15-The Package Insert and Prescription
EUGMP附录15确认与验证-中英文
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Hale Waihona Puke 翻译：武晋娴 校对：陈国笋
Principle 原则 This Annex describes the principles of qualification and validation which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products and may also be used as supplementary optional guidance for active substances without introduction of additional requirements to EudraLex, Volume 4, Part II. It is a GMP requirement that manufacturers control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process. Any planned changes to the facilities, equipment, utilities and processes, which may affect the quality of the product, should be formally documented and the impact on the validated status or control strategy assessed. Computerised systems used for the manufacture of medicinal products should also be validated according to the requirements of Annex 11. The relevant concepts and guidance presented in ICH Q8, Q9, Q10 and Q11 should also be taken into account. 本附录描述了确认和验证的原则，适用于药品生产的设施、设备、公用系统和工艺；也可作 为在欧盟药品法规第四卷第 II 部的未提到的有额外要求的原料药的可选性补充指南。它是 GMP 的要求，要求生产商通过贯穿于药品和工艺的产品生命周期的确认和验证，控制其生 产操作的关键环节。需要正式记录任何可能影响药品质量的设施、设备、公用系统和工艺的 计划性变更，需要评估对于验证状态或控制策略的影响。用于药品生产的计算机化系统应按 照附录 11 的要求进行验证。相关概念和指南参见 ICH Q8，同时参考 Q10 和 Q11。
package+insert
this type of medicine for you, and if so, how much to give and when.
药理作用的常见相关标题
Clinical Pharmacology Clinical Data Clinical Use Clinical Effect Mode of Mechanism of Action Pharmacological Actions Therapeutical Action Toxicology
Package Insert
药品说明书
The information in a package insert follows a standard format for every medication. After some identifying information such as the Brand Name and Generic Name of the product, the following sections appear:
sections
Package inserts for some medicines also include sections such as Drug Interactions, Drug Abuse and Dependence. If matters on Drug Abuse and Dependence are potential problems, and some begin with "Box Warnings," which highlight especially serious (often life-threatening) adverse reactions lifethat have been reported.
药学英译短语
Unit One Vitamins1维生素vitamin2水溶性维生素water-soluble vitamin3脂溶性维生素fat-soluble vitamin4复合维生素compound vitamins5维生素以字母命名V itamins are named by the letters of the alphabet.6预防坏血病的维生素C scurvy –preventing vitamin C7治疗脚气病的维生素B1 vitamin B1 for curing beriberi8维生素A与生长、发育vitamin A and growth and development9维生素A缺乏与眼疾vitamin A deficiency and eye disease10维生素D缺乏与佝偻病lack of vitamin A and rickets11维生素B2与皮肤、眼睛和毛发vitamin B2 and the skin, eye and hair12有机营养物organic nutrients13维生素为生长、健康所必需V itamins are essential for growth and good health14维生素含量高high vitamin content15维生素缺乏症vitamin deficiency syndrome16新鲜水果、蔬菜、蛋、奶、鱼肝油、米糠、豆子、谷类等富含多种维生素Fresh fruits, vegetables, eggs, milk, fish liver oil, rice husks beans, cereals, etc. are rich in vitamins.Unit 3 Anesthetics1麻醉剂和镇静药anesthetic and sedative2针刺麻醉acupuncture anesthesia3在脂肪和水中的溶解度solubility in fats and water4作用于神经having effect on the nerves5物理和化学性质physical and chemical property6对痛不敏感insensitive to pain7无信号通过神经传至大脑No message are transmitted to the brain through nerves8通过呼吸道给麻醉药administration through respiratory tract9注入脊柱射(给药) be injected into spine10麻醉作用anesthetic action11过多地破坏脂肪和神经组织destruction of too much fatty and nerve tissue12不同麻醉剂的不同生理作用varying physiological effects of the different anesthetics13吸入乙醚inhalation of ether14深度松弛deep relaxation15失去知觉，术后恢复知觉loss of consciousness/ unconscious, to regain consciousness afteroperation16无术后恶心症状free from postoperative nauseaUnit 4 How does the human body fight diseases?1肺炎、肺结核pneumonia and tuberculosis2 细菌释放毒素germs giving off a toxin3皮肤和粘膜skin and mucous membranes4炎症inflammation5聚集在感染部位gather at the place of infection6红、肿、热、痛redness, swelling, heat and pain7抗感染fight against infection8吞噬、消化微生物engulf and digest microbes9淋巴管lymph vessels10抗体、抗原antibody and antigen11抗毒素antitoxin12人工免疫artificial immunityUnit 5 Green pharmacy —herbal medicine1绿色药物--草药green pharmacy – herbal medicine2中草药Chinese material medica3中医、中药traditional Chinese medicine and Chinese medic inals4开处方write a prescription5药店销售的处方药、非处方药prescribed drug and OTC drug ( over-the –counter drug) 6心脏病药cardiac drug7止痛药pain killer8抗疟疾药anti-malarial9抗炎药anti-inflammatory drug10标准化的化学药物 a standardized chemical medicine11药物成分medical constituents12病机disease mechanism13疗效therapeutic effect / effect / efficacy14植物药plant-derived drugs15合成的衍生物和变异体synthetic derivatives and variants16植物的生物活性成分biologically-active plant constituents17粉剂、浓缩剂和冲剂power, extract and infusion18分离、提取有效成分isolate and abstract active constituents19高血压、失眠、精神疾病hypertension, insomnia and mental disease20特有的药性characteristic pharmacological properties21民间医学folk medicineUnit Six Introduction to organic chemistry1有机、无机化学organic and inorganic chemistry2物理化学physical chemistry3生物化学biochemistry4化学符号和结构式chemical symbols and formulas5电子、离子、原子、分子electron, iron, atom and molecule6分子量molecular weights7元素周期表periodic table8运用符号和概念的方法methods of manipulating symbols and concepts9化学反应chemical reaction10有机化合物organic compounds11二氧化碳carbon dioxide12含有碳元素的物质substance containing carbon13合成物质synthetic materials14大量的原料abundant raw materials15品质更佳、用途更广、优势独特superior qualities, greater versatility, and unique advantages Lesson 8 Development of New Drugs (I)1生产特效药to produce the novel therapeutic agents2由天然植物资源提取to extract from natural plants and animal sources3化学合成药 a drug synthesized chemically4人工生产药物agents produced artificially5药物的特异作用及毒性specificity of action and toxicity6 基因工程的发展development of genetic engineering7 单克隆抗体monoclonal antibody 8 beta受体阻断剂beta receptor blocker9实验药理学experimental pharmacology10几种模型包括：细胞培养或细菌培养，部分提取酶或亚细胞间质，分离的组织，灌注的器官完整的动物several models include: cell culture or bacteria, partially purified enzymes or subcellular particles, isolated tissues , perfused organs, intact animals11慢性毒性实验chronic toxicity testing 12代谢方法patterns of metabolism13疗程duration of treatment14 实验组、对照组、安慰剂组、空白组、the experimental group ，control group, placebo group and untreated group15 临床指症clinical indication 16 生化药理学biochemical pharmacology17 FDA Food and Drug AdministrationLesson 8 Development of New Drugs (II)1 临床评价clinical evaluation / assessment2 毒理研究toxicological studies3 化学纯度和药物稳定性chemical purity and pharmaceutical stability4 罕见的疾病、威胁生命、不治之症rare diseases, life-threatening and untreatable diseases5 无严重症状与毒性without serious symptoms or toxicity6 药物剂量的研究dose-ranging studies7 施药（给药）drug administration / administration of drugs8 临床试验许可证CTC clinical trial certificate9 单盲或双盲试验single blind or double blind experiment10 副作用adverse effect, side-effect, unhealthy effect11 促销marketing and promotion12 医药代表representative of the pharmaceutical manufacturerUnit 10 Minimum information for sensible use of self-prescribed medicines1最有效地用药use medicine to the best effect2非处方药（自用药）self-prescribed medicine3药品说明书package leaflet, insert, directions4提醒使用者所有可能的有害作用warning the user about all the possible harmful