Enhancing Workflows in Biologics Drug Substance Process Development Through Automation

Abstract

In the face of increasing competition, increasing pipeline complexity, and increasing resource requirements for bringing new drugs to market, streamlining process development is an important means of controlling costs and achieving competitive advantage in the biopharmaceutical industry. One potential means of achieving such improvements in process development is through the implementation of high throughput technologies, equipment (and associated methods and software) used to generate and process large amounts of data in little time. It is important, however, that implementation of these solutions is optimized across the entire process development organization rather than applications be deployed piecemeal within specific functions.

This thesis develops a framework for identifying promising opportunities for use of high throughput technologies and quantifying the value that can be derived from their implementation. Though the framework is more broadly applicable than just to research and development organizations, the thesis is focused on its application to biologics process development within Amgen. It is used to assess the value of implementing a specific high throughput platform, Sartorius ambr® 250 systems, in upstream biologics process development.

Through mapping and analyzing the workflows of Amgen’s Biologics Drug Substance Technologies (Biologics DST) group, the implementation of this system was identified as a promising opportunity for employing high throughput technologies. In particular, a net present value (NPV) analysis was performed to show that investment in ambr 250 systems is likely to yield a positive NPV. However, the expected NPV depends strongly on both the expected useful lifetime of the systems and their capacity utilization. In addition, high throughput technologies provide substantial upside potential not captured in the NPV. Specifically, for the ambr 250 this includes cutting 6.5 weeks off development time for projects where process development is on the critical path. Using ambr 250 for Process Characterization (PC) on such programs could increase highly valuable weeks of sales.

A framework was also developed for assessing how three models of staffing support for high throughput technologies affect the value that can be derived from their implementation. This framework was applied to the use of ambr 250 systems at Amgen to determine how to realize the maximum possible value from investment in this equipment. The assessment found that a dedicated team model is most likely to successfully facilitate the high capacity utilization and maximum potential useable life that are critical for achieving positive NPV. A formal subject matter expert (SME) model may also achieve these goals at lower cost, though at higher risk. The informal champion model, however, is advised against.

The recommended path forward is to purchase one or two ambr systems to use in Commercial Process Development (CPD) and to establish whether they can be used for PC. Once it is established that the ambr 250 can be used for PC, it is recommended that the existing systems be used immediately thereafter on key projects for which increased development speed can increase speed to market, and that a third system be purchased to expand capacity.

Though this work focuses specifically on process development at Amgen, the frameworks developed herein are broadly applicable to many types of organizations, from R&D to manufacturing to the service sector. In any industry where high throughput technologies exist, these frameworks can be used to identify promising opportunities for their implementation, quantify the value they can provide to determine if investment is worthwhile, and decide how they should be supported to maximize the value realized by the organization.