Substitution and interchangeability: time for a conversation?

Author byline as per print journal: Chad Rieger1, MBA; Lisa Hall1, PhD; David Lim2,3, DPH

Abstract:
Bandiera et al. (2002) identified the potential for competitors’ promotional materials to use certain terms with technical meanings, such as ‘interchangeable’ and ‘substitution’, in a misleading way in Australia.

Submitted: 30 June 2022; Revised: 4 July 2022; Accepted: 5 July 2022; Published online first: 18 July 2022

The blurring of language used within the Australian Pharmaceutical Benefits Scheme (PBS) and the conflicting elements within the system contribute to the resultant tenuous uptake of biosimilar medicines in Australia

Whilst ‘substitution’ and ‘interchangeability’ are likely to represent the same thing in the clinicians’ and consumers’ minds when it comes to small molecule generics, there is a real likelihood of confusion and subsequent delay in biosimilars uptake in Australia where such terms are used [1, 2]. The potential for confusion between ‘substitution’ and ‘interchangeability’ has real implications for the uptake of biosimilars in Australia and other countries where there is a lack of legislative definition and/or clarity of what ‘interchangeability’ entails.

There are only two mentions of ‘interchangeable’ in the enabling legislation in Australia, one with regard to the functions of the Pharmaceutical Benefits Advisory Committee (section 101, National Health Act 1953), and the second permitting the Minister to receive advice from the Pharmaceutical Benefits Advisory Committee whether a pharmaceutical may be interchangeable (section 84AG). Unlike the US, the term ‘interchange(ability)’ is not formally defined in the Australian pharmaceutical legislation [2]. Consequently, in some jurisdictions within Australia, state and territory governments have unintentionally used the terms ‘substitution’ and ‘interchangeability’ in their lay language [2]. This is likely contributing to confusion around how these terms apply to biosimilars and the implications for applications in patient care settings.

Examples of this confusion are playing out frequently and are magnified by structural elements that exist around allowable substitution within the PBS. Similar to the US Food and Drug Administration concept of the ‘Purple Book’, the Australian PBS provides a schedule of bioequivalence brands of Australian Government subsidised biological pharmaceuticals. These so-called ‘a-flagged’ biosimilars may be substituted for another brand at the point of dispensing
by the community or hospital pharmacists without the requirement to reference the clinician, provided there is no explicit ‘substitution not permitted’ designation on the prescription [3]. Furthermore, pharmacists are granted the authority to substitute a different biological under the new National Health (Pharmaceutical Benefits) (Pharmacist Substitution of Medicines without Prescription during Shortages) Determination 2021. The term ‘substitution’ is a multivalent term in Australia, contained in the National Health Act 1953 and refers to the practice of dispensing. This designation was first applied to biosimilars within the PBS with the introduction of the etanercept biosimilar, followed by adalimumab [4]. Enabling pharmacists to decide which biosimilars and/ or originator to dispense has created an interesting dynamic. Some clinicians who prescribe biologicals are not accepting of this approach in part or in whole [3, 5]. As a result of their concerns, some clinicians have taken the step of indicating ‘substitution not permitted’ on the prescription, effectively preventing the pharmacist from substituting a biosimilar for the originator. In recent time, some peak medical bodies in Australia have supported the use of biosimilars, recognizing that biosimilar medicines can be expected to deliver the same clinical outcomes for patients and at a lower cost [6]. Further hampering the uptake of biosimilars in Australia is the manner in which ‘substitution’ of biosimilars has been implemented. The Australian Government has indicated that they are in favour of pharmacists substituting biosimilars [7] but have also indicated that the prescribers have the final word on this and can block this action using the ‘substitution not permitted’ designation on the prescription. So where does this leave Australia? Three viable options exist:

1. Clinicians allow the pharmacist to substitute the product to a biosimilar, across
biosimilars, or back to the reference medicine.
2. Clinicians indicate ‘Substitution Not Permitted’ on prescription and pharmacists
are not allowed to substitute.
3. Clinicians and pharmacists develop collaborative relationships and communicate
clearly with each other the boundaries, clinical goals, appropriate approaches to biosimilar substitution, and where substitution may or may not be appropriate.

We assert here that the preferable approach is the latter. While this may require more substantial efforts to develop and manage these relationships, it is the approach that will most likely lead to long-term success with biosimilars and is in concordance (but an extension to) with the current Australian Government Biosimilar Awareness Initiative.

While there are no specific roadmaps for opening these clinician-pharmacist conversations about biosimilars, the first step is to pick up the phone or strike up a conversation, and to maintain a co-operative approach. Each conversation between pharmacists and clinicians, the boundaries they set, and the ways of cooperating will differ. However, foundational to each conversation should be that biosimilars are safe and effective and will be critical to reducing healthcare system cost burdens when used appropriately and in co-operative agreement between patients, clinicians, and pharmacists, in concordance with both Australia’s Quality Use of Medicines and Medicines Safety policy on medication safety.

Competing interests: None for Lisa Hall and David Lim. Chad Rieger is the Medical Manager of Biosimilars with Sandoz. Chad is not paid for his involvement in the manuscript. Neither Lisa nor David was paid for their involvement in the manuscript. Chad’s involvement in the manuscript was in his private and personal capacity as PhD candidate with The University of Queensland.

Provenance and peer review: Not commissioned; internally peer reviewed.

Authors


Chad Rieger1, MBA
Lisa Hall1, PhD
David Lim2,3, DPH

1School of Public Health, Faculty of Medicine, The University of Queensland
2Translational Health Research Institute, School of Health Sciences, Western Sydney University
3College of Medicine and Public Health, Flinders University

Author for correspondence: David Lim, DPH, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia

Disclosure of Conflict of Interest Statement is available upon request.

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