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 the final product a unique, heterogeneous mix that cannot be copied exactly. So follow-on biologic forms of a drug can only be similar to the original, not identical.
Because of the complexity of biologics, there's more regulation. In comparison with common chemical drugs that can have generic versions -- such as penicillin -- which only require 50 to 60 manufacturing tests for safety and quality, biologics require at least four times that number.
For The Record
Los Angeles Times Tuesday, April 29, 2008 Home Edition Main News Part A Page 17 Editorial pages Desk 1 inches; 36 words Type of Material: Correction
Complex drugs: An Op-Ed article on Monday on subsequent versions of biologic drugs stated that worldwide spending on these drugs is estimated to grow to $10 billion by 2010. The figure should have been $105 billion.
So the policy challenge is to provide incentives for innovation while also ensuring that any follow-on forms of biologics that enter the market are safe.
The key lies in something called "data exclusivity," which is a legal mechanism for allowing a company to keep confidential the data associated with a drug's development. Data exclusivity usually lasts for several years and spurs innovation by protecting new inventions. This is the current rule for small-molecule drugs, and it should be applied to biologics as well. Strong data exclusivity is critical for biologics, which are about 50% more expensive to develop than small-molecule medicines.
However, the current state of science makes ensuring safety of follow-on biologics difficult. Currently, the technology to map out the exact chemical structure and function of one large biologic versus another is not available. That makes safety reviews inexact. And follow-on forms may induce unpredictable adverse reactions.
Several years ago, a fully tested biologic created in the U.S. was cooperatively licensed overseas to be made in Europe. But the new version caused patients to suffer "pure red cell aplasia," whereby their bodies could not make red blood cells. This may have contributed to the deaths of some patients and permanent injury to others. 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 product that does not undergo full testing should be of concern. Recognizing this reality, the European Union has developed a system of assessment that requires clinical testing of follow-on products in Europe before approval.
U.S. policymakers should take note. Relevant clinical data and testing should be required to ensure safety of any follow-on biologic product being considered for patient use in the U.S. And appropriate data exclusivity should be put in place to foster innovation.
If chemical drugs were toy planes, biologics would be 747s, the cutting edge of medicine. Because of their complexity, any follow-on forms must be held to a higher safety standard. As we have learned in aviation, safety is no accident.
