药典注射剂通则

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药典注射剂通则

附录ⅠB 注射剂注射剂系指药物与适宜的溶剂或分散介质制成的供注入体内的溶液，乳状液或混悬液及供注入体内的溶液、乳状液或混悬液及供临用前配制或稀释成溶液或混悬液的粉末或浓溶液的无菌制剂。

注射剂可分为注射液、注射用无菌粉末与注射用浓溶液。

注射液包括溶液型、乳状液型或混悬型注射液，可用于肌内注射、静脉注射、静脉滴注等。

其中，供静脉注射用的大体积（除另有规定外，一般不小于100ml）注射液也称静脉输液。

注射用无菌粉末系指药物制成的供临用前用适宜的无菌溶液配制成澄清溶液或均匀混悬液的无菌粉末或无菌块状物。

可用适宜的注射用溶剂配制后注射，也可用静脉输液配制后静脉滴注。

无菌粉末用溶剂结晶法、喷雾干燥法或冷冻干燥法等制得。

注射用浓溶液系指药物制成的供临用前稀释后静脉滴注用的无菌浓溶液。

注射液在生产与贮藏期间应符合下列有关规定。

一、溶液型注射液应澄明；除另有规定外，混悬型注射液中药物粒度应控制在15µm以下，含15～20µm （间有个别20～50µm）者，不得超过10%，若有可见沉淀，振摇时应容易分散均匀，混悬型注射液不得用于静脉注射或椎管注射；乳状液型注射液应稳定，不得有相分离现象，不得用于椎管注射。

静脉用乳状液型注射液中乳滴的粒度90%应在1µm以下，不得有大于5µm的乳滴。

除另有规定外，静脉输液应尽可能与血液等渗。

二、注射剂所用的原辅料应从来源及工艺等生产环节进行严格控制并应符合注射用的质量要求。

注射剂所用溶剂必须安全无害，并不得影响疗效额质量。

一般分为水性溶剂和非水性溶剂。

（1）水性溶剂最常用的为注射用水，也可用0.9%氯化钠溶液或其他适宜的水溶液。

（2）非水性溶剂常用的为植物油，主要为供注射用大豆油，其他还有乙醇、丙二醇和聚乙二醇等溶剂。

供注射用的非水性溶剂，应严格限制其用量，并应在品种项下进行相应的检查。

三、配制注射剂时，可根据药物的性质加入适宜的附加剂。

中美欧药典注射剂通则比对.pdf

• 多剂量容器包装的注射用制剂必需添加防止微生物生长的适宜物质，不论其灭菌方法，但不包括下列情况之一：（1）各品种正文另有规定；（2）添加物含有物理半衰期少于24小时的核素；（3）有效成分本身为抗菌药。这类添加剂的使用浓度应能防止注射用制剂的微生物的生长或杀灭注射用制剂的微生物。
三溶剂和添加剂
• 不皂化物 - 脂肪油 10ml 与氢氧化钠溶液（1→6）15ml 和乙醇30ml蒸汽浴回流，时时振摇直至混合物澄清。将溶液转移到平皿，蒸汽浴上挥去乙醇，残渣加水100ml，应生成澄清的溶液。
• 游离脂肪酸 -用于中和10g脂肪油中的游离脂肪酸所需的 0.020N 氢氧化钠溶液不得过 2.0ml （见脂肪和脂肪油<401>）
三溶剂和添加剂
• 添加剂-为提高稳定性和方便使用，注射用制剂中可加入适当的物质，这些物质应在该药量下无害，不影响疗效，不干扰规定的含量测定和检查。肠道外给药的溶液中不得添加仅为对最终制剂着色的着色剂（并见凡例中的添加剂项和附录抗菌效率检查<51>）。
三溶剂和添加剂
一定义
• USP术语和定义 • NOMENCLATURE AND DEFINITIONS • 术语和定义 • Nomenclature* • 术语
•. • 下列术语适用于5种注射给药的一般剂型。这些制剂
可能含有缓冲剂、防腐剂或其他添加剂。
一定义
• 1．[药物]注射液- 药物或其溶液的液体制剂。 • 2．注射用[药物]- 干固体，加适宜溶剂制成的溶液符合
• Vehicles and Added Substances
• 成分
• 溶剂和添加剂

