Sandoz Executive Argues for Safety of Nonmedical Switching

Although the FDA and European Medicines Agency (EMA) differ in their policies on switching between a reference product and a biosimilar, there is an overwhelming amount of evidence that switching is safe, according to Hillel Cohen, PhD, executive director of scientific affairs for Sandoz.

Sandoz currently has 8 biosimilars in its portfolio, including Zarzio (filgrastim) the first FDA-approved biosimilar, and Omnitrope (somatropin), the first biosimilar to receive marketing authorization in Europe. Sandoz is also testing a denosumab biosimilar in a phase 3 clinical trial.

Cohen spoke in a July 23 webinar entitled “Switching from Reference Medicines to Biosimilars,” presented by The Academy of Managed Care Pharmacy.

“You have growing evidence. Two years ago, there were 90 studies. Now, there are 178 studies that are confirming that switching from a reference product to a biosimilar and vice versa is safe,” said Cohen.

Of those 178 studies that involved data from at least 1 switching event, 79% (140) were observational, real-world evidence studies and 21% (38) were randomized clinical trials. Overall, the studies included observed switching of 10 molecules across 21,000 patients in total.

“The nature of the study designs varies. That's both a weakness in that you can't say they all have the same design, but it's also a strength showing you, irrespective of the design of the study itself, and even the molecules, they've all come to the same conclusion,” said Cohen. "That's really quite amazing."

The Issue With Interchangeability

Overall, Cohen said that the FDA and EMA both agree that switching from a reference product to a biosimilar once is safe. However, the 2 agencies differ on the safety of multiple nonmedical switches.

Cohen highlighted that the main policy difference between the FDA and EMA regarding switching is that the FDA requires biosimilar manufacturers to seek an interchangeability designation for biosimilars to allow nonmedical switching to take place at the pharmacy level without requiring permission from a physician. The EMA does not have an official policy regarding interchangeability.

Cohen explained that the FDA’s main concern for whether nonmedical switching is safe is the risk of immunogenicity, or provocation of a severe immune response. Of the 178 studies Cohen cites, 71 demonstrated no increased risks for immunogenicity.

“The FDA says this concern is relevant only if you go back and forth [between a biosimilar and the reference product] multiple times. European regulators go even further and say it's really overrated,” he said.

For a manufacturer to receive an interchangeability designation, they must perform additional clinical trials including a pharmacokinetic switching study.

“Let's be clear. It's a regulatory category in the United States. Literally, it's written into law. It's not necessarily science….It's a regulatory and legal category, not a quality category,” said Cohen.

There are no biosimilars in the United States current approved as interchangeable with reference products. Cohen explained that interchangeability designations would apply only to products in the retail and specialty pharmacy settings, where pharmacists would make the decision to switch without physician input. For products administered in a physician office, hospital, or treatment clinic, the decision to switch remains a matter between the physician and the patient.

Europe’s Complicated Views on Switching

Although the EMA, the agency that evaluates and supervises drugs, and European Commission, which makes the final decision on drug marketing approvals, agree that nonmedical switching of biosimilars is safe and have put out guidance for physicians and patients on its safety, Cohen said that switching regulations can differ on a country to country basis within the European Union.

In most European countries, switching is permitted but a physician must be involved in the decision. In the case of France, Cohen explained that switching at the pharmacy level is permitted but only for treatment-naïve patients.

Some countries have single tender systems, which allow for increased competition between biosimilar products and award exclusivity to 1 biosimilar during each tender cycle. In other words, every patient who requires a certain medication receives the same product.

However, Cohen explained that this is going away with time, using Denmark as an example of a country that has abandoned the single tender system in favor of a multiple tender system. Multiple tender systems allow multiple biosimilars to compete in the marketplace and avoid discouraging biosimilar makers from participating in national biosimilar markets.