"One of the greatest thrills of my scientific career has been leading the technical development team that converted a great research idea, antibody-drug conjugates (ADCs), into a commercial product. What amazing opportunities I’ve been given by virtue of working for a company dedicated to trying to improve the treatment outcomes for some of the most challenging diseases."
After earning a Chemistry PhD at MIT in 1981 in the lab of Professor Chris Walsh, I moved west to UC Berkeley for a post-doc in Biochemistry working with Bruce Ames (“Ames test”). More than 30 years later, I still live in Berkeley.
My first, and last, “real job” has been working for Genentech in Process Technical Development. I started out in 1986 as a Scientist in Fermentation and Cell Culture Process Development where my group developed assays for recombinant protein product quality, culture medium nutrients and metabolites, and systems for on-line analysis and control of nutrient feeds. In 1997 I moved to the Protein Analytical Chemistry Department. My current group (of 10 Scientists, RAs, and contractors) is responsible for assay development and product characterization of protein therapeutics in late-stage research through to product launch (and beyond). Since 1999 the major focus of our effort has been antibody-drug conjugates (ADCs) where we’ve been responsible for developing the analytical tools needed to characterize the molecular structure, identify product-related variants, and test for product quality as part of manufacturing.
In addition to being a group leader in Protein Analytical Chemistry, I was also the “part-time” Technical Development Team leader for a commercial product from the time it entered our clinical development portfolio until approval. Our team was responsible for delivering a robust, reliable, and properly scaled manufacturing process and quality control testing required by global health authorities. In addition to its approval by the US FDA, the commercial product is now licensed in over 50 countries including Japan, Canada, Korea, Brazil, and the entire EU. The team is now focused on improving the commercial supply-chain through post-approval changes requiring approval from global health authorities.
The role of the Protein Analytical Chemistry department (PAC) is to focus on analysis and structural understanding of the biotherapeutic products in our development and commercial portfolios. Our scientists are highly collaborative, supporting gRED efforts in Late Stage Research, pre-clinical, and early development, and then working within Process Technical Development to understand the impact of manufacturing processes on the quality of our protein products. As products progress through our clinical pipeline we are responsible for understanding and documenting what molecular changes, if any, have occurred due to alterations in the manufacturing processes. This information is an important element of Investigational New Drug Applications (INDs) for our clinical products and of the BLA/MAA (Biological License Application/Market Authorization Applications) for products being submitted for commercial approval. We play an important role in responding to questions from global health authorities during the review of our regulatory documents. Once a product has been licensed, PAC scientists are responsible for helping teams making post-approval changes that ensure uninterrupted supply to the market.
For the last 15 years my research has focused on developing the analytical tools needed to meet the requirements for a relatively new class of drug; the ADC (antibody drug conjugate). My group’s research has led to a better understand of how the conjugation process and the quality of the constituents of the ADC (the antibody, cytotoxic drug and the linker that holds them together) contribute to the safety and efficacy of the final product. The assays we have developed have formed the basis of the product control strategies that are being used to support our entire ADC platform. We apply state-of-the-art tools (such as mass spectrometry, high performance liquid chromatography and capillary electrophoresis) to characterizing our products and also evaluate novel analytical technologies for the ability to improve our knowledge of our ADC products. We are continuing to work with scientists in gRED to evaluate the next generation of ADCs based on new cytotoxic drugs and new linker technologies.