FDA批准诺华口服铁螯合剂Jadenu在美国上市

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美国辉瑞充液胶囊美珈满溢牌系列保健品介绍

满溢网，维生素A+D 让您天天健康美国辉瑞Capsugel 公司生产的美珈满溢牌维生素A+D充液胶囊。

纯正美国进口美国辉瑞Capsugel公司授权商标在中国使用。

维生素A是维护正常视力防治青光眼，维护正常骨骼发育，皮肤细胞功能的成分，如人缺少维生素A 可导致眼干﹑夜盲症﹑皮肤弹性下降﹑干躁粗糙﹑失去光泽。

维生素D是促进钙吸收的主要成分，如人体缺少维生素D儿童会患佝偻病，成人软骨病关节痛，牙齿松动。

销售网址满溢网，维生素A+D充液胶囊强壮骨骼助健康纯真天然维生素A+D取至天然鱼肝油是人体生长发育不可取少的维生素，由美国辉瑞Capsugel公司生产，美珈满溢牌充液胶囊维生素A+D 纯正美国生产最新引进中国，充液胶囊维生素A+D含量高吸收好。

对胃无刺激获美国FDA认证，美国联邦政府农业部自由销售认可。

美珈满溢充液胶囊维生素A+D对皮肤组织的完整性﹑视力﹑生殖器官﹑血﹑钙﹑磷的恒定﹑骨骼﹑牙齿的生长发育都有重要的作用。

并可保护眼睛视力，预防近视。

促进钙质吸收，强健骨骼和牙齿。

满溢网，番茄红素充液胶囊男人更需要美国辉瑞Capsugel公司科学家研制出品的番茄红素充液胶囊与目前市场上所销售的番茄红素有着本质的区别。

美珈满溢牌番茄红素充液胶囊吸收率高对胃无刺激特别是有效物不容易被氧化吸收率高达98%。

美珈满溢牌番茄红素对男性前列腺疾病有明显效果，男性前列腺，肾上腺等器官都含有大量的番茄红素。

尤其是在前列腺上高含64%，说明男性是离不开番茄红素的。

番茄红素充液胶囊和锯棕榈充液胶囊是男性前列腺健康的保护神。

番茄红素和锯棕榈是男性健康的黄金搭档。

满溢网，番茄红素充液胶囊给您真正的健康美珈满溢牌番茄红素充液胶囊，美国辉瑞Capsugel公司生产荣获诺贝尔给药技术奖，美国辉瑞Capsugel商标授权中国使用。

美珈满溢牌番茄红素充液胶囊对降低血液胆固醇含量改善动脉硬化有明显的作用同时番茄红素充液胶囊有预防前列腺癌﹑乳房癌﹑子宫癌和抑制肿瘤细胞的生长并可改善皮肤过敏症﹑皮肤干燥﹑糖尿病引起的皮肤瘙痒。

朗道多项生化定值质控

0843PAGE 1 OF 24LIQUID ASSAYED CHEMISTRY CONTROL PREMIUM PLUS - LEVEL 1 (LIQ CHEM ASY PREMIUM PLUS 1)Cat. No . LAL 4213 Lot No . 153UL Size : 12 x 5 ml Expiry : 2015-02INTENDED USEThis product is intended for in vitro diagnostic use, in the quality control of diagnostic assays. The Liquid Assayed Chemistry Control Premium Plus is for the control of accuracy.DEVICE DESCRIPTIONThe Liquid Assayed Chemistry Control Premium Plus is supplied at 3 levels, level 1, 2 and 3. Target values and ranges are supplied for the analytes listed in the values section at all three levels.SAFETY PRECAUTIONS AND WARNINGSFor in vitro diagnostic use only. Do not pipette by mouth. Exercise the normal precautions required for handling laboratory reagents.Human source material from which this product has been derived has been tested at donor level for the Human Immunodeficiency Virus (HIV 1, HIV 2) antibody, Hepatitis B Surface Antigen (HbsAg), and Hepatitis C Virus (HCV) antibody and found to be NON-REACTIVE. FDA approved methods have been used to conduct these tests.However, since no method can offer complete assurance as to the absence of infectious agents, this material and all patient samples should be handled as though capable of transmitting infectious diseases and disposed of accordingly.Health and Safety Data Sheets are available on request.STORAGE AND STABILITY OPENED: Store refrigerated (+2ºC to + 8ºC). Thawed serum is stable for 7 days at +2ºC to +8ºC, with the followingexceptions: Troponin T is stable for 3 days at +2ºC to +8ºC. Only the required amount of product should be removed. After use, any residual product should NOT BE RETURNED to the original vial.UNOPENED: Store frozen at -20ºC to -70ºC. Stable to expiration date printed on individual vials (see Limitations).LIMITATIONSFor Total Acid Phosphatase, the material should be stabilised by adding 1 drop (25 µl – 30 µl) of 0.7M Acetic acid solution to 1ml of the serum after thawing. After stabilisation, Total Acid Phosphatase is stable for 7 days at +2ºC to +8ºC. Bilirubin in the serum is light sensitive and it is recommended that the serum is stored in the dark.ALT, Total Acid Phosphatase, Alkaline Phosphatase, Total and Direct Bilirubin values may gradually decrease during the products shelf life.Bacterial contamination of the thawed serum will cause reductions in the stability of many components. The control should not be used as a calibration material.PREPARATION1. Allow the frozen control to thaw at room temperature (+15ºC to +25ºC) until completely thawed. Swirl the contents to ensurehomogeneity.2. Refer to the Control section of the individual analyser application.3. Refrigerate any unused material. Prior to reuse, mix contents thoroughly.MATERIALS PROVIDEDLiquid Assayed Chemistry Control Premium Plus - Level 1 12 x 5 mlMATERIALS REQUIRED BUT NOT PROVIDED NoneASSIGNED VALUESEach lot of serum is submitted to a number of external laboratories. Values are assigned from a consensus of results obtained by these laboratories and internal testing conducted at Randox Laboratories Ltd. With each batch, a control range is provided for individual parameters and each parameter method.If an instrument specific value is not available, refer to the Mean of all Instruments section. If necessary, contact Randox Laboratories – Customer Technical Services, Northern Ireland, Tel: +44 (0) 28 9445 1070 or email Technical.Services@29 Nov 13 rwPage 2 of 2429/11/2013___________________________________________________________________________________________________RANDOX Laboratories Ltd., 55 Diamond Road, Crumlin, Co. Antrim, United Kingdom, BT29 4QYTel: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912Email: applications@ Website: Page 3 of 24 29/11/2013___________________________________________________________________________________________________RANDOX Laboratories Ltd., 55 Diamond Road, Crumlin, Co. Antrim, United Kingdom, BT29 4QYTel: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912Email: applications@ Website: Page 4 of 24 29/11/2013___________________________________________________________________________________________________RANDOX Laboratories Ltd., 55 Diamond Road, Crumlin, Co. Antrim, United Kingdom, BT29 4QYTel: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912Email: applications@ Website: Page 5 of 2429/11/2013___________________________________________________________________________________________________RANDOX Laboratories Ltd., 55 Diamond Road, Crumlin, Co. Antrim, United Kingdom, BT29 4QYTel: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912Email: applications@ Website: Page 6 of 2429/11/2013___________________________________________________________________________________________________RANDOX Laboratories Ltd., 55 Diamond Road, Crumlin, Co. Antrim, United Kingdom, BT29 4QYTel: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912Email: applications@ Website: Page 7 of 2429/11/2013___________________________________________________________________________________________________RANDOX Laboratories Ltd., 55 Diamond Road, Crumlin, Co. Antrim, United Kingdom, BT29 4QYTel: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912Email: applications@ Website: Page 8 of 2429/11/2013___________________________________________________________________________________________________RANDOX Laboratories Ltd., 55 Diamond Road, Crumlin, Co. Antrim, United Kingdom, BT29 4QYTel: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912Email: applications@ Website: Page 9 of 2429/11/2013___________________________________________________________________________________________________RANDOX Laboratories Ltd., 55 Diamond Road, Crumlin, Co. Antrim, United Kingdom, BT29 4QYTel: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912Email: applications@ Website: Page 10 of 2429/11/2013___________________________________________________________________________________________________RANDOX Laboratories Ltd., 55 Diamond Road, Crumlin, Co. Antrim, United Kingdom, BT29 4QYTel: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912Email: applications@ Website: Page 11 of 2429/11/2013___________________________________________________________________________________________________Page 12 of 2429/11/2013___________________________________________________________________________________________________Page 13 of 2429/11/2013___________________________________________________________________________________________________Page 14 of 2429/11/2013___________________________________________________________________________________________________Page 15 of 2429/11/2013___________________________________________________________________________________________________Page 16 of 2429/11/2013___________________________________________________________________________________________________Page 17 of 2429/11/2013___________________________________________________________________________________________________Page 18 of 2429/11/2013___________________________________________________________________________________________________Page 19 of 2429/11/2013___________________________________________________________________________________________________Page 20 of 2429/11/2013___________________________________________________________________________________________________Page 21 of 2429/11/2013___________________________________________________________________________________________________Page 22 of 2429/11/2013___________________________________________________________________________________________________Page 23 of 2429/11/2013___________________________________________________________________________________________________Page 24 of 2429/11/2013___________________________________________________________________________________________________。

