Application Number: 35376.1 IP-LS
Application Title: ET_JOIN (Endotoxin_Join)
Health authorities require that pharmaceutical products for humans must be free of cell mass and of highly pyrogenic endotoxins (ETs). Recent downstream processes in biopharmaceutical companies involve a separate clarification and respectively a high cost chromatographic step. The project aims at developing novel multilayer, scalable and high capacity filter sheets/systems that remove cell mass and specifically ETs in one-step. The biotech companies will need to develop/perform only one DSP production step instead of two. DSP will be substantially more economical. Filter development is based on FILTROX owned FILTRODISC™ BIO SD and PURAFIX® ET-R depth filtration technologies. The final aim is to obtain economical, fully functional system(s) with a huge market potential. They will be produced in Switzerland.
Today quantification of ETs is an expensive and tedious task using the common biological tests as the LAL (Limulus Amoebocyte Lysate) assay. These tests do not work for samples with high matrix load (e.g. bioreactor broth) and at high ET content e.g. about 10e9 EU/mL as present in bioreactor E.coli cell suspensions. They have a huge measurement error (LAL test Charles River 200%) and a very small dynamic concentration range, especially making testing of samples with unknown ET content very expensive. During EUREKA/CTI project (17986 “ETpure”), HES-SO Valais established a novel unique chemical HPLC-FLD based ET assay, which allows ET quantification in clarified solutions and filtrates from 10e9 EU/mL to 50 EU/mL with a maximal assay error of 10%. The result is cost efficient monitoring of filter and filtration process development.
During this project, the assay is developed further to allow accurate ET quantification in complex matrices such as cell suspensions or APIs. Furthermore, since the United States Pharmacopeia lists specific maximum ET contents for different drugs ranging from 90 to 0.07 EU/mg, we aim to decrease the current LOQ of 50 EU/mL to 0.01 EU/mL.