Teva shared details of its approach at Biotech Week Boston, telling delegates modified cleaning-in-place (CIP) and sterilization-in-place (SIP) processes allowed it to increase the lifespan of a batch MabSelect SuRe Protein A resin from around 100 to 150 monoclonal antibody production cycles.
“We have introduced a new SIP and CIP strategy to regenerate and clean MabSelect SuRe chromatography resin and we found Protein A lifetime stability has been improved,” Lu Wang, senior scientist in CMC Development of Teva Biopharmaceuticals, said.
Increased life of Protein A resin can have cost advantages. The resin costs $12,000 per litre - it needs to be made under GMP compliant conditions - and, according to some analyses, accounts for as much as 30% of the total cost of making a monoclonal antibody.
“We all know this resin is expensive so we like to use it as long as we can if possible. In order to achieve this goal we need a robust and efficient CIP and SIP strategy,” she said. “This can help us ensure the product quality improve the resin’s lifetime and help us save production cost.”
Teva's strategy was to look at how concentrations of chemicals used in CIP/SIP could be used to extend the life of the resin without compromising its efficacy or the efficiency of the processes.
The new SIP strategy involved reducing NaOH concentration to 100mM from the standard 200mM, she said enhances resin stability and prolongs its life time, while adding a 1% benzyl alcohol solution to improve microbial killing efficiency. The CIP change added a 2% benzyl alcohol solution in 100mM of acetic acid.
And presenting results of a resin lifecycle study, she said Teva was able to do 150 product cycles on a single batch of MabSelect SuRe - a Protein A resin supplied by GE Healthcare.
“After 150 cycles the yield is maintained at greater than 90%, so we did not see any significant yield reduction. Meanwhile for the monomer percentage purity we analysed after every 20 cycles and we can say the percentage purity is consistent across cycles.”
When asked, Wang told Biopharma-Reporter the CIP/SIP strategy is already being used by Teva in commercial production.