第三期美欧GMP设备规范(印刷版)

美欧GMP专题现场培训全面地科学地理解与实施美欧GMP规范(浙江海正专场)★美欧GMP设备规范（本资料仅供企业内部培训使用）Shanghai NovoScience上海加中生物技术有限公司1美欧GMP 设备规范上海加中生物技术有限公司上海国际药政高级培训中心执行经理程毓渡博士2程毓渡博士（Dr. Frank Cheng）在北美制药领域拥有十几年学习、研究与工作经历，先后在美国JOHNS HOPKINS大学、加拿大国家科学院生物技术研究所、加拿大新科药业、加拿大生化制药、日本第一制药等著名大学、研究所、制药企业工作、合作与交流，在原料药、仿制药、创新药开发、生产与市场准入规范方面具有广泛的专业知识与国际人脉资源。

作为一个在中国工作的加籍华人专家，程毓渡博士目前担任上海加中生物技术有限公司执行总裁，专注于为国内外药企客户提供美欧GMP（ICH Q7A/cGMP）符合性培训与审计服务、为美欧公司和中国药企承担独立第三方GMP审计工作，亦提供面向美欧市场药品合同制造方面的项目管理。

程毓渡博士上海中生物技术有限公司执行经理上海国际药政高级培训中心执行经理3美欧GMP 规范专题现场培训全面地科学地理解与实施美欧GMP 规范•美欧GMP设施规范•美欧GMP物料规范•美欧GMP设备规范•美欧GMP生产规范•美欧GMP质保规范•美欧GMP质控规范•美欧GMP文件规范•美欧GMP审计规范4美欧GMP 设备规范培训序言根据美国FDA 对04/05年的原料药和制剂生产厂家GMP 审计结果统计，涉及违反设施与设备规范方面的缺陷占总缺陷的17%，这些缺陷来自设施设备与工艺设备的设计、调试、确认、验证、清洁、维保、变更等。

美欧GMP 设备规范还包括工艺设备的计算机系统，而这部分涉及的缺陷包括控制系统未经确认或验证、控制程序未经验证、密码管理系统与示踪系统未能建立等。

设施设备和工艺设备对于原料药和制剂的质量控制具有直接作用，本课程将对设施中的空调设备、水设备、空气压缩设备和生产中的主要工艺设备以及计算机系统的GMP 规范和实施进行科学解读，促进贵药厂遵循美欧GMP 在设施和工艺设备方面的管理规范，为通过美欧GMP 认证水平奠定坚实的基础！5美欧GMP 设备规范培训提纲美欧GMP设备规范解读ICHQ7A 第5节（工艺设备）与第12节（验证）中关于设备确认和验证方面的规范条例总共有28条（不包括计算机系统的10条规范），为药厂在设备管理方面实施GMP 提供了原则和依据，科学地和恰当地解读这些规范条例以建立这些规则与管理实施之间的有机联系是药厂的责任……美欧GMP设备规范实施美欧GMP 设备规范的实施涉及设备的设计、构造、调试、确认、操作、清洁等，通过对HVAC 系统、工艺水系统、工艺气体系统、反应罐、离心过滤机、干燥机、制粉机等设施系统和设备的确认以掌握规范实施方法……6美欧GMP 设备规范解读ICHQ7A第5节（工艺设备）与第12节（验证）中关于设备方面的规范条例总共有28条，为药厂在设备管理方面实施GMP提供了依据和规则，科学地和恰当地解读这些规范条例以建立这些规则与管理实施之间的有机联系是药厂的责任……7美欧GMP设备规范解读ICH Q7A 5 工艺设备–ICH Q7A 5.1 设计与构造–ICH Q7A 5.2 设备维护与清洁–ICH Q7A 5.3 校验ICH Q7A 12 验证–ICH Q7A 12.3 确认–ICH Q7A 12.7清洁验证ICH Q7A官方网站：ICH FDA EMEA85.1 设计与构造：5.10Equipment used in the manufacture ofintermediates and APIs should be of appropriate design and adequate size, and suitably located for its intended use, cleaning, sanitization (where appropriate), and maintenance.用于中间体和原料药生产的设备应做到设计合理、体积适中、放置恰当，以符合其使用、清洁、卫生（如有必要）和维护的要求。

OMG助剂介绍

环保催化剂 Borchi® Kat
金属类型
有机酸
活性
载体
PU树脂合成 PU涂料应用
metal chemical base reactivity supply form PU synthesis PU coating
Borchi Kat 0243 混合
新癸酸
++
metal-mix neodecanoate
全配方HMP用量
聚丙烯酸 / 氨基树脂清漆白色聚酯 / 氨基树脂面漆
MEK 擦拭数值
111 55
115 61
186 135
191 156
0%
1%
10 Advanced Organics - Additives
2%
3%
OMG Shanghai
环保催化剂 Borchi® Kat
有机金属化合物路易斯酸
使用 0.5 - 4% 的 Additive TI 或 Additive OF
即可解决所有这些问题
6 Advanced Organics - Additives
OMG Shanghai
吸水剂 Additive TI / Additive OF
脱水反应时间对比
Additive TI
Additive OF
5 Advanced Organics - Additives
OMG Shanghai
Additive TI & Additive OF
吸水剂 Additive TI / Additive OF
水分可能通过溶剂、颜料、填料和聚醇(比较少见)被带入聚氨酯体系
• 由此可能引起泡沫形成(CO2)以及失光、混浊和涂膜黄变 • 单组分PUR-体系可能与潮气反应产生气体，失去贮存稳定性

