BACKGROUND & AIMS: :With the development of innovative cancer treatments over recent decades, the cost of cancer care has risen exponentially, limiting patient access to patented originator biotherapeutics in many countries. The introduction of biosimilars to the market has created new opportunities as well the need for changes in practice within healthcare institutions. A ‘biosimilar’ is a biotherapeutic product which is highly similar in terms of quality, safety and efficacy to an already licensed originator product. Although biosimilars lack clinically meaningful differences in therapeutic activity as compared to the originator product, these complex biological molecules are not considered identical chemical copies, unlike generics, and minor differences in molecular structure and inactive compounds may exist. A thorough understanding of these differences and their clinical implications is necessary for optimising medicines-use practices involving biosimilars. This position statement, developed by the International Society of Oncology Pharmacy Practitioners Biosimilars Taskforce, aims to provide the global oncology pharmacy community with guidance to support decisions around biosimilar use. The 11 statements cover the regulation and evaluation of biosimilars, practical issues around local implementation, the education of healthcare staff and patients, and the requirement for ongoing pharmacovigilance and outcome monitoring.

背景与目标： ：随着近几十年来创新型癌症治疗方法的发展，癌症治疗的费用成倍增加，在许多国家限制了患者使用获得专利的生物治疗药物的机会。将生物仿制药推向市场不仅创造了新的机遇，还为医疗机构内部的实践变革带来了需求。 “生物仿制药”是一种生物治疗产品，其质量，安全性和功效与已获许可的原始产品高度相似。尽管与仿制药相比，生物仿制药在治疗活性上缺乏临床上有意义的差异，但与仿制药不同，这些复杂的生物分子不被视为相同的化学拷贝，并且分子结构和非活性化合物可能存在细微差异。对这些差异及其临床意义的透彻了解对于优化涉及生物仿制药的药物使用实践是必不可少的。该立场声明是由国际肿瘤药学从业者协会生物仿制药特别工作组制定的，旨在为全球肿瘤药学界提供指导，以支持围绕生物仿制药使用的决策。这11项声明涵盖生物仿制药的监管和评估，本地实施的实际问题，医护人员和患者的教育以及持续进行药物警戒和结果监测的要求。

BACKGROUND & AIMS: :Introduction: Many tumor necrosis factor (TNF)-alpha 'biosimilar' agents have been approved for the treatment of psoriasis and other autoinflammatory conditions. These biosimilars have the same structure as the originator biologic and have been shown to be equivalent in terms of safety and efficacy. However, given the method by which biosimilars are manufactured, they are not exact replicas of the originator, unlike generic forms of non-biologic medications. Therefore, there is controversy regarding whether these agents should be considered interchangeable with their originator biologics.Areas covered: The objective of this review is to summarize the safety data for each of the approved TNF-alpha biosimilars to determine whether or not these agents have appropriate safety profiles to replace their originator biologics.Expert opinion: Based on extrapolation of phase III investigations in patients with rheumatologic diseases, each of the approved anti-TNF agents have comparable efficacy, tolerability, and safety profiles to their originators. Studies in patients with psoriasis are more limited. Transitioning from a biologic to its biosimilar has also been shown to be similarly safe and immunogenetic compared to maintenance therapy with the originator. More post-marketing studies are needed to demonstrate the long-term safety in patients with psoriasis.

背景与目标： ：简介：许多肿瘤坏死因子（TNF）-α“生物仿制药”药物已被批准用于治疗牛皮癣和其他自体炎症。这些生物仿制药与原始生物仿制药具有相同的结构，并已被证明在安全性和功效上是等效的。但是，给定制造生物仿制药的方法，与非生物药物的一般形式不同，它们不是原始仿制药的精确复制品。因此，关于这些药物是否应与其原始生物制剂互换使用存在争议。研究范围：本综述的目的是总结每种批准的TNF-α生物仿制药的安全性数据，以确定这些药物是否具有适当的适用性。专家意见：根据对风湿病患者进行的III期研究的推断，每种批准的抗TNF药物均具有与其始发者相当的功效，耐受性和安全性。银屑病患者的研究更为有限。与使用始发者进行的维持治疗相比，从生物制剂过渡到其生物仿制药也已被证明具有相似的安全性和免疫遗传性。需要更多的上市后研究来证明牛皮癣患者的长期安全性。

