Improving Success Rate
To reduce the risk associated with drug development, companies have been analyzing the time, resources, expense, and expertise they can allocate. As a result, during the 1980s and 1990s, companies were able to improve their success rates for recombinant protein (rDNA) and monoclonal antibody (mAb) therapeutics. The Tufts Center for Drug Development (CSDD) found that the overall success rate for a 1990–1997 cohort of rDNA therapeutics entering clinical trials was 35% compared with only 26% for a 1980–1997 cohort.
Yet, despite these improvements, CSDD identified efficient manufacturing as one of the core areas to be addressed if further advances were to be made in biotech success rates.
BioPlan’s analyses have shown that since the 1970s when genetic engineering was still in its infancy, there has been little basic change in the technologies used for commercial-scale manufacture of biopharmaceutical products. Virtually all current products are being manufactured by the same old, familiar technologies—primarily using E.coli, CHO cells, and Saccharomyces cerevisiae as hosts. Therefore, while cutting edge can be used to describe the general approach to biopharmaceutical drug development, the same term can, by no means, be used to describe the approach to their manufacture.
Certainly, regulatory factors come into play, but this lack of progress is baffling. There have been genuine advances in terms of platform technologies that offer companies significant advantages. This includes vast improvements in product yield and improved product quality and lowered operating and infrastructure costs. Furthermore, in such a competitive field, these technologies can provide a route for innovators to make their products unique.
In fact, the industry has been trending toward engineering its proteins with a focus on improving not just yield but also quality and clinical performance. According to Patrick Lucy, global business development leader for Dowpharma’s Pfenex business, “Expression system platforms today must have the depth and breadth to meet both production and clinical expectations.”
Lucy anticipates an increase in prokaryotic expression platforms due to their short cycle time in the fermentor and ease of genetic manipulation. “We are seeing a steep increase in inquiries from pharmaceutical companies that are now evaluating expression systems that exhibit efficient expression. Some of these companies had previously been defaulting to older mammalian cell culture simply because they have investments in large-scale mammalian production facilities.”
Lucy feels that the older technologies are simply not sustainable over time. “Nearly all of our clients are indicating that they are making these shifts as a result of the high cost of manufacturing a pipeline of new molecules using older technologies. These products could and should be made more efficiently and to higher clinical standards in newer expression systems.”
And, it’s not just microbial systems that are generating interest. “Over the past 12 months, we have seen interest in new biopharmaceutical mammalian expression systems grow rapidly,” explained Andrew Sandford, vp at Selexis. “Already, we have more than doubled the number of companies who have begun to actively change the way they plan their early development and manufacturing strategy. Many are now finding that they are able to start process development four to six months earlier; perhaps 50% have developed cell lines achieving titers of greater than 1 gram per liter productivities in, as yet, un-optimized conditions.”