UK project looks to transform oligonucleotide medicines manufacturing
The partners are looking to develop a scalable, sustainable and more cost-effective medicines manufacturing process for oligonucleotides: short strands of synthetic DNA or RNA. They will utilize their combined expertise across scale-up, analytics and process development to achieve those goals.
Oligonucleotides, which are short strands of synthetic DNA or RNA, can be used as medicines by interfering with how genes are expressed. While they have shown success in the treatment of rare diseases, this next-generation therapeutic class is now being explored to treat chronic diseases that affect much larger patient populations, said CPI.
“However, inefficiencies inherent to their existing manufacturing process are limiting the potential of this exciting class of medicines. With many prospective oligonucleotide-based medicines already in development and clinical trials, a cost-effective, sustainable and scalable manufacturing method is urgently required to meet current and future manufacturing needs.”
AstraZeneca has a rich pipeline of oligonucleotide-based drug candidates that reportedly have the potential to benefit from overcoming the challenges of large-scale oligonucleotide manufacturing that this collaboration seeks to address.
The project is supported by the Medicines Manufacturing Innovation Centre, which was established by a collaboration between CPI, the University of Strathclyde, UK Research and Innovation, Scottish Enterprise and founding industry partners, AstraZeneca and GSK, and aims to develop a more agile, responsive medicines supply chain through improved manufacturing processes.
Initial activities will take place at Exactmer’s facilities in Dagenham, London, with the large scale later phases taking place at the Medicines Manufacturing Innovation Centre in Renfrewshire, Scotland.
Inclisiran, a small interfering RNA used in the treatment of atherosclerotic cardiovascular disease (ASCVD), would be the first medicine produced at scale as a result of this collaboration.
The first phase of the project will focus on the development of scale-up strategies for liquid phase processes exploiting Exactmer’s Nanostar Sieving technology, which is based on membrane separation, said the partners.
The project will also aim to enhance the efficiency and yield of the manufacturing process and reduce the consumption of a critical raw material (acetonitrile) of which global supply challenges the feasibility of large-scale manufacturing of oligonucleotides.
It is expected to span three years, with the final output being the demonstration of the commercial feasibility of manufacturing large-scale oligonucleotide batches using these improved methods.
Mene Pangalos, executive vice president, BioPharmaceuticals R&D, AstraZeneca, said: “Recent advances in genomics has led to a myriad of potential new drug targets and with it, the opportunity for oligonucleotide-based therapeutics to have a real impact on disease. Collaboration is essential to advancing science and this project is a great example of bringing the best talent to bear to solve a tough problem.”
Steffen Lang, global head of Novartis Technical Operations, said: “This collaboration is testament to the breadth of our commitment to that ambition, looking not only at the development of innovative new medicines, but also the way in which we optimize bringing those to patients at scale. We are taking this opportunity to explore new and sustainable approaches that will allow us to serve our patients in the best possible way, leveraging the UK’s deep commitment to life sciences.”