还没有女朋友的DJ节后上班告诉我，五一节哪儿都没去，只是一人到上海市内的公园附近拍了一些花。

真有情调，我随口答。

“那是无聊啊。”DJ说。

为了宽慰他，忙说比他更无聊的是我。

长假宅家三日，而且是三人同宅，对足72小时，连门都没出的那种百般聊赖。无聊到最后，三人总结共煮了多少餐饭，煲汤几顿。竟想不起来。

买了一帐篷，昨日送来，浅绿色。月月尖叫不止。

想远行，又觉不但花钱还要饱受舟车劳顿，家有一小露台，外面养了些许花草，夜晚挂灯在自家露营，也许跟旅游差不多。

电影《绿卡》里，大鼻子法国情圣和迷死人的安迪·麦克道威尔二人在家布景拍照假装环球旅行，模仿他二人倒也实在。

今年工作调整，少写采访报道文章，倒是读了许多国外资讯。

今日读小石头翻译的稿子，讲美国药物滥用成风，奥巴马政府宣布行动计划，“阿片类REMS计划”在以州为单位的处方药监控体系的支持下，建立一个全国性减少处方药滥用的监管组织。

等等，我想说的不是这些。

为支持这项计划，白宫国家药品管理政策的主任Gil Kerlikowske、健康与人类服务部的助理秘书Howard Koh 医学博士、美国FDA局长Margaret A. Hamburg 医学博士以及美国司法部药品管理局（DEA）局长Michele M. Leonhart就这份标题为《流行》的“奥巴马政府全面行动计划”联合发表了声明。

而就在搜索健康与人类服务部的助理秘书Howard Koh的过程中，发现了一个美国摄影记者Jay Premack的博客，他曾经以“Power Brothers”为主题为Howard Koh在白宫拍摄了一组照片。并记录了采访心得。

于是，这个叫Jay Premack的人的网站被我收录下来了。他拍摄了大量人物、婚庆和许多许多许多小bb，比如这张：

照片中透露温情，典型的新闻摄影风格。

最优秀的摄影师大多在媒体工作。此话当真。

不具有专业背景的我，这些日子断断续续很艰难地读完了《美国药品监管法规核心理念概述——药品注册批准前检查》的前三章，居然觉得有点意思。

以下是在阅读第一章用铅笔划下的语句，有些是为防止瞌睡划下的，有一些是精神振奋时划下的，有些词汇从未接触，有些如此熟悉。

1.在审批过程中增加了一个新的步骤——达标审查。

2.Compliance 在国外制药行业常指符合法规要求，反义词为违规。“达标”的提法在1998年前首先出现于我国GMP检察的官方文件中。

3.当产品研发结束时，研发历史报告、通用技术文件（CTD）/NDA以及从产品研发转为生产的技术转移文件。

4.确保临床试验、生物利用度研究以及安全性研究所用物质的生产工艺与注册申报工艺之间存在相关性。

5.目标是促进减少FDA所要求的药品注册批准前监查的数据，以使FDA能将资源更有效地应用于批准后监查或cGMP检查。

6.如果企业能够证明对生产工艺有透彻的理解，那么FDA将给予他们灵活性。这个协议将为新药申请的化学、生产和控制（CMC）部分指定一个管理办法，意在为注册申报的灵活性提供一个框架。

7.。。。。哪些内容是信息性的（即阐述产品和工艺的研发历史），哪些是注册申请中将来应遵守的承诺。

8.。。。促进ICH Q8药品研发和ICH Q9质量风险管理的有效实施。

9.在批准后做各种变更时，此系统（process analytical technology,PAT）也为监管/注册审评提供了灵活性。

10.在通用技术文件药品研发章节中，有对工艺深入了解的论证。

11.通过对产品与工艺知识的阐述，证明质量已经建立在系统之中，从而给FDA以某种信心。

12.在Janet Woodcock博士撰写的FDA白皮书中，她认为目前药品的研发过程已无法跟上基础科学创新的步伐。。。研发人员仍用20世纪的研发手段来评估21世纪的发明。

