仿制药一致性评价国内外研究进展

在我国药品市场中仿制药占据绝大部分市场份额,然而仿制药的质量参差不齐,严重影响了广大患者的用药安全,因此,如何提升仿制药的质量在政府、学术界以及整个医药行业中一直备受关注。本文整理了国内外学者们针对仿制药一致性评价问题的研究,从我国仿制药的发展现状,仿制药一致性评价原则与方法,仿制药一致性评价对医药行业的影响,完善仿制药一致性评价体系的对策等角度细致展开,以期为开展仿制药一致性评价研究提供参考.     

对仿制药一致性评价政策的解读

仿制药一致性评价工作是医疗改革的重要组成部分。通过一致性评价的仿制药具有质量可靠、价格较低的优势,可降低医疗费用,因此在提升整体医疗服务水平方面具有重要作用,并可产生较好的经济效益和社会效益。该文集中解读了中国现阶段仿制药一致性评价工作的相关政策,回顾了美国、日本仿制药一致性评价相关政策的历史,并对政策落实过程中可能产生的问题进行了探讨。     

仿制药一致性评价工作的进展与展望

目的 研究分析当前仿制药质量和疗效一致性评价的现状及存在问题,提出推进仿制药一致性评价的建议。方法 梳理并分析我国基本药物化学药品目录中口服固体制剂的品种情况、持有文号的生产企业情况、参比制剂公布情况及实施仿制药一致性评价中的问题。结果 低价药、独家品种开展一致性评价比例偏低,未来可及性风险不容忽视。结论 生产企业要落实评价主体责任,以提高质量作为企业发展要务;相关管理部门应加快出台激励政策,助推企业开展仿制药一致性评价。     

仿制药质量一致性评价各部门职责

2012年初,国务院下发药品安全“十二五”规划,明确提出将全面提高仿制药质量。本文根据国家食品药品监督管理总局发布的《仿制药质量一致性评价工作方案》,对仿制药质量一致性评价工作中所涉及部门的职责做出了更为详细的解读。     

仿制药一致性评价现状调查及对策

为提升已上市的仿制药质量水平,淘汰内在质量和临床疗效达不到要求的品种,国家食品药品监督总局全面启动了仿制药一致性评价工作。在调查我国仿制药现状的基础上,本文分析了当前仿制药一致性评价工作面临的一些制约因素,并最终有针对性地提出了解决对策,供业内及监管部门参考。     

仿制药一致性评价的背景、实施及结局

我国是仿制药大国,开展仿制药质量和疗效一致性评价是国际惯例,也是我国经济、技术水平进步的必然结果。仿制药一致性评价适应国家新政,选择合适终点指标进行研究,目的是提高社会认可、实现仿制药与原研药的真正互换。仿制药一致性评价从简单的体外溶出度试验到系统的药学评价再到生物等效性评价,评价方法正在逐步完善,同时明确化学仿制药参比制剂遴选原则以减少仿制过程中的质量差异。仿制药一致性评价不仅能够提升我国制药行业的整体发展水平,促进医药产业升级和结构调整,同时可以节约医疗费用,保证患者用药安全。     

仿制药一致性评价中杂质研究的常见问题探讨

杂质研究是药品质量一致性评价的重点内容,关系到药品的安全性、有效性和质量可控性.本文结合具体品种,汇总分析了杂质研究的常见问题及关注点,并提出相应的处理建议,旨在为后续口服固体制剂和注射剂仿制药一致性评价的研究提供更多参考.     

中药仿制一致性评价的思考

目的:探讨中药仿制一致性评价问题,寻找合适的评价方法。方法:结合中药仿制一致性研究的总体思路、中药及其仿制研究的特殊性,分析中药仿制一致性研究的现状与特殊性。结果:基于源头管理、中间监督、质量标准等一致性的理念,提出辨状论质+化学检测+生物学检测为一体的多元化检测的中药仿制一致性评价的模式。结论:该评价模式为保障中药仿制与原研药的一致性提供借鉴与思考。     

日本药品品质再评价工程对我国仿制药一致性评价的借鉴

目的 为改进和完善我国仿制药一致性评价工作提供参考。方法 对日本药品品质再评价工程与我国仿制药一致性评价进行比较。结果与结论 加强我国仿制药一致性评价工作,应在进一步完善法律法规体系的基础上,提升相关人员的水平,建立有效的激励机制,制订我国药品品种的橙皮书。     

基于中文文献的盐酸二甲双胍仿制药一致性评价

目的:了解盐酸二甲双胍仿制药的一致性,以促进临床用药选择的有效与安全。方法:计算机检索CNKI与CBM数据库,纳入对比国产制剂与格华止的体外溶出试验、生物等效性试验和临床有效性与安全性的随机对照试验,按类型进行定性或定量分析。结果:分别纳入7、10、5篇研究。纳入评价的国产制剂与格华止的体外溶出度与溶出参数存在显著差异;部分生物等效性试验显示部分国产制剂与格华止不等效;格华止普通片在部分有效性指标上可能优于国产缓释片,在安全性方面可能优于国产普通片。结论:现有证据无法充分支持国产二甲双胍仿制药与原研药具有一致性,部分仿制药在药学特性、生物等效性和临床一致性方面与原研药相比可能有一定差距。     