注射剂(2010年版药典三部附录ⅠA)

注射剂
2010年版药典三部附录ⅠA
注射剂
注射剂系指以生物制品原液为原料药物，加入适宜稳定剂或其他辅料等制成的可供注入体内的无菌溶液、乳液、混悬液及临用前用无菌溶剂复溶为溶液、混悬液的无菌冻干制剂。注射剂可分注射液、注射用无菌粉末。注射液包括溶液型、乳液型或混悬型注射液。可用于皮下注射、皮内注射、肌内注射、静脉注射和静脉滴注。其中，供静脉滴注用的大体积（除另有规定外，一般不小于50ml）注射液也称静脉输液。注射用无菌粉末系指供临用前以适宜的无菌溶液配制成澄明溶液或均匀混悬液的无菌固体制剂。可用适宜的注射用溶剂配制后注射，也可用静脉输液配制后静脉滴注。以冷冻干燥法制备的无菌粉末，称为注射用冻干制剂。
除另有规定外，注射剂应进行以下相应检查。
【装量】注射液照下述方法检查，应符合规定。检查法单剂量供试品标示装量为2ml或2ml以下者，取供试品5支（瓶）；2ml以上至50ml 者，取供试品3支（瓶）；50ml以上者，取供试品1瓶。将内容物分别用相应体积的干燥注射器及注射针头抽尽，然后缓慢连续地注入经标化的量入式量筒内（量筒的大小应使待测体积至少占其额定体积40%．不排尽针头中的液体），在室温下检视。标示装量为10ml以上者，可将供试品开盖后直接缓慢倾入标化的量筒，室温检视。也可采用重量除以相对密度计算装量。准确量取供试品，精密称定，求出每1ml供试品的重量（即供试品的相对密度）；精密称定用干燥注射器及注射针头抽出或直接缓慢倾出供试品内容物的重量，再除以供试品相对密度，得出相应的装量。混悬液和乳液在抽取和相对密度测定前充分混匀；开启时注意避免损失；黏稠液体倾出后，将容器倒置15分钟，尽量倾净。每支（瓶）注射液的装量均不得低于其标示量。多剂量供试品取供试品1瓶（支），按照标示的剂量数和每剂的装量，分别用注射器抽出，按照单剂量的步骤测定单次剂量，应不低于标示量。预装式注射器和弹筒式装置的供试品ml以上至50ml者，取供试品3支。供试品与所配注射器、针头或活塞装配后将供试品缓慢连续注入容器（不排尽针头中的液体），按单剂量供试品要求进行装量检查，应不低于标示量。（支）不符合规定，应另取10瓶（支）复试，应符合规定。