BACKGROUND & AIMS: :The World Health Assembly in 2014 adopted a resolution that mandates both Member States and the WHO Secretariat to facilitate access to biotherapeutic products in a way that ensures their quality, safety and efficacy. The availability of biosimilars is expected to increase access to biotherapeutic products by providing more treatment options triggering competition which would lead to a consistent reduction in the average price of treatment. Since the WHO guidelines for regulatory evaluation of biosimilars were issued in 2009, WHO has provided immense effort towards harmonizing the terminology and the regulatory framework for biosimilars globally. This article describes the progress made and the regulatory landscape changes for biosimilars in 21 countries during the past ten years. Based on the information from regulators and from publicly available data, the following has been identified: 1) WHO guidelines have contributed to setting the regulatory framework for biosimilars in countries and increasing regulatory convergence at global level; 2) terminology used for biosimilars is more consistent than in the past; 3) biosimilars are now approved in all participating countries; and 4) the dominant product class for candidate biosimilars under development is monoclonal antibodies.

背景与目标： ：2014年世界卫生大会通过了一项决议，授权会员国和世卫组织秘书处以确保其质量，安全性和有效性的方式促进获取生物治疗产品的便利。通过提供更多的治疗选择引发竞争，预计生物仿制药的可用性将增加获得生物治疗产品的机会，这将导致治疗平均价格的持续下降。自2009年发布世卫组织生物仿制药监管评估指南以来，世卫组织为协调全球生物仿制药的术语和监管框架做出了巨大努力。本文介绍了过去十年来21个国家/地区中生物仿制药所取得的进展和监管格局的变化。根据来自监管机构的信息和可公开获得的数据，确定了以下内容：1）世卫组织准则有助于在各国建立生物仿制药监管框架，并在全球范围内促进监管趋同； 2）用于生物仿制药的术语比过去更加一致； 3）现在所有参与国都批准了生物仿制药； 4）正在开发的候选生物仿制药的主要产品类别是单克隆抗体。

BACKGROUND & AIMS: OBJECTIVES:To examine physicians' perceptions of the uptake of biosimilars. DESIGN:Systematic review. DATA SOURCES:MedLine Ovid and Scopus databases at the end of 2018. ELIGIBILITY CRITERIA:Original scientific studies written in English that addressed physicians' perceptions of the uptake of biosimilars. DATA EXTRACTION AND SYNTHESIS:The search resulted in altogether 451 studies and 331 after removing duplicates. Two researchers examined these based on the title, abstract and entire text, resulting in 20 studies. The references in these 20 studies were screened and three further studies were included. The data of these 23 studies were extracted. All the publications were quality assessed by two researchers. RESULTS:Most of the selected studies were conducted in Europe and commonly used short surveys. Physicians' familiarity with biosimilars varied: 49%-76% were familiar with biosimilars while 2%-25% did not know what biosimilars were, the percentages varying from study to study. Their measured knowledge was generally more limited compared with their self-assessed knowledge. Physicians' perceptions of biosimilars also varied: 54%-94% were confident prescribing biosimilars, while 65%-67% had concerns regarding these medicines. Physicians seemed to prefer originator products to biosimilars and prescribed biosimilars mainly for biologic-naive patients. They considered cost savings and the lower price compared with the originator biologic medicine as the main advantages of biosimilars, while their doubts were often related to safety, efficacy and immunogenicity. 64%-95% of physicians had negative perceptions of pharmacist-led substitution of biologic medicines. CONCLUSIONS:Physicians' knowledge of and attitudes towards biosimilars vary. Although physicians had positive attitudes towards biosimilars, prescribing was limited, especially for patients already being treated with biologic medicines. Perceptions of pharmacist-led substitution of biologic medicines were often negative. Education and national recommendations for switching and substitution of biologic medicines are needed to support the uptake of biosimilars.