effects5常见的、严重的、罕见的副作用common, serious and rare side-effect6药理学家、临床药剂师pharmacologist and clinical pharmacist7标准的专利名、非专利名standard proprietary names and non-proprietary names8用于缓解轻度疼痛症状for symptomatic relief of minor aches and pains9消炎to relieve inflammation10（止痛）的首选量、推荐量preferred dose or recommended dose for pain11成人剂量的一半one-half adult dose12将药片碾碎或溶于水crush or dissolve tablets in water13如可能，同奶一起服用（用奶送服）或饭后服Take with milk if possible, or after food 14胃不适、烧心、胃出血stomach discomfort, heart burn, stomach bleeding15耳鸣、眩晕ringing in the ears and dizziness药品说明书【药品名称】Drug Name通用名称：Generic Name商品名:Trade Name化学名（Chemical Name）英语名：English Name汉语拼音：Hanyu Pinyin【成份】Composition【性状】Description【功能主治】Actions and Indications／【适应症】Indications【规格】Specification【用法用量】Administration and Dosage【不良反应】Unwanted Effects/ Adverse/ Side Effects【禁忌】Contraindications【注意事项】Warning/ Caution【孕妇及哺乳期妇女用药】 Women in pregnancy and lactation【儿童用药】 Children【老年用药】 The Elderly【药物相互作用】Interaction【临床试验】Clinical Experiment【药理毒理】Pharmacological Toxicology【药代动力学】Pharmacokinetics【贮藏】Storage【包装】Package【有效期】Validity【执行标准】The Implementation of Standards【批准文号】Approval Number【生产企业】Manufacturer企业名称：生产地址：Address邮政编码：Code电话号码：Tel传真号码：Fax注册地址：Registered Address网址：Website中医方剂剂型常用的英译表述如下：1）汤剂 decoction 2) 散剂 powder 3）丸剂 bolus( 大丸), pill（小丸）4）油膏剂 paste, ointment, plaster 流浸膏 liquid extract 浸膏extract 煎膏 decocted paste 软膏 ointment, paste 硬膏 plaster 5）药露 syrup 6）锭剂 troche, lozenge 7）糖浆剂 syrup8）片剂 tablet 9）冲服剂 granule 10）针剂 injection 11）栓剂 suppository Lesson 11 The Scope of Pharmacology1 药物的物化性质physical and chemical properties2 化合及生化生理作用compounding, biochemical and physical effects3 作用机理mechanism of action4 具有广博的植物学知识have a broad botanical knowledge5 药物制剂medicinal preparation6 生药学，药理学pharmacognosy, pharmacology7 剂型dosage form8药物动力学研究药物吸收、分布、生化和排泄。
临床药学导论各章复习思考题
2015年秋季学期，“临床药学导论〞各章复习思考题汇总第一章绪论〔蒋学华〕名词解释：1、临床药学〔clinical pharmacy〕2、临床药师〔clinical pharmacist〕3、合理用药〔rational administration of drug〕4、药学监护〔pharmaceutical care，PC 〕5、个体化用药〔personalized medicine/individualized medication〕6、临床药学思维〔clinical pharmaceutical thinking〕……简答：1、临床药学学科的特点；2、临床药师的职业特点；3、怎样理解合理用药的相对性.……第二章药学与药品〔自学〕名词解释：1、药品〔drugs，medicine〕2、处方药〔prescription drugs 〕3、非处方药〔nonprescription drugs, over the counter, OTC〕4、药学〔pharmacy〕……简答：1、简述药品及药品的特殊性。
2、简述临床药学与药学的相互关系。
3、药品上市的过程有哪些根本环节.4、药学学科体系包括哪些二级学科.……第三章疾病与临床〔周静〕名词解释：1、疾病〔disease〕2、安康〔health〕3、亚安康 (sub-health)4、病因〔cause of disease〕……简答：1、常见疾病的病因……第四章医疗机构药品应用管理〔蒋学华〕名词解释：1、医疗机构药事管理〔Institutional pharmacy administration)2、处方〔Prescription〕3、药品说明书〔Package Insert/ Instructons/ Directions/Descriiption/ Leeflet/Data Sheets〕……简答：1、请简单描述药事管理与药物治疗学委员会〔组〕的组成与职责。
药品说明书、标签管理规定的英文翻译
Administrative Regulation for Insert and packaging Labels of drug(SFDA Order No.24)State Food and Drug Administration OrderNo.24“Administrative Regulation for Insert and packaging Labels of Drug” had been evaluated & agreed by the management meeting of SFDA by Mar.10, 2006, and publish here, the same to be implemented since June 1st, 2006.SFDA Director: Shao Ming LiMar. 15, 2006 Administrative Regulation for the Insert and Packaging Labels of DrugSection I General rulesNo.1 For standardizing the administration for the insert and packaging labels of drug on the basis of “Drug Administration law of the P. R. of China” and “Regulations for Implementation of the Drug Administration Law of the P. R. of China”.No.2 Relevant inserts and packaging labels for all the drugs which are sold in china to be in line with the requirements from present regulation.No.3 The Inserts and packaging labels of drugs should be approved by SFDA.The packaging labels of drugs to be drafted as per the insert, their text should not exceed the range of insert, and should not contain the character and mark which suggests the efficacy, mislead uses and unsuitable publicity the product.No.4 The label should be printed or stickled on the package for drug as per relevant regulations, and can’t carry any other character, audiovisual, or material for introduction or publication propaganda for product and / or manufacturer.The smallest pack sold in market from the pharmaceutical manufacturer should contain insert.No.5 The text expression for drug’s insert and labels should be scientific, standard and accurate.The text expression for the insert for OTC drug should be easy for understanding for the patients whom could be able to self judges, selects and uses.No.6 The text of drug’s insert and labels should be clear and easy to be differentiated, the mark should be clear and striking, the appearance with dropping words or unstick etc. should not appear, and can't be modified or supplemented by sticking, cutting or altering.No.7 The standard Ch. Character published by State Spoken and Written Language Committee should be used for the insert and labels of drug, the Ch. Character expression will be the criterion when has additional other language for reference.No.8 For the purpose of protecting the public health and guiding the drug to be used by a right and rational way, the pharmaceutical manufacturer may raises forwardly to add the warnings on the drug’s insert or labels, SFDA also may require relevant pharmaceutical manufacturer to add the warnings on the insert or labels.Section II Drug’s insertNo.9 Drug’s insert should contain the important and scientific data, results and information about the safety and efficacy of drug, so that can be able to guide the safe and rational uses of drug.The detail format, contents and written requirement for drug’s insert are drafted and issued by SFDA.No.10 The expression of the disease names, pharmaceutical specialized nouns, drug name, clinical test names and results in the drug’s insert should use the special and standard vocabulary or that one issued by state, and the weights and measures to be in line with the requirements of national standard.No.11 All the APIs or crude drugs in the formula to be listed in the drug’s insert. All the excipients for the injection and OTC drugs are also to be listed in the insert.That’s to be indicated if the formula contains the ingredient(s) or excipient(s) which may cause a serious adverse reaction.No.12 The pharmaceutical manufacturer should track forwardly the safety and efficacy status of drug post market, and should raise the application in time for the modification of drug’s insert if necessary.According to the monitor results for the adverse reactions of drug and the re-evaluation of drug, SFDA also may require the pharmaceutical manufacturer to modify the drug’s insert. No.13 The pharmaceutical manufacturer should inform the modified contents to relevant pharmaceutical business companies, used units and the concerned depts. immediately after the modified insert was approved, and implement the modified insert and labels in time as per the requirements.No.14 Drug’s insert should contain enough information of adverse reactions of drug, and indicate the