《中国药典》通则9201使用的药品类型

《我国药典》通则9201使用的药品类型一、引言我国药典是我国国家药典委员会颁布的一部权威的中药和中药材标准集合。

它对于我国的药品行业具有重要的指导作用，涵盖了丰富的药品和药材信息。

《我国药典》的通则9201主要规定了药品的使用类型，包括了常见的药品类型和用法用量等内容。

二、药品类型1.西药西药是指以化学合成方法或生物技术制备的药品，按照其药理作用和化学结构可分为多个类别，例如抗生素、抗病毒药、消炎药等。

在《我国药典》中，对于西药的使用类型主要包括了口服药、注射剂和外用药等。

其中，口服药适合于溶解度好、生物利用度高且不会被胃酸破坏的药物，而外用药适合于表皮疾病的治疗，注射剂适合于需要快速治疗的急危重症患者。

2.中药中药是指在我国传统医学理论指导下，采用天然药材为原料制剂的药品。

按照中药的性味归经可分为寒热药、温凉药、苦甘药等，而根据用法用量分类可分为口服剂、外用剂、注射剂等。

中药的使用类型在《我国药典》中有着详细的规定，强调了中药对于疾病的治疗特点和注意事项。

3.生物制品生物制品是指通过生物技术手段获得的治疗性制剂，例如血液制品、疫苗、生物制剂等。

根据其来源和用途可分为人血及其制品、动物源药品、细菌和真菌制品等。

生物制品的使用类型在《我国药典》中有着严格的规定和标准，旨在确保生物制品的安全性和有效性。

4.药物辅料药物辅料是指制药过程中所使用的辅助剂，例如赋形剂、增稠剂、溶剂等。

根据其用途和性质可分为固体辅料、液体辅料、气体辅料等。

《我国药典》对药物辅料的使用类型进行了规范和标准，以保证药品的制造过程和质量。

5.其他药品除了上述提到的药品类型，还有一些特殊的药品类型也被纳入了《我国药典》的规范范畴中，例如中草药提取物、中药配方颗粒、中药饮片等。

这些药品类型在药品的生产、质量控制和临床应用方面都有着特殊的要求，需要根据《我国药典》的规定进行操作。

三、结语《我国药典》通则9201使用的药品类型规范了药品的类别和使用要求，为我国的药品行业提供了重要的指导和标准。

药典中注射剂对抗氧剂的要求

药典中注射剂对抗氧剂的要求
中国药典2015年版四部 0102 注射剂通则中：配制注射剂时，可根据需要加入适宜的附加剂，如渗透压调节剂、pH 值调节剂、增溶剂、助溶剂、抗氧剂、抑菌剂、乳化剂、助悬剂等。

所用附加剂应不影响药物疗效，避免对检验产生干扰，使用浓度不得引起毒性或明显的刺激性。

常用的抗氧剂有亚硫酸钠、亚硫酸氢钠和焦亚硫酸钠等，一般浓度为0.1% 〜0.2%。

但一些产品由于其结构的特殊性，其主要成份在空气中极易氧化，有可能其抗氧剂用量需要超过0.2%时，主药才能比较稳定。

但有人说，如果抗氧剂用量比如亚硫酸氢钠用量大后，其过多的氢离子可能增加药液对血管的刺激性。

我们有一注射剂产品因主药成份极易氧化，虽然进行充氮处理并控制其残氧量，但稳定性并不是很好，通过对抗氧剂亚硫酸氢钠等用量的筛选，确定浓度为0.3%比较合适，同时进行了过敏性、溶血性、血管刺激性等试验，结果表明：家兔每日耳缘缓慢静脉滴注浓度为2.0mg/ml的该产品8ml/kg，另侧给予等体积的生理盐水，连续3次，于末次给药后24h取家兔耳缘静脉观察未见明显刺激反应。