临床研究协调员参与的基于风险的闭环式质量控制模式探讨

根据本院药物临床试验机构实际质量控制管理经验,初步探讨了临床研究协调员(CRC)参与的基于风险的闭环式质控模式。基于风险的质控模式增加了质控效率,闭环式质控使得质控真正能发挥作用, CRC的引入充实了质控团队。该质控模式为药物临床试验机构的质控提供了一种新的途径。     

Evaluation of information for generic drugs based on importance and necessity

Limited use of generics in Japan has been justified on the basis of problematic quality, distribution and information. Of these three problem areas, the state of provision of information in particular has never been objectively evaluated. We therefore sought to evaluate information according to its necessity and importance to medical practice. To establish criteria for evaluation, we weighted 36 separate pieces of drug information found in package inserts and interview forms according to necessity and importance, based on the results of a survey of nationwide medical institutions with DI offices. We then used the evaluation criteria to evaluate currently available drugs with 20 or more products per formulation. We evaluated 14 formulations (324 products). Generic drugs were found to have 25.3+/-18.7 to 46.1+/-14.2% (Mean+/-S.D.) the information of brand name drugs when products were compared for quantity of information by formulation. However, comparison according to manufacturer returned a larger range of variation at 14.4+/-8.6 to 64.3+/-14.2% (Mean+/-S.D.). These data reveal that manufacturer differences play a large role in the provision of drug information. Drug information was also compared separately by category for both brand name and generic drugs. Generic drugs were found to have insufficient information on clinical data, pharmacokinetics, safety, side effects, and nonclinical tests. Brand name drugs also scored low points for information on pharmacokinetics. It is imperative that both brand name and generic drugs provide more information on pharmacokinetics.     

六西格玛质量改善模型在仿制药小试研究过程中的应用

目的 为提高我国制药企业的仿制药小试研究水平,避免许多药企在研发过程中存在的缺陷,探究在小试过程中运用六西格玛质量改善模型（DMAIC）的可行性。方法 通过查阅文献和实例的方式,利用DMAIC模型,以某仿制原料药还原工艺为例,评估其实施效果。结果 DMAIC模型在该案例中得到成功运用。该模型有助于合理进行小试团队建设,帮助研发人员找到关键质量属性和关键工艺参数等,保证实验数据的真实性和完整性,可为后续工业生产提供宝贵经验并满足注册申报要求。结论 DMAIC模型可以有效解决诸如统筹安排差、与生产衔接不畅、管理不规范等问题,体现质量源于设计（QbD）的理念,对国内仿制药小试研究有良好的借鉴意义。     

The impact of generic antiviral drugs

The HIV/AIDS epidemic has spread worldwide, with approximately 40 million people who were infected by the end of 2006. Antiretroviral therapy (ART) has proven to be lifesaving, and can convert AIDS into a chronic but manageable disease. Until a few years ago, the annual cost of treating one patient with HIV/AIDS was between US $10,000 and $12,000--beyond the affordability of most individuals. In 2001, the offer of a triple generic therapy at a cost of less than US $1 per day from the Indian company Cipla stunned the world. Although there were some initial challenges, this approach to HIV/AIDS treatment galvanized a reaction that had never occurred previously. Governments, the WHO, NGOs and other bodies quickly attempted to make ART available in the developing world. By 2006, almost 1.3 million patients were receiving ART (comprising mostly generic drugs), a 5-fold increase compared with five years earlier; however, significant challenges in ART availability remain. With international patent laws now being applicable in India (and in most developing countries), generics companies may no longer be able to provide HIV/AIDS-afflicted countries with new third-generation drugs at low prices. Innovative solutions will need to be obtained urgently to address this issue.     

Equivalence studies of pravastatin original and generic drugs by dissolution test

There are various opinions regarding the different functions of original and generic drugs. We used the paddle method to perform dissolution tests on pravastatin sodium tablets (10 mg) to investigate the causes for these differences. We used water and buffer solutions adjusted to pH 1.2 (JP1) and pH 6.8 (JP2), which are described in the Japanese Pharmacopoeia. The pravastatin concentration was measured by UV spectroscopy and HPLC. There were significant differences in the percentages dissolved of original and generic drugs after 5 and 10 min. On the other hand, the dissolution behaviors using water and JP2 measured by HPLC were similar to the results obtained by UV spectroscopy. However, the percentage dissolved of pravastatin using JP1 decreased with time because pravastatin degraded in JP1. There were also significant differences in the pravastatin concentrations of the original and generic drugs at 5, 15, 30, and 45 min. Based on the above results, since the original drug has a slower dissolution rate than the generic drugs, it is necessary to be cautious about the degradation of pravastatin in the stomach and the bioavailability of pravastatin due to the different dissolution rates and the different residual amount of pravastatin in the stomach.     

Modern approaches to quality evaluation of generic drugs for their registration (a review)

At present the quality of generic drugs for registration in the Russian Federation is checked by studying their bioequivalence. According to FDA and WHO guidelines, some generic drugs can be registered on the basis of only in vitro data (dissolution test) without testing for the bioequivalence in vivo. A biowaiver procedure that is based on a biopharmaceutical classification system is developed for such a simplified registration scheme.