adverse reactions in detail. If the pharmaceutical manufacturer had not modified the insert in time on the basis of the safety and efficacy status of drug post market or didn’t indicate enough the adverse reactions of drug in the insert, the harmful result caused to be borne by relevant manufacturer.No.15 The approval date and revised date of drug’s insert to be indicated clearly in the insert.Section III Labels of drugNo.16 The labels of drug refer to the contents which are printed or pasted in the package of drug, it divides into internal label or outer label. The internal label refers to that label used for immediate pack, and the outer label refers to that labels used for other packs except internal label.No.17 The internal label of drug should contain the contents of generic name, indications or efficacy, strength, dosage and administration of drug, mfg date, batch No. expiry date, manufacturer etc.If the pack size is too small and can’t be able to cover all the contents above, at least, that contents of generic name of drug, strength, batch No., expiry date etc. should be indicated. No.18 The outer label of drug should indicate the contents of the generic name of drug, ingredient(s), description, indications or efficacy, strength, dosage and administration, adverse reactions, contraindication, warnings & precautions, storage, mfg date, batch No.permission No., manufacturer etc. If the full contents of indications or efficacy, dosage and administration, adverse reactions, contraindication and warnings & precautions can’t be able to be covered, then the major contents to be indicated and note “that details are exhibited in the insert”.No.19 Shipper label should indicate the necessary contents of the generic name of drug, strength, storage, mfg date, batch No., expiry date, permission No., manufacturer etc., also may indicate the package quantity and transport warnings and other mark if necessary.No.20 The label for API should indicate the necessary contents of drug name, storage, mfg date, batch No., expiry date, specification No., permission No., manufacturer etc., and also indicate the pack side and the transport warnings.No.21 For the same drug with same strength and pack size from the same pharmaceutical manufacturer, the text, format and color of the label to be same, for the different strength or pack size, the label should be clearly different or the strength to be indicated clearly.The same drug from the same pharmaceutical manufacturer which is administered for prescription drug as well as OTC drug, the color for both packages should be clearly distinguished respectively.No.22 For the drug which storage has special requirement, the storage to be indicated in a striking place of the label.No.23 The expiry date in the label of drug should be labeled as per the sequence of year-month-date, the year is expressed as 4 numerals, the month and the date is expressed as 2 numerals respectively. The detail format is labeled as expiry by “XXXX year XX month” or “expiry by XXXX year XX month XX date”, also may be labeled as “expiry by XXXX.XX.”or “expiry by XXXX/XX/XX” etc. with the numeral or other symbol.The expiry period for preventative biological products should be labeled as per the SFDA approval specification. For the biological products for treatment, the expiry period to be counted since the repackaging date, but for other drugs, that to be counted since mfg. Date.If the expiry period is labeled up to the date, then the expiry date should be the previous date corresponding the year-month-date against the initial date. If the expiry period is labeled up to the month, then the expiry date should be the previous month corresponding the year-month against the initial date.Section IV Use of drug name and registered trademarkNo.24 The drug name labeled in the insert and labels should be in line with the nominated principle for drug generic name and brand name which is issued by SFDA, and identical with the approval certificate.No.25 The generic name of drug should be notable and outstanding, its font, size and color should be accordant, and in line with the requirements below:(1)For the horizontal label, the generic name of drug should be exhibited within the upperthird area at a marked place.For the standing label, the generic name of drug should be exhibited within the third areaof right at a marked place.(2)The font which is not easy to be identified, i.e. grass hand, seal character can’t beselected, and the font can’t be modified with italic, central emptily, hatching forms etc.(3)The color of font should be black or white, to produce a strong contrast against the tintor dark background.(4)The generic name can’t be written in different rows except the pack size is too small andthe full name can’t be exhibited.No.26 The brand name can’t be set in the same row with the generic name, the font and color of brand name is not more extrusive and distinct than the generic name, the area of single font is not more than the half area of the font of generic name.No.27 The trademark which is not registered and other drug name which is not approved by SFDA are inhibitive to be used for the insert and labels of drug.The registered trademark which is used for drug label should be printed in the side cornerof drug label, if it contains the character, then the area of single font is not more than thequadrant area of the generic name.Section V Other regulationNo.28 For the anaesthetic, psychoactive, medical toxicity drug, radioactive drug and the drug for exterior use and OTC etc. which has special mark issued by state, their inserts and labelsshould print the special mark. The insert and labels which have special requirement will be identified by SFDA.No.29 The administrative regulation for the labels of crude Chinese traditional medicine or dry pieces will be drafted by SFDA by supplementary document.No.30 The insert and labels of drug which didn’t complied with this regulation to be punished as per relevant requirements Drug Administration law of the P. R. of China.Section VI Supplementary articlesNo.31 This regulation will be implemented since June 01, 2006. The SFDA Order No.23 issued by Oct 15, 2000 will be disused synchronously.。
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。
how to read a package insert
Dosage form
For example: capsules, tablets, liquid The way it is administered (for example, pill, shot, cream) Pharmacological or therapeutic class (for example, antibiotic, pain reliever, antidepressant)
For example
Generic Name: paracetamol Trade Name: Acetaminophen/ 扑热息 百服宁/必理通 泰诺/泰诺林 痛/百服宁 必理通 泰诺 泰诺林 百服宁 必理通/泰诺 泰诺林 Chemical Name: N-(4-hydroxyphenyl) acetamide Empirical formula: C8H9NO2 Molecular weight: 151
Overdosage
This section describes the signs, symptoms and laboratory findings associated with an overdosage of the drug, as well as complications that can occur with it.
