Writing in the European Medical Journal, Anna La Noce, MD, PhD, and Marcin Ernst, MD, MBA, explain that much confusion about switching between biosimilars and reference products in the United States versus in the European Union arises from different uses of the term “interchangeability.”
While the debate over the interchangeability and switching of biosimilars rages on in the United States, the European Union, with more than 40 approved biosimilars, has taken a markedly different approach to regulating and using biosimilars.
Writing in the European Medical Journal, Anna La Noce, MD, PhD, and Marcin Ernst, MD, MBA, explain that much of the confusion about switching between biosimilars and reference products in the United States versus in the European Union arises from different uses of the term “interchangeability.”
In the EU context, “Interchangeability is a comprehensive medical and scientific term referring to the medical practice of changing a medicine for another one expected to have the same clinical effect,” and can be carried out by either switching a patient’s therapy (on the physician’s part) or by automatic substitution (on the pharmacist’s part).
However, in the US context, interchangeability is a regulatory standard, and qualifying products may be substituted automatically after they have demonstrated to the FDA’s satisfaction that they may be expected to produce the same result as the reference in any given patient via a study that includes at least 3 switches.
While individual state law in the United States will guide the eventual automatic substitution of approved interchangeable products (of which there are currently none), in the European Union, individual EU member states are allowed to regulate automatic substitution according to local laws.
Not all EU member states have issued guidance on the matter, but, write the authors, “It appears that all states share the opinion that further clinical studies dedicated to assessment of switching are not required, differing from the opinion of the FDA.” In the European context, a thorough comparability study, together with a growing body of real-world evidence on the safety of switching, is sufficient to settle the question of automatic substitution.
This pragmatic approach has been a boon for nations with fewer financial resources, where the availability of a biosimilar can be used to negotiate lower prices through a variety of policy means. In many lower-income nations, access to biologics has grown with biosimilar availability. However, US stakeholders might find some of the practices in the European market surprising; for example, in Bulgaria, national tenders for medicine are conducted frequently, which can require patients to switch among therapies multiple times.
Real-world evidence to date, however, has demonstrated a low risk of any safety concerns of loss of efficacy with switching (though most available data focus on single switches rather than repeated switching), and higher discontinuation rates of therapies after switching have largely been attributed to the “nocebo effect.” The authors explain that properly managed switching programs that actively engage all stakeholders have resulted in successful switches, demonstrating the ability of education to overcome the nocebo effect.
La Noce A Ernst M. Switching from reference to biosimilar products: an overview of the European approach and real-world experience so far. [Published online September 4, 2018.] Eur Med J. https://emj.europeanmedical-group.com/wp-content/uploads/sites/2/2018/09/Switching-from-Reference....pdf. Accessed September 6, 2018.