Speed Matters: Gene to GMP in Nine Months

The 2018 BPI Theater at BIO

Igor Fisch, chief executive officer, Selexis, SA

Fisch first posed this question: “How can we accelerate the number of drugs going into the clinics?” Speed matters because the faster a drug can get into clinical testing, the faster it can make it to market. He discussed both Selexis and KBI Biopharma and their collaboration, which started in 2012 when KBI developed a heterodimer purification process. JSR acquired both companies with an interest in entering the life sciences business.

Selexis has best-in-class cell-line development and manufacturing. It has been a part of more than 100 clinical programs, three commercial products, 154 patents, and nine key technology launches. KBI has 101 product development programs, 101 manufacturing batches, over 12 investigational new drugs (INDs) per year, and more than 240 analytical services projects. It has collaborated on 10 Selexis cell lines.

Using the SUREtechnology platform, the companies work together for speed and high-performance research cell banks. This platform includes advanced gene transfection technology and procedures with proprietary vectors; the solid foundation of a proprietary CHO-K1 cell line, media, and feed strategies; and now whole-genome sequencing of the Chinese hamster ovary (CHO) cell line with full annotation of its genes. That has led to understanding the complexities of the CHO-K1 cell line and an ability to certify and authenticate recombinant cell lines, provide complete regulatory packages, and barcode recombinant cell lines in the future.

Fisch described the workflow from transfection to a pool of possibilities to the top four clones to testing. He described KBI’s abilities in analytical services and innovation using new equipment and technologies. For example, KBI was the first CDMO to implement 2,000-L single-use CGMP operations. Because of KBI’s analytical know-how, the company can work on an upstream process for a product that still is at the pool stage. Titers have been measured for monoclonal antibodies (MAbs) at 9.5 g/L and for bispecifics and Fc-fusions at 6.4 g/L. MAb and non-MAb process platforms provide titers of 2–10 g/L.

From DNA transfection through developing a research cell bank to producing a drug substance with all necessary process and analytical development, timelines of nine months are achieved. Analysis includes considerations of clonality, purity, transgene integrity, site of integration, and gene surveys that identify mutations and adventitious agents.

The next challenge is to speed up that process even more and deliver in six to eight months. One improvement is to deliver a clonal research cell bank in nine weeks. A second strategy is to improve the original host cell line by creating virus-free CHO cells and developing a platform process, both upstream and downstream, to go with it for which fewer purification steps will be needed.

“It takes a village to make a MAb.” Drug discovery programs can range from three to five years, then a company must overcome challenges such as the cost of manufacturing, safety, and markets for the drug. Finally, the cell clone must be produced. Then the decision is made whether to proceed. Good partners such as Selexis and KBI can help to make these steps and decisions easier.