European Industry Groups Urge Caution on Biosimilar Switching

Three European Union (EU) biopharma industry groups have issued a position paper urging prescribing physicians to exercise caution when considering switching patients from reference biologics to biosimilars. The industry groups—European Biopharmaceutical Enterprises, the European Federation of Pharmaceutical Industries and Associations, and the International Federation of Pharmaceutical Manufacturers & Associations—state that physicians are the individuals best placed to assess their patients and potential treatments and whether and how to switch a biological product for another one. Physicians should balance risk and uncertainties against the availability of evidence on a case-by-case basis, the group strongly recommends. The 3 groups industry groups represent member biopharma companies who have billions in revenue at stake when more biosimilar products are approved.

The position paper notes that to qualify for approval, a biosimilar should be compared in terms of quality, safety, and efficacy with its reference product alone—there is no regulatory authority requirement for biosimilars to the same reference product to be compared with each other. Therefore, this type of data may not be available to refer to when evaluating a switch between 2 biosimilars to the same reference product, the group cautions.

The position paper reminds physicians of the complex nature of biological molecules, which are being used to treat patients who have multifaceted, chronic diseases, and concludes that there are 2 scenarios in which switching from a reference product to a biosimilar (or between any products within a similar group of related products) is not recommended:

  1. When the initial treatment choice (reference product or biosimilar) loses efficacy or when there are tolerability issues, switching to a similar product within the same group of related products is not recommended because these products are expected to have similar clinical efficacy and safety to each other, without incremental clinical benefit to the patient.
  2. If the physician feels that, on balance, a switch is likely to compromise the patient’s future treatment options (eg, with an alternate biologic therapy), a switch is not advisable. However, little is known about the consequences of multiple exposures to the same group of related products and the consequences on immunogenicity of future treatments with biologics.

Gillian Woollett, PhD, senior vice president at Avalere Health, has a different perspective. In an interview with Nature Review Drug Discovery, she argues that the regulatory agency in Europe, the European Medicines Association, does not have an interchangeability designation; national health authorities there allow switching, as yet without safety issues. Woollett notes that Dutch, Finnish, German, and Norwegian regulators analyzed 10 years of switching studies and concluded that it is unlikely and very difficult to substantiate that 2 products, comparable on a population level, would have different safety or efficacy in individual patients upon a switch. “I would argue that as a scientific matter, once your product is deemed biosimilar it is already interchangeable,” she says.

Switching studies that would be required by the FDA to show interchangeability can be cumbersome and expensive, and are likely to contribute to a higher entry bar for biosimilar developers. The cost of biosimilar development can be $250 million or more, while the cost of generic drug development is typically $1 million to $4 million. Without flexibility, no biosimilar will ever be designated as interchangeable by the FDA, Woollett advises.