After months of writing about it, and even raising the issue among regulatory stakeholders, SAHPRA has now finally agreed to amend the guideline and publish a statement to declare that biosimilars are interchangeable with their reference products (or vice versa) and also with other biosimilars of the same reference medicine. As much as I would like to take credit for this, I have to admit that the catalyst for the Biological Medicines Expert Advisory Committee (BMEAC) meeting, where this issue was deliberated and a recommendation drafted for ratification by the CEO, was the change in the EMA position on interchangeability. In a joint statement with the Heads of Medicines Agencies (network of the heads of the National Regulatory Authorities (NRAs) of countries in the European Economic Area), the EMA announced on September 19th of last year, that it now considers biosimilars to be interchangeable with their reference products from a scientific perspective.1 The main reason for the EMA’s formal statement was to remove the uncertainty around the use of biosimilars among all stakeholders (especially clinicians and patients) and promote its use in clinical practice. Now that SAHPRA has taken a similar position, it is important for the organisation not only to publish or publicly announce its decision, but also to emphasise the fact that both patients and physicians can expect the same therapeutic outcome with biosimilars as they have obtained with the reference products. This amendment to the guideline will provide the impetus to expand the role of biosimilars in clinical practice in South Africa, which should drive down the cost of treatment with biologics.
The decision to interchange a patient’s therapy, i.e., switch the patent to a biosimilar from its reference medicine, can only be done by, and under the supervision of, his or her treating physician. Automatic substitution in terms of Act 101 of 1965 (i.e., the practice of dispensing a different product by a pharmacist to that specified on the prescription without the prior informed consent of the patient’s physician) is still not allowed. Pharmacy-level substitution is allowed in France 2, Australia3, and in a few states in Canada4, but usually with restrictions. In France, substitution can be carried out at the initiation of treatment and if the prescribing physician has not indicated that the prescribed biologic is non-substitutable. Similarly in Poland and Australia, pharmacy-mediated substitution can occur if the patient’s physician has not indicated otherwise. Finland allows substitution but only in hospital pharmacies5. In Germany, the Federal Joint Committee (G-BV) held a hearing on July 13, 2022 to determine whether stakeholders were supportive of automatic substitution. Only payers (the head organisation for all healthcare funds (GKV-SV)) was in favour of automatic substitution at pharmacy-level; clinicians, pharmacists and the pharmaceutical industry were against the regulation because they were concerned about patient safety and the nocebo effect (where patients developed side effects or worsening of symptoms induced by a negative attitude to a switch in medication such as from the original product to a biosimilar)6.
Although automatic substitution by pharmacists may further increase the uptake of biosimilars, the sentiment among regulators was that before such an amendment can be implemented for biosimilars in South Africa, a comprehensive educational programme for pharmacists must be launched. Until then, substitution in terms of Act 101 will not extend to biosimilars.
Finally, it is important to note that biosimilar companies will have to apply for a variation to the PI and PIL, along with any special warnings or precautions, before they can promote their products as interchangeable.
1. EMA statement on the scientific rationale supporting interchangeability of biosimilar medicines in the EU. https://www.ema.europa.eu/en/documents/public-statement/statement-scientific-rationale-supporting-interchangeability-biosimilar-medicines-eu_en.pdf
2. Johanna Harelimana. The return of biosimilar substitution in France. March 28, 2022. BioTalk (website). https://bio-talk.law/general/the-return-of-biosimilar-substitution-in-france
3. Chad Rieger, Lisa Hal, David Lim. Substitution and interchangeability: time for a conversation? Generics and Biosimilars Initiative Journal. 2022; 11(2): 49-50. DOI: 10.5639/gabij.2022.1102.009.
4. Michael S Reilly, Professor Philip J Schneider. A critical review of substitution policy for biosimilars in Canada, Generics and Biosimilars Initiative Journal. 2021;10(3):123-9. DOI: 10.5639/gabij.2021.1003.016
5. Hannah Larkin, Judith Macdonald, Rebecca Lumsden, PhD. Pharmacy-mediated substitution of biosimilars – a global survey benchmarking country substitution policies. Generics and Biosimilars Initiative Journal. 2017;6(4):157-64. DOI: 10.5639/gabij.2017.0604.034
6. Anja Pownel. Automatic substitution with biosimilars by pharmacies should start next month in Germany – How will it work? July 18, 2022.