The future of drug development and the FDA’s Critical Path Initiative

The advances in biomedical research during recent decades have created great expectations for the pharmaceutical industry to generate new, safe and effective therapies. However, there are some signals of serious limitations in its ability to meet these expectations.

For example, in spite of millions of dollars spent on preclinical testing, only one in 10 drugs that enter clinical testing receive eventual approval from the FDA.

Likewise, in spite of millions of dollars spent for phase 1 and 2 research that indicate that a drug should have clinical utility, it has only a 50% chance of success in phase 3. Furthermore, the recent high profile drugs that have been removed from the market due to safety problems are another sign that the current drug development process needs to be examined.

A wake-up call

In March 2004, the FDA released a report entitled “Innovation or Stagnation, Challenge and Opportunity on the Critical Path to New Medical Products.”

Raymond Woosley

This is now generally known as the Critical Path Report because it called for improved methods to move drugs efficiently along the “critical path” from the laboratory to the patient.

The paper contained alarming data on the state of drug development. Although the rising cost of drug development was already widely known, few appreciated that during the previous decade a 250% increase in research and development expenditures was associated with a 50% decline in new product submissions to the FDA for review.

The report also identified the increasing and unacceptable rate of the failure of drugs in clinical development, especially in phases 2 and 3.

The billions of dollars invested in basic biomedical research and development of new medical products are yielding fewer innovative products. The long and expensive process to develop innovative products has become a major impediment for new product development and a disincentive for innovation.

The report concluded that the major contributor to the increasing time and inefficiency in development was the absence of innovative new methods for preclinical and clinical testing of drugs.

Figure 1A. Biomedical research spending. Source: FDA

The FDA’s recommendation

In March 2006, the FDA released the Critical Path Opportunities List of 76 projects that they believe, if pursued, will increase efficiency, predictability and productivity in the development of new medical products. The projects fell into six general topic areas:

• Biomarker development
• Streamlining clinical trials
• Bioinformatics
• Manufacturing
• Antibiotics and countermeasures to combat infection and bioterrorism
• Developing therapies for children and adolescents

The report called for a national infrastructure to support and continually improve the Critical Path sciences and new ways to collaborate and share data to accomplish common goals. The FDA correctly notes that no single company, university or government agency will be successful with these tasks and that collaboration will be essential.

In most industries competition fosters innovation, but competition can also foster stalemates and stagnation when there is an absence of standards and core technologies required for process improvement.

Figure 1B. Submission of medical innovations for FDA review Source: FDA

Lessons from other technologies

In the 1980s, the semiconductor industry was facing a crisis due to high rates of computer chip failure and aggressive competition from Asia. Semiconductor Manufacturing Technology, a public-private partnership, was jointly created by the U.S. government and 14 chip manufacturers and has been credited with bringing the U.S. industry back into international competitiveness.

The food industry created the Center for Food Safety Technology and the cable industry created CableLabs. The goals in each case were to develop the standards that were needed to advance the entire industry and to conduct research that served all companies.

In recent months, the FDA and the pharmaceutical industry began new collaborations and consortia to conduct the needed work called for in the Critical Path Opportunities List.

Conclusions

Advances in pharmaceutical and biomedical technologies are a major component of global efforts to improve public health and well-being. Unfortunately, until recently, little attention has been given to modernization of the processes for developing and testing new medical products.

The FDA’s Critical Path Initiative has clearly defined the problems and laid out a path to correct the deficiencies that have led to the declining efficiency of development.

New and sustained collaborations are essential but, for them to succeed, society must find ways to fund and reward work that is not glamorous but is essential process improvement.

Raymond Woosley, MD, PhD, is Vice President for Health Sciences and Dean of the College of Medicine at the University of Arizona. He is section editor of the Cardiovascular Pharmacology section of Cardiology Today’s Editorial Board.

For more information:

• Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov. 2004;3:711-715.
• Mervis J. Productivity counts--but the definition is key. Science. 2005;309:726.
• FDA. Innovation or stagnation: challenges and opportunity on the critical path to new medical products. 2004; http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html.
• FDA. Critical path opportunity list. 2006; http://www.fda.gov/oc/initiatives/criticalpath/reports/opp_list.pdf.
• Irwin DA, Klenow PJ. SEMATECH: purpose and performance. Proc Natl Acad Sci USA. 1996;93:12739-12742.