Biosimilars and interchangeability

In a study by researchers from the Tufts Center for the Study of Drug Development (Tufts CSDD) the question of interchangeability around the world was one of the topics investigated [1].

The US Food and Drug Administration (FDA) approved its first biosimilar, Sandoz’s Zarxio (filgrastim-sndz), on 6 March 2015 [2]. The biosimilar was approved in all five indications of Amgen’s originator product (Neupogen). However, it was not approved as interchangeable with Neupogen, even though FDA has the authority to designate a biosimilar as interchangeable with its reference product.

FDA considers a biosimilar to be interchangeable with its reference product if it produces the same clinical result in any given patient and that there is no extra risk with switching [3]. However, the agency is yet to issue guidelines detailing exactly how biosimilars should demonstrate these properties [4].

In the European Union (EU), decisions on the interchangeability or substitution of biosimilars and originator biologicals are not made by European Medicines Agency (EMA), but at the national level. This is despite the fact that biosimilars developed in line with EU requirements are considered by EMA to be therapeutic alternatives to their reference biologicals [5]. In Germany, pharmacists may substitute a biosimilar, unless the physician forbids it, as part of the ‘Aut-idem-Regelung’*. However, most EU Member States do not explicitly authorize the substitution of biologicals from different manufacturers, and a number of EU Member States have gone as far as banning this practice [6]. Legislation introduced in France will, if decrees are passed, allow pharmacists to substitute a biosimilar for the prescribed (reference) biological under certain conditions [7]. The Finnish Medicines Agency, Fimea, recommended interchangeability of biosimilars for their reference biologicals in May 2015. The Fimea 'interchangeability' recommendation, however, does not recommend automatic substitution at the pharmacy level without involvement of the prescriber [8].

Australia’s Pharmaceutical Benefits Advisory Committee (PBAC) recommended at its April 2015 meeting that biosimilars are suitable for substitution at the pharmacy level [9]. South Africa has prohibited automatic substitution of biosimilars for reference products. Japan also does not allow automatic substitution of biosimilars for originator biologicals.

Conflict of interest
The authors of the research paper [1] declared that there were no conflicts of interest.

Editor's comment
The German 'Aut-idem-Regelung' only applies for biosimilars that (a) have been approved with reference to the same reference product and which (b) have been produced by the same manufacturer with the same manufacturing process. The only difference between such substitutable products is their trade name.

Readers interested to learn more about interchangeability of biosimilars are invited to visit www.gabi-journal.net to view the following manuscript published in GaBI Journal:

Interchangeability. An insurmountable fifth hurdle?

If you are interested in contributing a research article in a similar area to the GaBI Journal, please send us your submission here.

Related article
AE reporting for biologicals

Biosimilar naming and AE reporting

References
1. Stergiopoulos S, Getz K. Evaluating AE reporting of two off-patent biologics to inform future biosimilar naming and reporting practices. Drug Saf. 2015;38(8):687-92.
2. GaBI Online - Generics and Biosimilars Initiative. FDA approves its first biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Nov 13]. Available from: www.gabionline.net/Biosimilars/News/FDA-approves-its-first-biosimilar
3. GaBI Online - Generics and Biosimilars Initiative. FDA calls for comment on biosimilars interchangeability [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Nov 13]. Available from: www.gabionline.net/Guidelines/FDA-calls-for-comment-on-biosimilars-interchangeability
4. GaBI Online - Generics and Biosimilars Initiative. FDA finalizes biosimilars guidelines [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Nov 13]. Available from: www.gabionline.net/Guidelines/FDA-finalizes-biosimilars-guidelines
5. GaBI Online - Generics and Biosimilars Initiative. Efficacy, extrapolation and interchangeability of biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Nov 13]. Available from: www.gabionline.net/Biosimilars/Research/Efficacy-extrapolation-and-interchangeability-of-biosimilars
6. GaBI Online - Generics and Biosimilars Initiative. Use of biosimilars in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Nov 13]. Available from: www.gabionline.net/Reports/Use-of-biosimilars-in-Europe
7. GaBI Online - Generics and Biosimilars Initiative. France to allow biosimilars substitution [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Nov 13]. Available from: www.gabionline.net/Policies-Legislation/France-to-allow-biosimilars-substitution
8. GaBI Online - Generics and Biosimilars Initiative. Finnish drug regulator recommends interchangeability of biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Nov 13]. Available from: www.gabionline.net/Policies-Legislation/Finnish-drug-regulator-recommends-interchangeability-of-biosimilars
9. GaBI Online - Generics and Biosimilars Initiative. Australia’s PBAC recommends substitution of biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Nov 13]. Available from: www.gabionline.net/Biosimilars/General/Australia-s-PBAC-recommends-substitution-of-biosimilars

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