Chemical name of the drug Other --important chemical or physical information, if appropriate
Clinical Pharmacology ----Clinical pharmacology refers to the
Indications and Usage This section contains information about the treatment of the particular diagnosis or diagnoses for which the FDA has approved the drug.
Package Insert
肌肉注射后30-60分钟之间妥布霉素的平 均血药浓度达到峰值。
2. Therapeutically, ATP injection exhibits effects, especially such as activation of the function and metabolism of the nerve, and also coronary and peripheral vasodilation to increase the blood stream.
solution
tablets
溶液
片剂
gas
molecular formular molecular weight
气体
分子式 分子量
derivative 衍生物
liquid powder
液体 粉末
solid injection
固体 注射剂
4.药理作用（Pharmacological Actions)
药品说明书 (package insert)
英文药品说明书包含的项目，也是从简
到繁，昔日药品说明书不过三四项内容 （药名，成分，适应症，剂量用法）， 现在美国FDA规定为十项，但实际项目 已经远远超过十项。
比如：
1. Animal Pharmacology and Animal
Toxicology
（二）常用给药途径
orally
intramuscularly intravenously sublingually subcutaneously intragluteally Intraarterially
口服给药
肌肉注射 静脉注射 舌下给药 皮下给药
by mouth(os)
The Package Insert and Prescription Y的副本 [自动保存]
![The Package Insert and Prescription Y的副本 [自动保存]](https://img.taocdn.com/s3/m/25714312804d2b160b4ec0a2.png)
在儿科用药实践中，没有得到FDA核准为安全有效的儿童药物每 天都在使用。这是部分缘由这样—个现实：自1962年以来进入市 场的许多药在药品说明书中都有“孤儿条款”，比如：“不可用 于儿童，因为没有足够的临床研究可以提供该人群使用建议”。
➢ pediatrics
儿科
What is the status of the package insert? Is it a legal directive to the physician, or is it intended as a guide for the physician in prescribing a drug?
he must be prepared to defend his position in
court if there is a malpractice suit.
但是一旦他无视药品说明书中的说明用药而出现了不 良反应，他就必须做好准备应付法庭诉讼，辩护是否 存在医疗事故。
➢ deviate v. 偏离；脱离 n. 叛离者；偏差；不正常的人或物 adj. 离经叛道的
The information it contains is derived from data supplied by investigators and submitted by the pharmaceutical firm to the FDA.
根握《联邦食品药物化妆品法案》的法律定义，药 品说明书是药品正式的信息文献。它包含的信息来 自审查人员提供的、医药公司提交给FDA的数据。
National Academy of Sciences-National Research
Council, the FDA is now requiring revision of these
Package Insert
肌注后约30~60分钟之间妥布霉素的平均血药浓度达到
高峰。
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三、药理作用
例2. Halcion（海乐神，好而睡） is a potent shortacting hypnotic agent, which produces its hypnotic activity from the first night of administration.
（1）音译：Tamoxifin它莫西芬, Amikacin 阿米卡星 （2）意译：cholic Acid 胆酸，Tetracyline四环素 （3）音意合译：Coumadin香豆定；Neo-Octin新渥克丁 （4）谐音译意：Antrenyl安胃灵；Doriden多睡丹 （5）化学名称的翻译
| Page 7
5.2 本项常用词及短语 1）孕妇、妊娠期或哺乳期，幼童等 pregnant woman 孕妇 lactation 哺乳期 in pregnancy 妊娠期 children under …years of age …岁以下儿童
the first trimester (3 months) of pregnancy 妊娠期的最
起的感染。
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五、禁忌症
5.1 常用标题 Restrictions on Use 限制使用 Contraindications 禁忌症
Precautions (Note) 注意事项
Warning 警告
Pregnancy and Lactation 妊娠与哺乳
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五、禁忌症
| Page 2
一、药品名称
| Page 3
R：表示该产品已经本国的有关部门核准，取得了此 项专用的注册商标
瓜蒌皮注射液安全性再评价
白内障诊疗流程
白内障诊疗流程Cataracts are a common eye condition that affects many people as they age. It can cause blurry vision, difficulty seeing in dim light, and trouble with glare from lights. When diagnosed with cataracts, the first step is to consult with an ophthalmologist for a comprehensive eye exam.这是一个常见的眼睛疾病，随着年龄的增长会影响许多人，容易导致视力模糊，夜间视力困难以及对光照耀的敏感。
诊断出患有白内障后，第一步是咨询眼科医生进行全面的眼睛检查。
During the examination, the ophthalmologist will assess the severityof the cataracts and determine if surgery is necessary. Cataract surgery is the most effective treatment for cataracts and involves removing the cloudy lens and replacing it with an artificial lens.手术后，眼科医生会评估白内障的严重程度，并确定是否需要手术治疗。
白内障手术是最有效的治疗方法，包括去除浑浊的晶状体，并替换成人工晶状体。
The preoperative assessment includes measuring the shape and size of the eye, as well as determining the power of the intraocular lens that will be implanted during surgery. Patients will also undergo a series of tests to ensure they are healthy enough for surgery and toidentify any other eye conditions that may affect the outcome.术前评估包括测量眼睛的形状和大小，确定手术期间将植入的人工晶状体的度数。
Hemophilia 产品 - 斐尔氏血小板因子：Vonvendi（滴入性）说明书
Hemophilia Products – von Willebrand Factor:Vonvendi®(Intravenous)Document Number: IC-0344 Last Review Date: 03/01/2022Date of Origin: 12/16/2014Dates Reviewed: 12/2014, 04/2015, 05/2015, 09/2015, 12/2015, 03/2016, 06/2016, 12/2016, 06/2017, 09/2017, 11/2017, 11/2018, 03/2019, 10/2019, 02/2020, 06/2021, 03/2022I.Length of AuthorizationUnless otherwise specified*, the initial authorization will be provided for 3 months and may be renewed.Note: The cumulative amount of medication the patient has on-hand will be taken into account for authorizations.Up to 5 ‘on-hand’ doses for the treatment of acute bleeding episodes will be permitted at the time of the authorization request.*Initial and renewal authorization periods may vary by specific covered indicationII.Dosing LimitsA.Quantity Limit (max daily dose) [NDC Unit]:−Vonvendi 450-850 units: 82 vials per 90-day supply−Vonvendi 900-1700 units: 41 vials per 90-day supplyB.Max Units (per dose and over time) [HCPCS Unit]:−36,800 billable units per 90 day supplyIII.Initial Approval Criteria 1-3Coverage is provided in the following conditions:•Patient is at least 18 years of age; ANDVon Willebrand Disease (v WD) †•Diagnosis of von Willebrand disease has been confirmed by blood coagulation and von Willebrand factor testing; ANDo Used for the treatment of spontaneous and trauma-induced bleeding episodes in at least one of the following:▪Patient has severe vWD▪Patient has mild or moderate vWD and the use of desmopressin is known orsuspected to be ineffective or contraindicated▪Used for perioperative management of bleeding (Note: Authorizations valid for 1 month); ORo Used for routine prophylaxis to reduce the frequency of bleeding episodes; AND▪Patient has severe Type 3 vWD and is receiving on-demand therapy†FDA Approved Indication(s); ‡ Compendia recommended Indication(s); Ф Orphan DrugIV.Dispensing Requirements for Rendering Providers (Hemophilia Management Program) −Prescriptions cannot be filled without an expressed need from the patient, caregiver or prescribing practitioner. Auto-filling is not allowed.−Monthly, rendering provider must submit for authorization of dispensing quantity before delivering factor product. Information submitted must include:▪Original prescription information, requested amount to be dispensed, vial sizes available to be ordered from the manufacturer, and patient clinical history(including patient product inventory and bleed history)▪Factor dose should not exceed +1% of the prescribed dose and a maximum of three vials may be dispensed per dose. If unable to provide factor dosing within therequired threshold, below the required threshold, the lowest possible dose able to beachieved above +1% should be dispensed.Prescribed dose should not be increased tomeet assay management requirements.−The cumulative amount of medication(s) the patient has on-hand should be taken into account when dispensing factor product. Patients should not have more than 5 extra doseson-hand for the treatment of acute bleeding episodes.