Session 6: Oligonucleotide Synthesis: Overcoming Production Scale Limitations
4:00 PM – 4:45 PM | East Red Level, Suite 10
Given the relative novelty of oligonucleotide synthesis process technologies, the current method of DNA/RNA synthesis is primarily carried out at the laboratory scale (batches less than 1 mMol). As large-scale facility designs become more prevalent, scaling up from the pilot lab environment to a robust, full production-scale facility presents unique infrastructure challenges. A phased approach to designing a facility of this complexity is a necessary, but challenging step that allows for production at current capacity and room for future expansion. The engineering design team (DPS) and process technology team (clients) have to work closely together to understand equipment and material flows, scale limitations for batches, and intended operational philosophies of each unit operation. Designing a facility for any technology is highly dependent on scalability and forecasted market trends, but oligonucleotides have specific limitations when scaling up, including: 1. Raw Material Preparation – From bottles and bags to stainless vessels, preparation and distribution of raw materials presents a stark contrast from existing operations in a facility looking to scale-up. Flexibility, portability, and ease-of-operation all come into question when manual procedures in a benchtop fume hood become full-size solid weighing and dispensing, closed solvent charging, and pressure-transferred operations. 2. Equipment Selection – Process skids, distribution equipment, and utility systems must be viable across all production scales. A balance between dedicated equipment for increased capacity and mobile equipment for flexibility must be met to meet all levels of manufacturing need. 3. Solvent Usage – Logistics for distribution of fresh solvents and disposal of solvent wastes become problematic when transitioning from bottles and drums to reusable containers and tank farms. At larger scales, an efficient solvent recovery system is paramount to managing distribution issues with truck traffic and delivery, waste disposal, and excess costs associated with both.
Speaker: Jeff Heil, Processing Engineering Discipline Manager, Arcadis DPS Group
Jeff Heil brings over 15 years of process engineering and technical project management expertise in a diverse portfolio of engineering applications. He is a subject matter expert in mRNA, oligonucleotide, and vaccine development – working on some of the most notable projects in the United States. He has unique insight into the design challenges associated with the processing of compressible, multi-phase, and hazardous materials in brownfield and greenfield applications. Jeff is also experienced in the design and validation of process safety systems, providing independent technical assurance of engineering work, and working directly with clients to solve complex engineering problems in a variety of applications.