Sowing confusion in the field: the interchangeable use of biosimilar terminology

McKinley, Laura; Kelton, John M.; Popovian, Robert

doi:10.1080/03007995.2018.1560223

Cited by 10 publications

(16 citation statements)

References 2 publications

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“…Although the FDA has the authority to grant an interchangeability designation, the decision of whether to actually implement pharmacy-level auto-substitution rests with individual states (i.e., there is no federal mandate) [ 5 , 13 , 14 ]. Of the 45 states currently with laws regarding the substitutability of a biosimilar, only one (Kansas) does not require a product to first have been designated as interchangeable by the FDA prior to allowing auto-substitution [ 15 ].…”

Section: Definitions Of Interchangeabilitymentioning

confidence: 99%

“…The interchangeability of a biosimilar (Table 1) for its innovator (or vice versa) is a complex topic that has generated much discussion [1][2][3][4][5][6][7]. Interchangeability is closely linked to nonmedical switching (NMS), the practice of switching treatment in patients with stable disease for non-clinical reasons, such as cost (Table 1) [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable

et al. 2021

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In the USA, an interchangeability designation provides biosimilar sponsors with a pathway for achieving what is standard for small-molecule generics: pharmacy-level auto-substitution for an innovator. No other major health authority links interchangeability to automatic substitution, as all require the involvement of the prescriber or patient in a medication change. This editorial considers the clinical impact and practicality of auto-substitution. First, interchangeability is linked to non-medical switching (NMS), the practice of switching treatment in patients with stable disease for non-clinical reasons. NMS may generate negative sentiment in those unwilling or reluctant to switch, which can adversely impact treatment outcomes (i.e., nocebo effect). Indeed, in real-world studies of tumor necrosis factor inhibitors, discontinuation rates have been shown to be higher in patients switched to biosimilars for non-medical reasons than in historical cohorts maintained on innovators. Second, interchangeability may impede pharmacovigilance and traceability, as not all jurisdictions require innovators and biosimilars to have distinct biologic names. Third, an interchangeability designation from the US Food and Drug Administration only permits a biosimilar to be automatically substituted for its innovator, not other biosimilars (if available). Pharmacist education would be needed to avoid off-label, automatic substitution among biosimilars of a single innovator. Last, once granted, an interchangeability designation exists in perpetuity under current US federal law. However, the supply chains of innovators and biosimilars are maintained independently, with no requirement for reconfirmation of biosimilarity or interchangeability. We feel that additional guidance is needed for the auto-substitution of biosimilars and innovators to become a reality.

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Section: Definitions Of Interchangeabilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable

et al. 2021

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“…Subjects in the reference product arm are then re-randomized and, in the second stage, the dedicated switching study design is followed to evaluate interchangeability between the two products ( Fig. 2) [3].…”

Section: Design Of Studies Expected By the Fda To Support The Interchmentioning

confidence: 99%

“…The FDA guidance provides recommendations to conduct clinical interchangeability studies in patients rather than in healthy volunteers, and to use PK parameters, rather than efficacy or safety endpoints, as primary endpoints. The guidance states that "the primary endpoint in a switching study or studies should assess the impact of switching or alternating between the use of the proposed interchangeable product and the reference product on clinical PK and PD (if available), since these assessments are generally most likely to be sensitive to changes in immunogenicity and/or exposure that may arise as a result of alternating or switching" [2,3].…”

Section: Design Of Studies Expected By the Fda To Support The Interchmentioning

confidence: 99%

“…According to the Biologics Price Competition and Innovation Act (BPCIA) in the United States (US), a biosimilar can be designated as "interchangeable", whereby it may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product [3]. This enables pharmacy-mediated substitution, where state laws allow [2].…”

Section: Introductionmentioning

confidence: 99%

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Interchangeability of Biosimilars: What Level of Clinical Evidence is Needed to Support the Interchangeability Designation in the United States?

et al. 2020

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A biosimilar is a biologic drug that is "highly similar to a reference (originator) product, with no clinically meaningful differences between the two products in safety, purity, and potency". Regulatory approval of a biosimilar is based on analytical, structural, and functional comparisons with the reference product, comparative nonclinical (in vivo) studies, clinical pharmacokinetics and/or pharmacodynamics, and immunogenicity. In addition, comparative clinical efficacy and safety assessments are usually conducted and, taken together, comprise the "totality of the evidence" supporting biosimilarity. For a biosimilar to meet the additional designation of interchangeability in the United States (US), the applicant must demonstrate that the biological drug can be expected to produce the "same clinical result as the reference product in any given patient" and "if the biological drug is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological drug and the reference product is no greater than the risk of using the reference product without such alternation or switch". The challenges faced in conducting clinical studies to support a designation of interchangeability, as defined in the final interchangeability guidance from the US Food and Drug Administration, are considered. Potential alternative approaches to generating adequate and sufficient clinical data to support a designation of interchangeability are also presented.

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Is There Any Research Evidence Beyond Surveys and Opinion Polls on Automatic Substitution of Biological Medicines? A Systematic Review

et al. 2021

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Background Biosimilars are expected to decrease growing health care expenditures. Given that uptake of biosimilars has been modest, automatic substitution has been suggested to increase their use, but the practice is not yet allowed or implemented in many jurisdictions. Methods A systematic review was performed by searching databases Scopus, Medline (Ovid), CINAHL, and Web of Science. Peer-reviewed, original studies written in English and published during the period January 1, 2006 to April 24, 2021 reporting any interventions, pilots or any other studies including experiences or perceptions of any relevant stakeholders on automatic substitution of biologics were included without limitation by setting or geography. The quality of the included studies were evaluated by pre-determined criteria. Results Altogether, 27 studies fulfilled the inclusion criteria, of which 23 were surveys, and four semi-structured interviews reporting mainly stakeholders' perceptions on automatic substitution. Most of the studies (56%, 15/27) were from Europe. Studies were conducted among prescribers (n = 12), pharmacists (n = 5), patients (n = 4), payers (n = 1), and mixed stakeholders (n = 5). The primary objective of the majority (81%, 22/27) of the studies was to investigate some other biosimilar topic than automatic substitution. The reported perceptions of substitution were mainly negative. Studies evaluating risks, safety or effectiveness, or reporting real-life experiences of biologic substitution were lacking except one intervention and two prospective risk management studies. The overall quality of the studies was low to moderate, and the results were not generalizable due to convenience sampling not representing the populations of interest, and low response rates. Conclusions The current research evidence on the automatic substitution of biologics is scarce and of low to moderate quality, reflecting low stakeholder knowledge and their cautious attitude towards biosimilars. The safe and efficient implementation of automatic substitution requires well-designed practices, pilot studies, and evolving legislation.

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Sowing confusion in the field: the interchangeable use of biosimilar terminology

Cited by 10 publications

References 2 publications

The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable

The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable

Interchangeability of Biosimilars: What Level of Clinical Evidence is Needed to Support the Interchangeability Designation in the United States?

Is There Any Research Evidence Beyond Surveys and Opinion Polls on Automatic Substitution of Biological Medicines? A Systematic Review

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