−Dispensing requirements for renderings providers are a part of the hemophilia management program. This information is not meant to replace clinical decision makingwhen initiating or modifying medication therapy and should only be used as a guide.V.Renewal Criteria 1-3Coverage may be renewed based upon the following criteria:•Patient continues to meet the indication-specific relevant criteria identified in section III;AND•Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: symptoms of allergic-anaphylactic reactions (anaphylaxis, dyspnea, rash, etc.),thromboembolic events (thromboembolism, pulmonary embolism), development ofneutralizing antibodies (inhibitors), etc.; AND•Any increases in dose must be supported by an acceptable clinical rationale (i.e., weight gain, half-life study results, increase in breakthrough bleeding when patient is fullyadherent to therapy, etc.); AND•The cumulative amount of medication(s) the patient has on-hand will be taken into account when authorizing. The authorization will allow up to 5 doses on-hand for the treatment ofacute bleeding episodes as needed for the duration of the authorization; AND Treatment of acute bleeding episodes/Treatment of spontaneous and trauma-induced bleeding episodes/On-demand treatment of bleeding episodes/Routine prophylaxis to prevent or reduce the frequency of bleeding episodes•Renewals will be approved for a 6 month authorization periodVI.Dosage/Administration 1-3VII.Billing Code/Availability InformationHCPCS Code & NDC(s):VIII.References1.Vonvendi [package insert]. Lexington, MA; Baxalta US Inc.; January 2022. AccessedFebruary 2022.2.MASAC Recommendations Concerning Products Licensed For The Treatment OfHemophilia And Other Bleeding Disorders. 2016 National Hemophilia Foundation.MASAC Document #249; October 2016. Available at: . AccessedJanuary 2019.3.Guidelines for the Management of Hemophilia. 2nd Edition. World Federation ofHemophilia. 2013. Available at: https:///publication/files/pdf-1472.pdf.Accessed January 2019.4.Annual Review of Factor Replacement Products. Oklahoma Health Care Authority ReviewBoard. Updated April 2016. Access January 2019.5.Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obesepatient. Haemophilia. 2014 Mar;20(2):226-9.6.Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products.Haemophilia. 2015 May;21(3):285-8.7.Mingot-Castellano, et al. Application of Pharmacokinetics Programs in Optimization ofHaemostatic Treatment in Severe Hemophilia a Patients: Changes in Consumption,Clinical Outcomes and Quality of Life. Blood. 2014 December; 124 (21).8.MASAC Recommendation Concerning Prophylaxis. 2016 National Hemophilia Foundation.MASAC Document #241; February 2016. Available at: .Accessed January 2019.9.MASAC Recommendations Regarding the Treatment of von Willebrand Disease. MASACDocument #266; March 2021. Available at: 266.pdf (). Accessed April 2021.10.Connell NT, Flood VH, Brignardello-Petersen R, et al. ASH ISTH NHF WFH 2021guidelines on the management of von Willebrand disease. Blood Advances, Volume 5, Issue1, 2021, Pages 301-325, https:///10.1182/bloodadvances.2020003264.11.Franchini M, Seidizadeh, Mannucci P, et al. Prophylactic management of patients with vonWillebrand disease. Ther Adv Hematol. 2021; 12: 20406207211064064. Published online2021 Dec 22. doi: 10.1177/2040620721106406412.First Coast Service Options, Inc. Local Coverage Article: Billing and Coding: HemophiliaClotting Factors (A56482). Centers for Medicare & Medicaid Services Inc. Updated on02/05/2021 with effective date 01/01/2021. Accessed February 2022.13.Palmetto GBA. Local Coverage Article: Billing and Coding: Guidance for Anti-InhibitorCoagulant Complex (AICC) National Coverage Determination (NCD) 110.3 (A56065).Centers for Medicare & Medicaid Services Inc. Updated on 02/01/2021 with effective date 01/01/2021. Accessed February 2022.14.Novitas Solutions, Inc. Local Coverage Article: Billing and Coding: Hemophilia FactorProducts (A56433). Centers for Medicare & Medicaid Services Inc. Updated on 05/07/2021 with effective date 04/08/2021. Accessed February 2022.Appendix 1 – Covered Diagnosis CodesAppendix 2 – Centers for Medicare and Medicaid Services (CMS)Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Articles (LCAs) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: https:///medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCA/LCD):。
15-ThePackageInsertandPrescription
15-ThePackageInsertandPrescriptionIn 1937, sulfanilamide, the first sulfa antimicrobial drug, was marketed. The diluent for this sulfa preparation wasdiethylene glycol, a chemical analog of antifreeze. More than 100 people, many of whom were children, died after receiving the drug. As a result, the US Congress enacted the 1938 Federal Food, Drug and Cosmetic Act, which required proof of safetybefore the introduction of a new drug into clinical practice. This act also changed the focus of the FDA from a policing agency, with an emphasis on confiscation of adulterated drugs, to a regulatory agency supervising the evaluation of new drugs.In the practice of pediatrics, drugs which are not approved by the Food and Drug Administration (FDA) as safe and effective in children are prescribed daily. This is due in part to the fact that many drugs released since 1962 carry an “orphaning clause” in the package insert such as, “not to be used in children, since clinical studies have beeninsufficient to establish recommendations for its use.” What is the status of the package insert? Is it a legal directive to the physician, or is it intended as a guide for the physician in prescribing a drug?The package insert, by legal definition of the Federal Food, Drug and Cosmetic Act, is the official information piece for a drug. The information it contains is derived from data supplied by investigators and submitted by the pharmaceutical firm to the FDA. The insert is written and printed by the drug manufacturer, but its contents must be approved by the FDA.The Food, Drug and Cosmetic Act, as amended in 1962, requires full disclosure of all known facts pertaining to the use of the drug. Therefore, a great deal of information is included in the insert, including the chemical structure of the drug, a summary of its pharmacological and toxicological action, its clinical indications and contraindications, precautions, reported adverse reactions, dosage recommendations, and available dosage forms.Many drugs have package inserts approved by the FDA before the Drug Amendments of 1962 when manufacturers were requiredto show the safety but not the effectiveness of their products. On the basis of evaluations of the efficacy of these older drugs by panels of experts selected by the National Academy of Sciences-National Research Council, the FDA is now requiring revision of these package inserts to eliminate unsupported claims and thus to make them more useful to the practitioner.Is the pediatrician breaking the law when he prescribes drugs for his patients which carry the “orphaning clause?” No, he is not. The physician may exercise his professional judgment in the use of any drug. However, if he deviates from theinstructions in the package insert and adverse reactions occur, he must be prepared to defend his position in court if there is a malpractice suit.Many drugs are used by clinicians in the treatment of conditi ons not listed in the package insert. The FDA cannot requirea pharmaceutical firm to include a new use for the drug product in the insert even if it has been clinically tested and founduseful for a given problem. Economic considerations are among a number of factors that may influence such a policy on thepart of the company. If a new use for a drug is not yet included in the package insert, the manufacturer cannot advertisehis product for that particular use. The package insert is legally binding on the manufacturer in limiting the conditions under which he can promote the use of the drug.Another fact not generally recognized is that a physician’s failure to use a drug approved as effective treatment for a specific disease might be construed as malpractice. In regard to this, it is important that the physician be informed about the availability of the drug and bases his decision to use it or not to use it on rational grounds. It would be unlikely that information taken from the package insert could be used successfully as evidence against the physician in a liability suit.The dilemma