Bioequivalence studies play an important role in the drug development as well as during the post-approval period for both new drugs and generic drugs. In principle, the goals of these studies are two-fold: (1) serve a...Bioequivalence studies play an important role in the drug development as well as during the post-approval period for both new drugs and generic drugs. In principle, the goals of these studies are two-fold: (1) serve as bridging studies to provide supportive evidence for safety and efficacy of a drug product; and (2) ensure product quality and performance throughout the life time of a drug product in the presence of changes in formulation or manufacturing. Additionally, in the context of generic drugs, the current U.S. regulation dictates that evidence of bioequivalence and pharmaceutical equivalence provides the assurance of therapeutic equivalence, hence interchangeability. The conventional wisdom for bioequivalence studies indicates that the testing is best performed using the most accurate, sensitive, and reproducible approach available for the drug under examination. Accordingly, to date, comparative pharmacokinetic studies have been used in most cases for bioequivalence determination. In vitro tests are seldom utilized while pharmacodynamic studies and clinical trials are employed for locally acting drug products or when drug levels cannot be measured in the blood. This trend, however, is changing with the recent advances in pharmaceutical science and technology. For example, the introduction of the Biopharmaceutics Classification System (BCS) has provided a valuable tool for predicting drug absorption and bioavailability. The rapidly growing knowledge of pharmacogenetics/genomics combined with formulation science may facilitate a better understanding of the potential interplay between pharmaceutical characteristics and biological system in humans. In the future, an enhanced prediction and assessment of bioequivalence may be achieved through the rational design of formulations and use of in vitro, in situ or in silico test methods. Implicit in the inclusion of pharmaceutical equivalence as part of the definition of therapeutic equivalence has been the regulatory objective of achieving ’sameness’ to the greatest extent possible between a generic and innovator product, thereby avoiding unnecessary in vivo human testing. Perceivably, the better the drug substance and product are characterized, the more accurate and precise the determination of pharmaceutical equivalence will be. An increased assurance of pharmaceutical equivalence based on state-of-the-art science and technology may lessen the uncertainty of ’sameness’ in the clinical responses and reduce the burden for requiring in vivo evidence of bioequivalence. Over the last three decades, scientists have worked diligently to develop guidance and recommendations on how to demonstrate bioequivalence and pharmaceutical equivalence (hence therapeutic equivalence). Approaches to establishing any type of equivalence depend on the scientific knowledge and tools available at the time of evaluation. Continuing efforts and research are encouraged to improve the current approaches, and ensure product quality and performance over time for both new and generic drug products.展开更多
目前大多数国家在进行纳米铁原研药的仿制制剂审批时,采用的是标准的小分子化学药物途径,即仅需要证实与参比制剂具有相同的生物利用度即可,然而越来越多的证据显示,该监管方法存在缺陷。大量临床和非临床研究证实,纳米铁仿制药的有效...目前大多数国家在进行纳米铁原研药的仿制制剂审批时,采用的是标准的小分子化学药物途径,即仅需要证实与参比制剂具有相同的生物利用度即可,然而越来越多的证据显示,该监管方法存在缺陷。大量临床和非临床研究证实,纳米铁仿制药的有效性与原研药存在显著差异,进而导致二者的安全性明显不同。对于该类药物仿制药物的审批,需要调整既往的监管途径,要与现有的小分子化合物仿制药审批途径有所区分,同时应当提出明确的数据要求。本文探讨了对纳米铁制剂的临床治疗等效性进行评价时所存在的难点,并提出了与监管相关的一些关键概念。已有的临床研究报道表明,标准的生物等效性研究虽然非常必要,但不足以证实药物间相同的有效性和安全性。为了对临床治疗等效性进行科学的评价,除开展非临床研究外还需进行前瞻性、对比性临床研究。此外,药物安全性报告中的药物名称应包含国际非专利名称(International non patent name,INN)以及商品名,以便对仿制药和原研药进行有效的安全性监测。展开更多
文摘Bioequivalence studies play an important role in the drug development as well as during the post-approval period for both new drugs and generic drugs. In principle, the goals of these studies are two-fold: (1) serve as bridging studies to provide supportive evidence for safety and efficacy of a drug product; and (2) ensure product quality and performance throughout the life time of a drug product in the presence of changes in formulation or manufacturing. Additionally, in the context of generic drugs, the current U.S. regulation dictates that evidence of bioequivalence and pharmaceutical equivalence provides the assurance of therapeutic equivalence, hence interchangeability. The conventional wisdom for bioequivalence studies indicates that the testing is best performed using the most accurate, sensitive, and reproducible approach available for the drug under examination. Accordingly, to date, comparative pharmacokinetic studies have been used in most cases for bioequivalence determination. In vitro tests are seldom utilized while pharmacodynamic studies and clinical trials are employed for locally acting drug products or when drug levels cannot be measured in the blood. This trend, however, is changing with the recent advances in pharmaceutical science and technology. For example, the introduction of the Biopharmaceutics Classification System (BCS) has provided a valuable tool for predicting drug absorption and bioavailability. The rapidly growing knowledge of pharmacogenetics/genomics combined with formulation science may facilitate a better understanding of the potential interplay between pharmaceutical characteristics and biological system in humans. In the future, an enhanced prediction and assessment of bioequivalence may be achieved through the rational design of formulations and use of in vitro, in situ or in silico test methods. Implicit in the inclusion of pharmaceutical equivalence as part of the definition of therapeutic equivalence has been the regulatory objective of achieving ’sameness’ to the greatest extent possible between a generic and innovator product, thereby avoiding unnecessary in vivo human testing. Perceivably, the better the drug substance and product are characterized, the more accurate and precise the determination of pharmaceutical equivalence will be. An increased assurance of pharmaceutical equivalence based on state-of-the-art science and technology may lessen the uncertainty of ’sameness’ in the clinical responses and reduce the burden for requiring in vivo evidence of bioequivalence. Over the last three decades, scientists have worked diligently to develop guidance and recommendations on how to demonstrate bioequivalence and pharmaceutical equivalence (hence therapeutic equivalence). Approaches to establishing any type of equivalence depend on the scientific knowledge and tools available at the time of evaluation. Continuing efforts and research are encouraged to improve the current approaches, and ensure product quality and performance over time for both new and generic drug products.
基金Carry out quality evaluation research of generic medicinal product control based on domestic product,NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,Beijing,China。
文摘目前大多数国家在进行纳米铁原研药的仿制制剂审批时,采用的是标准的小分子化学药物途径,即仅需要证实与参比制剂具有相同的生物利用度即可,然而越来越多的证据显示,该监管方法存在缺陷。大量临床和非临床研究证实,纳米铁仿制药的有效性与原研药存在显著差异,进而导致二者的安全性明显不同。对于该类药物仿制药物的审批,需要调整既往的监管途径,要与现有的小分子化合物仿制药审批途径有所区分,同时应当提出明确的数据要求。本文探讨了对纳米铁制剂的临床治疗等效性进行评价时所存在的难点,并提出了与监管相关的一些关键概念。已有的临床研究报道表明,标准的生物等效性研究虽然非常必要,但不足以证实药物间相同的有效性和安全性。为了对临床治疗等效性进行科学的评价,除开展非临床研究外还需进行前瞻性、对比性临床研究。此外,药物安全性报告中的药物名称应包含国际非专利名称(International non patent name,INN)以及商品名,以便对仿制药和原研药进行有效的安全性监测。
