personalized therapies coming to the market, that treat individual genetic disorders or only very small patient groups. These therapies require sterile solutions,” Jana explains.
To meet the needs of the future, a plan to expand R&D and production capacities was formed and the construction of a campus was initiated last year, adding new production capacities that will also include clean rooms allowing for sterile production.
Jana Krapež Trošt, Co-Managing Director of Sartorius BIA Separations, together with Sartorius Executive Board Members Joachim Kreuzburg and René Fáber at the ribbon cutting ceremony for construction start of the Ajdovščina campus in Slovenia
Sartorius initiates construction of Ajdovščina campus in Slovenia
Jana is looking forward to what’s ahead: "For me, it’s hard to imagine working in any other industry once you get a chance to collaborate with our customers. Being part of the solution in developing treatments that give patients hope, where there was none before, I believe, there is no more rewarding work than this.”