13.一同寻找和解决。。。这项工作包括两方面：一是识别出最重要的工艺方面的问题，并且排列出优先次序；二是鉴别出能够获得最大重大改进的领域。。。一旦将这些领域鉴别出来，FDA将和研发单位一起，确定并解决关键的研发问题。

14.2006年初，FDA推出了一项重大举措，就是放宽了I期临床试验药品生产的cGMP要求。。。目的是在保证研发早期阶段药品的安全性和有效性的同时，简化并促进药品研发过程。

15.企业原先每年为符合联邦法规CFR 210和211而收集产生的数据需848625个工时，法规变更后，将会缩减至50000个工时。

16.这些要求对于I期临床的早期研究来说实在是太繁重了，以至很多顶级的医药研究机构无法在他们的实验室中进行这些发明性研究。

17.“企业、社会和FDA的共同目标是使药品生产部门达到一个最高效、最灵活、最富有弹性的理想状态，从而在没有大量法规监管的条件下也能可靠地生产出高质量的药品。”

18.质量源于设计的目标是确保企业对于他们的药品生产工艺有更深刻的以知识为基础的理解。（理解一词画圈）

19.要求企业在产品研发阶段根据所掌握的知识，形成对关键工艺、产品属性、设计控制、检测方法的科学见解。（科学见解一词画圈，就是FDA要求。。。具有科学见解）

20.设计空间关注的是一个生产工艺中某一个关键步骤的温度控制，而不是此温控设备的类型。

21.企业确立特定药品设计空间的能力（能力一词画圈），能证明他们对产品和工艺的知识水平。

22.质量综述并不降低药品研发所要求的研究数量，它只是减少了审评员在审核时必须研究资料信息的数量和种类。

23.质量综述将有助于快速解决潜在问题或争论的早期鉴定，以便获得第一轮的注册批准。。。质量综述将最终促进企业和监管者之间的信心和信任。

24.很多公司都处于极度紧张忙乱的状态，以临时抱佛脚的状态准备FDA的注册批准前监查。令人欣慰的是，如今那种短期的疯狂已被长期的努力准备所取代。

19位作者分别来自药厂、CRO，无一来自FDA。为什么制药工业界对FDA每一次具体细小的规则都那么当真？

组织本书翻译的郑强告诉我：

这点恐怕是美国与中国的主要差别。FDA关注的是制定和解释法规，以及对企业合规的检查和评判。批准前检查是专有名词，目的是FDA要到现场核实企业申报的工艺确实可以在满足GMP的条件下实施。这个检查的科学成分是很重的。

FDA历来承认企业比他们对工艺更了解，对工艺实施中的质量控制（GMP）更熟悉。所以，FDA检查时关注的重点是听企业讲述它的工艺实施和GMP保障是如何做的，其科学合理性如何。

我们的企业通常科研能力不够，对工艺和GMP的科学理解弱，注重点是应对GMP检查，而不是搞清工艺实施与GMP保障之间的关系。所以，国内更关注SFDA或地方药监局是怎么说，尤其是在职的人怎么说。

