美国FDA药品监管体系发展分析

目的：为发展和完善我国药品监管体系提供建议。方法：介绍美国FDA药品监管体系的发展,分析美国FDA监管系统改革举措。结果与结论：美国FDA药品监管体系建立了系统、连续的体系,监管方面的改革具有一定先进性和灵活性,我国可借鉴美国的相关经验,在监管体系改革过程中做出相关改进。     

探讨新修订的《药品管理法》对药品监管工作的挑战和应对策略

目的：新修订的《药品管理法》引入了国际通行的药品监管理念并吸纳了近几年来药品审评审批制度改革的成果,这些新变化给药品监管工作带来了新的挑战。本文旨在通过对新变化中出现的典型问题进行分析,提出可行的应对举措和建议,推动药品监管模式创新。方法：针对目前药品监管中的实际问题和预期风险,将新修订的《药品管理法》中的新变化、新要求与ICH相应指导原则中的相关理念、技术要求进行对照分析,并结合上海市药品审评审批改革中积累的相关试点经验进行探讨。结果与结论：药品监管部门以药品上市许可持有人制度为切入点,探索建立以品种为主线的全链条监管新模式,落实新修订《药品管理法》中的监管要求,实现对药品的全生命周期监管。     

美国药品标识监管体系研究

目的：通过研究和分析美国药品说明书和标签监管体系,重点阐述现有监管制度上的环节要求,以期为完善我国药品说明书和标签监管体系提供较为全面的参考和借鉴,进一步提高用药安全水平。方法：采用非接触性研究中的内容分析方法,广泛查询FDA及美国联邦政府的官方网站、中国知网数据库等,收集整理与美国标识监管体系相关的资料,包括法律文件8个、指南36个及50余个FDA官网网页资料和报告文件等。结果与结论：围绕上市前、上市后和信息公开管理,并通过不断修订加强法律法规,美国药品标识逐步形成了法律、法规及指南3个层面的逻辑清晰的完整监管体系。我国药品说明书和标签监管体系建设工作相差明显,应尽快建立我国药品说明书和标签功能定位监管认识的新视角,完善上市前、上市后和信息公开管理制度机制,抓住《药品管理法》修订的契机,系统性安排药品说明书和标签立法工作计划,开展全国调研,为全面规范药品说明书和标签管理提供科学保障。     

美国FDA鼻用制剂监管科学研究进展及启示

目的 介绍美国食品药品监督管理局（Food and Drug Administration，FDA）鼻用制剂监管科学进展，为中国鼻用制剂开发、生产、质量控制、监管提供参考和借鉴。方法 通过对法规和文献进行翻译、整理与研究，介绍FDA关于鼻用制剂的监管科学研究项目和最新进展，并分析目前鼻用制剂发展中遇到的难点和未来的发展方向。结果 FDA鼻用制剂监管科学主要方向为评价潜在的生物等效性方法作为比较临床终点生物等效性研究的替代方案，运用数字技术建立计算机模型研究鼻部吸收影响因素、药动学和药效学特征，以及儿童用药研究、鼻脑递送等，旨在开发新工具、新方法、新标准，为优化监管策略、提高监管效率提供科学依据。结论 本文总结了FDA鼻用制剂监管科学最新研究成果，为监管机构管理人员提供参考，为提升中国药品监管质量和效率、实现国际接轨提供新思路与新方法。     

Extended-release gabapentin in post-herpetic neuralgia

Introduction: In early 2011, the FDA gave approval to a new preparation of gabapentin, licensed for the treatment of post-herpetic neuralgia (PHN). Gabapentin is commonly used worldwide for multiple indications, which include neuropathic pain. The new drug combines generic gabapentin with a polymeric delivery system allowing for extended release and is licensed to be given only as a once-daily dosing regimen.

Areas covered: The article aims to review the available evidence relating to the pharmacokinetics, tolerability and efficacy of extended-release gabapentin (GpER). It addresses the current state of the drug's progress through regulation and the intention of its manufacturer for the market.

Expert opinion: Although GpER has been approved by the FDA for once-daily use in PHN, there is a relative paucity of data for both its efficacy and the optimum dosing schedule (once or twice a day). There are no data directly comparing GpER with the immediate-release preparation or other first-line treatments for PHN. Therefore, the true status of GpER as a treatment option needs to be enhanced with additional experimental evidence for its efficacy and favourable side-effect profile.     

