Interchangeability switching between biosimilar and originator drug

This article was written in collaboration with Liese Barbier, Yannick Vandenplas, and Teresa Barcina Lacosta.

After the expiry of patents and other market exclusivities of originator biological medicines, similar versions with proven equivalent clinical outcomes, i.e., biosimilars, are allowed to enter the market. Biosimilars receive marketing authorization based on a comprehensive comparability exercise, demonstrating high similarity in terms of efficacy, safety, and immunogenicity profile.1,2 The robustness of their regulatory evaluation is confirmed by positive in-market experience and reassuring results in switching studies, showing that there is no reason to assume that switching from an originator biological to its biosimilar would lead to differences in clinical outcomes.3,4 However, even after 15 years of positive experiences with biosimilars and a solid EU biosimilar pharmacovigilance track record,2,5  one of the remaining issues still dominating the debate is whether or not biosimilars can be considered interchangeable with their reference biological product6 or with biosimilars of the same reference product. In recent years, several scientific papers have been published discussing biosimilar interchangeability.

Interchangeability has different implications across the world, depending on which regulatory or legal framework applies.6 In general, interchangeability refers to the possibility of exchanging one medicine for another with the same clinical effect. This implies replacing the reference biological product with its biosimilar (or vice versa) or exchanging biosimilars of the same reference product with each other. Such a replacement can occur at two different levels: by the prescribing physician (i.e., switching or transitioning) or by the pharmacist (i.e., substitution).2 Here, we provide an up-to-date overview of regulatory and practical considerations regarding biosimilar interchangeability with an emphasis on the European perspective.

Educating Doctors and Patients on Biosimilars

This article was written in collaboration with Liese Barbier, Teresa Barcina Lacosta, and Yannick Vandenplas.

Since the introduction of biosimilar medicines in the European market in 2006, biosimilars have made their mark in multiple therapeutic areas, including oncology, inflammation, hematology, and endocrinology (1).  As of March 2021, the EMA has authorized over 65 biosimilar products and in the next 10 years, a considerable number of originator biologicals is expected to lose market exclusivity and be exposed to biosimilar competition (2,3). 

Biosimilars have been safely and effectively used, exceeding a total clinical experience of 2 billion patient treatment days across Europe (4). Currently, biosimilars represent a 60% year-on-year growth in the share of the total biologics market in Europe, and this figure is expected to increase, based on the considerable number of biologics expected to lose market exclusivity in the next 10 years (3). Altogether, these data underline that biosimilars are here to stay. In this context, it is essential to ensure that the different stakeholder groups receive trustworthy and clear information about the principles and the value proposition of biosimilars.

Successful implementation of biosimilars

This article first appeared in the Info-BioSim e-newsletter produced by Panacee Conseil Inc., April 2018.

With almost 40 biosimilars licensed over the past 12 years by the European Medicines Agency, it is safe to say the licensing pathway is well established. Hundreds of thousands of European patients are using biosimilars, and there has not been a single serious incident with any of them. Moreover, pharmacovigilance programs have shown that the risks involved in using biosimilars are no different than with the innovator products.

However, if we look at biosimilars in Europe, we see a large variation in the uptake of these low-cost alternatives to high-cost innovative biologics. The northwestern part of Europe (Scandinavia, United Kingdom, Germany, the Netherlands) have seen big cost reductions due to the use of biosimilars, while in the southern part of Europe the uptake is much lower, which raises the question: Why is that so?

Cost effectiveness of medicines

This article first appeared in the Canadian Pharmacy Newsletter, March 2019.

Biosimilars and the European Regulatory System

In the 1990s, governments and regulators in Europe began thinking about how to regulate biological medicines once patents expired and market exclusivity ended. Given the extensive experience regulators already had at that time assessing the manufacturing changes of biologics, they concluded that a simple generic pathway would not be advisable. As a result, Directive 2001/83/EC (translated in the laws of all EU member states) was amended with the addition of Article 10(4), which introduced the concept of “similarity.”

Research and development of medical drugs

This article first appeared as a contribution to the 'Key Opinion Leader' series produced by Panacee Conseil.

All physicians and pharmacists involved in the prescribing and dispensing of medicines know that adopting a positive attitude when providing patients with a medicine can markedly enhance its therapeutic effect. If a patient has positive expectations, it is more likely the drug will have a beneficial effect than if the patient is skeptical about the drug. In this way healthcare professionals can significantly enhance the effect of a drug, which is why the double blind placebo-controlled trial was invented, to eliminate this influence in drug efficacy studies. So, what do we see in such trials? The placebo has beneficial effects, but can also generate a variety of side effects about which the patient was told in the informed consent procedure.

Since the 1970s, we know that the reverse can also be true: If a patient has the impression that a medicine may be less effective or is inferior in quality (sometimes perceived as such, due to a lower price) then its pharmacological efficacy may be compromised and there is a chance the patient will experience decreased benefits and possibly also increased side effects. This phenomenon was first studied extensively when generic medicines with exactly the same composition, even those from the same manufacturer, induced unwanted effects in patients. Could it possibly be something like a reverse-placebo effect? The answer is yes. Patients who are told that their medicine may not be exactly the same (similar but not identical) or that it could cause side effects (not necessarily different from the original) may have a different therapeutic outcome.

  1. My Journey with Biosimilars - How I Went from Sceptic to Convert