表明该药血管刺激性试验符合要求。

欧洲药典注射剂通则

EUROPEAN PHARMACOPOEIA 6.0ParenteralpreparationsMucoadhesive preparations DEFINITION Mucoadhesive preparations contain one or more active substances intended for systemic absorption through the buccal mucosa over a prolongedperiodof time.They may be supplied as mucoadhesive buccal tablets or as other mucoadhesive solid or semi-solid preparations.Mucoadhesive buccal tablets are prepared by compressionof mono-or multi-layeredtablets.They usually containhydrophilic polymers,which on wetting with the salivaproduce a flexible hydrogel that adheres to the buccal mucosa.PRODUCTION In the manufacture of mucoadhesive buccal tablets,measures are taken to ensure that they possess suitablemechanical strength to resist handling without crumbling or breaking.This may bedemonstratedby examining the Friability of uncoated tablets (2.9.7)and the Resistance to crushing of tablets (2.9.8).TESTS Dissolution .Unlessotherwisejustified and authorised,a suitable test is carried out to demonstrate the appropriate release of the active substance(s).01/2008:0520PARENTERAL PREPARATIONS Parenteralia The requirementsof this monograph do not necessarily apply to products derived fromhuman blood,toimmunological preparations,or radiopharmaceutical preparations.Special requirements may apply to preparations for veterinary use depending on the species of animal for which the preparation is intended.DEFINITION Parenteral preparations are sterilepreparations intended for administration by injection,infusion or implantation into the human or animal body.Parenteral preparations may require the use of excipients,for example to make the preparation isotonic with respect to blood,to adjustthe pH,to increase solubility,to prevent deterioration of the activesubstancesor to provideadequateantimicrobial properties,but not to adversely affect the intended medicinal action of the preparation or,at the concentrations used,to cause toxicity or undue local irritation.Containers for parenteral preparations are made as far as possible frommaterialsthat are sufficiently transparentto permit the visual inspection of the contents,except for implants and in other justified and authorised cases.Where applicable,the containers for parenteral preparations comply with the requirements for Materials used for the manufacture of containers (3.1and subsections)and Containers (3.2and subsections).Parenteral preparations are supplied in glass containers (3.2.1)or in other containers such as plastic containers (3.2.2,3.2.2.1and 3.2.9)and prefilled syringes.The tightness of the containeris ensured bysuitablemeans.Closuresensure a good seal,prevent the access of micro-organisms and other contaminants and usually permit the withdrawal ofa part or the whole of the contents without removal of the closure.The plasticmaterials or elastomers (3.2.9)used to manufacture the closures are sufficiently firm and elastic to allow the passage of a needle with the least possible shedding ofparticles.Closures for multidose containers aresufficiently elastic to ensure that the puncture is resealedwhen the needle is withdrawn.Severalcategories of parenteral preparations may be distinguished:—injections,—infusions,—concentrates for injections or infusions,—powders for injections or infusions,—gels for injections,—implants.PRODUCTIONDuringthe developmentof a parenteral preparation,theformulation for which contains an antimicrobial preservative,the effectiveness of the chosen preservative shall be demonstratedto the satisfaction of the competent authority.A suitable test method togetherwithcriteria forjudgingthe preservative properties of the formulation are provided under Efficacy of antimicrobial preservation (5.1.3).Parenteral preparations are prepared using materials and methods designed to ensure sterility and to avoidthe introduction of contaminants and thegrowth ofmicro-organisms.Recommendations on this aspect areprovided in the text on Methods of preparation of sterile products (5.1.1).Water used in the manufacture of parenteral preparationscomplies with the requirements of water for injections in bulk stated in the monograph on Water for injections (0169).TESTSParticulate contamination:sub-visible particles (2.9.19).For preparations for human use,solutions for infusion orsolutions for injection comply with the test.Inthe case of preparations for subcutaneous or intramuscular injection,higher limits may be appropriate.Radiopharmaceutical preparations are exempt from these requirements.Preparations for which the label states thatthe product is to be used with a final filter are exempt from these requirements,providing it has been demonstrated that the filter delivers a solution that complies with the test.For preparations for veterinary use,whensupplied in containers with a nominal content of more than 100ml and when the content is equivalent to a dose of more than1.4ml per kilogram of body mass,solutions for infusion orsolutions for injection comply with the test for particulate contamination:sub-visible particles.Sterility (2.6.1).Parenteral preparations comply with the test for sterility.STORAGEIn a sterile,airtight,tamper-proof container.LABELLINGThe label states:—the name andconcentration of any added antimicrobial preservative,—where applicable,that the solution is to be used in conjunction with a final filter,—where applicable,that the preparation is free frombacterial endotoxins or that it is apyrogenic.General Notices (1)apply to all monographs and other texts 735Parenteral preparations EUROPEAN PHARMACOPOEIA6.0InjectionsDEFINITIONInjections are sterile solutions,emulsions or suspensions. They are prepared by dissolving,emulsifying or suspending the active substance(s)and any added excipients in water,in a suitable non-aqueous liquid,that may be non-sterile where justified,or in a mixture of these vehicles.Solutions for injection,examined under suitable conditions of visibility,are clear and practically free from particles. Emulsions for injection do not show any evidence of phase separation.Suspensions for injection may show a sediment which is readily dispersed on shaking to give a suspension which remains sufficiently stable to enable the correct dose to be withdrawn.Multidose preparations.Multidose aqueous injections contain a suitable antimicrobial preservative at an appropriate concentration except when the preparation itself has adequate antimicrobial properties.When a preparation for parenteral use is presented in a multidose container, the precautions to be taken for its administration and more particularly for its storage between successive withdrawals are given.Antimicrobial preservatives.Aqueous preparations which are prepared using aseptic precautions and which cannot be terminally sterilised may contain a suitable antimicrobial preservative in an appropriate concentration.No antimicrobial preservative is added when:—the volume to be injected in a single dose exceeds15ml, unless otherwise justified,—the preparation is intended for administration by routes where,for medical reasons,an antimicrobial preservative is not acceptable,such as intracisternally,epidurally,intrathecally or by any route giving access to thecerebrospinal fluid,or intra-or retro-ocularly.Such preparations are presented in single-dose containers.PRODUCTIONIn the manufacture of injections containing dispersed particles,measures are taken to ensure a suitable and controlled particle size with regard to the intended use. Single-dose preparations.The volume of the injection in a single-dose container is sufficient to permit the withdrawal and administration of the nominal dose using a normal technique(2.9.17).TESTSUniformity of dosage units.Single-dose suspensions for injection comply with the test for uniformity of dosage units (2.9.40)or,where justified and authorised,with the test for uniformity of content shown below.Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.Uniformity of content(2.9.6).Unless otherwise prescribed or justified and authorised,single-dose suspensions for injection with a content of active substance less than2mg or less than2per cent of the total mass comply with test A for uniformity of content of single-dose preparations.Ifthe preparation contains more than one active substance, the requirement applies only to those substances that correspond to the above conditions.Bacterial endotoxins-pyrogens.A test for bacterial endotoxins(2.6.14)is carried out or,where justified and authorised,the test for pyrogens(2.6.8).Recommendations on the limits for bacterial endotoxins are given in chapter2.6.14.Preparations for human use.The preparation complies with a test for bacterial endotoxins(2.6.14)or with the test for pyrogens(2.6.8).Preparations for veterinary use.When the volume to be injected in a single dose is15ml or more and is equivalent to a dose of0.2ml or more per kilogram of body mass,the preparation complies with a test for bacterial endotoxins (2.6.14)or with the test for pyrogens(2.6.8).Any preparation.Where the label states that the preparation is free from bacterial endotoxins or apyrogenic,respectively, the preparation complies with a test for bacterial endotoxins (2.6.14)or with the test for pyrogens(2.6.8),respectively.InfusionsDEFINITIONInfusions are sterile,aqueous solutions or emulsions with water as the continuous phase.They are usually made isotonic with respect to blood.They are principally intended for administration in large volume.Infusions do not contain any added antimicrobial preservative.Solutions for infusion,examined under suitable conditions of visibility are clear and practically free from particles. Emulsions for infusion do not show any evidence of phase separation.PRODUCTIONIn the manufacture of infusions containing dispersed particles,measures are taken to ensure a suitable and controlled particle size with regard to the intended use. The volume of the infusion in the container is sufficientto permit the withdrawal and administration of the nominal dose using a normal technique(2.9.17).TESTSBacterial endotoxins-pyrogens.They comply with a test for bacterial endotoxins(2.6.14)or,where justified and authorised,with the test for pyrogens(2.6.8).For the latter test inject10ml per kilogram of body mass into each rabbit, unless otherwise justified and authorised. Concentrates for injections or infusions DEFINITIONConcentrates for injections or infusions are sterile solutions intended for injection or infusion after dilution.They are diluted to a prescribed volume with a prescribed liquid before administration.After dilution,they comply with the requirements for injections or for infusions.TESTSBacterial endotoxins-pyrogens.They comply with the requirements prescribed for injections or for infusions,after dilution to a suitable volume.Powders for injections or infusions DEFINITIONPowders for injections or infusions are solid,sterile substances distributed in their final containers and which,when shaken with the prescribed volume of a prescribed sterile liquid rapidly form either clear and736See the information section on general monographs(cover pages)EUROPEAN PHARMACOPOEIA 6.0Patches,transdermal practically particle-free solutions or uniform suspensions.After dissolution or suspension,they comply with therequirements for injections or for infusions.Freeze-dried products for parenteral use are considered aspowders for injections or infusions.PRODUCTION The uniformity of contentand uniformityof mass offreeze-dried products for parenteral use are ensured by the in-process control of the amount of the solution prior to freeze-drying.TESTS Uniformity of dosage units .Powders for injections or infusions comply with the test for uniformity of dosage units (2.9.40)or,where justified and authorised,with the tests for uniformity of content and/or uniformity of mass shown below.Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.Uniformity of content (2.9.6).Unless otherwise prescribed or justifiedand authorised,powders for injections or infusions with a content of active substance less than 2mgor less than 2per cent of the total mass,or with a unit mass equal to or less than 40mg comply with test A for uniformity of content of single-dose preparations.If the preparation contains more than one active substance,the requirement applies only to those substances that correspond to the above conditions.Uniformity of mass (2.9.5).Powders for injections or infusions complywith the test for uniformity of mass ofsingle-dose preparations.If the test for uniformity of content is prescribed for all the active substances,the test for uniformity of mass is not required.Bacterial endotoxins-pyrogens.Theycomplywith the requirements prescribed for injections or for infusions,after dissolution or suspension in a suitable volume of BELLING The label states the instructions for the preparation of injections and infusions.Gels for injections DEFINITION Gels for injections are sterile gels with a viscosity suitable to guarantee a modified release of the active substance(s)at the site of injection.Implants DEFINITION Implants are sterile,solid preparations of a size and shape suitable for parenteral implantation and release of the active substance(s)over an extended period of time.Each dose is provided in a sterile container.01/2008:1011PATCHES,TRANSDERMALEmplastra transcutaneaDEFINITIONTransdermal patches are flexible pharmaceutical preparations of varying sizes,containing one or more activesubstances.Theyare intendedto be applied to the unbrokenskin in order to deliver the active substance(s)to the systemiccirculation after passing through the skin barrier.Transdermalpatches normally consist of an outer covering which supports a preparation which contains the activesubstance(s).The transdermal patches are covered on thesite of the release surface of the preparation by a protective liner,which is removed before applying the patch to the skin.The outer covering is a backing sheet impermeable to the active substance(s)and normally impermeable to water,designed to support and protect the preparation.The outer covering may have the same dimensions as the preparation or it may be larger.In the latter case the overlapping border of the outer covering is covered by pressure-sensitive adhesive substances which assure the adhesion of the patchto the skin.The preparation contains the active substance(s)togetherwith excipients such as stabilisers,solubilisers or substances intended to modify the release rate or to enhance transdermal absorption.It may be a single layer or multi-layer solid orsemi-solid matrix,and in this case it is the compositionand structure of the matrix which determines the diffusion pattern of the active substance(s)to the skin.The matrix may contain pressure-sensitive adhesives which assure theadhesion of the preparation to the skin.The preparation may exist as a semi-solid reservoir one side of which is amembranewhich may control the release and the diffusion of the active substance(s)from the preparation.The pressure-sensitive adhesive substances may,in this case,beapplied to some or all parts of the membrane,or only aroundthe border of the membrane of the outer covering.When applied to the dried,clean and unbrokenskin,thetransdermalpatch adheres firmly to the skin by gentle pressure of the hand or the fingers and can be peeled offwithout causing appreciable injury to the skin or detachment of thepreparation from the outer covering.The patch mustnot be irritant or sensitising to the skin,even after repeated applications.The protective liner generally consists of a sheet of plastic ormetal material.When removed,the protective liner does notdetach the preparation (matrix or reservoir)or the adhesive from the patch.Transdermal patches are normally individually enclosed in sealed sachets.PRODUCTIONInthe manufacture,packaging,storage and distributionof transdermalpatches suitable means are taken to ensuretheir microbial quality;recommendations onthis aspect are provided in the text on Microbiological quality ofpharmaceutical preparations (5.1.4).TESTSUniformity ofdosageunits .Transdermal patchescomplywith the test for uniformity of dosage units (2.9.40)or,where justified and authorised,with the test for uniformity General Notices (1)apply to all monographs and other texts 737。

