For oligonucleotide api manufacturers, putting in place capacity and sustainability solutions will be essential to meet increased demand. The molecules will be needed in ever greater quantities to fulfil rising needs as new uses are found in research, diagnosis and drug development. Seamus White, Bachem business development manager, tells Chemical Industry Journal how oligonucleotide therapeutics could simplify the work of pharma and biotech companies.
What motivated Bachem to get involved in the field of oligonucleotides in 2008?
Oligonucleotide-based medicines are increasingly being recognised for their role in treating rare diseases and their potential therapeutic benefits for chronic diseases. It’s likely that as these molecules get the attention they deserve, demand will continue to grow.
At Bachem, we noticed that needs around capacity, cost-effectiveness and sustainability aren’t yet being met in this field. We saw this as an opportunity to support the development of API by taking advantage of existing expertise and equipment, and to expand our customer base.
We believe our work will help our customers make significant, innovative strides in this area and can bring huge improvements for larger numbers of patients by improving supply.
What has Bachem been able to achieve so far?
Our first actions were to buy and install synthesis automates and to dedicate resources to designing and creating a unique cleavage and deprotection system, which is used for complex siRNAs synthesis in multi-hundred gram quantities. This enabled us to release the first GMP batch for use in clinical investigations in 2019.
The qualification of the pilot plant, which will be used for the downstream processing of oligonucleotides, was finalised in 2021, and will enable greater efficiency in processing materials in quantities that fall within the single kilogram range under GMP conditions. Another exciting development has been the recent installation of the first of our large-scale equipment trains. Collaboration with other pharma and biotech companies has already begun for this line, which is designed for oligonucleotides and the process of synthesising multi-kilogram batches.
What are the key innovations in your manufacturing process?
Over the last few decades, we’ve been working to perfect our specialised engineering methods for large-scale solid-phase synthesis, chromatographic purification and lyophilization. Some solutions can be adapted for use with peptide APIs and also for oligonucleotides. A key example of this is crude material purification using MCSGP technology in continuous chromatography mode. We believe that this technology has the potential to reduce both costs and waste. More broadly, we are also utilising the knowledge and experience of our scientists in solid phase synthesis and protecting group chemistry to develop multi-faceted solutions to boost the scalability and sustainability of the oligonucleotide synthesis process.
What are your thoughts on the future market?
The potential for oligonucleotide medicines in curing rare diseases is beginning to be realised, as shown by the approval of 14 medicines by the FDA and EMA. This progress is accelerating, with roughly 200 clinical and 600 pre-clinical trials currently ongoing for oligo-based products. We want to support our pharmaceutical and biotech partners in developing and manufacturing their oligo-based therapeutics, so that they can keep pace with this growing market and make a real difference to patients’ lives.
How is Bachem responding to market demand?
In short, we have to ensure continued investment in our peptide and oligonucleotide manufacturing capacities and capabilities on a global level. This is already beginning with our plans to invest in $500 million worth of new equipment and production facilities in the coming years, and with construction of a new TIDES manufacturing facility at our Bubendorf site. This facility will include further equipment trains to enable the commercial-scale production of oligonucleotide APIs.
What are your predictions for oligonucleotide therapeutics?
The need for progress in regards to the scalability and sustainability of oligo manufacturing will become increasingly clear. Bachem has recently begun an internal innovation programme to find these solutions. We are beginning to observe developments in medicinal chemistry and oligonucleotide conjugation, and the increasing complexity of molecules, with a range of conjugation moieties and backbone modifications. This will allow new pharmaceutical targets outside of the liver to be addressed with oligonucleotide medicines.
What does the future hold for your oligonucleotide treatments?
We believe our therapeutics are well paced thanks to our experience in the conjugation chemistries of peptides, lipids, PEG and many more, as well as our capacity for expert analysis. We hope that our innovations will be transformational for our clients and partners, and, of course, for patients.