Patient Safety Threatened by Biosimilars

The top priority in the development of all medicines must be patient safety. Because of the complex process required to create biologics, the ways in which companies prove safety must be different than traditional chemical drugs. Even a slight change in the manufacturing process of a biologic can cause undetected changes in the biological composition of the product. Those changes can in turn undermine the safety and effectiveness of the drug in patients.

Chemical drugs are typically made by mixing together chemicals in controllable “recipes” that follow the formulas and the predictable rules of organic chemistry. The same final product can sometimes be obtained through a very different process, and the product can be analyzed in a laboratory to confirm that it is exactly what it is supposed to be. It is a relatively straightforward process to show that a generic chemical product is the same as a branded product since ultimately the generic must prove it is identical to the innovator drug, which has already been proven safe and effective, new evidence from clinical trials is not necessary and cannot be submitted in an application for a generic product.

Biologics, on the other hand, are made by genetically engineering living cells that are inherently variable and susceptible to slight changes in their environment that can significantly alter the results they are engineered to produce. Because no two living cell lines are identical and different manufacturing processes will be used, biosimilars will be different than the innovator product.

In addition, the complexity of biologics currently makes it impossible to show in the laboratory that a biosimilar will work the same as the brand name product does in patients. The effects of the differences between biosimilars and brand name biologics can only be determined by subjecting the biosimilar to clinical testing in patients to prove that it is safe and effective.

One unique concern regarding the safety of biologics is immunogenicity. This occurs when our bodies attack a biologic with antibodies. Unlike chemical drugs, all biologics have the potential to stimulate antibody production in patients and such responses are highly unpredictable. Sometimes the antibodies produced in response to a biologic have no effect. In still other cases, biologics have induced “neutralizing antibodies” which both binds to and inactivates the product. Switching back and forth among products might also cause a harmful immunogenic reaction.

The human body is sensitive and biologic medicines are complex. To ensure biosimilars do not cause any adverse impact in humans, clinical testing must be required.