Drug Substance and Drug Product Manufacturing Strategy Assessment for siRNAs

Abstract

Amgen currently has its first siRNA program, Asset #1 in phase 2 clinical trials. Until recently, Amgen has been outsourcing the Drug Substance (DS) and Drug Product (DP) manufacturing to external manufacturers, but with a growing siRNA portfolio even beyond Asset #1, the building of a new facility is of great interest and value.

As there are hundreds of potential manufacturing scenarios, this thesis will first shortlist those into three most feasible ones to be analyzed with a supply chain model and eventually a business model. The supply chain model will include resilience and weak link analysis, which will result in a risk-to-cost input for the overall business model, currently built only for Asset #1 due to limited information on other assets in earlier development phases. The business model, equipped with mixed integer program, calculates the 20-year Present Value of Expense (PV of Expense) to identify the optimal capacity progression and scenario, even beyond the three predefined ones, with the least expense.

It was eventually found that the best scenario is indeed beyond the three predefined ones, suggesting internalization very soon after Asset #1’s commercial launch. However, it is decided on the delay to see what product demand would be, so that Amgen would only invest if the program showed a need/showed a profitable outcome. It is recommended that Amgen keep updating the model and continue monitoring the market to understand supply and demand dynamics on siRNA, as well as innovating on Amgen’s siRNA process.