背景与目标： 目的：检查医生对生物仿制药使用的看法。
设计：系统评价。
数据来源：2018年底的MedLine Ovid和Scopus数据库。
资格标准：以英语撰写的原始科学研究，涉及医生对生物仿制药的吸收的看法。
数据提取与合成：检索共进行451项研究，除去重复项后进行331项研究。两名研究人员根据标题，摘要和全文研究了这些内容，从而进行了20项研究。筛选了这20项研究中的参考文献，并纳入了三项进一步的研究。提取了这23项研究的数据。所有出版物均由两名研究人员进行质量评估。
结果：大多数选定的研究是在欧洲进行的，并且是常用的短期调查。医生对生物仿制药的熟悉程度各不相同：49％-76％的人对生物仿制药很熟悉，而2％-25％的人不知道什么是生物仿制药，不同研究的百分比不同。与他们自己评估的知识相比，他们测得的知识通常更受限制。医师对生物仿制药的看法也各不相同：54％-94％的人对开具生物仿制药有信心，而65％-67％的人对这些药物感到担忧。医生似乎更喜欢原始产品，而不是生物仿制药和开具生物仿制药的处方药，主要是针对未接触过生物的患者。他们认为与仿制生物药品相比，节省成本和降低价格是生物仿制药的主要优势，而他们的疑问通常与安全性，功效和免疫原性有关。 64％-95％的医生对药剂师主导的生物药物替代品持否定态度。
结论：医师对生物仿制药的了解和态度各不相同。尽管医师们对生物仿制药持积极态度，但开处方是有限的，特别是对于已经接受过生物药物治疗的患者。由药剂师主导的生物药物替代品的认识通常是负面的。需要为转用和替代生物药物提供教育和国家建议，以支持生物仿制药的使用。

BACKGROUND & AIMS: :Although complex, biologic agents are key components of modern therapy in multiple disciplines, particularly oncology. However, despite the fact that biosimilars (eg, filgrastim-sndz, bevacizumab-awwb, trastuzumab-dkst, rituximab-abbs) have been approved in the United States, many clinicians are poorly informed about their unique pathway for approval. At the NCCN 2019 Annual Congress: Hematologic Malignancies, Dr. Andrew D. Zelenetz, Memorial Sloan Kettering Cancer Center, outlined important issues regarding the use of biosimilars, including extrapolation, interchangeability, and naming.

背景与目标： ：尽管复杂，但生物制剂是现代疗法在多个学科（尤其是肿瘤学）中的关键组成部分。然而，尽管在美国已经批准了生物仿制药（例如非格司亭-sndz，贝伐单抗-awwb，曲妥珠单抗-dkst，利妥昔单抗），但许多临床医生对其独特的批准途径知之甚少。在NCCN 2019年会上：血液系统恶性肿瘤，纪念斯隆·凯特琳癌症中心的Andrew D.Zelenetz博士概述了有关生物仿制药使用的重要问题，包括推断，互换性和命名。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: PURPOSE:The aim of this study was to assess the safety profiles of two biosimilar medicines (rituximab and trastuzumab) in the treatment of cancer patients within a Portuguese oncology hospital. METHODS:This hospital-based prospective observational study followed a cohort event monitoring approach focused on signalling suspected adverse drug reactions (ADRs). Patients undergoing treatment with rituximab biosimilar CT-P10 (Truxima®) or trastuzumab biosimilar CT-P6 (Herzuma®) were recruited over an 11-month and a 6-month period, respectively. Clinicians identified eligible patients and used paper-based forms to report all ADRs associated with biosimilar medicines. ADR case reports were assessed for seriousness, expectedness and causality in the Pharmacovigilance Unit of Coimbra. RESULTS:Ninety-four patients received biosimilar medicines (rituximab, n = 35; trastuzumab, n = 59). Of those, 4 patients (11.4%) experienced 16 ADRs with rituximab and 1 patient (1.7%) experienced 5 ADRs with trastuzumab. All case reports contained serious and expected ADRs that were at least probably related with biosimilar medicines under study. Based on the MedDRA PT coding, the most reported ADR for rituximab CT-P10 was chest discomfort (n = 4; 19.1%), followed by odynophagia (n = 2; 9.5%). Trastuzumab CT-P6 was associated with back pain, headache, pain in extremity, tachypnoea and tremor (each, n = 1; 4.8%). CONCLUSION:The results of this study suggest that using biosimilar rituximab and biosimilar trastuzumab to treat cancer patients in the real-world clinical setting is associated with acceptable safety profiles. No new safety problems were identified.