facing the physician is illustrated by imipramine (Tofranil) when used in the treatment of enuresis. In 1965a controlled study was published showing that this drug was useful in “training enuretic children to be dry.” Its mechanism of action was not defined, but it appeared to be effective when given to children between the age of 5 and 12 years in a dosage up to 50 mg at bedtime. Following publication of this paper, imipramine became widely used for the treatment of enuresis. A straw poll of 15 pediatricians in the Cleveland area showed that 12 had prescribed imipramine for this condition.When one examines the package insert supplied with imipramine, two points are clear: (1) the treatment of enuresis isnotlisted under conditions for the use of this drug; and (2) there is a clear statement that the drug is not recommended for use in patients under 12 years of age. If a severe reaction occurred and litigation followed, how would a court react if a physician admitted to the use of this drug for the treatment of enuresis in view of the prohibitions in the package insert?Possibly, if other physicians made themselves available to give expert medical testimony and if other physicians in the community used the drug for this purpose, would the published clinical study, plus the physician’s judgment in prescribingthe drug, suffice?The purpose of the FDA control of the package insert is not to legislate for the practice of medicine. As in the past, the physician is the individual prescribing the drug. The fact that he followed the recommendations in the package insert does not absolve him from responsibility for harm resulting to his patient, nor does failure to follow the recommendations in the package insert necessarily render him legally culpable.The statements made in the package insertand approved by the FDA are not in themselves legally binding on the physicianin his practice of medicine. Furthermore, no physician should rely on the package insert as his sole source of druginformation. Drug dosages, as given in the insert, are guides for instituting therapy. The dose may have to be increased or decreased, depending on the patient’s response. And, each time a drug is used, the question of benefit versus risk to the patient must be considered.American Academy of Pediatrics Committee on Drugs has taken the view that the insert should be viewed as a useful guide to the physician; its recommendations should be judged on an equal footing with other publications and research reports. Thepackage insert contains useful information, but the physician’s decision on therapy should be based on cumulative knowledgederived from many sources. When sound scientific data exist which have shown that a drug is reasonably safe and effective in the treatment of a specific disease in adults, it should not necessarily be withheld from a sick child with the same disease just because its use has not been studied in children. However, if used under these circumstances the physician should becautious and the use of the drug should be reported to the manufacturer, FDA, or in the medical literature to add to the knowledge concerning such use. The foregoing situation must be distinguished from use of the drug when the package insertstates that the drug is contraindicated in infants or children on the basis of studies showing it to be unsafe or ineffective in these age groups.The Committee feels that the pediatrician is likely to ignore the “orphan clause” in the insert if, in his judgment, his patient requires a particular medication for optimal treatment. Whether or not this places him in unusual legal jeopardyis a question not yet resolved by the courts. It is the opinion of the Committee that this practice should not be a problemif the physician is well informed on the pharmacology and toxicology of the drugs he uses and closely follows his patient’s response to treatment.Changing the directives in the package insert, except to disclose pertinent new data, will not solve the problem of “therapeutic orphans.” Echoing Dr. Harry Shirkey’s stand, the Committee believes that the ultimate solution requires the development of programs in pediatric clinical pharmacology to ensure that all drugs used in infants and children are adequately tested for safety and efficacy.According to an FDA poll, the majority of physicians use the package insert compiled in the “Physicians Desk Reference”.To them,1. “Labeling s hall contain the essential scientific information needed for the safe and effective use of the drug.2. Labeling shall be informative and accurate without being promotional, false, or misleading.3. The labeling shall be based on data providing substantial evidence of safety and effectiveness.”Today, the FDA’s regulatory scope and authority include ensuring the safety and purity of foods, drugs, medical devices, nutritional supplements, vaccines, and cosmetics. Of particular concern to the anesthesiologist is the timely access to drugevaluation, pharmacologic and medical device data. With the dramatic upsurge in the number of new prescription drugs and over-the-counter supplements, the need for up-to-date drug information has never been more crucial.。
药品说明书、标签管理规定的英文翻译
Administrative Regulation for Insert and packaging Labels of drug(SFDA Order No.24)State Food and Drug Administration OrderNo.24“Administrative Regulation for Insert and packaging Labels of Drug” had been evaluated & agreed by the management meeting of SFDA by Mar.10, 2006, and publish here, the same to be implemented since June 1st, 2006.SFDA Director: Shao Ming LiMar. 15, 2006 Administrative Regulation for the Insert and Packaging Labels of DrugSection I General rulesNo.1 For standardizing the administration for the insert and packaging labels of drug on the basis of “Drug Administration law of the P. R. of China” and “Regulations for Implementation of the Drug Administration Law of the P. R. of China”.No.2 Relevant inserts and packaging labels for all the drugs which are sold in china to be in line with the requirements from present regulation.No.3 The Inserts and packaging labels of drugs should be approved by SFDA.The packaging labels of drugs to be drafted as per the insert, their text should not exceed the range of insert, and should not contain the character and mark which suggests the efficacy, mislead uses and unsuitable publicity the product.No.4 The label should be printed or stickled on the package for drug as per relevant regulations, and can’t carry any other character, audiovisual, or material for introduction or publication propaganda for product and / or manufacturer.The smallest pack sold in market from the pharmaceutical manufacturer should contain insert.No.5 The text expression for drug’s insert and labels should be scientific, standard and accurate.The text expression for the insert for OTC drug should be easy for understanding for the patients whom could be able to self judges, selects and uses.No.6 The text of drug’s insert and labels should be clear and easy to be differentiated, the mark should be clear and striking, the appearance with dropping words or unstick etc. should not appear, and can't be modified or supplemented by sticking, cutting or altering.No.7 The standard Ch. Character published by State Spoken and Written Language Committee should be used for the insert and labels of drug, the Ch. Character expression will be the criterion when has additional other language for reference.No.8 For the purpose of protecting the public health and guiding the drug to be used by a right and rational way, the pharmaceutical manufacturer may raises forwardly to add the warnings on the drug’s insert or labels, SFDA also may require relevant