FDA批准的放射性药物都有哪些？

FDA批准的放射性药物都有哪些？展开全文中华医学会核医学分会放射性药物学组整理1、药物名称：Carbon-11 choline（11C-胆碱）生产商：Mayo Clinic 商品名：—用途：前列腺癌复发诊断2、药物名称：Carbon-14 urea（14C-尿素）生产商：Kimberly-Clark 商品名：PYtest用途：胃中幽门螺杆菌感染诊断3、药物名称：Fluorine-18 florbetaben（18F-AV1）生产商：Piramal Imaging 商品名：Neuraceq™用途：阿尔茨海默（AD）患者和痴呆患者评价4、药物名称：Fluorine-18florbetapir（18F-AV45）生产商：Eli Lilly 商品名：Amyvid™用途：阿尔茨海默症诊断与治疗5、药物名称：Fluorine-18sodium fluoride（18F-氟化钠）生产商：Various 商品名：—用途：成骨能力的骨显像剂6、药物名称：Fluorine-18fludeoxyglucose（18F-FDG）生产商：Various 商品名：—用途：肿瘤、癫痫病灶糖代谢异常检测7、药物名称：Fluorine-18flutemetamol（18F-PIB）生产商：GE Healthcare 商品名：Vizamyl用途：阿尔茨海默（AD）患者和痴呆患者评价8、药物名称：Gallium-67 citrate（67Ga-柠檬酸）生产商：Lantheus MedicalImaging、Mallinckrodt商品名：—用途：霍奇金病、淋巴瘤、支气管癌以及一些急性炎症病变诊断9、药物名称：Indium-111capromab pendetide（111In-卡罗单抗喷地肽）生产商：AytuPharmaceuticals 商品名：ProstaScint®用途：前列腺癌患者、前列腺癌术后高度怀疑转移患者的检测10、药物名称：Indium-111 chloride（111In-氯化铟）生产商：GE Healthcare、Mallinckrodt 商品名：Indiclor™用途：用于放射性标记11、药物名称：Indium-111 pentetate（111In-DTPA）生产商：GE Healthcare 商品名：—用途：放射性核素脑池造影12、药物名称：Indium-111oxyquinoline（111In-羟基喹啉）生产商：GE Healthcare 商品名：—用途：用于自体白细胞标记，炎症及感染的诊断13、药物名称：Indium-111pentetreotide（111In-奥曲肽）生产商：Mallinckrodt 商品名：Octreoscan™用途：原发性和转移性内神经分泌肿瘤生长抑素受体定位14、药物名称：Iodine I-123iobenguane（123I-MIBG）生产商：GE Healthcare 商品名：AdreView™用途：原发或转移性嗜铬细胞瘤或神经母细胞瘤的辅助诊断15、药物名称：Iodine I-123 ioflupane（123I-氟潘）生产商：GE Healthcare 商品名：DaTscan™用途：对疑似帕金森症患者的评估16、药物名称：Iodine I-123sodium iodide capsules（123I-碘化钠胶囊）生产商：Cardinal Health、Mallinckrodt 商品名：—用途：甲状腺功能及形态学评价17、药物名称：Iodine I-125 humanserum albumin（125I-人血清白蛋白）生产商：IsoTex Diagnostics 商品名：Jeanatope用途：全血及血浆容量测定18、药物名称：Iodine I-125iothalamate（125I-酞酸盐）生产商：IsoT ex Diagnostics商品名：Glofil-125用途：肾小球滤过率的评价19、药物名称：Iodine I-131 humanserum albumin（131I-人血清白蛋白）生产商：IsoTex Diagnostics 商品名：Megatope用途：全血及血浆量、心脏输出、心脏及肺血容量、蛋白质周转研究、脑肿瘤定位等20、药物名称：Iodine I-131sodium iodide（131I-碘化钠）生产商：DRAXIMAGE、Mallinckrodt 商品名：HICON™用途：甲状腺疾病的诊断与治疗21、药物名称：MolybdenumMo-99 generator（钼锝发生器）生产商：GE Healthcare、Lantheus MedicalImaging、Mallinckrodt商品名：DRYTEC™、T echnelite、UltraTechneKow®DTE用途：放射性药物的制备22、药物名称：Nitrogen-13 ammonia（13N-氨水）生产商：Various 商品名：—用途：心肌灌注评价冠状动脉疾病23、药物名称：Radium-223 dichloride（223Ra-二氯化镭）生产商：Bayer HealthCarePharmaceuticalsInc. 商品名：Xofigo®用途：去势性前列腺癌治疗24、药物名称：Rubidium-82 chloride（82Ru-氯化铷）生产商：Bracco Diagnostics 商品名：Cardiogen-82®用途：心肌灌注显像剂25、药物名称：Samarium-153lexidronam（153Sm-EDTMP）生产商：Lantheus MedicalImaging 商品名：Quadramet®用途：减轻骨转移患者的疼痛26、药物名称：Strontium-89 chloride（89Sr-氯化锶）生产商：GE Healthcare商品名：MetastronTM用途：减轻骨转移患者的疼痛27、药物名称：T echnetium-99mbicisate（99mT c-ECD）生产商：Lantheus MedicalImaging 商品名：Neurolite®用途：脑卒中患者卒中的诊断与治疗28、药物名称：Technetium-99mdisofenin（99mTc-地索芬宁）生产商：Pharmalucence 商品名：Hepatolite®用途：急性胆囊炎诊断29、药物名称：Technetium-99mexametazine（99mTc-HMPAO）生产商：GE Healthcare 商品名：C eretec™用途：脑卒中患者血脑灌注、白细胞标记显像用用于腹腔感染及肠道炎症定位30、药物名称：T echnetium-99mmacroaggregatedalbumin （99mT c-MAA）生产商：DRAXIMAGE 商品名：—用途：肺灌注评价、腹静脉分流畅通性评价31、药物名称：Technetium-99mmebrofenin（99mT c-甲溴苯宁）生产商：Bracco Diagnostics、Pharmalucence 商品名：Choletec®用途：肝胆显像剂32、药物名称：Technetium-99mmedronate（99mTc-MDP）生产商：DRAXIMAGE、GE Healthcare、Pharmalucence 商品名：MDP-25、MDP Multidose用途：骨显像剂33、药物名称：Technetium-99mmertiatide（99mTc-MAG3）生产商：Mallinckrodt 商品名：TechnescanMAG3TM用途：肾动态显像34、药物名称：Technetium-99moxidronate（99mT c-HDP）生产商：Mallinckrodt 商品名：Tec hnescan™HDP用途：骨显像剂35、药物名称：Technetium-99mpentetate（99mT c-DTPA）生产商：DRAXIMAGE 商品名：—用途：脑显像、肾显像36、药物名称：T echnetium-99mpyrophosphate（99mTc-PYP）生产商：Mallinckrodt、Pharmalucence 商品名：Technescan™、PYP™用途：骨显像、心脏显像剂、血池显像剂37、药物名称：Technetium-99m redblood cells（99mT c-红细胞）生产商：Mallinckrodt 商品名：UltraTag™用途：血池造影、消化道出血定位38、药物名称：T echnetium-99msestamibi（99mTc-MIBI）生产商：Cardinal Health、DRAXIMAGE、Lantheus MedicalImaging、Mallinckrodt、Pharmalucence商品名：Cardiolite®用途：心肌灌注，用于检测缺血、评价心机功能，乳腺成像39、药物名称：Technetium-99msodium pertechnetate （99mT c-高锝酸钠）生产商：GE Healthcare、Lantheus MedicalImaging、Mallinckrodt商品名：—用途：脑显像、甲状腺显像、胎盘定位、膀胱显像等40、药物名称：Technetium-99msuccimer（99mT c-DMSA）生产商：GE Healthcare 商品名：—用途：肾显像41、药物名称：Technetium-99msulfur colloid（99mT c-硫胶体）生产商：Pharmalucence 商品名：—用途：肝、脾、骨髓显像等42、药物名称：Technetium-99mtetrofosmin（99mTc-替曲膦）生产商：GE Healthcare 商品名：MyoviewTM用途：心肌灌注剂43、药物名称：Technetium-99mtilmanocept（99mTc-替马诺噻）生产商：NavideaBiopharmaceuticals,Inc. 商品名：Lymphoseek®用途：淋巴结定位44、药物名称：Thallium-201chloride（201Tl-氯化铊）生产商：GE Healthcare、Lantheus MedicalImaging、Mallinckrodt商品名：—用途：心肌灌注显像45、药物名称：Xenon-133 gas（133Xe气体）生产商：Lantheus MedicalImaging 商品名：—用途：肺功能评估与肺显像、脑血流评估46、药物名称：Yttrium-90chloride（90Y-氯化钇）生产商：MDS Nordion、Eckert＆ZieglerNuclitec商品名：—用途：放射性标记47、药物名称：Yttrium-90ibritumomab tiuxetan（90Y-替伊莫单抗）生产商：SpectrumPharmaceuticals商品名：Zevalin®用途：非霍奇金氏淋巴瘤治疗截止至2015年8月1日。

新型口服铁离子螯合剂Exjade在美国上市

第5课《秋天的怀念》教学设计《秋天的怀念》是统编版2024新教材七年级语文上册第5课，单元主题为亲情，学习重点是朗读。

《秋天的怀念》正是一篇饱含深情的怀念母亲的散文，作者用凝重的笔触表达了对母亲的深深愧疚和怀念之情，一个个平凡的细节为读者诠释了伟大母爱的内涵。

对于七年级学生来说，理解本文的主题并不难，但是让学生内心受到震撼，唤起真切的情感体验不容易。

所以在教学中，结合单元目标，我想以朗读指导为途径，创设一个诵读活动情境，引导学生在朗读中抓住作品细节和关键词句，体味人物内心情感，真正领悟作品内涵。

1.掌握文中生字词，并了解作者相关文学常识。

2.通过多种形式的朗读，继续巩固朗读技巧，丰富审美创造体验。

3.在朗读中梳理文章思路，把握全文感情基调的变化；揣摩文中多处人物和细节描写，分析作品情境，理解人物情感，提高思维能力。

4.激发学生的感恩之情，深入体会伟大母爱；理解“好好儿活”的含义，树立乐观向上的生活信念。

教学重点：揣摩文中多处人物和细节描写，分析作品情境，理解人物情感，提高思维能力。

教学难点：激发学生的感恩之情，深入体会伟大母爱；理解“好好儿活”的含义，树立乐观向上的生活信念。

第一课时世间爹妈情最真，泪血溶入儿女身。

殚竭心力终为子，可怜天下父母心！《孔子家语》中有这样一句话，“树欲静而风不止，子预养而亲不待。

”这句话多用于孩子想向父母尽孝时，但父母却已亡故。

今天，我们要学习的这篇文章，就是作者在母亲猝然长逝后，对母亲深刻怀念的作品。

我们齐读课题：秋天的怀念【走近作者】史铁生（1951年1月4日—2010年12月31日），出生于北京，1969年去延安一带插队。

后因双腿瘫痪，于1972年回到北京。

1979年开始发表作品。

自称是“职业是生病，业余在写作”。

代表作品有小说《我的遥远的清平湾》《务虚笔记》《命若琴弦》，散文《我与地坛》《合欢树》《病隙碎笔》等。

【背景资料】20岁时不幸因病瘫痪，风华正茂的史铁生不得不终生以轮椅为伴，永远离开了正常人的生活。

中国汽车有害物质分类管控清单 2015.8

的测定》；
（ 9 ） GB19601-2004 《染料产品中 23 种禁用偶氮的限量和检测
方法》；
（10）GB/T 23344-2009 《纺织品 4-氨基偶氮苯的测定》；
（11）GB/T 24101-2009 《染料产品中 4-氨基偶氮苯的限量及测
定》。
国外管控法规
备注
P 臭氧层破坏物质
制冷剂
包含橡胶或塑料部件的多种消费品中的 PAHs 含量进行限制。
3
序号物质中文名称
CAS number
英文名称
限值要求
GADSL
（质量百分数）等级
BbFA、BjFA、BkFA、 DBAhA 任一项含量≤
1mg
中国汽车有害物质分类管控清单
危害特性
主要用途
高风险零部件
目前国内企业管控现状
替代方案可行性
用要求，表中所列只是
一部分
中国汽车禁用物质要求
1、做为金属及合金中的元素，电子元器件
如轴承钢、钢材、铜合金、铝（豁免）、深
影响智力和骨骼发育，破坏肾
整车企业均列入企
电感耦合等离子体发
D/P
合金等等；
色塑料、橡胶
含铅焊料已替代
及免疫功能。
标，已禁用
射光谱
2、铅化合物，如含铅的稳定剂、件、金属（豁
中国汽车禁用物质要求
全球 GADSL
全球斯德哥尔摩公约
/ asbestos
不得使用
暴露于（长期吸入）一定量的
石棉纤维或元纤维可引发多种
刹车片、垫片
疾病，如：肺癌、胃肠癌、间
石棉纤维可以织成纱、线、绳、等零件的耐
皮癌、胸膜或腹膜癌、石棉沉