背景与目标： 目的：本研究的目的是评估两种生物仿制药（利妥昔单抗和曲妥珠单抗）在葡萄牙肿瘤医院内治疗癌症患者的安全性。
方法：这项基于医院的前瞻性观察性研究采用了队列事件监测方法，重点关注可疑药物不良反应（ADR）的信号传递。分别招募接受利妥昔单抗生物仿制药CT-P10（Truxima®）或曲妥珠单抗生物仿制药CT-P6（Herzuma®）治疗的患者，疗程分别为11个月和6个月。临床医生确定了合格的患者，并使用纸质表格报告了与生物仿制药相关的所有ADR。在科英布拉药物警戒科评估了ADR病例报告的严重性，预期性和因果关系。
结果：94例患者接受了生物仿制药（利妥昔单抗，n = 35；曲妥珠单抗，n = 59）。在这些患者中，有4名患者（11.4％）接受了16例利妥昔单抗的ADR治疗，有1名患者（1.7％）经历了5种曲妥珠单抗的ADR。所有病例报告均包含严重的和预期的ADR，至少与所研究的生物仿制药有关。根据MedDRA PT编码，报告最多的利妥昔单抗CT-P10的ADR为胸部不适（n = 4，占19.1％），其次是咽痛（n == 2，占9.5％）。曲妥珠单抗CT-P6与背痛，头痛，四肢疼痛，呼吸困难和震颤有关（每例，n = 1； 4.8％）。
结论：这项研究的结果表明，在现实世界的临床环境中使用生物仿制药利妥昔单抗和生物仿制药曲妥珠单抗治疗癌症患者具有可接受的安全性。没有发现新的安全问题。

BACKGROUND & AIMS: :A biosimilar is a copy of an approved biological medicine whose patent protections have expired. Biosimilars of antibodies to tumour necrosis factor α (TNFα) are becoming important in the treatment of inflammatory bowel diseases (IBD). The first one introduced commercially is an infliximab biosimilar. The aim of this study was to provide an overview of anti-TNFα biosimilars. The literature on biosimilars of monoclonal anti-TNFα antibodies was reviewed, including their manufacture and approval pathways, concerns about efficacy, safety, immunogenicity, extrapolation, switching and labelling. Previous experience with biosimilars of epoetin and other growth factors was also reviewed. The infliximab biosimilar CT-P13 was the first biosimilar monoclonal antibody registered for the treatment of IBD. The major advantage of biosimilars is the reduced cost of therapy. Concerns have arisen, however, about the efficacy and safety of CT-P13 in IBD, the extrapolation of results from rheumatologic trials to IBD and the free interchangeability of CT-P13 with infliximab. Experience with simple peptide biosimilars, such as epoetins and growth factors, has generally been positive, with these biosimilars having similar efficacy and safety as the original products, although immunogenicity remains a major concern. Upcoming postregistration studies will address concerns on biosimilars in IBD, including their efficacy, safety, immunogenicity, switching and interchangeability. Biosimilars active against the same epitopes, but with improved pharmacokinetic properties that enhance their efficacy and/or safety, may be the next stage in the development of biosimilars. Anti-TNFα biosimilars represent promising new treatment options for patients with IBD. However, data on their efficacy and safety in IBD are needed.

