Biosimilars: Challenges and path forward

Kim, Young Sik; Choi, Byung Wook; Yang, Sung Wook; Shin, Seon Mi; Nam, Sang Wook; Roh, Yun Sook; Lee, Jae Young; Lee, Kyung Jin; Kim, Yong Jick; Kwon, Jun-Young; Kim, Dong-Il

doi:10.1007/s12257-013-0756-8

Cited by 10 publications

(7 citation statements)

References 52 publications

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“…In 2012, mAbs constituted more than half of the 124.6 billion dollars global biopharmaceutical sales [16] . A recent Dutch study demonstrated that total healthcare expenditures in IBD has shifted from in-hospital care and sick leave to out-patient therapy; anti-TNFs constituted 64 and 31% of total therapeutic expenditure in CD and UC, respectively [17] .…”

Section: Why Bss?mentioning

confidence: 99%

“…A recent Dutch study demonstrated that total healthcare expenditures in IBD has shifted from in-hospital care and sick leave to out-patient therapy; anti-TNFs constituted 64 and 31% of total therapeutic expenditure in CD and UC, respectively [17] . Cost savings are estimated to be less than 40% or even lower if the manufacturer of the ORG reduces the price to maintain market competiveness [14][15][16] . Yet, budget impact analysis of introducing an IFX-BS in IBD in 5 EU countries estimated substantial cost savings based on 3 discount scenarios versus IFX (10,20, and 30%) and assuming that 50% of newly diagnosed and 25% of IFX exposed patients will start or switch to IFX-BS, respectively [18] .…”

Section: Why Bss?mentioning

confidence: 99%

“…Having no access to ORG proprietary data, a BS developer must set up his own production line from ground zero [2,4,16] . Pre-requisites are the in-depth knowledge of the manufacturing process and its QAs, adherence to MAA guidelines of the regulatory agency and a full 'quality-in design' system to ensure the synthesis of an appropriately folded molecule and control many post-translational molecular modifications, such as glycosylation, acetylation, phosphorylation, etc.…”

Section: Manufacturing Process Process Drift and Product Evolution Cmentioning

confidence: 99%

“…Pre-requisites are the in-depth knowledge of the manufacturing process and its QAs, adherence to MAA guidelines of the regulatory agency and a full 'quality-in design' system to ensure the synthesis of an appropriately folded molecule and control many post-translational molecular modifications, such as glycosylation, acetylation, phosphorylation, etc. Even subtle structural differences may result in considerable deviations in clinical efficacy and safety of the BS to its ORG [14,16,25] . The final product is not an exact but a highly similar version of the ORG mAb.…”

Section: Manufacturing Process Process Drift and Product Evolution Cmentioning

confidence: 99%

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Anti-TNFs: Originators and Biosimilars

Mantzaris

2016

Dig Dis

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In the last 20 years, the advent of anti-tumor necrosis factor alpha (TNFα) biologics has revolutionized the treatment of patients with inflammatory bowel disease (IBD) but the cost of biologic therapy now constitutes a large proportion of all healthcare expenditures. Patent expiration has sparked the healthcare industry's interest in the production of biosimilar (BS) versions of first generation biologics (originators [ORGs]) for market sharing. Having no access to the production line of the ORG, the sponsor of a BS needs to develop his own manufacturing process to produce a highly similar version of the reference product. Similarity in structure, physicochemical properties, biologic activity, efficacy and safety must be demonstrated by a comprehensive comparability exercise that includes the most sensitive in vitro tests, models and clinical condition with pre-defined equivalence margins. Extrapolation of indications, inter-changeability and automatic substitution between BS and ORG depend on a legal framework that varies between different agencies. It is not, therefore, unexpected that marketing authorization by the European Medicines Agency and other regulatory agencies (but not Health Canada) of CT-P13 (Remsima™/Inflectra™) as infliximab (Remicade®) BSs for IBD by indication extrapolation has led to stormy discussions in the IBD community and beyond regarding the scientific adequacy of this decision. However, as we now have to live with BSs, we hope that the impeding automatic substitution in association with post-marketing pharmacovigilance, full traceability, registries and new studies will settle the controversy and will increase the confidence of physicians and patients. A universally adopted legal framework should be implemented because, as expected, the non-anti-TNFα BSs will be soon on the stage.

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Section: Why Bss?mentioning

confidence: 99%

Section: Why Bss?mentioning

confidence: 99%

Section: Manufacturing Process Process Drift and Product Evolution Cmentioning

confidence: 99%

Section: Manufacturing Process Process Drift and Product Evolution Cmentioning

confidence: 99%

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Anti-TNFs: Originators and Biosimilars

Mantzaris

2016

Dig Dis

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“…A microgram of therapeutic protein is often good enough for the monthly treatment of a patient, while your automobile burns kilograms of bioethanol in an hour. But as the patents of blockbuster biomedicines started to expire since 2012 [1], the need for advanced bioprocess for high efficiency, low cost production of biosimilars has been steeply increasing. Actually, the advances in bioprocess technology have increased the production scale of biosimilars, a major factor for price competitiveness, which extends the reach of Red biotechnology to the last man.…”

mentioning

confidence: 99%

Editorial: Bioprocess beyond the large scale production

Koo

Penjit

2015

Biotechnology Journal

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Monoclonal Antibody and Fusion Protein Biosimilars Across Therapeutic Areas: A Systematic Review of Published Evidence

et al. 2016

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BackgroundDespite regulatory efforts to formalize guidance policies on biosimilars, there remains a need to educate healthcare stakeholders on the acknowledged definition of biosimilarity and the data that underpin it.ObjectivesThe objectives of the study were to systematically collate published data for monoclonal antibodies and fusion protein biosimilars indicated for cancer, chronic inflammatory diseases, and other indications, and to explore differences in the type and weight (quantity and quality) of available evidence.MethodsMEDLINE, Embase, and ISI Web of Science were searched to September 2015. Conference proceedings (n = 17) were searched 2012 to July 2015. Included studies were categorized by originator, study type, and indication. To assess data strength and validity, risk of bias assessments were undertaken.ResultsAcross therapeutic areas, 43 named (marketed or proposed) biosimilars were identified for adalimumab, abciximab, bevacizumab, etanercept, infliximab, omalizumab, ranibizumab, rituximab, and trastuzumab originators. Infliximab CT-P13, SB2, and etanercept SB4 biosimilars have the greatest amount of published evidence of similarity with their originators, based on results of clinical studies involving larger numbers of patients or healthy subjects (N = 1405, 743, and 734, respectively). Published data were also retrieved for marketed intended copies of etanercept and rituximab.ConclusionsThis unbiased synthesis of the literature exposed significant differences in the extent of published evidence between molecules at preclinical, clinical, and post-marketing stages of development, providing clinicians and payers with a consolidated view of the available data and remaining gaps.Electronic supplementary materialThe online version of this article (doi:10.1007/s40259-016-0199-9) contains supplementary material, which is available to authorized users.

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Biosimilars: Challenges and path forward

Cited by 10 publications

References 52 publications

Anti-TNFs: Originators and Biosimilars

Anti-TNFs: Originators and Biosimilars

Editorial: Bioprocess beyond the large scale production

Monoclonal Antibody and Fusion Protein Biosimilars Across Therapeutic Areas: A Systematic Review of Published Evidence

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