2014 年美国仿制药市场研发动态（I）

本期报告介绍了2014 年第1 季度各国获得简化新药申请（ANDA）批准、《药品管理档案》（DMF）申报、遭遇专利挑战的情况，以及生物仿制药市场、仿制药行业交易和相关仿制药企业的进展。     

Celltrion公司的抗体生物仿制药在韩国获得批准

2012年7月23日,韩国食品与药品管理局（KFDA）批准了韩国Celltrion公司申请的风湿病治疗药Remicade（英利昔单抗,infliximab）生物仿制药。抗体的生物仿制药除了印度Dr．Reddy公司在销售Reditux（利妥昔单抗,rituximab）之外,还没有其他国家批准过。通过发达国家的审查标准,被批准的抗体仿制药实属世界首例。     

“创新药物研发高层论坛”专家观点

对2015年1月30日召开的“创新药物研发高层论坛”的专家报告内容进行归纳总结,旨在为从事药品注册、创新药及仿制药研发、 药物临床试验质量管理规范（GCP）及药品非临床研究质量管理规范（GLP）工作的人士提供信息参考。     

生物仿制药在美国的开发其Ⅲ期临床试验陆续实施

2012年美国出台了生物仿制药（Biosimilars）的指南法案，也重新启动了审查手续费的程序，但是还没有批准任何生物仿制药。为了获得批准需要进行哪些试验，这需要在与美国FDA商谈的基础上实施个案处理。基本原则是，通过comparativebioequivalence试验能证明具有等效性的就不需要实施Ⅲ期临床试验。     

2015年生物仿制药市场规模将达37亿美元

英国知名的行业分析公司Datamonitor的研究显示,到2015年生物仿制药（biosimilars）的全球市场规模将由2010年的2．43亿美元增长到37亿美元。     

特殊制剂一致性评价的开发策略

2016 年 3 月 5 日,国务院办公厅《开展仿制药质量和疗效一致性评价的意见》正式对外公布,提出了全面提高仿制药质量,开 展仿制药质量一致性评价,确保中国仿制药质量不低于美国、欧盟、日本的标准。文章介绍了美国和日本的一致性评价背景,根据中国国情, 结合政策法规,阐述如何科学性、合理性地开展仿制药一致性评价,重点介绍低剂量和微丸压片特殊口服固体制剂一致性评价的开发策略。     

中国生物仿制药发展分析

近几年,生物仿制药研发热潮逐渐兴起,本文简要综述了生物仿制药的市场情况,我国生物仿制药发展现状及相关的法律法规。     

仿制药市场——中国药企的机遇在哪里？

全球仿制药市场近年来增长迅速,至2013年化学仿制药市场容量预期将高达2500亿美元,发达国家仍为最大的市场。此外在2020年前预计约有450-500亿美元的生物制药的专利也将到期,这对于生物仿制药意味着重要发展机遇。“对仿制药市场影响最大的因素主要包括专利到期,法律法规与政府政策、新兴市场发展、降价趋势以及药品采购代理和药品费用支付方的影响。”     

琥珀的真真假假

正随着琥珀价格的攀升,对琥珀的伪造一直层出不穷,常见的仿制琥珀材料主要有柯巴脂、玻璃、酚醛树脂、赛璐珞、酪蛋白、现代塑料。对这些仿制的材料,只需要进行简单的测试,就可以一辨真伪。酚醛树脂、赛璐珞和酪蛋白仿制的琥珀曾广泛出现在18世纪的装饰品中,而其他材料的伪     

仿制药一致性评价中有关物质研究的思考

有关物质是药品的关键质量属性之一,也是仿制药一致性评价的重要内容,其涉及药品的安全性及其质量的可控性。文章梳理了 仿制药有关物质的来源及研究重点,评估仿制药有关物质的文献分析方法,总结归纳仿制药与被仿制药实际样品的杂质谱分析比较及其 意义,探讨杂质限度的确定原则与方法。     

创建大型复合低压舱扩大医学实验平台种类

本文主要阐述了一种大型复合低压舱的研制及其在医学实验中的应用。该复合低压舱可模拟高原低气压,高温、低温、干热、紫外线照射等环境因素,其可模拟单一气候条件,也可以通过调控模拟出各种现场的复合气候环境。本舱为西北部队卫勤保障研究提供了实验平台,满足极端气候条件下战创伤救治及药物等相关研究及急进高原人员习服性训练等。本研究的成果扩大了动物实验平台建设,完善了实验医学平台的种类。     

A novel method of determination of the internal enzyme distribution within porous solid supports and the deactivation rate constant

This article presents a method for determining the rate constant for deactivation and the internal distribution of immobilized enzyme. This method makes use of the parallel deactivation process in a diffusion-controlled regime, in which the internal activity profile behaves like a penetration front. This front basically traces through the initial active enzymatic profile, and one can determine the internal profile and the rate constant for deactivation from the experimentally observable bulk concentration versus time. This method is applied to the experimental data of the system of hydrogen-peroxide-immobilized catalase on controlled pore glass and Si-Al particles.     