背景与目标： ：生物仿制药是专利保护已过期的已批准生物药品的副本。肿瘤坏死因子α（TNFα）抗体的生物仿制药在治疗炎症性肠病（IBD）中变得越来越重要。商业上第一个引入的是英夫利昔单抗生物仿制药。这项研究的目的是提供抗TNFα生物仿制药的概述。综述了有关单克隆抗TNFα抗体生物仿制药的文献，包括其制备和批准途径，对功效，安全性，免疫原性，外推，转换和标记的关注。还回顾了以往使用依泊汀和其他生长因子的生物仿制药的经验。英夫利昔单抗生物仿制药CT-P13是第一个注册用于治疗IBD的生物仿制药单克隆抗体。生物仿制药的主要优点是降低了治疗成本。然而，有关CT-P13在IBD中的功效和安全性，风湿病试验结果向IBD的推断以及CT-P13与英夫利昔单抗的自由互换性等问题引起了人们的关注。简单的肽类生物类似物（如表蛋白和生长因子）的经验通常是积极的，尽管免疫原性仍然是主要关注的问题，但这些生物类似物具有与原始产品相似的功效和安全性。即将进行的注册后研究将解决对IBD中生物仿制药的关注，包括其功效，安全性，免疫原性，转换和互换性。生物仿制药对相同的表位具有活性，但具有改善的药代动力学特性，可增强其功效和/或安全性，可能是生物仿制药开发的下一阶段。抗TNFα生物仿制药代表了IBD患者的有希望的新治疗选择。但是，需要有关其在IBD中的疗效和安全性的数据。

BACKGROUND & AIMS: :As the patents for many biologic anticancer drugs expire, significant growth in the use of biosimilars is predicted, offering an opportunity to help combat the rising costs of treatment and increase patient access to biologic therapy. Attainment of regulatory approval, involving numerous nonclinical and clinical comparative studies versus each reference product, is only one of several barriers to realize the potential gains offered by biosimilars. It is important to understand the current perceptions and informational needs of different stakeholders if biosimilars are to be accepted and widely used in the clinic. We discuss these considerations and refer to recent experiences with CT-P13, a biosimilar of the TNF inhibitor infliximab used to treat rheumatoid arthritis and other inflammatory disorders.

背景与目标： ：随着许多生物抗癌药的专利到期，预计生物仿制药的使用将显着增长，这将提供一个机会来应对不断上升的治疗费用并增加患者获得生物疗法的机会。与每种参考产品相比，涉及许多非临床和临床比较研究的监管批准的获得，只是实现生物仿制药潜在收益的几个障碍之一。如果要在临床上接受并使用生物仿制药，了解不同利益相关者的当前看法和信息需求非常重要。我们讨论这些考虑因素，并参考CT-P13的最新经验，CT-P13是用于治疗类风湿性关节炎和其他炎症性疾病的TNF抑制剂英夫利昔单抗的生物仿制药。

BACKGROUND & AIMS: PURPOSE:Historical perspective on the use of biotechnology for drug product development, terminology used for biotechnology drug products, potential benefits of biotechnology, applications of biotechnology to drug product development, pharmacy considerations in the use of biopharmaceuticals, and the classification of biotechnology products by the Food and Drug Administration (FDA) are discussed. SUMMARY:Applications of biotechnology to medicine have a long history, and the pace of new applications has accelerated in recent decades. Various terms, including biosimilars, follow-on biologics, and follow-on proteins, have been used to refer to biotechnology products that are highly similar to the reference product, notwithstanding minor differences. New approaches to the production of drug products have been made feasible through biotechnology, facilitating the prevention, cure, and treatment of diseases. Recombinant DNA technology, monoclonal antibodies, and gene therapy are among the applications of biotechnology processes to drug development. Storage, handling, preparation, and administration are among the pharmacy considerations in the use of biopharmaceuticals. The FDA has not defined or developed a pathway for establishing therapeutic equivalence of biosimilar and innovator products. Payers may attempt to make decisions about therapeutic equivalence in order to reduce costs. CONCLUSION:Considerable confusion surrounds biosimilars. Pharmacists can help resolve the confusion by explaining to lawmakers and health-system decision-makers the terminology and science of biotechnology processes and the implications for use of biotechnology products in the future.

