Janssen Biotech Inc. signed an agreement with Genmab on August 30th, 2012, for the rights to develop, manufacture and commercialize Daratumumab (DARZALEX). The drug substance process used to generate material at that time was suitable for Phase 1 supplies, but was not commercially viable and not consistent with the Janssen mAb platform so a conscious decision was made to modify the process to fit the Janssen platform once the cell line was made available to Janssen, approximately three months after the deal had been signed. Daratumumab received Breakthrough Therapy Designation from FDA in May, 2013 which further increased projected material demands. Overall, the following process changes were made in the six months prior to scale up and the start of large scale clinical manufacturing: the basal medium and all feeds were changed to the Janssen platform through a series of cross company, cross site nested design of experiments over a three month period, the downstream purification process was redesigned to introduce commercially robust resins and filters and a more robust control strategy was implemented to maintain control of product quality. The dose and number of patients enrolled in trials which drove a relatively high demand for material early in the program. The first approval for DARZALEX occurred in November, 2015, two months from the date that the Biologics License Application (BLA) was accepted for Priority Review by the FDA and just less than three years from the start of process development. Meeting demands for ongoing clinical programs, a large expanded access program, and projected market demands required very large quantities of product prior to launch. So, although the Gen1 process was reasonably productive, the Janssen Biogen collaboration was again leveraged to rapidly develop and validate a robust second generation process with nearly a three fold increase in bioreactor titer and an intensified downstream process while continuing to meet the complex set of product quality targets determined from the Gen1 product. This work required both companies to work closely and contribute prior knowledge and expertise to the program.

How the Janssen-Biogen partnership enabled delivery of a breakthough therapy for multiple myeloma patients and rapid process optimization to meet market demand

255th National Meeting (2018)

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