By: Nick Hutchinson
Closing gaps and integrating steps
Günter Jagschies (GE Healthcare) challenged five recurring themes that the biopharmaceutical industry often discusses. Jagschies was speaking during a session on Recovery and Purification at the BioProcess International Conference & Exhibition, 2016. He said annual production requirements for MAbs are in the range of 10 kilos to 2 tonnes per year. It is essential that companies meet the market demands from patients and be responsive to new business scenarios while achieving continuous improvement to reduce CoGs and carefully manage the financial resource of the corporation.
Reducing manufacturing costs
Jagschies explained that it is the responsibility of employees working in biomanufacturing to control costs, however, we should recognise that drug product manufacturing costs make-up only 5-7% of drug revenues. Small cost savings in manufacturing are unlikely to have a significant effect on profitability at current drug prices. However, Jagschies believes this could change if drug prices begin to decrease significantly. His analysis showed that the consensus of experts is that the industry can reduce the cost of antibodies to $20-50/g through a number of different routes. The approach that firms adopt will depend on their risk tolerance and commercial judgement.
The biopharmaceutical industry has often tried to increase productivity by generating higher bioreactor titers. 30 years ago, companies considered a titer of 0.5 g/L to be high. Nowadays firms are achieving titers of 7-10 g/L. Jagschies showed that beyond 5 g/L process engineers would get diminishing returns from these efforts if they could not increase facility output. Not only do higher titers make the process slower but they can also change the critical quality attributes of the MAb. Cost reduction requires increased facility output or the use of smaller and lower cost facilities. He proposed that reducing the processing time during seed train operations might allow high facility throughputs. He said that process intensification could allow firms to halve the time for performing bioreactor seed steps.
Novel and disruptive technologies to address bioprocess challenges are often in demand by the industry. Jagschies explained that the industry has evaluated many new technologies, such as precipitation, crystallization or extraction, and there is often evidence that these technologies work well. Yet companies have not necessarily always adopted them. In this opinion, this is because these novel technologies have failed to deliver sufficiently large performance improvements to justify the expense of their implementation.
Larger bioreactor farms
Is there a need for large bioreactor farms? Jagschies believes while these very large scales are still required, MAb titer improvements are allowing annual production requirements to also be met using smaller-scale bioreactors. For example, a facility with 4 x 2000L bioreactors can produce over 400 kilos of MAb each year. This in turn allows for a facility with a smaller footprint and significantly lower costs. He believes that very large bioreactor farms are often not required and he favours a “right-size facility” concept. Jagschies estimates that a 2000 L facility costs between $40-60 million to build these days. Scaling-down the manufacturing facility allows for single-use processing and a significant reduction in CAPEX expenditure giving a company improved cash flows.
The final theme that Jagschies addressed was the need to implement single-use processing. He described data that showed there is still a large amount of stainless steel production capacity. Single-use production capacity is typically of a smaller scale and Jagschies reiterated that both approaches would co-exist within the industry for some years to come.
In Jagschies’ final remarks, he added that due to the work of Genzyme and others, the future of bioprocessing might well be small and continuous.