Understanding the end-to-end management of chemistry, manufacturing, and controls (CMC) resources provides the opportunity to enhance long-term planning, leverage development options, manage resource trade offs, and track progress against plans. The goal is to improve the pharmaceutical development process to deliver the pipeline. This article provides an overview of the organizational structure of Process Research and Development (PR&D) and the CMC teams at Genentech; the alignment of resources based on CMC contracts, process development activity maps and project resource plans; and the business economic analysis for evaluating development options.
Sue E. Steven, PhD, MBA
Genentech, Inc., like many biotechnology and pharmaceutical companies helps patients by developing medicines through great science. The Process Research and Development department at Genentech has three key business imperatives that must be met to support the company's goals. These include (1) deliver the pipeline, (2) be efficient, and (3) innovate.
Deliver the Pipeline
Genentech makes significant investments in research and development in an ongoing effort to discover and develop novel medicines. Consequently, the pipeline at the company is growing rapidly. In addition, Genentech's product platform is expanding from one primarily based on monoclonal antibodies to one that also includes small molecules, antibody-drug conjugates, novel delivery systems and devices, and other protein products. So, from the PR&D point of view, the pipeline is really a collection of distinct "mini-pipelines." Within Genentech, the process development (PD) organization strives to keep CMC activities, where practical, off the critical path in the development of new molecules.
PR&D staff at Genentech review updated PD activity maps.
The lead time to develop PR&D infrastructure (buildings, staff, and equipment) is often greater than the speed at which new molecules can exit research or be licensed in through business development. Readiness to handle the influx from the pipeline cannot depend on a scale up of staff or laboratory space. Moreover, Genentech, like all companies, strives to keep the cost of drug development in check. Therefore, efficiency is essential.
The best way to deliver the pipeline efficiently is to innovate. Innovation may involve expansion of the PD knowledge base with cutting-edge science and technology; the use of science to influence regulatory policy; or application of the latest business practices to streamline activities and decision-making.
This article describes some of the approaches that the PR&D department at Genentech has taken while pursuing these objectives.
PR&D has made several fundamental changes to its functional organization.
1 Bioprocess development (e.g., cell culture and purification) was split into two groups: early-stage bioprocess development and late-stage bioprocess development. Early-stage bioprocess development focuses on developing the upstream and downstream processes needed to produce materials for Phase 1 and 2 clinical trials, and supporting studies. Today, the early-stage group is on the critical path with activities involved in the production of stable cell bank through delivery of good laboratory practices (GLP) supplies for toxicology studies. Therefore, its business focus and improvement efforts are concentrated on speed. Late-stage bioprocess development focuses on delivering the processes and materials for Phase 3 trials. This group must ensure regulatory success in a business environment in which product quality and manufacturing robustness, and efficiency are paramount. These two drivers—speed and regulatory success—result in different, but appropriate, balances of scientific and business approaches in the two groups.