SAN DIEGO

A MODEL PLANE has just a handful of parts. A Boeing 747 has several million.

This makes sense. Toy planes are small, simple children’s models, while 747s are large, high-performance aircraft that travel over 500 miles an hour with thousands of systems acting together. While the models cost a few dollars each because they are easily made, the commercial 747 jet costs upwards of $225 million because of its highly complex nature, testing and the need to ensure safety. And safe they are: In 2007, there were zero commercial airline deaths in the United States.

This comparison is worth keeping in mind as the debate heats up over “follow-on biologics,” or mimicked versions of fully-tested biotechnology protein drugs. Biologics are today’s most advanced medicines, revolutionizing treatment by providing targeted therapy to victims of cancer and other diseases.

Congressional legislation is pending that would allow follow-on biologics to enter the biologics market with limited testing and safety tracking, similar to a traditional generic drug. Unfortunately, there’s no such thing as a “generic” biologic drug.

In other words, they’re confusing copying a simple model airplane with copying a highly complex, multi-system jet.

Most drugs we’re familiar with, such as the pills we get from the pharmacy, are “small-molecule drugs.” They are simple chemical compounds, and have structures that are easily manufactured and copied identically. Aspirin, for example, is composed of just 21 atoms.

This is why generic forms can be identical to the brand name version and rely on the brand-name company’s testing. And that’s good. Since these small-molecule drugs can be copied perfectly, they don’t need safety testing, cost less to make, and are cheaper. This allows more patients to obtain the benefits of pharmaceuticals.

But biologics are huge. Herceptin, a biologic that’s widely used to treat cancer, is composed of roughly 25,000 atoms. Other biologics are even larger-thousands to millions of times larger.

And biologics aren’t made by combining chemicals in a flask; they’re made by life forms such as cells, yeast and bacteria. Like humans, these life forms exhibit diversity in metabolism and composition, making each’s product a unique, heterogeneous mix that can’t be exactly copied. So follow-on biologics can only be similar, not identical generic versions.

That’s why there is more regulation of biologics. In comparison to common genericized chemical drugs, such as penicillin, which have only 50-60 required manufacturing tests for safety and quality, biologics require much more, at least four times that number, with production capability far more expensive to create and maintain.

So the policy challenge is to provide incentives for innovation while also ensuring that any follow-on forms that enter the market are safe.

Data exclusivity has accomplished the innovation goal for small-molecule medicines. Data exclusivity allows brand-name companies the right to keep data associated with a drug’s development confidential for several years to spur innovation and additional applications for a drug. Such data exclusivity would be even more important for biologics, which are 50-percent more expensive to develop than small-molecule medicines.

Ensuring safety is more difficult. Currently the technology to map out the exact nature of one large biologic versus another is not available. That makes characterization and safety review inexact except through clinical testing in humans.

What that means is that follow-on forms may be different, and may induce unpredictable adverse reactions. Unfortunately, this was illustrated several years ago in Europe. A fully tested biologic created here, which was cooperatively licensed overseas to be made there, induced patients to experience "pure red cell aplasia," whereby their bodies could not make red-blood cells. Patients died, and many are permanently injured. Yet today after eight years of research, the cause of these reactions is still unknown.

If even cooperative company efforts can result in unpredictable adverse reactions, any follow-on products without the benefit of full testing that relies on another company’s safety results surely must be of concern. Recognizing this reality, European Union authorities have developed a system of assessment that requires clinical testing of follow-on products there before approval.

Hence, any legislative effort here for follow-on biologics should learn the lessons of history. Appropriate data exclusivity should be put into place to ensure innovation. Relevant clinical data and testing should be required to ensure safety of any follow-on biologic product being considered for patient use here.

Biologics are the cutting edge and promise of medicine. But we need to safeguard safety of any products that patients are prescribed in our health-care system. As such, we should learn a lesson the aviation world learned long ago: safety is no accident.

Let us hope that policymakers remember that mantra when they consider any regulatory pathways for follow-on biologics.

Bryan A. Liang, M.D., is executive director of the Institute of Health Law Studies at California Western School of Law and co-director of the San Diego Center for Patient Safety at the University of California at San Diego School of Medicine. He is also a pilot and has a law degree.