背景与目标： 目的：关于使用生物技术进行药品开发的历史观点，用于生物技术药品的术语，生物技术的潜在利益，生物技术在药品开发中的应用，使用生物药品的药学注意事项以及生物技术产品的分类讨论了食品和药物管理局（FDA）。
摘要：生物技术在医学上的应用历史悠久，近几十年来，新应用的发展步伐加快了。尽管有微小差异，但包括生物仿制药，后续生物制剂和后续蛋白质在内的各种术语已用于指代与参考产品高度相似的生物技术产品。通过生物技术使药物生产的新方法变得可行，从而促进了疾病的预防，治疗和治疗。重组DNA技术，单克隆抗体和基因疗法是生物技术过程在药物开发中的应用。储存，处理，制备和给药是生物药物使用中的药学考虑事项。 FDA尚未定义或开发出建立生物仿制药和创新药物等效性的途径。付款人可以尝试就治疗等效性做出决定，以降低成本。
结论：生物仿制药存在相当大的困惑。药剂师可以通过向立法者和卫生系统决策者解释生物技术过程的术语和科学以及未来使用生物技术产品的含义，来帮助解决这种困惑。

BACKGROUND & AIMS: :A sea change is occurring in the off-patent drug manufacturing industry with a first wave of biotechnologically derived products reaching the end of their patent lives. However, recombinant proteins are in a different league from their chemical predecessors in terms of molecular complexity. Small differences in manufacturing processes can affect the efficacy and safety of the recombinant proteins in a manner which is not always measurable using analytical or in vitro techniques. Thus, comparable clinical profiles do not automatically follow from physicochemical likeness and can only be demonstrated through clinical studies. It is essential for patient safety that both innovator and biosimilar manufacturers ensure consistency in their production, by performing rigorous purity and activity profiling between batches, and implement tailored pharmacovigilance plans.

背景与目标： ：在非专利药物制造行业中发生了巨变，第一波生物技术衍生产品的专利生命期即将结束。但是，就分子复杂性而言，重组蛋白与其化学前身处于不同的联盟。制造过程中的细微差异可能会以无法始终使用分析或体外技术进行测量的方式影响重组蛋白的功效和安全性。因此，可比较的临床特征不会自动从理化相似性中得出，而只能通过临床研究来证明。对于患者安全而言，创新者和生物仿制药制造商都必须执行严格的纯度和批次间活性分析，并实施量身定制的药物警戒计划，以确保其生产的一致性，这对患者而言至关重要。

BACKGROUND & AIMS: :Introduction: Little is known about market access to biosimilars from a health economic perspective, except for studies that compute the budget impact of biosimilar use. Areas covered: This comprehensive health economic guide to the market access of biosimilars focuses on the role of biosimilars in pharmaceutical innovation and competition, the objective of biopharmaceutical policy, the budget impact of biosimilars, and the cost-effectiveness of biologic therapy in the presence of biosimilars. Expert opinion: We argue that the objective of biopharmaceutical policy in a health system should be to create a competitive and sustainable market for off-patent reference biologics, biosimilars, and next-generation biologics that makes biologic therapy available to patients at the lowest cost. Market access of biosimilars can contribute to this objective as a result of the lower price of biosimilars and price competition with alternative therapies. The resulting improvement in the cost-effectiveness of biologic therapy needs to be accounted for by revisiting reimbursement decisions and conditions. When examining the cost-effectiveness of biologic therapy following patent expiry, stakeholders need to consider residual uncertainties at the time of biosimilar marketing authorization, the nocebo effect, market entry of a second-generation reference biologic with a different administration form than the biosimilar, and value-added services.

