The Tortoise and the Hare: Evolving Regulatory Landscapes for Biosimilars

Konara, Chamindika S.; Barnard, Ross; Hine, Damian; Siegel, Evan B.; Ferro, Vito

doi:10.1016/j.tibtech.2015.10.009

Cited by 16 publications

(23 citation statements)

References 28 publications

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“…Looming patent expirations for lucrative protein drugs have led to a surge in development, regulatory filings, and approvals for biosimilar products. 1 Infliximab was the first biosimilar monoclonal antibody (mAb) to receive approval by the European Medical Agency and, recently, by the US Food and Drug Administration. 2,3 The approved biosimilar Remsima TM , or Inflectra TM , is developed by Celltrion (Incheon, South Korea) and is a copy of Remicade Ò , marketed by Janssen.…”

Section: Introductionmentioning

confidence: 99%

Biosimilarity under stress: A forced degradation study of Remicade® and Remsima™

Pisupati

Benet

Tian

et al. 2017

mAbs

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Remsima™ (infliximab) is the first biosimilar monoclonal antibody (mAb) approved by the European Medical Agency and the US Food and Drug Administration. Remsima™ is highly similar to its reference product, Remicade®, with identical formulation components. The 2 products, however, are not identical; Remsima™ has higher levels of soluble aggregates, C-terminal lysine truncation, and fucosylated glycans. To understand if these attribute differences could be amplified during forced degradation, solutions and lyophilized powders of the 2 products were subjected to stress at elevated temperature (40-60°C) and humidity (dry-97% relative humidity). Stress-induced aggregation and degradation profiles were similar for the 2 products and resulted in loss of infliximab binding to tumor necrosis factor and FcγRIIIa. Appearances of protein aggregates and hydrolysis products were time- and humidity-dependent, with similar degradation rates observed for the reference and biosimilar products. Protein powder incubations at 40°C/97% relative humidity resulted in partial mAb unfolding and increased asparagine deamidation. Minor differences in heat capacity, fluorescence, levels of subvisible particulates, deamidation and protein fragments were observed in the 2 stressed products, but these differences were not statistically significant. The protein solution instability at 60°C, although quite significant, was also similar for both products. Despite the small initial analytical differences, Remicade® and Remsima™ displayed similar degradation mechanisms and kinetics. Thus, our results show that the 2 products are highly similar and infliximab's primary sequence largely defines their protein instabilities compared with the limited influence of small initial purity and glycosylation differences in the 2 products.

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Section: Introductionmentioning

confidence: 99%

Biosimilarity under stress: A forced degradation study of Remicade® and Remsima™

Pisupati

Benet

Tian

et al. 2017

mAbs

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“…Считается, что биосимиляры* полностью сопоставимы по качеству, эф-фективности и безопасности, подтвержденными строги-ми регулирующими органами национальных и наднацио-нальных структур. В отличие от производителей непатен-тованных препаратов на производителей как оригиналь-ных биопрепаратов, так и биоаналогов в равной степени действуют требования международного стандарта GMP (good manufacturing practice), в том числе процессуальные нормы процедуры одобрения [3,4].…”

Section: результаты и обсуждениеunclassified

Efficiency of using the gonadotropin Follitrope for ovarian stimulation in controlled ovarian induction protocols

Тапильская¹,

Буценко²,

Tapilskaya³

et al. 2016

Ross. vestn. akush.-ginekol.

