Dr Hans Ebbers, Regulatory Project Leader of the Pharmacotherapeutic Group III at the Medicines Evaluation Board (MEB/CBG) in The Netherlands discussed how to establish interchangeability at the European Commission stakeholder event on biosimilar medicinal products, which was held in Brussels, Belgium on 5 May 2017.
When a biosimilar is approved it is concluded by the regulatory authorities that the product is ‘highly similar’ to its reference product in terms of quality, efficacy and safety. The question, according to Ebbers, is whether the conclusion on biosimilarity is in itself sufficient to make a conclusion on interchangeability, or whether additional data is required to conclude this. The regulatory agencies, e.g. US Food and Drug Administration (FDA) and various EU Member States, differ in their views. In fact, US legislation makes a clear distinction between biosimilars and interchangeable biosimilars in terms of clinical evidence [1]. The agency issued draft guidance on interchangeability in January 2017 [2].
If more clinical data are needed to establish interchangeability, what kind of data should this be? Ebbers says that this depends on what is considered to be the key unknown to determine interchangeability: immunogenicity, pharmacokinetics, safety, efficacy or usability.
According to Ebbers:
- Thus far there is no evidence that switching to/from biosimilars causes safety issues [3, 4].
– Differences in efficacy/safety may be hard to establish
– Hard to draw definitive conclusions from switching studies, other than a general reassurance that no problems have occurred as a result from the switch
- Mostly switching studies have been performed, alternating studies are rare.
– Alternating studies may increase following US guidance
- If the key concern is immunogenicity, then anti-drug antibodies (ADAs) in relation to clinical outcomes or trough levels should be determined [5].
– Limited data available, but no issues identified so far
- More focus is needed on the impact of differences in presentation, e.g. device, in relation to interchangeability
– This is not really addressed in the European Union (EU) guidance.
A recent case did, however, highlight a loss of efficacy after switching to biosimilar infliximab in Behcet’s patients [6].
The series of two articles that follow discuss the situation in Europe and the US.
Disclaimer
Dr Hans Ebbers stated that the views expressed in his presentation are the personal views of the presenter and are not to be understood or quoted as being made on behalf of, or reflecting the position of the MEB/CBG or any other regulatory agency, or one of its committees or working parties.
Related articles
Establishing interchangeability for biosimilars in the US
Interchangeability and switching study designs for biosimilars
References
1. GaBI Online - Generics and Biosimilars Initiative. US guidelines for biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Dec 8]. Available from: www.gabionline.net/Guidelines/US-guidelines-for-biosimilars
2. GaBI Online – Generics and Biosimilars Initiative. FDA issues draft guidance on biosimilar interchangeability [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Dec 8]. Available from: www.gabionline.net/Guidelines/FDA-issues-draft-guidance-on-biosimilar-interchangeability
3. Ebbers HC, Muenzberg M, Schellekens H. The safety of switching between therapeutic proteins. Expert Opin Biol Ther. 2012;12(11):1473-85.
4. Kurki P, van Aerts L, Wolff-Holz E, Giezen T, Skibeli V, Weise M. Interchangeability of biosimilars: a European perspective. BioDrugs. 2017;31(2):83-91.
5. Ebbers HC, Chamberlain P. Interchangeability. An insurmountable fifth hurdle? Generics and Biosimilars Initiative Journal (GaBI Journal) 2014;3(2):88-93. doi:10.5639/gabij.2014.0302.022
6. GaBI Online – Generics and Biosimilars Initiative. Loss of efficacy after switching to biosimilar infliximab in Behcet’s patients [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Dec 8]. Available from: www.gabionline.net/Biosimilars/Research/Loss-of-efficacy-after-switching-to-biosimilar-infliximab-in-Behcet-s-patients
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