背景与目标： ：简介：从健康经济学的角度对生物仿制药的市场准入知之甚少，但有关计算生物仿制药使用的预算影响的研究除外。涵盖的领域：这份有关生物仿制药市场准入的全面卫生经济指南，重点关注生物仿制药在药物创新和竞争中的作用，生物制药政策的目标，生物仿制药的预算影响以及存在生物仿制药的成本效益。生物仿制药。专家意见：我们认为，卫生系统中生物药物政策的目标应该是为专利非专利参考生物制剂，生物仿制药和下一代生物制剂创建一个竞争性和可持续性市场，以最低的成本为患者提供生物治疗。由于生物仿制药的较低价格以及与替代疗法的价格竞争，生物仿制药的市场准入可有助于实现这一目标。需要通过重新考虑报销决定和条件来说明生物治疗成本效益的最终改善。在检查专利到期后生物疗法的成本效益时，利益相关者需要考虑生物仿制药上市授权时的残留不确定性，nocebo效应，具有与生物仿制药不同的管理形式的第二代参考生物制剂的市场准入，以及增值服务。

BACKGROUND & AIMS: :Our aim was to compare the efficacy and safety of two recently developed biosimilars of pegfilgrastim, a pegylated form of the recombinant human granulocyte-colony stimulating factor (G-CSF) analog filgrastim with those of the reference pegfilgrastim. We retrospectively analyzed data from patients diagnosed with diffuse large B-cell lymphoma (DLBCL) who were treated with first-line R-CHOP chemotherapy and received pegylated G-CSF for primary prophylaxis. The following pegylated G-CSFs were analyzed in this study: reference pegfilgrastim (Neulasta® ) and two of its biosimilars (tripegfilgrastim; Dulastin® and pegteograstim; Neulapeg® ). In total, 296 patients were enrolled. The number of patients with at least one episode of neutropenia during R-CHOP chemotherapy was the lowest in the reference cohort (pegfilgrastim: 127 of 193 patients, 65.8%; tripegfilgrastim: 64 of 69 patients, 92.8%; pegteograstim: 28 of 34 patients, 82.4%, P < .001). The number of patients with at least one episode of febrile neutropenia was also lowest in the reference cohort (pegfilgrastim: 67 of 193 patients, 34.7%; tripegfilgrastim: 38 of 69 patients, 55.1%; pegteograstim: 16 of 34 patients, 47.1%, P = .009). There were no differences in the duration of neutropenia and febrile neutropenia or treatment outcomes (rate of complete response or relapse and survival). There were no reports of grade 3 or higher adverse events requiring discontinuation of prophylactic pegylated G-CSF in any group. The safety of the pegfilgrastim biosimilars for prophylactic purposes was comparable to that of the reference pegfilgrastim; however, in terms of their efficacy, the incidence of neutropenia and febrile neutropenia tended to be higher than that when using pegfilgrastim. The clinical relevance of these results in the biosimilar cohorts should be explored.

背景与目标： ：我们的目的是比较两种新近开发的pegfilgrastim生物仿制药的功效和安全性，pegfilgrastim是一种聚乙二醇化形式的重组人粒细胞集落刺激因子（G-CSF）类似物非格司亭的聚乙二醇化形式，与参考pegfilgrastim的仿制药相似。我们回顾性分析了诊断为弥散性大B细胞淋巴瘤（DLBCL）的患者的数据，这些患者接受了一线R-CHOP化疗并接受了聚乙二醇化G-CSF的一级预防。在本研究中分析了以下聚乙二醇化的G-CSF：参比非格司亭（Neulasta®）及其两种生物仿制药（tripegfilgrastim;Dulastin®和pegteograstim;Neulapeg®）。总共招募了296名患者。在参考队列中，R-CHOP化疗期间发生至少1次中性粒细胞减少症的患者人数最低（pegfilgrastim：193名患者中的127名，占65.8％; tripegfilgrastim：69名患者中的64名，占92.8％; pegteograstim：34名患者中的28名，82.4％，P <.001）。在参考队列中，至少发生一次发热性中性粒细胞减少症的患者人数也最低（pegfilgrastim：193例患者中的67例，占34.7％; tripegfilgrastim：69例患者中的38例，占55.1％; pegteograstim：34例患者中的16例，占47.1％， P = .009）。中性粒细胞减少和发热性中性粒细胞减少的持续时间或治疗结果（完全缓解率或复发率和生存率）没有差异。在任何组中均没有3级或更高级别不良事件需要预防性聚乙二醇化G-CSF停药的报道。 pegfilgrastim生物仿制药在预防方面的安全性与参考pegfilgrastim相似。然而，就其功效而言，中性粒细胞减少和发热性中性粒细胞减少的发生率往往比使用培非非司亭时高。这些结果在生物仿制药研究中的临床意义应予以探讨。