美FDA批准含最低剂量雌激素的复合口服避孕药LO Loestrin FE

式很难有市场。
机互补的销售模式，提高普药营销的质量和效率；针对不同市场的特点采取不同的促销战术，如集中小型推广会形式、大棚车配送形式和在卖场现场进行促销活动等。但差异化的实施也有风险，企业要根据自身产品的特点、企业自身的实力、消费者心理和竞争对手的优劣等多方面闪素实施适合自己的差异化战略，避免无意义差异化、过分差异化及竞争者模仿等不利冈素给企业带来的风险。３３集中化战略．集中化战略是指将企业的战略重点集中于某一特定的购买群体、产品线的某一部分或某一地区市场，通过为这个小市场的购买群体提供比竞争对手更好、更有效的服务来建立竞争优势的一种战略。集中化战略与成本领先战略、差异化战略的区别是：中化战略的注意力集集中于整体市场的一个狭窄部分，而其它战略则以广大市场为目标。对大多数普药企业来说，很难在整个市场上建立成本领先优势，也难以在整个市场上完全实施差异化战略。因此，对它们来说，可行的办法是将三种战略组合使用，更如将成本领先战略与集中化战略组合为低成本集中战略，将差异化战略与集中化战略组合为差异化集中战略，在细分市场中寻求低成本优势和差异化优势。例如，根据不同的产品属性和目标市场选择不同的品牌推广和销售推广方式等。如找对细分市场并根据企业自身特点选择适宜的成本领先和差异化策略，普药企业就一定能在激烈的市场竞争中脱颖而出，赢得良好的发展前景。
（）：５－６１３３．

IVD行业国外原料主要供应商

.aaltobioreagents.ie .aaltoscientific..aetltd..biocell..npods.ru.diarect..endocrinetech..scipac..eastcoastbio..haemtech. .immunovision..mainebiotechnology. .operon.es.equitech-bio..quadfive..promeddx..seracare..chemogen..modiquest..seramon..midlandbio..capricornproducts. .instruchemie.nl.sheffield-products. .biogenes.de.biocheckinc..biospacific..bioprocessinginc..fitzgerald-fii..microbix..inventdiagnostica.de .biomarket.fi.calbioreagents..xema-medica..scrippslabs..silverlakeresearch..ssi.dk.virostat-inc..virusys..oycus..accessbiologicals. .anshlabs..arlingtonscientific..auditmicro..brt-us..cardinalbiologicals. .diasource.be.diazyme..dsitaly..icllab..immunoreagents. .magsphere.丹麦提供诊断试剂盒和抗体、抗原和血清，有特色的产品是 CE认证的NGAL诊断试剂盒，MBL试剂盒重症监护和止血，临床化学仪器，试剂盒日本提供诊断试剂盒产品的公司，特色产品是低密度LDL 和胱抑素C 试剂盒。

产品涉及质控品，转染病，糖尿病，肿瘤，生殖，甲状腺等试剂盒Acris 是一家德国的著名抗体公司，提供近 3 万种各种优质抗体、蛋白及抗体纯化试剂盒，产品X 围涉及免疫学、细胞生物学、细胞神经信号传导、蛋白组学、肿瘤生物学等。

Farxiga(dapagliflozin,达格列净片)说明书

(8.1)（2）哺乳母亲：终止FARXIGA或终止哺乳. (8.3)（3）老年人：与减低血管内容量相关不良反应发生率较高。

(5.1，8.5)（4）肾受损：与减低血管内容量和肾功能相关不良反应发生率较高。

(5.2，6.1，8.6)完整处方资料1 适应证和用途FARXIGA(dapagliflozin)适用作为辅助在成人中对饮食和运动改善血糖控制有2型糖尿病[见临床研究(1 4)]。

1.1 使用限制建议FARXIGA不为1型糖尿病患者或为糖尿病酮症酸中毒治疗。

2 剂量和给药方法2.1 推荐给药FARXIGA的推荐起始剂量是5 mg每天1次，早晨服用，有或无食物。

在耐受FARXIGA 5 mg每天1次患者需要另外血糖控制时，剂量可增加至10 mg每天1次。

在有血容量不足患者中，建议在开始FARXIGA前纠正这种情况[见警告和注意事项(5.1)，在特殊人群中使用(8.5，8.6)，和患者咨询资料(17)]。

2.2 有肾受损患者建议开始FARXIGA治疗前和其后定期地评估肾功能。

在eGFR低于60 mL/min/1.73 m2患者中不应开始FARXIGA。

在有轻度肾受损患者(eGFR为60 mL/min/1.73 m2或更高)无需剂量调整。

当eGFR持续地低于60 mL/min/1.73 m2时应终止FARXIGA[见警告和注意事项(5.2)和在特殊人群中使用(8.6)]。

3 剂型和规格● FARXIGA 5 mg片是黄色，双凸，圆，薄膜包衣片在一侧刻有“5”和另一侧“1427”。

● FARXIGA 10 mg片是黄色，双凸，菱形，薄膜包衣片一侧刻有“10“和另一侧“1428”。

4 禁忌证● 对FARXIGA严重超敏反应史[见不良反应(6.1)]。

● 严重肾受损，肾病终末期(ESRD)，或用透析患者[见在特殊人群中使用(8.6)]。

5 警告和注意事项5.1 低血压FARXIGA致血管内容积收缩。

开始FARXIGA后可能发生症状性低血压[见不良反应(6.1)]特别是在有肾功能受损患者中(eGFR低于60 mL/min/1.73 m2)，老年患者，或用袢利尿剂的患者。

Purdue制药公司的处方止痛药OxyContin的标签上将添加黑框警告

Purdue制药公司的处方止痛药OxyContin的标签上将添加黑框警告华盛顿，7月26日（路透社医学新闻）Purdue制药公司的OxyContin（氧可酮）的标签上将印上很明显的警示语，旨在帮助防止不适当的处方、滥用和转向使用问题。

OxyContin是一种被广泛滥用的止痛处方药。

OxyContin的滥用者通常会压碎药丸用鼻吸入或溶解后注射，以避开药物的控释给药系统。

今年早些时候公布的一项报告显示，司法部门认定至少有37例OxyContin滥用死亡事件。

为了突出与OxyContin滥用相关的危险性，FDA周三说，他们已和Purdue制药公司合作在药品的标签上作了不少修改，其中包括添加黑框的警示语，这是处方药中最有力的一种警示。