2015年版《中国药典》凡例和通则学习(1)

检查方法和限度
采用本版药典规定的方法进行检验时应对方法的适用性进行确认；采用其他方法检验时，应与药典方法作比较试验，在仲裁时，应以药典方法为准；限度：标准中规定的各种纯度和限度数值以及制剂的重(装)量差异，系包括上限和下限两个数值本身及中间数值。规定的这些数值不论是百分数还是绝对数字，其最后一位数字都是有效位，计算时可多保留一位。
项目与要求
2、鉴别：【鉴别】项下包括经验鉴别、显微鉴别和理化鉴别。显微鉴别中的横切面、表面观及粉末鉴别，均指经过一定方法制备后在显微镜下观察的特征。理化鉴别包括物理、化学、光谱、色谱等鉴别方法。
项目与要求
3、检查：包括反映药品的安全性与有效性的试验方法和限度、均一性与纯度等制备工艺要求等内容；对于规定中的各种杂质检查项目，系指该药品在按既定工艺进行生产和正常贮藏过程中可能含有或产生并需要控制的杂质（如残留溶剂、有关物质等）；改变生产工艺时需另考虑增修订有关项目。对于生产过程中引入的有机溶剂，应在后续的生产环节予以有效去除。除正文已明确列有“残留溶剂”检查的品种必须对生产过程中引入的有机溶剂依法进行该项检查外，其他未在“残留溶剂”项下明确列出的有机溶剂或未在正文中列有此项检查的各品种，如生产过程中引入或产品中残留有机溶剂，均应按通则“残留溶剂测定法”检查并应符合相应溶剂的限度规定。
标准品与对照品
两者皆可用于鉴别、检查、含量测定的标准物质。区别：标准品：系指用于生物检定或效价测定的标准物质，其特性量一般按效价单位计；对照品：指采用理化方法进行鉴别、检查或含量测定时所用的标准物质，其特性量值一般按纯度（%）计。
标准品与对照品
标准品与对照品的建立或变更批号，应与国际标准品或原批号标准品或对照品进行对比，并经过协作标定。然后按照国家药品标准物质相应的工作程序进行技术审定，确认其质量能够