Radiation countermeasure agents: an update (2011 – 2014)

Introduction: Despite significant scientific advances over the past 60 years towards the development of a safe, nontoxic and effective radiation countermeasure for the acute radiation syndrome (ARS), no drug has been approved by the US FDA. A radiation countermeasure to protect the population at large from the effects of lethal radiation exposure remains a significant unmet medical need of the US citizenry and, thus, has been recognized as a high priority area by the government.

Area covered: This article reviews relevant publications and patents for recent developments and progress for potential ARS treatments in the area of radiation countermeasures. Emphasis is placed on the advanced development of existing agents since 2011 and new agents identified as radiation countermeasure for ARS during this period.

Expert opinion: A number of promising radiation countermeasures are currently under development, seven of which have received US FDA investigational new drug status for clinical investigation. Four of these agents, CBLB502, Ex-RAD, HemaMax and OrbeShield, are progressing with large animal studies and clinical trials. G-CSF has high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the US FDA in the future.     

Expert opinion on existing and developing drugs to treat female sexual dysfunction

ABSTRACT

Introduction: Female sexual dysfunction (FSD) is a highly prevalent, yet commonly underdiagnosed and undertreated condition. This paper reviews the diagnostic terminology for FSD, and basic sexual physiology in women. The Food and Drug Administration (FDA) approved drugs for FSD are discussed, followed by investigational drugs for FSD currently in phase 2 or 3 clinical trials, reasons for failure of drug development, and potential future drug targets.

Areas covered: A literature review was conducted for available treatments for FSD: flibanserin, estrogen, ospemifene and prasterone. Potential treatments are assessed, as was the Pharmaprojects database which includes clinical trial information. Testosterone, bremelanotide, bupropion-trazodone, PDE-5 inhibitors, prostaglandins, tibolone and combination therapies, and the theoretical basis of potential drug targets are discussed.

Expert opinion: The lack of established endpoints for phase 3 studies of FSD has impeded approval of new treatments, and required additional studies for validation, resulting in proposed changes to the FDA draft guidance for FSD clinical trials in October 2016. Current DSM-5 diagnostic nosology also fails to capture the full range of symptomology. Several promising compounds have shown no movement for several years limiting women’s options. Overcoming socio-cultural bias against women’s sexual and reproductive health will be critical in the approval of new treatments for FSD.     

Some thoughts on drug interchangeability

Abstract

Current regulation for generic approval is based on the assessment of average bioequivalence. As indicated by the United States Food and Drug Administration (FDA), an approved generic drug can be used as a substitute for the innovative drug. FDA does not indicate that two generic copies of the same innovative drug can be used interchangeably even though they are bioequivalent to the same brand-name drug. In practice, bioequivalence between generic copies of an innovative drug is not required. However, as more generic drug products become available, it is a concern whether the approved generic drug products have the same quality and therapeutic effect as the brand-name drug product and whether they can be used safely and interchangeably. In this article, several criteria including a newly proposed criterion for assessing drug interchangeability are studied. In addition, comments on possible study designs and power calculation for sample size under a specific design are also discussed.     

The efficacy and safety of amifostine for the acute radiation syndrome

ABSTRACT

Introduction: A radiation countermeasure that can be used prior to radiation exposure to protect the population from the harmful effects of radiation exposure remains a major unmet medical need and is recognized as an important area for research. Despite substantial advances in the research and development for finding nontoxic, safe, and effective prophylactic countermeasures for the acute radiation syndrome (ARS), no such agent has been approved by the United States Food and Drug Administration (FDA).

Area covered: Despite the progress made to improve the effectiveness of amifostine as a radioprotector for ARS, none of the strategies have resolved the issue of its toxicity/side effects. Thus, the FDA has approved amifostine for limited clinical indications, but not for non-clinical uses. This article reviews recent strategies and progress that have been made to move forward this potentially useful countermeasure for ARS.

Expert opinion: Although the recent investigations have been promising for fielding safe and effective radiation countermeasures, additional work is needed to improve and advance drug design and delivery strategies to get FDA approval for broadened, non-clinical use of amifostine during a radiological/nuclear scenario.     

