article | 29 May 2024

Switch and substitution of biological medicinal products in pharmacies

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The Swedish Medical Products Agency (MPA) was tasked in 2023 with analysing the evidence for switch (substitution after renewal of a prescription) of biological medicinal products. Based on the outcome of the completed analysis, MPA was also to investigate the possibility of automatic substitution of biological medicinal products at pharmacy level. In September 2023, MPA published an interim report on switch, and now in April 2024 has published a final report on automatic substitution of biological medicinal products in pharmacies. The findings of the final report are summarized here.

But first some terminology.

A biosimilar is a biologically produced medicinal product that is very similar to and contains the same active substance as another biological medicinal product (the reference medicinal product) already authorized for sale in the EU. Switch refers to a change of medicinal product as a result of substitution of the original biological medicinal product to a biosimilar, as a result of alternating prescription or use in healthcare. Switch can be single switch, i.e. one substitution, or multiple. Multiple switch (double switch, triple switch etc.) refers to repeated switches between the reference medicinal product and the biosimilar, or between different biosimilars.

In its interim report, MPA concluded that there is at present no evidence to suggest that multiple switching of biological medicinal products would be a problem from an efficacy or safety perspective. The issue for the final report was the possibility of applying substitution for biological medicinal products in pharmacies, in addition to switches to or between equivalent medicinal products.

In the final report, MPA notes that from a legal point of view it is possible to apply the current system for determining substitution in pharmacies to biological medicinal products at pharmacy level. However, MPA notes several important factors that need to be taken into account in order for automatic substitution of biological medicinal products to be implemented in a patient-safe manner.

One such factor is that biological medicinal products often require administration devices that are unique to each product (e.g. a pre-filled pen), whereas information/training is needed if the patient is offered a biosimilar, in order for the patient to administer the product correctly. Insufficient information could increase the risk of a treatment error and of a nocebo effect, i.e. a negative experience caused by negative expectation of a treatment, if the patient is not confident about their treatment.

Further, some uncertainties also exist regarding the medical consequences of frequent switches, as the evidence for multiple switches is still limited. On that basis, MPA finds that to avoid inappropriately tightly spaced substitutions, the appropriate period for switches should be a minimum of six months. In addition, pharmacies would also be affected as the number of substitutional medicinal products with administration devices would increase significantly. Uncertainty also exists with regard to market dynamics, as biological medicinal products are more complex than synthetic ones in terms of manufacturing, distribution and storage.

Switching also makes it more difficult for healthcare providers to record medicinal product choices in clinical quality registers, and thus to monitor and evaluate which medicinal products the patient has received and how many tightly spaced substitutions have been made. This is more widely requested for biological than for synthetic medicinal products.

MPA therefore proposes that a next step, if the evaluation of automatic substitution of biological medicinal products is to be taken further, should be an economic analysis in which the benefit in the form of lower costs for medicinal products is set against increased costs regarding, for example, information provision and other measures to minimize the risk of treatment errors. In this analysis, aspects of market dynamics also need to be highlighted, in which the length of the substitution period is considered in relation to the ability of the companies to plan their production, in order to ensure that automatic substitution in pharmacies would not have negative consequences for the availability of medicinal products. According to MPA, another challenge is that biological medicinal products are often refrigerated goods which are not covered by the provisions on returns from pharmacies to wholesalers. As a result, this aspect requires further investigation.

If further evaluation shows that automatic substitution of biological medicinal products should be introduced, MPA believes that a stepwise introduction would be appropriate, where decisions on automatic substitution are first made for a group of medicinal products, preferably TNF-inhibitors (used to treat inflammatory conditions such as rheumatoid arthritis and psoriatic arthritis). This is because the most extensive experience and scientific evidence of switch exists for TNF inhibitors. MPA also states that it would be appropriate to exempt children under 18 years of age in the initial phase until more experience is available regarding multiple switches in children. That said, MPA also finds that introducing an exemption for children under the age of 18 would probably require statutory amendments regarding the substitution system.

From the final report, it may be concluded that several important aspects need to be investigated further and that any substitution of biological medicinal products in pharmacies should be introduced stepwise.

Setterwalls will monitor the next steps closely.


Practice areas:

Life Sciences

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