Object exchange between captive chimpanzees: a case report

Intelligent resource exchange usually has been thought of as a strictly human phenomenon. Some searchers demonstrated experimentally that chimpanzees have the necessary cognitive capacities to exchange food with humans. This short article presents the first example of an immediate and spontaneous exchange of objects between chimpanzees. This exchange between Spock and Maya is not a direct exchange of objects, from hand to hand, as would be observed among humans. This leads us to suppose that exchange, if it really occurs amongst wild chimpanzees, is done indirectly, through the more or less concomitant deposit of the objects or food items on the ground, maybe because chimpanzees are quadrupedal animals. This observation is discussed in relation to the notion of reciprocity used in anthropological and sociological studies.     

A stochastic bioburden model for spacecraft sterilization

An important factor in the calculation of sterilization cycles for spacecraft is the bioburden on the surface of the spacecraft at the start of the cycle. This bioburden must be predicted by the use of models. This paper presents a stochastic model for the prediction of the bioburden on the surfaces of spacecraft. This model has many desirable properties as well as being consistent with observations.This work was conducted under Contract No. W-12,853, Planetary Programs, Office, of Space Science and Applications, NASA Headquarters, Washington, D.C.     

Hypothesis Testing Procedures for a Series of Independent Fourfold Tables under Inverse Sampling

This paper considers four summary test statistics, including the one recently proposed by Bennett (1986, Biometrical Journal 28, 859–862), for hypothesis testing of association in a series of independent fourfold tables under inverse sampling. This paper provides a systematic and quantitative evaluation of the small-sample performance for these summary test statistics on the basis of a Monte Carlo simulation. This paper notes that the test statistic developed by Bennett (1986) can be conservative and thereby possibly lose the power when the underlying disease is not rare. This paper also finds that for given a fixed total number of cases in each table, the conditional test statistic is the best in controlling type I error among all test statistics considered here.     

Augmented Inverse Probability Weighted Estimator for Cox Missing Covariate Regression

This article investigates an augmented inverse selection probability weighted estimator for Cox regression parameter estimation when covariate variables are incomplete. This estimator extends the Horvitz and Thompson (1952, Journal of the American Statistical Association 47, 663-685) weighted estimator. This estimator is doubly robust because it is consistent as long as either the selection probability model or the joint distribution of covariates is correctly specified. The augmentation term of the estimating equation depends on the baseline cumulative hazard and on a conditional distribution that can be implemented by using an EM-type algorithm. This method is compared with some previously proposed estimators via simulation studies. The method is applied to a real example.     

Evaluation of nitrogen fixation by bacteria in association with roots of tropical grasses

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乳腺浸润性微乳头状癌的研究现状

乳腺浸润性微乳头状癌(IMPC)是乳腺浸润性癌的一种特殊类型,其发生率低,临床表现及影像学特征与普通的乳腺浸润性导管癌没有显著区别。这种病理类型可与普通浸润性导管癌混合出现,也可表现为单纯的浸润性微乳头状癌。但浸润性微乳头状癌具有独特的组织学形态及分子结构,决定了其病理学分级较高、易于发生淋巴结转移的侵袭性生物学行为特点。多数浸润性微乳头状癌在影像学上表现为边缘不清的不规则肿块影,常伴有微小钙化。其特征性病理形态为细胞膜上皮抗原(EMA)在肿瘤细胞簇外周的细胞和基质中腔隙边缘特异性染色,同时显微镜下瘤细胞表面发现微绒毛结构,说明了瘤细胞簇周围的空隙样结构实际上是管状腔隙,瘤细胞呈"极向倒转"方式排列。IMPC具有高度淋巴血管浸润倾向,局部复发率高,是一种预后较差的类型。本文对近年来关于乳腺浸润性微乳头状癌的研究进展进行了综述。     

Historical and Comparative Study of the First Spanish Vertebrate Paleoichnological Record and Bibliographic Review of the Spanish Chirotheriid Footprints

In 1897, Salvador Calderón y Arana published a study of the first vertebrate footprint from Spain. It was found in the Buntsandstein of Rillo de Gallo (Guadalajara), probably in the Rillo Mudstone and Sandstone Formation (middle Anisian-Landian). This isolated left pes imprint was classified as “Cheirotherium” sp. We conducted a historical study of this specimen, mentioned by several authors for more than a century, but never analyzed in detail. This well-preserved footprint, in which skin marks are present, is described here. Its characters are compared with those of valid chirotheriid ichnogenera. This work is complemented with a bibliographic analysis of the chirotheriid footprints recorded in Spain. This record is remarkable for its abundance and ichnodiversity.