pharmaceutical manufacturer to add the warnings on the insert or labels.Section II Drug’s insertNo.9 Drug’s insert should contain the important and scientific data, results and information about the safety and efficacy of drug, so that can be able to guide the safe and rational uses of drug.The detail format, contents and written requirement for drug’s insert are drafted and issued by SFDA.No.10 The expression of the disease names, pharmaceutical specialized nouns, drug name, clinical test names and results in the drug’s insert should use the special and standard vocabulary or that one issued by state, and the weights and measures to be in line with the requirements of national standard.No.11 All the APIs or crude drugs in the formula to be listed in the drug’s insert. All the excipients for the injection and OTC drugs are also to be listed in the insert.That’s to be indicated if the formula contains the ingredient(s) or excipient(s) which may cause a serious adverse reaction.No.12 The pharmaceutical manufacturer should track forwardly the safety and efficacy status of drug post market, and should raise the application in time for the modification of drug’s insert if necessary.According to the monitor results for the adverse reactions of drug and the re-evaluation of drug, SFDA also may require the pharmaceutical manufacturer to modify the drug’s insert. No.13 The pharmaceutical manufacturer should inform the modified contents to relevant pharmaceutical business companies, used units and the concerned depts. immediately after the modified insert was approved, and implement the modified insert and labels in time as per the requirements.No.14 Drug’s insert should contain enough information of adverse reactions of drug, and indicate the adverse reactions in detail. If the pharmaceutical manufacturer had not modified the insert in time on the basis of the safety and efficacy status of drug post market or didn’t indicate enough the adverse reactions of drug in the insert, the harmful result caused to be borne by relevant manufacturer.No.15 The approval date and revised date of drug’s insert to be indicated clearly in the insert.Section III Labels of drugNo.16 The labels of drug refer to the contents which are printed or pasted in the package of drug, it divides into internal label or outer label. The internal label refers to that label used for immediate pack, and the outer label refers to that labels used for other packs except internal label.No.17 The internal label of drug should contain the contents of generic name, indications or efficacy, strength, dosage and administration of drug, mfg date, batch No. expiry date, manufacturer etc.If the pack size is too small and can’t be able to cover all the contents above, at least, that contents of generic name of drug, strength, batch No., expiry date etc. should be indicated. No.18 The outer label of drug should indicate the contents of the generic name of drug, ingredient(s), description, indications or efficacy, strength, dosage and administration, adverse reactions, contraindication, warnings & precautions, storage, mfg date, batch No.permission No., manufacturer etc. If the full contents of indications or efficacy, dosage and administration, adverse reactions, contraindication and warnings & precautions can’t be able to be covered, then the major contents to be indicated and note “that details are exhibited in the insert”.No.19 Shipper label should indicate the necessary contents of the generic name of drug, strength, storage, mfg date, batch No., expiry date, permission No., manufacturer etc., also may indicate the package quantity and transport warnings and other mark if necessary.No.20 The label for API should indicate the necessary contents of drug name, storage, mfg date, batch No., expiry date, specification No., permission No., manufacturer etc., and also indicate the pack side and the transport warnings.No.21 For the same drug with same strength and pack size from the same pharmaceutical manufacturer, the text, format and color of the label to be same, for the different strength or pack size, the label should be clearly different or the strength to be indicated clearly.The same drug from the same pharmaceutical manufacturer which is administered for prescription drug as well as OTC drug, the color for both packages should be clearly distinguished respectively.No.22 For the drug which storage has special requirement, the storage to be indicated in a striking place of the label.No.23 The expiry date in the label of drug should be labeled as per the sequence of year-month-date, the year is expressed as 4 numerals, the month and the date is expressed as 2 numerals respectively. The detail format is labeled as expiry by “XXXX year XX month” or “expiry by XXXX year XX month XX date”, also may be labeled as “expiry by XXXX.XX.”or “expiry by XXXX/XX/XX” etc. with the numeral or other symbol.The expiry period for preventative biological products should be labeled as per the SFDA approval specification. For the biological products for treatment, the expiry period to be counted since the repackaging date, but for other drugs, that to be counted since mfg. Date.If the expiry period is labeled up to the date, then the expiry date should be the previous date corresponding the year-month-date against the initial date. If the expiry period is labeled up to the month, then the expiry date should be the previous month corresponding the year-month against the initial date.Section IV Use of drug name and registered trademarkNo.24 The drug name labeled in the insert and labels should be in line with the nominated principle for drug generic name and brand name which is issued by SFDA, and identical with the approval certificate.No.25 The generic name of drug should be notable and outstanding, its font, size and color should be accordant, and in line with the requirements below:(1)For the horizontal label, the generic name of drug should be exhibited within the upperthird area at a marked place.For the standing label, the generic name of drug should be exhibited within the third areaof right at a marked place.(2)The font which is not easy to be identified, i.e. grass hand, seal character can’t beselected, and the font can’t be modified with italic, central emptily, hatching forms etc.(3)The color of font should be black or white, to produce a strong contrast against the tintor dark background.(4)The generic name can’t be written in different rows except the pack size is too small andthe full name can’t be exhibited.No.26 The brand name can’t be set in the same row with the generic name, the font and color of brand name is not more extrusive and distinct than the generic name, the area of single font is not more than the half area of the font of generic name.No.27 The trademark which is not registered and other drug name which is not approved by SFDA are inhibitive to be used for the insert and labels of drug.The registered trademark which is used for drug label should be printed in the side cornerof drug label, if it contains the character, then the area of single font is not more than thequadrant area of the generic name.Section V Other regulationNo.28 For the anaesthetic, psychoactive, medical toxicity drug, radioactive drug and the drug for exterior use and OTC etc. which has special mark issued by state, their inserts and labelsshould print the special mark. The insert and labels which have special requirement will be identified by SFDA.No.29 The administrative regulation for the labels of crude Chinese traditional medicine or dry pieces will be drafted by SFDA by supplementary document.No.30 The insert and labels of drug which didn’t complied with this regulation to be punished as per relevant requirements Drug Administration law of the P. R. of China.Section VI Supplementary articlesNo.31 This regulation will be implemented since June 01, 2006. The SFDA Order No.23 issued by Oct 15, 2000 will be disused synchronously.。