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1 Санкт-Петербургский государственный педиатрический медицинский университет Минздрава россии, Санкт-Петербург, россия; 2 центр планирования семьи и репродукции, Санкт-Петербург, россия Фоллитроп (фоллитропин альфа) демонстрирует высокую эффективность в циклах контролируемой индукции овуляции, что делает препарат привлекательным для широкого клинического применения ввиду относительно низкой его стоимости. Цель исследования -оценить эффективность применения гонадотропина «Фоллитроп» для стимуляции яичников в протоколах контролируемой индукции овуляции у пациенток с нормогонадотропной ановуляцией. Материал и методы. выполнено сравнительное рандомизированное исследование по изучению режима применения препарата Фоллитроп с оценкой эффективности в циклах контролируемой индукции овуляции. всего было проведено 24 цикла лечения в группе пациенток (n=18) в возрасте от 28 до 35 лет с диагнозом вторичное бесплодие, ассоциированное с нормогонадотропной ановуляцией. рандомизацию по выбору стартовой дозы фоллитропа проводили в соотношении 3:2 -75 Ме (n=11): 150 Ме (n=7). Стимуляция овуляции проводилась под ультразвуковым контролем. Результаты. в подгруппе, в которой исполь-зовалась меньшая доза (75 Ме), только у 3 пациенток наблюдался адекватный рост фолликулов к 6-му дню с момента начала проведения протокола, что потребовало повышения дозы до 150 Ме; в подгруппе пациенток со стартовой дозой фоллитропа 150 Ме положительный ответ на терапию наблюдался во всех случаях. Среднее количество фолликулов в день введения триггера овуляции составило 2,2 (1-4) и 3,9 (1-7) в группах со стартовыми дозами 75 и 150 Ме соответ-ственно. все пациентки отметили хорошую переносимость и отсутствие побочных эффектов в момент лечения. у одной пациентки зарегистрирована гиперстимуляция яичников легкой степени. число случаев наступления беременности, диа-гностируемой по определению свободной β-субъединицы хорионического гонадотропина в когортной группе, включая повторную стимуляцию яичников с проведением искусственной инсеминации у 6 пациенток, составило 72,2% (у 13 из 18), клинической беременности -61,1% (у 11 из 18). Выводы. Клиническая эффективность препарата Фоллитроп наряду с его ценовыми характеристиками позволяют ему занимать определенную нишу в соответствующем сегменте фармацев-тического рынка.Авторы информируют об отсутствии конфликта интересов. Follitrope (follitropin alfa) demonstrates its high efficacy in the cycles of controlled ovulation induction, which makes the drug attractive for widespread clinical use due to its relatively low cost. Objective: to evaluate the efficiency of using the gonadotropin Follitrope for ovarian stimulation in controlled ovarian induction protocols in patients with normogonadotropic anovulation. Subjects and methods. A comparative randomized investigation was conducted to study a Follitrope dosage regimen and to evaluate its efficiency in the cycles of controlled ovulation induction. A total of 24 cycles were performed in a group of 28-to 35-year-old patients (n=18) diagnosed with secondary infertility assoc...

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“…Initial predictions expected biosimilar industry to have a worth of US$10-25 billion by year 2020 2 . However, biosimilar market entry and acceptance has been slower than what was initially anticipated 28 . Development of biosimilars continues to require extensive resources 24,[31][32][33] .…”

Section: Biosimilar Commercializationmentioning

confidence: 97%

“…Roche has since revised this position and now expects competition from biosimilars by year 2020 27 . Hence, despite the anticipated market potential for biosimilars, regulatory approval and subsequent market entry of biosimilars in the European Union (EU) and the U.S. has been slower than what was initially anticipated 28 .…”

Section: Potential For Biosimilarsmentioning

confidence: 99%

“…In addition to the technical complications associated with complex molecules, evolving regulatory processes, intellectual property issues, legal challenges initiated by originator biopharmaceutical to delay or prevent market entry, resistance from physicians and potential product pricing, and reimbursement issues have further hampered biosimilar development and commercialization process and increased the risk of investment in biosimilars 11,26,28,33,94 . This is clearly reflected by the differences in the cost and time involved in developing a biosimilar in comparison to a generic drug.…”

Section: Figure 2-2: How the Complexity Of Different Pharmaceutical Mmentioning

confidence: 99%

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Investigating Trends in the Duration of the Regulatory Approval Phase for Biosimilars in the European Union and the United States of America

Konara¹

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The Tortoise and the Hare: Evolving Regulatory Landscapes for Biosimilars

Cited by 16 publications

References 28 publications

Biosimilarity under stress: A forced degradation study of Remicade® and Remsima™

Biosimilarity under stress: A forced degradation study of Remicade® and Remsima™

Efficiency of using the gonadotropin Follitrope for ovarian stimulation in controlled ovarian induction protocols

Investigating Trends in the Duration of the Regulatory Approval Phase for Biosimilars in the European Union and the United States of America

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