Purdue制药公司还将向药剂师、医生和其他医务人员发送一封“致亲爱的医务人员”的信，以强调与该药相关的滥用和转向使用问题，并解释标签的变化。

FDA说：“新的警告旨在减少OxyContin被不恰当地用于比许可应用的程度轻的疼痛或其它不该用II级麻醉药的疾病的机会。

在开处方时一定要认真地考虑疼痛是否严重到需治疗的程度，而不仅是引起疼痛症状的疾病本身。

”OxyContin是一种阿片样物质激动剂，和它的“近亲”吗啡一样有成瘾性。

该药被批准用于需较长时间用药物控制的中至重度疼痛的患者。

由于所有的阿片样物质类药物都有滥用、误用和转向使用的问题，所以FDA还鼓励其它生产该类产品的厂商检查他们的药品标签，可能的话也进行修改。

FDA强调还要给那些真正需要止痛药治疗的患者的合理使用留有余地。

Purdue制药公司发言人告诉路透社医学新闻。

“公司很高兴能成为第一个在产品标签上作出这些修改的止痛药生产商。

阿片样物质激动剂的其它生产商还包括强生公司和葛兰素史克公司。

”发言人认为，OxyContin标签修改的范围不大，称这次修改“很大程度上是一次图形设计的改动”，而不是大幅度修改内容。

Purdue制药公司官员过去曾指出，在超过6,000名患者的临床试验中，并没有一人发生OxyContin成瘾。

美国DMF目录及要求

Drug SubstanceChemistry, Manufacturing, and Controls InformationDRAFT GUIDANCEThis guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 180 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.For questions regarding this draft document contact (CDER) Stephen Miller (301) 827-2392, (CBER) Chris Joneckis (301) 435-5681, or (CVM) Dennis Bensley (301) 827-6956.U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Review (CBER)Center for Veterinary Medicine (CVM)January 2004CMCDrug Substance Chemistry, Manufacturing, and Controls InformationAdditional copies are available from:Office of Training and CommunicationDivision of Drug Information, HFD-240Center for Drug Evaluation and ResearchFood and Drug Administration5600 Fishers LaneRockville, MD 20857(Tel) 301-827-4573/cder/guidance/index.htmorOffice of Communication, Training andManufacturers Assistance, HFM-40Center for Biologics Evaluation and ResearchFood and Drug Administration1401 Rockville Pike, Rockville, MD 20852-1448/cber/guidelines.htm.(Tel) Voice Information System at 800-835-4709 or 301-827-1800orCommunications Staff, HFV-12Center for Veterinary MedicineFood and Drug Administration7519 Standish PlaceRockville, MD 20855(Tel) 301-827-3800/cvm/guidanc/published.htmU.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Review (CBER)Center for Veterinary Medicine (CVM)January 2004CMCTABLE OF CONTENTS1I. INTRODUCTION (1)II. BACKGROUND (3)A. The Common Technical Document — Quality (CTD-Q) Format (3)B. Content of an Application (4)C. Additional Guidance (4)D. References to Other Applications or Master Files (MFs) (5)1. Other Applications (5)2. Master Files (MFs) (6)III. GENERAL INFORMATION (S.1) (8)A. Nomenclature (S.1.1) (8)B. Structure (S.1.2) (8)C. General Properties (S.1.3) (9)IV. MANUFACTURE (S.2) (10)A. Manufacturers (S.2.1) (10)B. Description of Manufacturing Process and Process Controls (S.2.2) (10)1. Flow Diagram (11)2. Description of the Manufacturing Process and Process Controls (12)3. Reprocessing, Reworking, Recycling, Regeneration, and Other Operations (15)C. Control of Materials (S.2.3) (18)1. Starting Materials (18)2. Reagents, Solvents, and Auxiliary Materials (19)3. Diluents (20)D. Controls of Critical Steps and Intermediates (S.2.4) (20)E. Process Validation and/or Evaluation (S.2.5) (23)F. Manufacturing Process Development (S.2.6) (23)V. CHARACTERIZATION (S.3) (24)A. Elucidation of Structure and Other Characteristics (S.3.1) (24)1. Elucidation of Structure (24)2. Physicochemical Characterization (25)3. Biological and Other Relevant Characteristics (26)B. Impurities (S.3.2) (27)VI. CONTROL OF DRUG SUBSTANCE (S.4) (29)1 Alphanumeric designations in parentheses that follow headings show where information should be placed in applications that are submitted in Common Technical Document (CTD) format.A. Specification (S.4.1) (29)B. Analytical Procedures (S.4.2) (34)C. Validation of Analytical Procedures (S.4.3) (35)D. Batch Analyses (S.4.4) (35)1. Batch Analysis Reports (36)2. Collated Batch Analyses Data (36)E. Justification of Specification (S.4.5) (37)VII. REFERENCE STANDARDS OR MATERIALS (S.5) (40)VIII. CONTAINER CLOSURE SYSTEM (S.6) (40)IX. STABILITY (S.7) (41)A. Stability Summary and Conclusions (S.7.1) (41)B. Postapproval Stability Protocol and Stability Commitment (S.7.2) (41)C. Stability Data (S.7.3) (41)1. Primary Stability Studies (41)2. Supporting Stability Studies (42)3. Stress Studies (42)X. APPENDICES (A) (43)A. Facilities and Equipment (A.1) (43)B. Adventitious Agents Safety Evaluation (A.2) (44)1. Nonviral Adventitious Agents (45)2. Viral Adventitious Agents (45)XI. REGIONAL INFORMATION (R) (46)A. Executed Production Records (R.1.S) (46)B. Comparability Protocols (R.2.S) (46)C. Methods Validation Package (R.3.S) (46)XII. LITERATURE REFERENCES (3.3) (47)ATTACHMENT 1: (48)STARTING MATERIALS FOR SYNTHETIC DRUG SUBSTANCES (48)ATTACHMENT 2: (56)STARTING MATERIALS OF PLANT OR ANIMAL ORIGIN (56)GLOSSARY (59)GUIDANCE FOR INDUSTRY2Drug SubstanceChemistry, Manufacturing, and Controls Information12345678910111213If you plan to submit comments on this draft guidance, to expedite FDA review of your14comments, please:15∙Clearly explain each issue/concern and, when appropriate, include a proposed revision and the rationale and/or justification for the proposed revision.1617∙Identify specific comments by line numbers; use the pdf version of the document whenever 18possible.19∙If possible, e-mail an electronic copy (Word) of the comments you have submitted to the20docket to cummingsd@.212223I. INTRODUCTION2425Information on the chemistry, manufacturing, and controls (CMC) for the drug substance must 26be submitted to support the approval of original new drug applications (NDAs), abbreviated new 27drug applications (ANDAs), new animal drug applications (NADAs), and abbreviated new28animal drug applications (ANADAs).3 This guidance provides recommendations on the CMC 29information for drug substances that should be submitted to support these applications. The30guidance is structured to facilitate the preparation of applications submitted in Common31Technical Document (CTD) format.3233This guidance addresses the information to be submitted for drug substances to ensure continued 34drug substance and drug product quality (i.e., the identity, strength, quality, purity, and potency).2 This guidance has been prepared by Drug Substance Technical Subcommittee of the Chemistry Manufacturing andControls Coordinating Committee (CMC CC) in the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluations and Research (CBER) and the Center for Veterinary Medicine (CVM) at the FDA.3 See 21 CFR 314.50(d)(1) and 514.1(b)This guidance provides recommendations on the information that should be included for the3536following topics:37∙Nomenclature, structure, and general drug substance properties3839∙Manufacture40∙Characterization41∙Control of drug substance42∙Reference standards or materials43∙Container closure system44∙Stability45The recommendations provided in this guidance apply to the following types of drug substances:464748∙Drug substances manufactured by chemical synthesis49∙Highly purified and well characterized drug substances derived from plants or animals 4 50∙Semisynthetic drug substances manufactured by the chemical modification of a highly 51purified and well characterized intermediate derived from plants or animals52∙The synthetic portion of the manufacturing process for semisynthetic drug substances53manufactured by the chemical modification of an intermediate produced by conventional 54fermentation.5556The guidance does not provide specific recommendations relating to the following:5758∙Monoclonal antibodies59∙Peptides60∙Oligonucleotides61∙Radiopharmaceuticals62∙Medical gases63∙Drug substances that are not well characterized (e.g., botanicals, some proteins) derived 64from plants or animals65∙Drug substances derived using transgenic technology66∙Drug substances derived directly from or manufacturing operations involving67fermentation (conventional fermentation or using rDNA technology) or tissue or cell68culture.6970More detailed guidance on the content of an application may be available in separate guidance 71documents for specific types of drug substances (see section II.C). Applicants with drug72substances not specifically covered by this (Drug Substance guidance) or another guidance can 73apply the content recommendations in this guidance, as scientifically appropriate, and/or can74contact the appropriate chemistry review teams for guidance.754 For purposes of this guidance, d rug substances derived from plants or animals does not include materials producedby plant cell fermentation, animal cell or tissue culture, or through use of transgenic technology (e.g.,biotechnology-derived protein drug products).FDA’s guidance docume nts, including this guidance, do not establish legally enforceable7677responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should 78be viewed only as recommendations, unless specific regulatory or statutory requirements arecited. The use of the word should in Agency guidances means that something is suggested or7980recommended, but not required.8182This guidance, when finalized, will replace the guidance entitled Submitting Supporting83Documentation in Drug Applications for the Manufacture of Drug Substances (February 1987).848586II. BACKGROUND8788A. The Common Technical Document — Quality (CTD-Q) Format89In November 2000, the International Conference on Harmonisation of Technical9091Requirements for Registration of Pharmaceuticals for Human Use (ICH) issued92harmonized guidance for the format of drug product applications (i.e., Common93Technical Document (CTD)). The CTD describes a format for applications that94(supplemented with regional information) can be used for submission to the regulatory 95authorities in the United States, European Union, and Japan. One focus of this effort was 96harmonizing the format for quality information (i.e., chemistry, manufacturing, and97controls) that will be submitted in an application. FDA’s guidance on M4Q: The CTD —98Quality describes the format for the quality information submitted in Module 3 of an99application and provides additional information on formatting aspects of an application. 100Applicants can submit NDAs, ANDAs, NADAs, and ANADAs using the CTD-Q101format.5Applicants should review FDA’s guidance on M4Q: The CTD — Quality and 102other related CTD guidance documents for detailed formatting recommendations on103preparing an application in CTD format.104105Module 3 of each NDA and ANDA should include the specified CTD sections: Drug 106Substance (3.2.S), Drug Product (3.2.P), Appendices (3.2.A), Regional Information107(3.2.R), and Literature References (3.3). In some cases, the majority of information to 108address the drug substance sections will be incorporated by reference from a master file 109(see section II.D.2). However, an applicant should still provide information to address 110some of the drug substance subsections. Recommendations on the content of the drug 111product section (3.2.P) of Module 3 will be the provided in the guidance Drug Product —112Chemistry, Manufacturing, and Controls Information (Drug Product guidance), when 113finalized.6 The Appendices, Regional Information, and Literature References sections 114include information for both drug substance and drug product, as appropriate.1155 The information in animal drug applications is commonly presented in the order of the required CMC informationspecified under section § 514.1(b)(4) and (5). Although the CTD-Q format was developed for human drugs, thedrug substance information to support NADAs and ANADAs can be formatted according to the CTD-Q format or any alternative format that provides the appropriate information to support the application.6 A draft version of this guidance published on January 28, 2003 (68 FR 4219).116This Drug Substance guidance has been organized in a format conforming to Module 3 of 117the CTD, and it provides CMC content recommendations specific to drug substance,118including recommendations for the Appendices, Regional Information, and Literature 119References sections. Alphanumeric designations in parentheses corresponding to the 120CTD format follow relevant headings and text to show where information is to be placed 121in the CTD.7 Recommendations specific to drug product, including recommendations for 122the Appendices, Regional Information and Literature References sections, will be123provided in the Drug Product guidance.124125Multiple Drug Substances in an Application126127When an application is submitted for a drug product involving two or more drug128substances (e.g., combination drug product, copackaged drug products), information for 129each drug substance should be presented separately in the application. Information130presented separately means one complete S section for one drug substance followed by 131other complete S sections for additional drug substances. All of the information pertinent 132to each one of the drug substances (general information, manufacture, characterization, 133control, standards, container closure system, and stability) should be provided in a single 134section.135136B. Content of an Application137The application should include information in every S subsection for each of the drug 138139substances and manufacturing schemes (e.g., alternative processes, manufacturing site) 140intended for approval under the application. Information should be provided in theAppendices, Regional Information, and Literature References sections for each of the 141142drug substances and manufacturing schemes, as appropriate. If an Appendices or143Regional Information subsection or the Literature References section is not applicable, 144this should be stated in the application.145146C. Additional Guidance147148This Drug Substance guidance and the Drug Product guidance, when finalized, will be 149the primary content guidances for NDA and ANDA applicants. For quality, the general 150format guidance is M4Q: The CTD — Quality. These are the first guidances an applicant 151should consider when preparing the quality section (i.e., chemistry, manufacturing, and 152controls) of an NDA or ANDA (Module 3).153This guidance references ICH guidance documents cited in the CTD-Q and FDA’s154155guidances on general technical topics (i.e., stability, container closure systems, analytical 156procedures and methods validation, sterilization process validation, drug master files, and7 Arabic numbers have been assigned to specific sections of the CTD. For example, the designation 3.2 before S, P,A, and R indicates Module 3, Body of Data section 2. Where this guidance discusses Module 3, Body of Datasection 2, for brevity, the initial designation 3.2 is not repeated throughout the rest of the guidance (e.g., 3.2.S.1.3reads S.1.3).157environmental assessments) rather than incorporating this detailed information. These 158guidances are referenced in the text and/or listed at the end of a section. An applicant159should refer to these guidances for recommendations on the detailed information that160should be included in the application to address the general technical topic.161162Finally, an applicant should consider guidances that are available for specific technical 163issues or type (e.g., synthetic peptides) of drug substance when preparing its application. 