对于一个好的企业，抓质量是它本身的事，因为质量是竞争力和生产力，是有内在动力的。

——非常给力的解释。

我感觉FDA期望的演变过程中，处处放置弹簧，扩张法规的灵活性以及强调企业的自理能力，这是信任和信心的来源。

于我而言唯一的启发是对月月的教育，要放弹簧。

小成成和我对吴宇森炒蛋不敢恭维。

《李纯恩大食游》一行来到北京，拜访在京工作的大导演吴宇森，吴当即在摄制组人员面前露两手，来了一个蛋炒豆角和蒸鲈鱼。

周日翡翠台播出的《李纯恩大食游》是最近两个固定收看的节目，另一个是每周三晚播出的《Cheese Slice》。

10年后在银屏上见香港著名记者和专栏作家李纯恩，发觉跟当年《锵锵三人行》一样，容颜未改，依旧皮光肉滑，一缕银色刘海遮住额头。

“豆角多了，切得太大，所以吴不得不用水煮，再用蛋炒，原本应是鸡蛋外包豆角，变成了豆角缝里粘鸡蛋。”我说。

进而总结，炒菜主次一定要分清，豆角不超过5根，切成薄片，用油爆。鸡蛋3个，温火炒，包围豆角。

“鲈鱼用鱼露，且把酱汁一起与鱼蒸煮，会不会带出更多腥味？”小成成说。

进而总结，蒸鱼定要抹干血水，蒸时只需放姜两片，时间刚好后，倒清水气，再大肆配置酱料薄薄浇淋一层即可。

再说Cheese，喜欢《李纯恩大食游》跟他轻松博学的主持风格有关，《Cheese slices》也如是。一中年老外为了一片小cheese，游历欧洲，“脑海里浮现阿尔卑斯山蹦跳的羊群”，如此诗意形容奶酪入口之感。

很多年前，为应对一次英语考试，搜集了大量资料，当时想如果考官问“What’s your favorite food?”，我该如何作答？

今找回当年拼凑的答案，鱼蛋(fish ball)依然是最爱。

I adore fish balls very much. I often bought fish balls in 7-11 and C-Store. Actually, this used to be an afternoon snack for me back home. I think fish balls are part of Guangdong cuisine culture like Dim Sum. The most popular one being spicy curry fish ball sold by street snack vendors in Beijing Road.

It’s funny to see groups of people holding a stick of spicy fish balls on one hand, sweating and gasping for air from the heat of the curry sauce, and trying not get the dripping sauce on their shoes.

For most Asian countries, fish balls are very common ingredient that can be found in everyday cooking. In Guangdong, fish balls are mostly used as toppings to noodle-based or soup-based dishes. Fish balls are very versatile and I often keep a packet of two of frozen fish balls in my fridge. I love cooking fish balls dishes.

In order to consolidate and deepen the internal institutional reform being implemented, the State Food and Drug Administration (SFDA) Center for Drug Evaluation (hereinafter referred to as “CDE”) has recently reviewed, approved and promulgated a corresponding supporting document of the Principles and Procedures for Drug Technical Review (hereinafter referred to as “Principles and Procedures”), and has posted it on the website.

According to the introduction made by Feng Yi, Director of Business Administration Department of CDE, based on the task categorization and risk level for review and approval, the Principles and Procedures has, ,centering upon the principle of scientificity, legality, ethics, openness, impartiality and equity for technology review and approval, specified corresponding decision-making procedures for the review and approval of Investigational New Drug (IND) Application, New Drug Application (NDA), Abbreviated New Drug Application (ANDA), etc., and invited the community to supervise over the operation of CDE in accordance with the Principles and Procedures.

Simplify and Adjust the Original Procedures

The internal institutional reform which began in January this year significantly adjusted the main duties and internal organizational structure of CDE. As a result, the reform intensified the communications and exchanges between the review professionals in the same subject and same profession, and at the same time consciously made a scientific classification of reviews on generic drugs and innovative drugs.

Compared to existing 3,000 persons in the Center for Drug Evaluation and Research (CDER) affiliated to U.S. FDA, CDE only has 120 persons. Over the years, SFDA has been looking for a scientific review path to reasonably allocate the resources based on the grades of drug related risks, in order to resolve the great pressure on the time limit of review.

Being oriented to the value of clinical therapy, U.S. FDA established review structure and mode based on the classification of indications. “However, this mode is supported by the enormous human and material resources from FDA”, says Li Ning, former Director of U.S. FDA Statistical Review of Cardiovascular Products & Senior Director of Sanofi-Aventis Pharmaceutical Affairs and of Medical Policy.

Feng Yi says that the institutional reform simplified and adjusted the original review procedures, so that the procedures and tasks of CDE became better coordinated; it also designed the new processes such as parallel review, sequential review, single-disciplinary review and simplified review, in order to speed up reviews and adjust the review strategy at the appropriate time.

