Evidence on automatic substitution of biologicals is limited

Biosimilars/Research | Posted 03/12/2021 post-comment0 Post your comment

A systematic review of the evidence on automatic substitution of biological medicines [1] finds that current research evidence is mainly based on opinion polls and surveys of low-to-moderate quality, with results that are not generalizable or suitable for guiding policy.

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Automatic substitution describes dispensing an interchangeable and equivalent medicine (such as a biosimilar) in place of another at the pharmacy level, without consulting the prescriber.

Automatic substitution is one potential strategy to increase uptake of biosimilar drugs, however, only a few countries (such as some EU Member States and Australia) allow automatic substitution of biological drugs in community pharmacies, and only under certain conditions (for example, for treatment-naïve patients).

In the US, there is a framework for automatic substitution of biologicals if considered interchangeable.

A review recently published in BioDrugs [1] systematically summarized the evidence on practices, experiences and perceptions on automatic substitution of biologicals.

The researchers searched Scopus, Medline (Ovid), CINAHL, and Web of Science and included peer-reviewed, original studies written in English and published in the years 2006–2021. They included studies that reported interventions, pilots or any other studies including experiences or perceptions of automatic substitution. The quality of the included studies was evaluated by pre-determined criteria, including the Survey Assessment Guide and the CASP Qualitative Studies checklist.

The search identified 27 eligible studies, including 23 surveys and four semi-structured interviews. Over half (56%) of the studies were conducted in Europe and almost half (44%) were conducted among prescribers. Other studies were conducted with pharmacists (19%), mixed stakeholders (19%), patients (15%) and payers (3%).

Perceptions of substitution were mainly negative, according to the analysis, reflecting mistrust of biosimilars among some stakeholders. The authors also found that the overall quality of the studies was low to moderate, and that results were not generalizable due to methods of sampling and low response rates. Only one study applied intervention design, and none assessed the safety and effectiveness of implementing automatic substitution in practice.

The authors conclude that currently available research evidence on the automatic substitution of biologicals is scarce and of low to moderate quality, reflecting low stakeholder knowledge and a cautious attitude towards biosimilars. They say that the currently available evidence is not sufficiently rigorous to draw conclusions on the automatic substitution of biologicals, which means that results are not suitable for guiding policy.

For the future, the researchers say that more research applying robust scientific methods is needed and, in particular, more studies on practices and strategies for safely implementing automatic substitution such as simulations, pilots, intervention studies with control groups and economic evaluations. Robust, scientifically valid, and generalizable studies on the practice of automatic substitution could help to improve stakeholder attitudes towards biosimilars and their substitution.

In a recent first study that comprehensively analyse pre-licensing and long-term safety data, as well as data on immunogenicity and interchangeability, for biosimilar monoclonal antibodies and fusion proteins [2], the authors conclude that biosimilar monoclonal antibodies licensed in the EU have comparable efficacy, safety and immunogenicity with their originator products, and that their results support the interchangeability of biosimilars licensed in the EU, suggesting that pharmacy-level substitution of these products is possible [2].

Conflict of interest
One of the studies included in the systematic review [1] was authoured by Tolonen et al. Tolonen also participated in a congress with a participation fee sponsored by Roche.

Editor’s comment
Readers interested to learn more about substitution of biologicals are invited to visit www.gabi-journal.net to view the following manuscripts published in GaBI Journal:

European prescribers’ attitudes and beliefs on biologicals prescribing and automatic substitution

A critical review of substitution policy for biosimilars in Canada

Pharmacy-mediated substitution of biosimilars – a global survey benchmarking country substitution policies

GaBI Journal is indexed in Embase, Scopus, Emerging Sources Citation Index and more.

Readers interested in contributing a research or perspective paper to GaBI Journal – an independent, peer reviewed academic journal – please send us your submission here.

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Related articles
Canada’s biosimilar substitution policy: effects on competition and patient safety

Different approaches to the interchangeability of biosimilars

Biosimilars in Europe: prescriber survey


The new section of the ‘Latin American Forum’ on GaBI has been launched. The objective of this new section is to provide you with all the latest news and updates on developments of generic and biosimilar medicines in Latin America in Spanish.

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1. Tolonen H, Falck J, Kurki P, et al. Is there any research evidence beyond surveys and opinion polls on automatic substitution of biological medicines? A systematic review. BioDrugs. 2021;35(5):547-61.
2. GaBI Online - Generics and Biosimilars Initiative. Data support the interchangeability of EU biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Dec 3]. Available from: www.gabionline.net/biosimilars/research/data-support-the-interchangeability-of-eu-biosimilars

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