164These guidances provide additional recommendations on unique scientific and technical 165aspects of the topic. Some references to these types of guidances are included in this166guidance. However, the references are given only as examples, and the list is not meant 167to be all-inclusive. Some examples of these types of guidance include the following:168∙Submission of Chemistry, Manufacturing, and Controls Information for Synthetic 169170Peptide Substances171∙Submission of Chemistry, Manufacturing and Controls Information for a172Therapeutic Recombinant DNA-Derived Product or a Monoclonal Antibody173Product for In Vivo Use, CBER/CDER (under development)174∙Botanical Drug Products (under development)∙Fermentation Derived Drug Substances and Intermediates and Associated Drug 175176Products (under development)177∙Synthetic Oligonucleotides; Submission of Chemistry, Manufacturing, and178Controls Information (under development)179∙Radiopharmaceutical Drug Products: Chemistry, Manufacturing and ControlsInformation (under development)180181182FDA continues to update existing and publish new guidance documents. An applicant 183should use current guidance when preparing an NDA, ANDA, NADA or ANADA184submission.8185186D. References to Other Applications or Master Files (MFs)1871881. Other Applications189190In some cases, chemistry, manufacturing, and controls information about drug substances 191is provided in one application by reference to pertinent information in another application. 192This situation is less common than inclusion of information by reference to a MF and193usually occurs when the same firm submits both applications.194An applicant must identify in the application all other referenced applications, and each 195reference to information submitted in another application must identify where the196information can be found in the referenced application (21 CFR 314.50(a)(1) and197514.1(a)). If the referenced application was submitted by a firm other than the applicant,the referencing application must contain a written statement that authorizes the reference, 1988Current guidance documents are available on the Internet at /cder/guidance/index.htm,/cber/guidelines.htm, and /cvm/guidance/published.htm.199signed by the holder of the referenced application (21 CFR 314.50(g)(1), 314.420(b). and 200514.1(a)).9 Copies of letters of authorization (LOAs) should be submitted in Module 1 of 201the NDA or ANDA or in the appropriate section of an NADA or ANADA.2022032. Master Files (MFs)204205This guidance describes chemistry, manufacturing, and controls information for drug206substances that should be submitted to the Agency as part of the process of seeking theapproval of an NDA, ANDA, NADA, or ANADA. When a drug substance is207208manufactured by a firm other than the applicant, much of this information is frequently 209provided by reference to one or more Type II MFs rather than directly in an application. 210The CMC information in a Type II MF can be organized in CTD-Q format. Under FDA's 211regulations, an application can incorporate by reference all or part of the contents of any 212MF to address particular drug substance issues if the MF holder provides written213authorization (i.e., LOA) to the applicant and the authorization is included in the214application (Module 1 for an NDA or ANDA or in the appropriate section of an NADAor ANADA). The authorization must specifically identify the material being215216incorporated by reference (21 CFR 314.420 and 514.1(a)). The incorporated material217should be identified by name, reference number, volume and page number of the MF, anddate of submission. See 21 CFR 314.420, CDER’s guidance on Drug Master Files, and 218219CVM’s guidance on Preparation and Submission of Veterinary Master Files for moreinformation.220221222Both the applicant and the drug substance manufacturer (MF holder) contribute to223establishing and maintaining the identity, strength, quality, purity, and potency of the224applicant's drug products by manufacturing and controlling the drug substance in225accordance with the information submitted in the application and, by reference, in the MF. 226The following recommendations pertain to location of information in the MF and/or227application when an applicant and Type II MF holder are different firms.228229∙General Information (S.110): Both the MF and the application should include this 230information. These sections should contain similar, though not necessarily identical, 231information. For example, if an applicant performed screening studies and232established the existence of multiple polymorphs, information concerning these233polymorphs might be present in the application but not in the MF.234235∙Manufacture (S.2): The application should identify in S.2.1 the manufacturers of 236each drug substance with appropriate administrative information (see section IV.A). 237The MF should include this information for its manufacturing operations and any9 CVM discourages the reference of NDAs or ANDAs for drug substance information. In these instances, CVMrecommends that the drug substance information be included in a master file or incorporated in the applicant’sNADA or ANADA.10 Alphanumeric designations in parentheses that follow headings show where information should be placed inapplications that are submitted in Common Technical Document (CTD) format.238contract facilities that are used (e.g., intermediate manufacturers, laboratories). In239general, a MF can be referenced for the information recommended in S.2.2 through240S.2.6. However, the information should be augmented by the applicant, as241appropriate. For example, if the applicant micronizes drug substance purchased from242a MF holder the information on the micronization process should be included in the243application.244245∙Characterization (S.3): In general, a MF can be referenced for this information.However, the information should be augmented by the applicant, as appropriate. For 246247example, characterization information on physical properties critical to the applicant’s248product, such as solid state form or particle size distribution, should be included in249S.3.1 by the applicant under certain circumstances (e.g., applicant manipulates the250physical property (micronizes), the MF holder has not characterized the physical251property). Furthermore, information on an applicant’s studies to characterizeimpurities (S.3.2) can be warranted to support the applicant’s drug substance controls. 252253254∙Control of Drug Substance (S.4): In general, information recommended in S.4 should be provided in both the MF and the application. However, reference to an MF 255256can be appropriate for some of the information in S.4.2 through S.4.5 if the MF257holder and applicant are working together to develop the drug substance controls.Both the MF and the application should include a drug substance specification (S.4.1). 258259The MF could include more than one drug substance specification if the holder sellsdifferent technical grades of the drug substance (e.g., micronized and nonmicronized). 260261262∙Reference Standards (S.5): In general, information should be provided in both the 263MF and the application. However, reference to a MF can be appropriate for some of264the information if the MF holder and applicant are working together to develop the265reference standard.266267∙Container Closure System (S.6): In general, MFs can be referenced for this268information. However, the information should be augmented by the applicant, as269appropriate.270271∙Stability (S.7): In general, MFs can be referenced for this information. However, the information should be augmented by the applicant, as appropriate. For example, 272273an applicant might perform stress studies to support the analytical procedures it used274to control the drug substance.275276∙Appendices (A): In general, MFs can be referenced for this information. However, 277the information should be augmented by the applicant, as appropriate.278279∙Regional Information (R): Comparability protocols can be included in both the MF 280and application (R.2.S). A methods validation package should be included in theapplication (R.3.S).281282∙Literature References (3.3): Both the MF and the application should include283284literature references as warranted.285Type II MFs for drug substance intermediates can also be submitted in the CTD-Q format. 286287However, not all sections of the CTD-Q format would apply (e.g., S.4). The CMC288information provided to support an intermediate should be appropriate for the particularsituation (e.g., process, complexity of the molecule).289290291III. GENERAL INFORMATION (S.1)292293294General information on the nomenclature, structure, and general properties of the drug substance, should be provided in S.1.295296297A. Nomenclature (S.1.1)298299All appropriate names or designations for the drug substance should be provided in S.1.1. 300Any codes, abbreviations, or nicknames used in the application to identify the drug301substance should also be listed, including the following, if they exist or have been302proposed. A name that has not yet been finalized should be identified as proposed in the 303list.304305∙United States Adopted Name (USAN)∙Compendial name11306307∙Chemical names (e.g., Chemical Abstracts Service (CAS), International Union of 308Pure and Applied Chemistry (IUPAC))∙Company names or laboratory codes309310∙Other nonproprietary names (e.g., International Nonproprietary Name (INN),311British Approved Name (BAN), Japanese Accepted Name (JAN))312∙Chemical Abstracts Service (CAS) Registry Number313314B. Structure (S.1.2)315316Information on the chemical structure of the drug substance should be provided in S.1.2. 317This information should include:318319∙one or more drawings to show the overall chemical structure of the drug substance, 320including stereochemistry321∙molecular formula322∙molecular weight323324For a naturally derived protein drug substance, the information should include:11 A compendial name is a name that appears in an official compendium as defined in the Federal Food, Drug, andCosmetic Act (e.g., United States Pharmacopeia (USP)) (§ 201(j) (21 U.S.C. 32(i)).325326∙the schematic amino acid sequence indicating glycosylation sites or other327posttranslational modifications∙ a general description of the molecule (e.g., shape, disulfide bonds, subunit328329composition)330∙number of amino acid residues331∙molecular weight332333C. General Properties (S.1.3)334A list should be provided of the general physicochemical properties of the drug substance. 335336Other relevant properties of the drug substance should also be listed. Relevant properties 337are those physical, chemical, biological and microbiological attributes relating to theidentity, strength, quality, purity, and/or potency of the drug substance and, as338339appropriate, drug product. The information should include, as appropriate:340341∙ A general description (e.g., appearance, color, physical state)342∙Melting or boiling points343∙Optical rotation344∙Solubility profile (aqueous and nonaqueous, as applicable)345∙Solution pH346∙Partition coefficients347∙Dissociation constants348∙Identification of the physical form (e.g., polymorph, solvate, or hydrate) that will 349be used in the manufacture of the drug product350∙Biological activities351352For a naturally derived protein drug substance, additional information should be included, 353such as:354355∙Isoelectric point356∙Extinction coefficient357∙Any unique spectral characteristics358359If the drug substance can exist in more than one physical form, the information included 360in S.1.3 should be for the form (or forms) of the drug substance that will be used in the 361manufacture of the drug product. Detailed information on the characterization (e.g., X-362ray powder diffraction data, thermal analysis curves) of these and other physical forms 363and conditions required to produce one form or another should be provided in S.3.1.364。