Improve Various Concept in Review Procedures

According to the report, after the completion of the institutional reform, the review tasks, based on the subject matters of applications, are divided into application for new drug clinical trial, application for registration of new drug production and marketing, application for registration of generic drug and supplementary application, etc. According to the general rules of drug development, different types of review tasks adopt the appropriate review procedures respectively. With respect to applications for new drug clinical trial and applications for registration of new drug production and marketing, the procedures for multi-disciplinary parallel review are adopted; with respect to applications for registration of chemical generic drugs, the procedures for one-department single-disciplinary review are adopted; with respect to supplementary applications, the procedures for single-disciplinary review and the procedures for simplified review may be adopted according to the type of changes. If any multi-disciplinary issue is encountered in the varieties applying the single-disciplinary review, the procedures for sequential review may be launched; for the review tasks applying procedures for sequential review, they will also be completed within the prescribed time limit.

It shall be noted that the institutional reform established a separate department of pharmacology and toxicology. The department is responsible for the technical review on the pharmacology and toxicology researching materials relating to the applications for clinical trial, applications for registration and relevant supplementary applications of traditional Chinese medicines, ethno-medicines, natural drugs, chemical drugs and biological products; it is also responsible for the comprehensive evaluation of the applications for clinical trial and relevant supplementary applications of Class 1 to Class 2 chemical drugs and traditional Chinese medicines, ethno-medicines and Class 1 to Class 5 natural drugs, preparing a technical review report and putting forward a clear conclusion and recommendation.

In contrast, the previous review tasks in the pharmacological and toxicological aspects are allocated to the several clinical review departments responsible for different indications. “After the reform, the reviewers of a same profession have been relatively concentrated, the communications and exchanges between the reviewers of a same discipline have been intensified, the unity in the scale of review and the uniformity of review speed have been enhanced, which all substantially promoted the reasonable coordination among the staff members.” Li Ning says.

Improve Various Concept in Review Procedures

In order to improve the efficiency of reviews and the scientificness of decision-making, communication and exchange is always advocated by the Drug Registration Department and CDE of SFDA. The professionals in the new drug development industry hold the opinion that the contribution of the Principles and Procedures is that the ways and means of communication and exchange are truly implemented.

Meanwhile, the Principles and Procedures also enhance the concept of communication and exchange onto a new height. The Principles and Procedures provide that, during the crucial stage of new drug development, the applicant may apply for communication and exchange with CDE concerning the major technical issues, and may also apply for communication and exchange with CDE concerning its annual R&D strategy, overall planning and layout in the process of drug development and other issues. Such exchanges will not only help companies resolve investment risk and terminate certain research and development projects as early as possible, but also help to understand the overall planning in the drug development process of the pharmaceutical companies, and help drug regulatory authorities reasonably deploy and distribute human resources.

With respect to the authorization and issuance of new drug technical review, the Principles and Procedures also made certain new attempts. The Principles and Procedures provide that the director of each review department shall be responsible for verifying the professional review reports and the relevant technical review report, and shall, with the authorization of Director of CDE, be responsible for issuance of the technical review reports corresponding to the applications for registration.

“It means transferring the power of issuance of the technical review report to the lower level, which is similar to the practices of U.S. FDA.” Li Ning comments.

In addition, another highlight of the Principles and Procedures is that it crystallized the “supervision” of the public and the pharmaceutical industry over the review. The Principles and Procedures provide that “the target review time limit of the review task proposed by each responsible review reporting department” must be disclosed to the applicant in advance. Moreover, the information about certain review conclusions must also be announced on the CDE’s website, particularly “the technical review report of the varieties where the materials are submitted in the form of common technical document (CTD) must be disclosed to the applicant” and “the first Overview of Drug Evaluation for new drugs on the domestic market” must be publicized to the public. These efforts will play a far-reaching significance in promoting the consistency of the scale of review and the predictability of results.

