Biopharmaceutical drug development has been experiencing one of its most productive periods in recent history. During the past decade, the total number of new chemical and biologic entities in the R&D pipeline has been rising 6% each year and now exceeds 10,000 active drug candidates targeting unmet and under-served medical needs .
A variety of discovery technologies have helped drive growth in the drug development pipeline.
To name a few: the speed of DNA sequencing has rapidly accelerated since the first genome was sequenced in the 1970s; high-throughput screening has resulted in a tenfold reduction in the cost of testing compound libraries; and combinatorial chemistry has increased 800-fold the number of new molecular entities to be potentially synthesized .
But throughout this productive period, the biopharmaceutical industry has had to manage a chal- lenging operating environment characterized by increasing costs; inefficient and lengthy cycle times; and high levels of risk, uncertainty, and complexity. Total spending worldwide on biophar- maceutical R&D, for example, will reach a record $140 billion (US$) in 2014, representing a 4.9% compound annual growth rate during the past ten years .
Success rates in bringing a drug from discovery through to commercialization are low and getting worse. Recent Tufts Center for the Study of Drug Development (CSDD) research indicates that only 11.3% of drugs that enter clinical testing will be approved in the United States, down from a 16.4% success rate ten years ago. Since at least 10 years are required to bring a single molecular entity through R&D and approval, the total average capitalized cost to successfully introduce a marketed drug — including the shared cost of compounds that fail in development — now exceeds $2.6 billion [3, 4].
Clinical testing phase durations have not improved since the early 1990s. The average clinical phase duration is 6.8 years and has increased 15% during the past decade. Longer clinical phase durations are in large part a function of the therapeutic classes that dominate research activity (e.g., oncology and CNS) as drugs targeting these diseases require more time to demonstrate safety and efficacy .
Tufts CSDD research has demonstrated that the rising cost and duration of drug development activ- ity are a function of increasing protocol design complexity. The average number of procedures per protocol, average number of eligibility criteria, average number of investigative sites and countries where clinical trials are conducted simultaneously, have all increased dramatically during the past ten years creating more demanding protocols both scientifically and operationally .
Study volunteer recruitment and retention have also gotten far more difficult during the past decade. A Tufts CSDD study of several hundred global clinical trials found that biopharmaceutical companies must typically double the planned enrollment period to give their investigative sites enough time to recruit study volunteers and complete a given clinical trial. Even with extended clinical trial durations, one out of every ten (11%) investigative sites, on average, in any multi-center global clinical trial will fail to enroll a single patient and one-out-of-four (39%) will under-enroll .
Biopharmaceutical companies have not idly accepted the growing challenges to the development
of new drugs. Companies are using a wide variety of innovative approaches to adapt the R&D and manufacturing process to the changing scientific landscape. These innovative approaches to drug discovery, development, and manufacturing shed light on a resilient enterprise making progress in improving the quality, performance and efficiency of R&D and manufacturing. This paper examines some of these approaches and provides profiles of actual examples being implemented by biopharmaceutical companies in the U.S.