去除内毒素

《纯化——重组蛋白》
■重组蛋白在设计、构建时应已融入纯化构想。样品多夹杂了破碎细胞或溶解产物，扩张柱床吸附技术 STREAMLINE 便很适合做粗分离。 Amersham Biosciences 提供三个快速表达、一步纯化的融合系统。一] GST 融合载体使要表达的蛋白和谷胱甘肽 S 转移酶一起表达，然后利用Glutathione Sepharose 4B 作亲和层析纯化，再利用凝血酶或因子 Xa 切开。二] 蛋白 A 融合载体使要表达的蛋白和蛋白 A 的 IgG 结合部位融合在一起表达，以 IgG Sepharose 6 FF 纯化。三] 含组氨酸标记 (Histidine-tagged) 的融合蛋白可用 Chelating Sepharose FF 螯合 Ni2+ 金属，在一般或变性条件 ( 8M尿素) 下透过组氨酸螯合融合蛋白。 HisTrap 试剂盒提供整套 His-Tag 蛋白的纯化方法。
214500预装柱平均应用特性最高ph价格颗粒稳定性美元mlminmpa工作一chelatingsepharosehighperformance金属螯合预装柱17040801hitrapchelating342303313110cystrp如巨球蛋白干扰素21417040901hitrapchelating34115同上200331310017040903hitrapchelating21453017040905hitrapchelatingml100843017524701histraphp3440mg同上而且ni0331320017524705histraphpml100214305017524901histraphpkit40017524801histraphp34200mg同上而且ni脱落极低动态载量高200331217017524802histraphp21468017524805histraphpml10010740二nhsactivatedsepharosehighperformance活化偶联预装柱17071601hitrapnhsactivated34通过游离氨快速与亲和配体结合0331212017071701hitrapnhsactivated34通过游离氨快速与亲和配体结合2003312120三小配体亲和预装柱17040601hitrapheparinmg纯化抗凝血激酶和别的凝集因子脂蛋白03510120autithrombinlll脂酶蛋白合成因子激素类固醇受体dna结合蛋白干扰素17040701hitrapheparin3415mg小牛atlll同上200351011017518901hitrap1610heparinff9060同上1001541260017511201hitrapstreptavidin300nmolbiotin利用生物素和抗生素的结合作用做亲和层03210530析

抗凝血药Pradaxa的首种逆转剂Praxbind获准上市

据药典及相关文献记载，栀子苷、甘草酸在２３８ｌｌｍ处有较大吸收＿７］．黄芩苷在２７８ｌｌｍ处有最大吸
收＿８］，连翘苷在２３０、２７７ｎｍ处有较大吸收［。本试验采用ＤＡＤ检测器在２００～３６０ｎｍ进行全波长
Ｔａｂｌｅ２Ｄｅｔｅｒｍｉｎａｔｉｏｎｒｅｓｕｈｓｏｆ４ｃｏｎｓｔｉｔｕｅｎｔｓｉｎＬｉａｎｇｇｅ
［８］姚帅，杨跃华，刘岩，等．ＲＰ．ＨＰＬＣ同时测定大卫颗粒中
（ｎ＝６）
组分
样品中加入测得回收平均回ＲＳＤ％
一的量／ｍｇ量／ｍｇ量／ｍｇ率／％收率／％
扫描，重点考察了２３８、２５４、２７８ｌｌｍ３个波长处的吸收情况。结果表明在２５４ｌｌｍ杂峰较多，在２７８１ｑｍ处
参考文献：
［１］许济群．方剂学［Ｍ］．上海：上海科技出版社，１９８５：１９０．
［２］王子接．绛雪园古方选注［Ｍ］．北京］周仕杰，杨宇．凉膈散的临床运用及衍生方浅析［Ｊ］．湖南中医杂志，２０１４，３０（９）：１２２．１２３．
药效的患者。
ＦＤＡ于２０１０年批准Ｐｒａｄａｘａ用于房颤患者预防中风和全身性血液凝固，以及用于深静脉血栓和肺栓塞的治疗和预防。Ｐｒａｘｂｉｎｄ是ＦＤＡ批准的首种针对Ｐｒａｄａｘａ的特定逆转剂，可中和Ｐｒａｄａｘａ的抗凝血作用。Ｐｒａｘｂｉｎｄ和Ｐｒａｄａｘａ都由勃林格殷格翰（ＢｏｅｈｒｉｎｇｅｒＩｎｇｅｌｈｅｉｍ）公司生产和销售。Ｐｒａｄａｘａ为口服胶囊剂，Ｐｒａｘｂｉｎｄ为静脉注射剂。

创新药周报：从辉瑞收购GBT看上半年生物医药“并购热潮”

证券研究报告| 行业周报2022年08月14日医药生物创新药周报：从辉瑞收购GBT看上半年生物医药“并购热潮”一、本周聚焦：辉瑞收购GBT及上半年并购事件回顾8月8日，辉瑞公司（Pfizer）和Global Blood Therapeutics（GBT）宣布，辉瑞将收购GBT公司。

根据交易条款，辉瑞将以总价约54亿美元现金收购GBT公司所有已发行的股票。

让辉瑞溢价收购的GBT公司究竟拥有怎样的“硬实力”？今年上半年生物医药还有哪些重大收购交易发生？本周周报，让我们一探究竟。

Global Blood Therapeutics聚焦血液疾病领域的千里马：公司致力于发现、开发和商业化治疗严重的血液疾病的新疗法，提供治疗镰状细胞病的口服药。

其核心产品Oxbryta（voxelotor）已于2019年上市。

其他在研管线中，Inclacumab是新型的全人源单克隆抗体P-选择素抑制剂，具备成为同类最佳潜质；GBT601具备低剂量下更好疗效潜力，公司在血液疾病领域的未来前景广阔。

核心产品Oxbryta填补镰状细胞病(SCD)治疗空白：辉瑞本次收购的主要目标是GBT及其主要产品Oxbryta（voxelotor），以加强其自身的产品组合和管线，辉瑞的血液学重点是镰状细胞病（SCD）和血友病。

镰状细胞病(SCD) 是一种影响血红蛋白的终生遗传性血液疾病，血红蛋白是一种由红细胞(RBC) 携带的蛋白质，可向全身组织和器官输送氧气。

SCD生存成本高昂，给患者和社会带来重大负担，而GBT公司开发的Oxbryta(voxelotor)是一种直接针对SCD根源的药物。

面对治疗手段匮乏的SCD，voxelotor将面临极具潜力的商业前景。

上半年21起并购交易，生物医药并购热潮来袭：上半年共发生21起并购交易，肿瘤和中枢神经是热门领域，辉瑞和葛兰素史克各进行了两次并购：✓辉瑞116亿美元现金收购Biohaven达成上半年最大规模并购交易；✓首家被中国药企并购的美国上市医药公司：中国生物制药收购F-star；✓再生元溢价335% 2.5亿美元收购Checkmate开启并购之路；✓葛兰素史克33亿美元收购Affinivax加强疫苗快速研发。

诺华制药产品分析

诺华制药产品分析2017~2022H1◼2019年诺华制药剥离了爱尔康(Alcon) 眼科护理业务，因此这里2017年、2018年和2019年内的收入数据均不包含爱尔康的收入部分。