Examination of risk evaluation and mitigation strategies and drug safety in the US

BackgroundThe Food and Drug Administration Amendment Act of 2007 (FDAAA 2007) enabled the US Food and Drug Administration (FDA) to require risk evaluation and mitigation strategies (REMS) for a drug or biologic to ensure that its benefits outweigh the risks.ObjectiveThis study sought to evaluate REMS approved and released by the FDA since the program inception in 2008, to assess the characteristics of REMS approved and to calculate the time lag between FDA drug application approval and REMS approval.MethodsData were derived from Approved Drug Products with Therapeutic Equivalence Evaluations, Approved REMS and Drugs@FDA. Data included generic availability, application type and approval date, therapeutic class and FDA review class, orphan designation, priority review and market status.ResultsThe FDA approved REMS for 259 marketing applications (217 new drug applications -NDAs, 10 abbreviated NDAs, and 32 biologic license applications) in the study period. The FDA granted orphan designation to 11.4% of active ingredients with REMS and priority review to 38.4% of the NDAs with REMS. The largest number of REMS approvals was for nervous system products (31.8% of total approved REMS) and antineoplastic and immunomodulating agents (15.3%).ConclusionsThe FDA approved REMS for one in three biologics and one in thirteen chemical entities available in the market. A pharmaceutical product can be in the market for an average of 14 years before the FDA identifies and evaluates the risk problems that warrant the approval of a REMS.     

FDA药品安全监管的PPP机制研究及启示

目的：为构建和完善我国药品安全监管公共部门和私人部门的合作伙伴关系，实现资源共享、优势互补、风险共担、利益分享，为公众提供更佳的公共产品和服务的公私合作伙伴机制（public-privatepartnership，PPP）提供建议。方法：运用文献综述法，首先对PPP机制的运行原理以及在药品安全监管中的作用进行理论分析，再对FDA药品安全监管PPP机制的运行模式及实践进行深入研究并得出启示，最后提出完善和构建我国药品安全监管PPP机制的对策与建议。结果： PPP机制在FDA药品安全监管中的应用收到了良好效果，减缓了药品监管部门的资金压力、构建了多种力量参与的药品安全监管网络、推进了医药管理制度改革。结论：我国应该借鉴FDA药品安全监管PPP机制的成功经验，既需要政府部门的有力支持，还要健全法律法规制度，要保证过程的透明和结果公开。     

美国和欧盟儿科用药审评机构职责与作用探析

目的：为提高我国儿科用药的审评质量和效率提供借鉴。方法：收集与整理美国、欧盟儿科用药审评、管理机构的职责与作用,并加以研究分析。结果与结论：近两年,我国成立了与两个儿科用药相关的专家委员会,分别隶属于药品审评中心及国家卫生和计划生育委员会,这两个专家委员会成员仍然都是儿科临床专家,相对于美国FDA和欧盟EMA,缺少了专门的药学、药理毒理、药物警戒、统计等方面的专家。目前,国家药品审评中心并没有专门的儿科用药审评团队。建议我国借鉴美国与欧盟的经验,在药品审评中心内部成立专门的儿科用药审评部门。为各审评机构在技术审评过程中遇到的与儿科用药相关问题提供日常内部咨询;为审评中心制定与儿科用药相关的技术规范、指导原则等做全面的统筹规划;为企业进行儿科用药研发提供科学建议。     

The Importance of Legislative Reform of the Fda

Abstract

The US Food and Drug Administration (FDA) has raised the regulatory burden on drug companies by continually introducing new requirements and policies, regardless of their potential to hinder the delivery of new and innovative therapies to patients who need them. the drug development system in the United States has become the slowest and most expensive in the world. In a climate of deregulation, FDA has sought to cultivate the image of an agency reforming itself from within—lessening the burden on regulated industry and lowering review times—but such “improvements” are largely illusory. FDA has shown itselfincapable of reforming itself, and only carefully crafted legislation will significantly improve the oversight of drug development.     

Taxane anticancer agents: a patent perspective

Introduction:Paclitaxel and docetaxel were two epoch-making anticancer drugs and have been successfully used in chemotherapy for a variety of cancer types. In the year 2010, a new taxane, cabazitaxel, was approved by FDA for use in combination with prednisone for the treatment of metastatic hormone-refractory prostate cancer. Albumin-bound paclitaxel (nab?-paclitaxel; abraxane) nanodroplet formulation was another notable invention (FDA approval 2005 for refractory, metastatic, or relapsed breast cancer). Abraxane in combination with gemcitabine for the treatment of pancreatic cancer was approved by FDA in 2013. Accordingly, there have been a huge number of patent applications dealing with taxane anticancer agents in the last 5 years. Thus, it is a good time to review the progress in this area and find the next wave for new developments.

