美新生物仿制药法案的最新解读

目的：解读2010年3月23日美国总统奥巴马签署的新医疗改革法案“Patient Protection and Affordable Care Act”中关于生物仿制药的条款及其对生物仿制药行业的影响。方法：检索和综述相关文献。结果和结论：该法案在美国历史上第一次为生物仿制药建立的快速批准上市途径。对生物制药公司影响深远。     

Perception of Biosimilar Biologics and Non-Medical Prescription Switching among Rheumatologists: A Saudi Society for Rheumatology Initiative

BackgroundThe aim of this study was to evaluate rheumatologists’ perceptions of biosimilar biologics and Non-Medical Switching (NMS).MethodsA cross-sectional survey was conducted among registered members of the Saudi Society for Rheumatology. The questionnaire focused on biosimilars and NMS. Logistic regression was performed to ascertain the effect of demographics and practice characteristics on the use of biosimilars and NMS.ResultsOut of 249 SSR members, 143 completed the survey, generating a response rate of 57.4%. Of those (59.44%) were men with a mean (±SD) age and years of practice of 42.3 ± 9.13 and 10.3 ± 8.9, respectively. Rheumatologists managing adult patients (81.82%) and Ministry of Health practice (43.36 %) were the majority of respondents. Previous experience in prescribing a biosimilar was reported by 43 (30.07%) participants, with a higher probability among women (p = 0.015). A total of 26 (18.18%) participants had performed NMS on eligible patients. Adequate knowledge on biosimilars was reported by 69 (48.25%) participants. The adequacy of evidence to grant biosimilar approval for the studied indication and extrapolation to treat other conditions was reported by 88 (61.5%) and 69 (48.3%), respectively. The concept of totality-of-the-evidence was well understood by 37.1%. Biosimilars had been previously used by 43 (30.07) participants in their practice. NMS had been attempted by 26 (18.18), while 86 (60.1%) participants believed that NMS might harm patients.ConclusionThere is a clear knowledge gap about the biosimilar approval process among adult and pediatric rheumatologists who took part in the survey. In addition, a large number of participants reported having negative opinions about NMS. There is a need to organize SSR-led educational activities, and develop national guidelines regarding biosimilars and NMS.     

Biopharmaceuticals for rheumatic diseases in Latin America,Europe, Russia,and India: Innovators,biosimilars, and intended copies

A biosimilar is a biopharmaceutical product intended to be comparable to a previously licensed biopharmaceutical agent. The goal of such products is to increase the accessibility of biopharmaceutical therapy for rheumatoid arthritis by reducing costs. They are not like generic drugs, in that they may differ from the reference products in manufacturing, composition, and formulation. Regulatory authorities strive to ensure the absence of clinically meaningful differences between biosimilars and their reference drugs. However, small molecular differences may potentially affect pharmacodynamics (including affinity), pharmacokinetics, and immunogenicity. Intended copies are non-innovator biopharmaceutical products that, unlike biosimilars, do not have enough clinical evidence to demonstrate biosimilarity. For approval of a biosimilar, most countries require preclinical and clinical studies demonstrating comparability with the reference drug. The margin for determining equivalence or non-inferiority is determined on a case-by-case basis in each country, as there are no general criteria. The European Medicines Agency and US Food and Drug Administration have stringent regulatory processes to ensure comparability of biosimilars with their reference drugs. There are also post-marketing surveillance requirements to monitor safety. Only one biosimilar, CT-P13, has been approved for rheumatoid arthritis. However, in countries with less stringent regulation, intended copies are being commercialized and safety problems have been documented. Consequently, in such countries, there is an urgent need for appropriate regulatory processes to be established. Attempts to close the affordability gap of biopharmaceuticals should not open another gap between patients treated with an innovator drug and an intended copy.     

生物类似物政策监管指南原则与要求研究综述——基于欧盟版生物类似物指南

本文通过文献综述,在明确界定生物类似物概念的基础上,阐述了生物药的特点及其研发生产过程.基于欧盟版生物类似物指南,介绍了其政策框架,并系统梳理了生物类似物政策监管指南原则与要求,包括生物相似性、安全性和免疫原性、适应症外推法、标签与命名、数据保护以及药物互换性与药物警戒等内容,旨在为促进我国生物类似物与生物制药产业的进一步发展提供政策参考与建议.     