英文处方示例作文
英文处方示例作文Title: Sample English Prescription。
Prescription Date: [Insert Date]Patient Name: [Insert Patient Name]Date of Birth: [Insert Date of Birth]Address: [Insert Patient Address]Prescription Number: [Insert Prescription Number] Doctor’s Name: [Insert Doctor’s Name]Medical License Number: [Insert License Number] Clinic Name: [Insert Clinic Name]Clinic Address: [Insert Clinic Address]Contact Number: [Insert Contact Number] Medication Prescribed:1. Medicine Name: [Insert Medicine Name] Dosage: [Insert Dosage]Frequency: [Insert Frequency]Duration: [Insert Duration]Instructions: [Insert Instructions] 2. Medicine Name: [Insert Medicine Name] Dosage: [Insert Dosage]Frequency: [Insert Frequency]Duration: [Insert Duration]Instructions: [Insert Instructions] 3. Medicine Name: [Insert Medicine Name] Dosage: [Insert Dosage]Frequency: [Insert Frequency]Duration: [Insert Duration]Instructions: [Insert Instructions] 4. Medicine Name: [Insert Medicine Name] Dosage: [Insert Dosage]Frequency: [Insert Frequency]Duration: [Insert Duration]Instructions: [Insert Instructions]5. Medicine Name: [Insert Medicine Name]Dosage: [Insert Dosage]Frequency: [Insert Frequency]Duration: [Insert Duration]Instructions: [Insert Instructions]Additional Instructions:[Insert any additional instructions or precautions here.]Patient Counseling:1. [Insert counseling information regarding the medication regimen, potential side effects, and the importance of adherence.]2. [Insert counseling on lifestyle modifications, if applicable.]3. [Insert any other counseling points specific to the patient's condition.]Follow-up:Please schedule a follow-up appointment on [Insert Date] to monitor the progress and adjust the treatment plan if necessary.Signature:[Doctor’s Signature]Date:[Date of Prescription]This prescription is valid for [Insert Duration] and should be used only as directed. If you have any questionsor concerns, please do not hesitate to contact the clinic.Disclaimer: This prescription is provided for informational purposes only and should not be considered medical advice. Please consult with your healthcare provider for personalized medical recommendations.。
药学英语翻译答案
药学英语翻译答案一、熟悉下列句子的翻译1. In addition to the revolution in new classes of drugs, an equally momentous revolution is taking place in drug delivery.除药物种类的革命外，药物给药系统也在进行一场同样令人震撼的革命。
2. The body can make about a trillion different antibodies, produced by shuffling and reshuffling their constituent parts.通过对构成成分的改组和再改组，机体可以产生约一万亿个不同的抗体。
3. Under current law, all new drugs need proof that they are effective, as well as safe, before they can be approved for marketing.现有法律要求，所有的新药都必须具有其有效、安全的证据才能被批准上市。
4(There is no agreement whether nursing mothers could use Alexan. 哺乳期妇女是否能用爱力生尚无统一意见。
5. The prescription must be signed and dated by the practitioner and include his address.处方必须由医生亲笔签名，并注明日期和医生的地址。
6. Cells possess a nucleus which contains genetic information in the form of DNA.细胞含有一个细胞核，其中含有以脱氧核糖核酸(DNA)形式表达的基因信息。
7. A drug that is not covered by patent rights may be available in several proprietary formulations of the same generic preparation.没有专利权保护的药物可以用于同一个仿制剂型的多个专利配方中。
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Another fact not generally recognized is that a physician’s failure to use a drug approved as effective treatment for a
to show the safety but not the effectiveness of their products. On the basis of evaluations of the efficacy of these older
drugs by panels of experts selected by the National Academy of Sciences-National Research Council, the FDA is now requiring
dosage up to 50 mg at bedtime. Following publication of this paper, imipramine became widely used for the treatment of
enuresis. A straw poll of 15 pediatricians in the Cleveland area showed that 12 had prescribed imipramine for this condition.
agency, with an emphasis on confiscation of adulterated drugs, to a regulatory agency supervising the evaluation of new
drugs.
In the practice of pediatrics, drugs which are not approved by the Food and Drug Administration (FDA) as safe and
he is not. The physician may exercise his professional judgment in the use of any drug. However, if he deviates from the
instructions in the package insert and adverse reactions occur, he must be prepared to defend his position in court if there
in patients under 12 years of age. If a severe reaction occurred and litigation followed, how would a court react if a
is a malpractice suit.
Many drugs are used by clinicians in the treatment of conditions not listed in the package insert. The FDA cannot require
specific disease might be construed as malpractice. In regard to this, it is important that the physician be informed about
the availability of the drug and bases his decision to use it or not to use it on rational grounds. It would be unlikely
the drug. Therefore, a great deal of information is included in the insert, including the chemical structure of the drug, a
summary of its pharmacological and toxicological action, its clinical indications and contraindications, precautions,
effective in children are prescribed daily. This is due in part to the fact that many drugs released since 1962 carry an
“orphaning clause” in the package insert such as, “not to be used in children, since clinical studies have been
In 1937, sulfanilamide, the first sulfa antimicrobial drug, was marketed. The diluent for this sulfa preparation was
diethylene glycol, a chemical analog of antifreeze. More than 100 people, many of whom were children, died after receiving
firm to the FDA. The insert is written and printed by the drug manufacturer, but its contents must be approved by the FDA.
The Food, Drug and Cosmetic Act, as amended in 1962, requires full disclosure of all known facts pertaining to the use of
The package insert, by legal definition of the Federal Food, Drug and Cosmetic Act, is the official information piece
for a drug. The information it contains is derived from data supplied by investigators and submitted by the pharmaceutical
that information taken from the package insert could be used successfully as evidence against the physician in a liability
suit.
The dilellustrated by imipramine (Tofranil) when used in the treatment of enuresis. In 1965
a controlled study was published showing that this drug was useful in “training enuretic children to be dry.” Its mechanism
of action was not defined, but it appeared to be effective when given to children between the age of 5 and 12 years in a
part of the company. If a new use for a drug is not yet included in the package insert, the manufacturer cannot advertise
his product for that particular use. The package insert is legally binding on the manufacturer in limiting the conditions
the drug. As a result, the US Congress enacted the 1938 Federal Food, Drug and Cosmetic Act, which required proof of safety
before the introduction of a new drug into clinical practice. This act also changed the focus of the FDA from a policing
When one examines the package insert supplied with imipramine, two points are clear: (1) the treatment of enuresis is not
listed under conditions for the use of this drug; and (2) there is a clear statement that the drug is not recommended for use
revision of these package inserts to eliminate unsupported claims and thus to make them more useful to the practitioner.
Is the pediatrician breaking the law when he prescribes drugs for his patients which carry the “orphaning clause?” No,