BACKGROUND & AIMS: :Aim: We aimed to improve oncology patients' knowledge and awareness of biosimilars. Subsequently, we conducted an assessment of this knowledge by use of an anonymous online survey. Patients & methods: Printed materials discussing major topics related to biosimilars were developed during Phase I of our educational initiative. The brochures contained a link to the online survey. Results: A total of 79 patients responded to our survey. More than 70% of survey participants selected the correct definition of biosimilars and nearly 80% did so on questions focused on regulation, adverse reactions reporting and cost issues related to biosimilars. Conclusion: Our results indicate a good level of both knowledge and awareness of major topics concerning biosimilars among our survey participants.

背景与目标： ：目的：我们旨在提高肿瘤患者对生物仿制药的了解和认识。随后，我们通过匿名在线调查对这种知识进行了评估。患者与方法：在我们的教育计划的第一阶段中，讨论了与生物仿制药有关的主要主题的印刷材料已经开发出来。宣传册包含在线调查的链接。结果：共有79位患者对我们的调查作出了回应。超过70％的调查参与者选择了正确的生物仿制药定义，将近80％的人选择了针对法规，不良反应报告以及与生物仿制药相关的成本问题的问题。结论：我们的结果表明，我们的调查参与者对生物仿制药的主要主题具有很高的知识和意识水平。

BACKGROUND & AIMS: :Biological products or biopharmaceuticals are medicinal products derived from living systems and manufactured by modern biotechnological methods that differ widely from the traditional synthetic drugs. Monoclonal antibodies are the most rapidly growing type of biologic. They are much larger and more complex molecules with inherent diversity; therefore, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, legal follow-on biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilarity is based on a comparability exercise whereby unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency follows the key principles established by the World Health Organization for the assessment of biosimilarity, although does not adopt the name 'biosimilar'. However, the agency also made a compromise on a standalone application pathway that does not require the usual comparability exercise with the reference product, originating nonbiosimilar copies. Interchangeability and the use of nonproprietary names are not regulated, giving rise to pressures on physicians and conflicts of interest in the decision making on biosimilar use. The scope of this article is to present the Brazilian regulation on biosimilars, its strengths and weaknesses, and to discuss it in the face of regulations in the USA and Europe.

背景与目标： ：生物产品或生物药品是衍生自生命系统并通过现代生物技术方法制造的药品，与传统的合成药物大不相同。单克隆抗体是生物增长最快的类型。它们是更大，更复杂的分子，具有固有的多样性。因此，即使使用相同类型的宿主表达系统和等效技术，不同的制造商也无法生产相同的生物产品。因此，专利到期后生产和销售的合法后续生物制剂通常被称为生物仿制药。生物相似性基于可比性演习，在该演习中必须评估不可避免的临床差异，并且必须符合等效性或非劣效性标准。生物仿制药需要遵守不同监管要求，以在不同地点进行市场授权。国家主管部门还需要定义其他一些相关问题，例如互换性，标签和处方信息。巴西卫生监督局遵循世界卫生组织为评估生物相似性而确立的关键原则，尽管未采用“生物相似性”这一名称。但是，该机构还对独立的应用途径做出了妥协，该途径不需要与非生物仿制药的参考产品进行通常的可比性测试。互换性和非专有名称的使用不受管制，这给医师带来了压力，并在生物仿制药使用的决策中产生了利益冲突。本文的范围是介绍巴西关于生物仿制药的法规，其优缺点，并与美国和欧洲的法规进行讨论。