This is the first in a series of columns in which we will explore today's rapid developments in expression system technology. We will identify emerging platform technologies and their effect on yield and quality, as well as regulatory, intellectual property (IP), and royalty issues associated with new expression systems.
BIOPHARMACEUTICAL INDUSTRY IN LIMBOThe need for innovation in the biopharmaceutical sector has a greater urgency than ever before. Our new report, Biopharmaceutical Expression Systems: Current and Future Manufacturing Platforms, explains that biopharmaceutical companies are only now beginning to address strategic innovation at the outset of their drug development processes. This is a recent shift, despite the fact that a range of promising technologies have been made available for some years.2 Even still, many companies continue to rely on outdated expression systems, which may compound the risks inherent in new drug development. This lack of forward thinking risks hampering companies all the way through R&D and is having a stifling effect on biopharmaceutical manufacturing.2 In this increasingly competitive environment, companies are recognizing that they cannot afford to continue along this path.
A DECADE OF DECLINE
As far back as 2001, it was suggested that for the industry to maintain even a modest growth rate, companies would need to triple the number of new molecular entities (NMEs) launched annually.3 Judging by media releases from the top 10 companies around this time period, such targets appeared eminently achievable.4–5 These public statements, however, were often designed to impress the financial sector and meet shareholder expectations. Between 1990 and 2000, pharmaceutical earnings per share increased by an average of 12%.3 Yet year-by-year, new drug output has continued to decline, despite continuing unmet medical needs.
Major companies have often publicized their commitment to innovation by highlighting their heavy investment in R&D, but there are several instances of major companies having struggled to even launch one NME in a given year. In contrast, much smaller biotech firms have frequently been able to outperform their larger counterparts. Financial analyses show that the global pharmaceutical industry is currently investing twice as much in R&D as it was 10 years ago, to generate two-fifths of the medicines it previously produced.6 Many are now challenging the accepted wisdom that increasing R&D investment will automatically generate NMEs. This new view includes evaluating novel expression systems.
INNOVATION REQUIRES EARLY COMMITMENT
Our recent expression systems study shows that despite the difficulties some companies are facing, there are substantial opportunities.2 At present, too many companies have held on to outdated technologies for commercial-scale manufacturing of biopharmaceutical products. Nearly all current products are being produced using E.coli CHO cells, and Saccharomyces as hosts. In effect, the biopharmaceutical sector is relying on technologies that were invented in the early 1970s and commercialized in the 1980s.
Many have shown reluctance to innovate. Many new platforms exist featuring new host cells and organisms, but many managers in biopharmaceutical companies appear to have overlooked their sophistication and increasing availability.2 Of course, regulatory factors play a major role here, as do issues surrounding IP (but even here, as many as 50% of biomanufacturers have indicated they would be willing to pay royalties for improved yield, for example).1