Clinical and Regulatory Concerns of Biosimilars: A Review of Literature

Abstract

Although biosimilars have been part of clinical practice for more than a decade, healthcare professionals (HCPs) do not fully accept them. This is because of the perception that biosimilars may not be like their originators in terms of quality, safety, and efficacy. This study aims to evaluate the current knowledge and attitudes of healthcare professionals toward biosimilar prescription, and to elaborate on their concerns. We reviewed the literature using PubMed, Cochrane Library, and Science Direct electronic databases in the period from 2018 to 2020. The knowledge and confidence of healthcare professionals vary between countries, between clinical profiles and between studies. Although most of the healthcare professionals had a positive attitude to prescribing biosimilars, they would still prefer to prescribe them in initial treatment. Generally, HCPs were against multiple switches and substitution of biosimilars at the pharmacy level. HCP’s key concern was interchangeability, with eventual consequences on the clinical outcome of patients. HCPs still approach biosimilars with caution and stigma. HCPs need to have an unbiased coherent understanding of biosimilars at clinical, molecular and regulatory levels. It was also observed that most of their concerns are more theoretical than science-based. Physicians are in an excellent position to accept biosimilars, but they need the additional support of regulatory authorities to approve and take into consideration the available scientific data regarding biosimilars.

Progress in oncology biosimilars till 2020: Scrutinizing comparative studies of biosimilar monoclonal antibodies

“…Generally, healthcare professionals have been against the multiple switching and exchange of biosimilars. 35 A qualitative insight has been given on the application of biosimilar medicines in advanced drug therapy. It was highlighted in this study that there is further requirement of educating the physicians and other health care professionals which are related in prescribing activities of biosimilars as lack of their knowledge would lead to retardation in required therapeutic results in patients, medication errors and adverse events.…”

General characteristics of clinical trials for biosimilar drugs

“…Although, biologics and their biosimilars are increasingly used in medicine, there seems to be a serious confusion about these products, and their distinguishing features from conventional drugs are not well understood. Regarding choice of generic drugs, a widespread audience among healthcare professionals and patients have negative knowledge, attitudes and behaviours, which are mostly inappropriate [5][6][7]. Considering this is the case even for the more simply understood conventional drugs, it is concerning that the problem may be even greater for "similars" of biologics, which are known to be more complex [6,8,9].…”

“…Especially based on the signs of rare adverse effects, the clinical safety of biosimilar medicinal products, including the ongoing benefit-risk assessment, can be closely monitored following approval. Also, the existing concerns can be addressed or the risks in question can be managed correctly [5][6][7][11][12][13][14][15]. As with all medicinal products, it is not mandatory to conduct Phase IV clinical trials after registration for biosimilar drugs.…”

“…In addition, the close cooperation of the parties such as the authorities and manufacturers during the clinical research process is of key importance in solving the problems that may arise regarding biosimilars and paving the way for these products. In evaluations related to biosimilars, instead of focusing on a single clinical trial phase, a holistic understanding of the entire process and the related evidence is needed [5][6][7][12][13][14][15][16]. Moreover, it is necessary to avoid unfair, nonstandard, non-transparent and shallow approaches, as those concern all stages of biosimilar clinical research and have the risks of adversely affecting both the national and international biosimilar market.…”

Analysis of the Regulatory Science Applied to a Single Portfolio of Eight Biosimilar Product Approvals by Four Key Regulatory Authorities

“…Despite many biosimilars now approved by the EMA [ 25 ] and a growing number of biosimilars authorized by the FDA [ 26 ], barriers remain to their adoption and use in clinical practice, driven by several issues, including concerns among healthcare providers and patients over their safety and effectiveness [ 27 ]. These reservations suggest that gaps may exist between the extent of the evidence required for biosimilars to gain RA approval and the evidence needed to achieve wider acceptance and use by physicians and patients [ 28 ]. When the development components and supporting data of a novel biologic and biosimilar are compared ( Figure 1 ), the unique aspects of biosimilar development are revealed as one potential root cause of this gap.…”