Area covered: This review covers the patent literature from the year 2010 to early 2015 on various aspects of taxane-based chemotherapies and drug developments.

Expert opinion: Three FDA-approved taxane anticancer drugs will continue to expand their therapeutic applications, especially through drug combinations and new formulations. Inspired by the success of abraxane, new nano-formulations are emerging. Highly potent new-generation taxanes will play a key role in the development of efficacious tumor-targeted drug delivery systems.     

Emerging drugs for prostate cancer

Introduction: Androgen deprivation therapy is the mainstay treatment for patients with prostate cancer who are not candidates for definitive treatment, are diagnosed with advanced disease on initial presentation or progress after primary treatment. Patients who stop responding to androgen deprivation therapy develop castration resistant prostate cancer (CRPC). Emerging drugs undergoing clinical evaluation and drugs that have recently received FDA approval for the treatment of CRPC are reviewed.

Areas covered: As the natural history and signaling pathways of prostate cancer are better understood, new treatments and targeted therapies will be developed. The FDA recently approved 5 medications that increase survival in patients with CRPC. Additional medications and drug classes are being explored that may eventually lead to new treatment options. Articles were identified using a PubMed database search.

Expert opinion: Recent FDA medication approvals and the development of emerging treatments are promising for the future of patients with prostate cancer. The addition of new medications challenges physicians to identify the optimal sequence and/or combination in which newer and older medications should be administered. Physicians treating patients with prostate cancer have a growing responsibility to keep pace with these new medications so that they may counsel and treat patients appropriately.     

Current Status of Ind/Nda Regulations

Abstract

In order to improve the investigational drug development process, the efficiency of the Agency's drug approval process and the Agency's dealings with applicants while still maintaining the high level of public health protection, the Food and Drug Administration has undertaken the revision of the current regulations and policies for investigational new drug applications and new drug applications. On October 19, 1982, the FDA published in the Federal Register a proposal for revision of the NDA regulations, and on June 9, 1983, the Agency published a proposal for revision of the IND regulations.

The status of the proposed revisions is discussed along with projections of their impact on the American public, pharmaceutical industry, and the FDA. Since the revised regulations will refer to several guidelines, the status and scope of the guidelines are described. In addition, changes that have already been put into effect prior to finalization of the proposed regulations are described.     

Animal models for acute radiation syndrome drug discovery

Introduction: Although significant scientific advances have been made over the past six decades in developing safe, nontoxic and effective radiation/medical countermeasures (MCMs) for acute radiation syndrome (ARS), no drug has been approved by the US FDA. The availability of adequate animal models is a prime requisite under the criteria established by the FDA ‘animal rule’ for the development of novel MCMs for ARS and the discovery of biomarkers for radiation exposure.

Areas covered: This article reviews the developments of MCMs to combat ARS, with particular reference to the various animal models (rodents: mouse and rat; canine: beagle; minipigs and nonhuman primates [NHPs]) utilized for the in-depth evaluation. The objective, pathways and challenges of the FDA Animal Efficacy Rule are also discussed.

Expert opinion: There are a number of well-defined animal models, the mouse, canine and NHP, that are being used for the development of MCMs. Additional animal models, such as the minipig, are under development to further assist in the identification, efficacy testing and approval of MCMs under the FDA Animal Efficacy Rule.     

Current Thoughts on Crossover Designs

Abstract

In this paper a historical perspective will be developed regarding the use by drug sponsors of crossover designs in clinical trials in reference to new drug application (NDA) submissions to FDA and FDA's concerns with these designs. From the standpoint of drug sponsors, drug researchers and FDA statistical reviewers the possible impact of a report by the former Biometric and Epidemiological Methodology Advisory Committee (BEMAC) of the FDA and of recommendations contained in 22 FDA clinical guidelines on the matter of crossover designs will be discussed. Additionally, current experience gained from the FDA's statistical evaluation of crossover designs will be briefly presented and some constructive suggestions will be made to guide drug sponsors and drug researchers regarding the use of crossover designs in clinical trials.