Final Word: Regulatory Evolution

How much do regulatory agencies know about nanotechnology or microfluidics? Yesterday, the answer was probably, "not much." Tomorrow, it may be "a lot." The reason is that new technologies push the agencies to expand their expertise.

Benjamin Locwin

Let's think about how the coyote alters the appearance of the hare over millennia. The coyote's pursuit of the hare changes the abilities of the hare by selecting for hares that escape capture. As the hares become faster or more stealthy, the coyotes must adapt to continue their pursuit. This changes the form and function of both entities.

This selection of better-adapted organisms over time is similar to the evolution of drug products and their regulation. The pharmaceutical industry advances at a rapid pace, and the regulatory agencies must keep up. The agencies themselves encourage industry advances, by requiring a certain amount of continuous rigor.

Is there a limit to this growth and evolution? In the microprocessing industry, Intel's cofounder Gordon Moore proposed a relationship ("Moore's Law") that roughly states that the number of transistors on a microprocessor will double every 18 months.¹ According to Moore's Law, the upper limit of this growth is determined by the inability of the chips to remove as much heat as they produce in the process of doing work.

So what governs the growth of pharmaceutical drug releases per year? And what is the upper limit? It would be difficult to determine a simple factor, like microprocessor heat, that limits the growth of drug products, because unlike transistors, drug development is not easy to quantify.

One limiting factor may be regulatory expertise and resources. As drug product complexity grows, the multidisciplinary demands on the regulatory agencies increase. Reviewers with more in-depth knowledge in a broader range of disciplines are needed to evaluate the long-term safety and efficacy of new submissions. And regardless of expertise, it may simply take longer to evaluate more complex submissions involving new technologies.

This pressure tends to divide the interests of the regulatory agencies between rapid release to market of new products, and the thorough evaluation of all of the new technologies.

So far, the regulators have not slowed down the speed of reviews. During the last eight years, the FDA's median review time for new drug applications has remained fairly constant, at about 12 months.² But how long will this trend continue? And how big will the agencies need to become to ensure their knowledge base keeps up with the varied pharmacological products, delivery technologies, and treatment methods into the future?

To continue to keep review times constant in an increasingly complex environment, one of two things must happen: 1) the relative review time per information piece must decrease; or 2) the resources to review each information piece must increase. Thus, we have a choice: either we understand that review times will increase in the future, or we equip regulatory agencies with extraordinary resources to keep review times short.

The co-evolution of drug development, production, and regulation isn't always seamless, but it is always valuable. I'd like to think that each year drug products get better and many lives are saved by avoiding the mistakes we made five, ten, or fifty years ago, because our systems have evolved to catch yesterday's pitfalls. Even if the evolutionary price of this improvement is that review times increase, that price is worth paying because it ensures better, safer products reach the market.

Benjamin Locwin is a project manager for operations excellence at Lonza Biologics, Inc., 603.610.4682, ben.locwin@lonza.com

REFERENCES

1. Moore GE. Cramming more components onto integrated circuits. Electronics. 1965 Apr: 114–117.

2. US FDA. Approval times for priority and standard NDAs and BLAs, 1993–2005. Rockville, MD; 2005. www.fda.gov/cder/rdmt/NDAapps93-05.htm.