生物类似药临床应用专家共识

生物类似药具有与参照药相似的质量、疗效和安全性,同时具有价格优势,对实现我国居民用药的更高可及性具有非常重要的意义。为加深对生物类似药这一新兴概念的正确认识,规范我国生物类似药的临床用药,共识专家组参考国内外相关循证医学证据,结合临床用药体会,经充分讨论沟通,达成以下共识:(1)生物类似药与参照药疗效等同、安全性相似,临床上可以替代使用;(2)根据“适应证外推”原则,生物类似药可获得参照药具有相同作用机制的其他所有适应证,而且对外推适应证的疗效和安全性与参照药相似;(3)对于正在接受治疗的患者,临床医生可根据患者情况,决定是否由使用参照药转换成使用生物类似药。     

Medical and ethical considerations on hematopoietic stem cells mobilization for healthy donors

Hematopoietic stem cell transplantation is a common procedure potentially beneficial to many individuals with cancer, hematological, or inherited disorders, and has highlighted the need of related or unrelated donors to perform allograft. Donation of hematopoietic stem cells, either through bone marrow harvest or peripheral blood stem cell collection, is well-established and widespread. Over the past two decades, the peripheral blood stem cell collection by aphaeresis has become the main source of hematopoietic stem cells for transplantation, due to faster engraftment and practicability and lower risk of relapse for high-risk patients. For peripheral blood stem cell donation, donors require mobilization of hematopoietic stem cells from bone marrow into the blood stream. This is performed by growth factors injections. This article is a review of reported applications of growth factors (original granulocyte colony stimulating factor and its biosimilars), for healthy donors’ peripheral blood stem cell mobilization, in terms of toxicity, side effects, efficacy and follow-up. There is still an ethical dilemma for clinicians involved in allograft, because they expose healthy donors to drugs. It is important to dispel some of the critical concerns regarding their use in healthy volunteers, particularly because they receive no personal therapeutic benefit from this procedure.     

A clinical comparison of the efficacy and safety of biosimilar G-CSF and originator G-CSF in haematopoietic stem cell mobilization

BackgroundRecombinant granulocyte colony-stimulating factor (G-CSF) is widely used to mobilize haematopoietic stem cells. We compared the efficacy and safety of a biosimilar G-CSF (Zarzio^®, Sandoz Biopharmaceuticals) with the originator G-CSF (Neupogen^®, Amgen) in patients with haematological malignancies.MethodsA total of 108 patients were included in this study, 59 of whom were female (49 male), with an overall median age of 51 years (range 19–69). Patients had multiple myeloma (n = 46), non-Hodgkin's lymphoma (n = 28), Hodgkin's lymphoma (n = 26), or other diagnosis (n = 8). After administration of mobilizing regimens (primarily high-dose etoposide, high-dose cyclophosphamide, intermediate-dose Ara-C or ESHAP), patients were randomized to a standard daily 10 μg/kg dose of biosimilar G-CSF (n = 54) or originator G-CSF (n = 54).ResultsMedian duration of G-CSF administration was 8 days with both biosimilar G-CSF (range 4–17) and originator G-CSF (range 4–14). Both groups had a median of one apheresis with a median time until first apheresis of 11 days. There were no statistically significant differences between groups in the mean ± SD number of mobilized CD34+ cells/μL in peripheral blood or the number of CD34+ cells/kg body weight. Five patients (9%) in the originator G-CSF group and six patients in the biosimilar G-CSF group (11%) did not mobilize sufficient CD34+ cells. The adverse event profile was similar between groups.ConclusionsA biosimilar G-CSF (Zarzio^®) demonstrated similar efficacy and safety as the reference originator G-CSF (Neupogen^®) in hematopoietic stem cell mobilization in patients with haematological malignancies.     

The regulatory landscape of biosimilars: Algeria's efforts and progress made from 2006 to 2021

Biologics are tremendously efficacious biological molecules that have enabled the treatment of many life-threatening diseases, which have previously been hard to treat. Biosimilars, also known as “follow-on biologics”, are highly similar versions of another already approved biologic, called the Reference Product. The European Union has been a pioneer in the regulation of biosimilars. WHO guideline on evaluation of biosimilars published in 2009 was an important landmark in biosimilar regulations worldwide, and several countries have adopted its principles in the development of their own regulatory pathway for the approval of biosimilars. Most countries in the Middle East North Africa (MENA) region still lack official and scientific guidelines for biosimilar approval pathways. This article explores the regulatory situation of biosimilar registration pathways in Algeria and describes the progress made and the regulatory landscape changes for biosimilars in Algeria during the past ten years. Our findings indicate that the development of biosimilar regulation in Algeria went through three major phases between 2006 and 2021, during which there has been much progress in drafting guidance documents for biosimilars. Since 2016, Algeria has used the EMA, FDA and WHO guidelines as the basis for approval of several biosimilars and no national guidelines or regulations have been adopted to date. Additionally, there has been no regulation on substitution/interchangeability. The Algerian regulatory authority has gained considerable experience with approval and use of increasingly complex biosimilars over the past 5 years and has the potential to create its own biosimilar-specific regulatory pathway in the near future.