(242c) Launching Clinical Antisense Oligonucleotide Manufacturing Capability in a Biologics Company

In 2013, Biogen entered into a series of agreements with Ionis (then Isis) Pharmaceuticals to develop a pipeline of oligonucleotide-based molecules to treat neuroscience diseases like Spinal Muscular Atrophy, ALS, and Alzheimer’s. Since the launching of this partnership, Biogen and Ionis have successfully brought to market a groundbreaking therapy for SMA and have transitioned six other oligonucleotides from research to development. In 2016, the antisense oligonucleotide manufacturing industry was saturated with demand as this industry began to take off. Based on limited existing capacity in ASO manufacturing and Biogen’s growing ASO pipeline, the company made the decision to internalize the capability to supply ASOs for their clinical and commercial products. Biogen is the first innovator to invest internal capital on an ASO facility, while others have chosen to outsource. By vertically integrating their ASO supply chain, Biogen has been able to significantly reduce turnaround time and reduce supply risk.

Biogen has historically been a protein therapeutic company, however in the last several years they have broadened their scope to include small molecules, antisense oligonucleotides, and gene therapies. However, their business processes were built to support biologics. There were many challenges associated with internalizing a new manufacturing platform inside a biologics company, which required creative solutions by the project team and focused execution. Among those challenges was establishing a manufacturing operations staff using only internal staff who had experience in biologics or small molecules, but not in ASOs. Staff selection, structure and culture building were key in enabling team success. The team leveraged their partnership with Ionis and with their technical development colleagues to accelerate learning concurrently with starting up a new factory.

The startup activities occurred over a period of about 17 months from capital funding approval to completion of the first clinical batch. The construction and tech transfer teams were closely integrated throughout the entire project to ensure a coordinated approach and to meet the extremely aggressive project schedule. The first batch demonstrated Biogen’s capability of manufacturing quality antisense oligonucleotides in their new manufacturing facility.