In the history of drug review in China, the Principles and Procedures for the first time provide that “all kinds of target review time limits of the review tasks are the important indicators to evaluate the quality and efficiency of reviews”, and also provide two fundamental principles that “the target review time limits of the review tasks relating to the applications for registration of new drug production and marketing shall satisfy the public demand for accessing to the latest therapies” and “the target review time limits of the review tasks relating to the applications for registration of generic drugs shall satisfy the public demand for timely accessing to such type of drugs”. With the implementation of these fundamental principles, “encouraging drug innovation” will no longer be empty words.

“CDE is an important department which evaluates the drug researching data and results by the scientific standards, norms and methods, and ensures the safety, efficacy and controllable quality of the approved marketing drugs. Each time of institutional or system reform in CDE is to make it better adaptive to the development of drug innovation trend and to better enhance the quality and efficiency of drug review.” Zhang Wei, Director of the Drug Registration Department of SFDA, comments on the recent institutional reform in CDE.

Author: Mao Donglei

我最最亲爱的哥哥，像我一样，隔一段时间，就会弄点小作品互相欣赏一下。这里是他最近用自己回国时拍摄的作品收集的数据制作的幻灯，向他的同事介绍了广州这座城市的交通系统。multilayer integrated transportation system in guangzhou

在高速公路上奔驰，看着那笔直无限伸向远方的柏油路，就会想起远在大洋彼岸的哥哥。他就是这样时常一个人在路边勘探，作业的吧。

海洋在植物园拍的，她让我带月月去看看，我记下了这个名字禾雀花。放上来就当是送给我的照片。

得知甘院长那儿将于今年7月份召开一个大约300余人关于生物样本库建设与管理的会议，我在这儿也帮忙宣传一下。

2011年上海生物样本库建设研讨会

国际标准化生物样本库的建设与管理

档次规格高：本次会议邀请国际和国内生物样本库建设中的顶级学者和专家分享其宝贵经验。所邀请的专家包括泛欧洲生物样本库BBMRI的负责人，UKbiobank的负责人，法国生物样本库标准的起草者，国内有中国医学科学院中华民族细胞库的建设者，泰州人群队列研究样本库的建设者，专家阵容之强大在国内该领域会议内无出其右；

影响面广：本次会议拟邀请参会听众200人，全部是中国各医院的主任级以上负责人员。他们是各单位生物样本库的建设规划的制定者和管理者。大会为厂家与用户交流提供了绝佳的平台；

专业性强：上海医药临床研究中心牵头上海生物样本库建设项目已有多年的经验，本次会议着重于讨论生物样本库的管理与质量控制，专业性强，针对性强，回答了目前国内从事生物样本库建设项目的科研人员最关心和最紧迫需要解答的问题；

• 生物样本库的建设与管理
• 生物样本库的质量控制
• 生物样本库建设中的伦理问题

• 上海医药临床研究中心
  电话：021-33676344
• 联系人：张扬
  传真：021-33676373
  E-mail: training@scrcnet.org
  网址：www.scrcnet.org
  公司地址：上海市徐汇区田林路140号10号楼(200233)

为巩固和深化正在实施的内部机构改革，国家食品药品监督管理局药品审评中心(CDE,下称药审中心)日前审议通过并出台了相应的配套文件《药品技术审评原则和程序》（下称《原则和程序》），并上网公示。

始于今年1月的内部机构改革，对中心主要职责和内设机构进行较大幅度的调整，加大了同学科同专业评审人员的沟通交流，同时，有意识地将仿制药和创新药评审进行科学分类。

《原则和程序》围绕技术审评科学、法制、伦理和公开、公平、公正的原则，按照审评任务分类和风险等级，分别针对新药临床试验申请（IND）、新药生产上市注册申请（NDA）、仿制药注册申请（ANDA）等，建立了相应的审评决策程序，并请社会根据此原则和程序对药审中心进行监督。

在以临床治疗价值为导向的基础上建立起来的以适应症分类的审评结构和模式，是美国FDA一个行之有效的经验。然而，这个模式的支撑来自于FDA巨大的人力和物力。FDA下属的药品审评与研究中心（CDER）现有编制已达3000人。对于只有120名编制的中国药审中心，多年来一直在寻找一条以药物风险等级合理分配审评资源的科学审评道路，从而化解审评时限带来的巨大压力。