◼从以上图表可见，诺华制药2021年销售收入达516亿美元。

其中，创新药占了81%，销售额达420亿美元，剩余为仿制药及生物类似药（Sandoz）公司的销售收入，为96亿美元。

近5年诺华制药的销售收入年均增长率为5%，除2020年以外，近5年年化增长率在5%以上。

诺华创新药的增长一直拉动整个诺华制药销售收入的增长，诺华创新药近5年来年均增长率将近7%。

而仿制药今年来的销售收入一直处于下降状态，诺华也一直在打算剥离Sandoz。

◼下图为诺华制药创新药的收入按照适应症的构成情况。

◼可见，诺华创新药收入中，血液病和实体瘤领域约占据了30%~40%。

而血液病和实体瘤在所有创新药的占比近年来逐年下降。

免疫肝病和皮肤病、神经学以及心血管肾病和代谢在总创新药收入的占比逐年上升。

眼科也有所收缩。

诺华制药收入类型构成百万美元201720182019202020212022H1创新药32,27834,89237,71439,01341,99520,637仿制药10,0609,8599,7319,6469,6314,675合计42,33844,75147,44548,65951,62625,312占比创新药76.24%77.97%79.49%80.18%81.34%81.53%仿制药23.76%22.03%20.51%19.82%18.66%18.47%增长率创新药8.10%8.09% 3.44%7.64%-1.72%仿制药-2.00%-1.30%-0.87%-0.16%-2.92%总收入增长率 5.70% 6.02% 2.56% 6.10%-1.94%数据来源：诺华制药年报8.10%8.09%3.44%7.64%-1.72%-2.00%-1.30%-0.87%-0.16%-2.92%-4%-2%0%2%4%6%8%10% -5,00010,00015,00020,00025,00030,00035,00040,00045,000201720182019202020212022H1诺华制药收入类型构成创新药仿制药创新药增长率仿制药年增长率诺华创新药收入按适应症划分百万美元201720182019202020212022H1血液病6,4936,7616,9277,7828,3633,770实体瘤5,7816,6677,4436,9297,1133,016免疫、肝病、皮肤病2,4743,3924,2224,8685,7772,995神经学3,2873,4293,7734,3235,0522,610眼科4,6214,5584,7764,4104,3301,356心血管、肾病、代谢5241,0501,7502,4983,5602,254呼吸和感染1,6171,7671,8251,9002,0651,017成熟品牌7,4817,2686,9986,3035,7353,619合计32,27834,89237,71439,01341,99520,637增长率8.10%8.09% 3.44%7.64%-1.72%0%20%40%60%80%100%201720182019202020212022H1诺华创新药收入按适应症划分血液病实体瘤免疫、肝病、皮肤病神经学眼科心血管、肾病、代谢呼吸和感染成熟品牌◼诺华是全球制药领域的头部企业，其产品在全球各地均有销售。

中国目前已通过美国FDA认证的原料药企业汇总

中国目前已通过美国FDA认证的原料药/企业汇总(转)中国目前已通过美国FDA认证的原料药/企业汇总，欢迎大家补充，更新！中国目前已通过美国FDA认证的原料药/企业汇总，希望这些信息能对大家有用.(注：只有DMF号，没有cGMP检查合格批准信的，不在统计范围内只通过欧洲cos认证，但没有通过FDA认证的，也不在统计范围内)序号原料药名称生产商备注1. 强力霉素Deoxycyline 昆山市东方制药厂抗生素2. 强力霉素一水物Deoxycyline Monohydrate 昆山市东方制药厂抗生素3. 盐酸四环素Tetracycline hydrocloride 宁夏启元药业有限公司抗生素4. 盐酸林可霉素Lincomycin hydrochloride 苏州第四制药厂抗生素5. 克林霉素磷酸酯Clindamycin Phosphate 苏州第四制药厂抗生素6. 盐酸克林霉素Clindamycin 重庆凯林制药公司抗生素7. 青霉素钾Penicillin Potassium 江西东风药业股份有限公司抗生素8. 土霉素Oxytetracycline 赤峰制药抗生素9. 盐酸土霉素Oxytetracycline Hydrocloride 赤峰制药抗生素10. 盐酸阿霉素Adriacin Hydrocloride 浙江海正药业股份有限公司抗生素11. 盐酸柔红霉素Daunomycin hydrochloride 浙江海正药业股份有限公司抗生素12. 丝裂霉素Mitomycin 浙江海正药业股份有限公司抗生素13. 妥布霉素碱Tobramycin Base 浙江海正药业股份有限公司抗生素14. 依维菌素Ivermectin 浙江海正药业股份有限公司抗生素15. 硫酸博莱霉素Bleomycin Sulphate 浙江海正药业股份有限公司抗生素16. 氟苷Fluorouracil Deoxyriboside 浙江海正药业股份有限公司抗病毒药,抗肿瘤药17. 异环磷酰胺Ifosfamide 江苏恒瑞医药股份有限公司抗肿瘤药18. 足叶乙甙Etoposide 江苏恒瑞医药股份有限公司抗肿瘤药19. 美司那Mesnaum, Sodium 2-mercaptoethanesulphonate 江苏恒瑞医药股份有限公司抗肿瘤药20. 噻替哌Thiophosphoramide 江苏恒瑞医药股份有限公司抗肿瘤药21. 长春瑞宾酒石酸Vinorelbine tartrate 江苏豪森药业股份有限公司抗肿瘤药22. 金刚烷胺Amantadine 东北制药抗病毒药23. Ramantadine 东北制药抗肿瘤药24. 盐酸左旋咪唑(levamisole hydrochloride) 桂林制药厂抗肿瘤药,驱虫药25. 阿昔洛韦Aciclovir 浙江车头药业有限公司抗病毒药26. 利巴韦林Ribavirin 广东肇庆星湖生物科技股份有限公司星湖生物化学制药厂抗病毒药27. SM2（磺胺二甲嘧啶）西南合成制药股份有限公司抗菌药上海三维制药有限公司北京第二制药厂浙江新赛科药业有限公司28. SM2Na（磺胺二甲嘧啶钠）西南合成制药股份有限公司抗菌药上海三维制药有限公司29. TMP（甲氧苄啶）西南合成制药股份有限公司抗菌药30. SMZ（磺胺甲恶唑sulfamethoxazolum）西南合成制药股份有限公司抗菌药31. SD（磺胺嘧啶sulfadiazine）西南合成制药股份有限公司抗菌药上海三维制药有限公司32. 磺胺喹噁啉Sulfaquinoxaline(SQ), 上海三维制药有限公司抗菌药33. 磺胺喹噁啉钠Sulfaquinoxaline Sodium 上海三维制药有限公司抗菌药34. 磺胺甲基嘧啶钠Sulfamerazine Sodium (SM1-Na) 上海三维制药有限公司抗菌药35. 磺胺噻唑Sulfathiazole 上海三维制药有限公司抗菌药36. 奥美普啉Ormetoprim (OMP), 上海三维制药有限公司抗菌药37. 氟苯尼考Florfenicol (FFC) 上海三维制药有限公司抗菌药38. 酮洛芬Ketoprofen 西南合成制药股份有限公司消炎镇痛药39. 布洛芬Ibuprofen 巨化集团公司制药厂消炎镇痛药新华制药40. 萘普生Naproxen 浙江车头药业有限公司消炎镇痛药41. 保泰松Butylpyridin 上海华氏制药有限公司（十五制药厂）消炎镇痛药42. 重酒石酸去甲肾上腺素Noradrenalini bitartras 武汉武药制药有限公司拟肾上腺素药43. 麻黄素Ephedrini hydrochloride 赤峰制药肾上腺素受体激动剂44. 麻黄浸膏粉Ephedrine Extract powder 赤峰制药肾上腺素受体激动剂45. 氯氮平Clozapine 上海华氏制药有限公司（十五制药厂）安定药广东惠州东江制药厂46. 茶碱Therophylline 新华制药利尿药,心脏兴奋药,平滑肌松弛药47. 布美他尼Bumetanide 桂林制药厂利尿药48. 赖诺普利Lisinopril 浙江华海药业有限公司降压药49. 卡托普利Captopril 山东潍坊制药厂有限公司降压药50. 盐酸二甲双胍Deltamine 上海华氏制药有限公司（十五制药厂）降血糖药51. 维库溴铵Vecuronium 浙江仙居制药股份有限公司肌松药52. 硫糖铝Sucralfate 东北制药抗溃疡抗酸药53. 愈创木酚甘油醚Guaifenesin 天药股份天津新新制药厂止咳化痰药54. 美索巴莫Methocarbamol 天药股份天津新新制药厂止咳化痰药55. 泼尼松Prednisone 天津天药药业股份有限公司糖皮质激素56. 氢化可的松Hydrocortisone 新华制药肾上腺皮质激素类药57. 环孢素（Cyclosporin A）福建科瑞药业有限公司免疫抑制剂58. 盐酸格拉司琼湖北百科药业肿瘤化疗止吐药59. 磷酸氟达拉滨湖北百科药业抗肿瘤药60. 多个品种（不明）乐山三九长征药业股份有限公司抗生素61. 两性霉素B（Amphotericin B）华药集团华胜公司抗生素62. 美托拉宗(Metolazone) 西安力邦制药有限公司利尿、降压药64. 盐酸左旋咪唑(levamisole hydrochloride) 陕西汉江制药厂抗肿瘤药,驱虫药。