此次机构改革，对原有审评工作程序进行简化和调整，使中心的程序和任务之间更加协调，并设计了平行审评、序贯审评、单专业审评和简化审评等新的流程，以加快审评进度，适时调整审评策略。

此次机构改革后，审评任务根据其申请事项主要分为新药临床试验申请、新药生产上市注册申请、仿制药注册申请、补充申请等。根据药物研发一般规律，不同类型审评任务采用相应的审评程序。新药临床试验申请和新药生产上市注册申请采用多专业平行审评程序；化学仿制药注册申请采用一个部门单专业审评程序;补充申请根据其变更类型可采用单专业审评程序及简易审评程序。单专业审评的品种如遇多专业问题可启动序贯审评程序。采用序贯程序的审评任务也应在其规定的时限内完成。

值得关注的是，此次机构改革单独成立了药理毒理学部门，该部门负责中药、民族药、天然药物、化学药物、生物制品临床试验申请、注册申请及相关补充申请的药理毒理学研究资料的技术审评工作；还负责化学药物1～2类以及中药、民族药、天然药物1～5类临床试验申请、相关补充申请的综合评价工作，形成技术审评报告，并提出明确结论意见及处理建议。

与之相比，以往新药毒理药理环节评审分在不同适应症的临床审评部门里。改革后同专业审评人员相对集中，加强了同学科评审员的沟通交流，加大了审评尺度的统一，以及审评速度的均匀性，对合理协调人员有极大的促进作用。

为提高审评效率和决策的科学性，沟通和交流一直是SFDA药品注册司和药审中心提倡的重要工作方向。《原则和程序》的贡献把沟通和交流的方法、方式真正落到了实处。同时，《原则和程序》又把沟通和交流的理念提到了一个新的高度，规定申请人可在新药研究进程中的关键阶段，就重大技术问题提出与中心进行沟通交流的申请。也可就其年度研发战略，药物研究进程中整体规划和布局等事项提出与中心进行沟通交流的申请。这种交流，不但可帮助企业化解投资风险，尽早终止某些研发项目。同时，对于制药企业药物研究进程中整体规划的了解，也可帮助中国药监机构合理计划和配备人力资源。

《原则和程序》在新药技术审评授权和签发上也有新的尝试，规定各审评部部长负责专业审评报告和相关技术审评报告的审核，并根据中心主任的授权，负责相应注册申请技术审评报告的签发。解读背后的含义，相当于技术审评签发权的下放，与美国FDA的做法已十分接近。

《原则和程序》的第四个亮点在于它把公众和药业对审评的“监督”更加具体化。《原则和程序》规定“各主审报告部提出的审评任务目标审评时间”要对申请人提前公开。同时，某些审评结论信息也须通过中心网站予以公布，特别是：“以通用技术文件（CTD）格式提交资料的品种的技术审评报告，向其申请人公布”，“首个国内上市新药的《新药评价概述》”向公众公布。这对促进审评尺度的一致性和结果的可预见性将起到深远的意义。

在中国药物审评的历史上，《原则和程序》第一次提出“各类审评任务的目标审评时间是评价审评质量和效率的重要指标”。同时，提出了“新药生产上市注册申请的目标审评时间应与满足公众获取最新治疗手段的需求相符合”和“仿制药注册申请的目标审评时间应与满足公众对该类药品可及性的需求相符合”的两项基本原则。随着这两项基本原则的提出，“鼓励药物创新”将再不是一句空话。

纵览国际研发趋势的药审中心的现实努力正努力削减甚至是消除中国新药研发和审批与国际差距差距。正如SFDA注册司司长张伟对此次机构改革的评价：“药审中心是用科学的标准、规范和方法评价药品研究数据和结果，保证批准上市药品安全有效质量可控的重要部门。中心每一次机构或机制的改革都是为了更好地适应药品创新趋势的发展，为了更好地促进药品审评工作质量和效率的提高。”

收到北京寄来的《药品注册批准前检查——美国药品监管法规核心理念概述》一书。