注射剂的基本要求

• (2)离子交换 • (3)凝胶滤过法:也称分子筛滤过法，当制备的注射剂其分子量明显大于热原
分子时，可用此法除去热原。 • (4)超滤法:3.0~15nm(<50nm)超滤膜，效果较好 • (5)反渗透法
(二)除去容器上热原的方法
(1)高温法:在洗涤干燥后，经180°C 加热2h或250°C，加热30min，可以破坏热原。 (2)酸碱法: 重铬酸钾硫酸清洗液或稀氢氧代钠溶液。
5.产品密闭不合格，在储存中被污染
二、使用过程中的污染
临床使用的器具如输液器、注射针筒针头、配满药器具等的污染会带入热原，中心配药室或临床科室配药过程，由于环境、操作、用品、混入的其他药品等因素的污染也可能带入热原。
Байду номын сангаас
(一)除去药液或溶剂中热源的方法
• (1)吸附法: 活性炭是常用的吸附剂，用量一般为溶液体积0.1-0.5%。活性炭除吸附热原外，还有脱色除臭、助滤作用
3.水溶性由于磷脂结构上连接有多糖，所以热原能于水，在水或水溶液中呈分子状态。
4.不挥发性热原本身不挥发，但必须注意在蒸馏时，防止随水蒸气雾滴带入药液或注射用水中，因此在配制和蒸馏水室的蒸发器上部设隔沫装置，以分离蒸汽和雾滴。 5.其他性质热原能被活性炭吸附，也能被强酸、强碱、强氧化剂破坏，超声波亦能破坏热原。
污染热源的途径
一、生产过程中的污染 1、从溶剂中带入
是热原污染的主要途径，主要指配制注射液用的注射用水，尽管水本身并非是微生物良好的培养基，但易被空气或含尘空气中的微生物污染。虽经蒸馏可将热原除去，但若操作不当或蒸馏设备结构不合理，水蒸气中带有细小的水滴则可将热原带入
另外，注射用水储存不当或储存时间过长被微生物污染也可产生热原。

新药典4部

名称为“《中国药典》2015年版总则” 内容包括2010版药典一部、二部、三部的附录（现改名为“通则”）
内容和药用辅料品种正文。
详情如下:
编号 0100
0101 0102 0103 0200 0251 0261 0291 0301 0400 0401 0402 0406
通则名称制剂通则
片剂注射剂胶囊剂其他通则药用辅料制药用水国家药品标准物质通则一般鉴别试验光谱法紫外-可见光光度法红外分光光度法原子吸收分光光度法
除另有规定外，取供试品10个，照各品种项下规定的方法，分别测定每一个单剂以标示量为100的相对含量，求其均值X和标准差S以及标示量与均值之差的绝对值A（A=|100-X|)
若A+2.2S≤L，则供试品的含量均匀度符合规定；若A+S＞L，则不符合规定；若A+2.2S>L,且A+S≤L，则应另取供试品20个复试。复试判定较2010版药典规
对于难溶性药物制成的口崩片，还应进行溶出度检查（通则0931），对于经肠溶材料包衣的颗粒制成的口崩片，还应进行释放度检查（通则0931）除另有规定外，非包衣片应符合片剂脆碎度检查法（通则0932）根据原料药物和制剂的特性，除来源于动、植物多组分且难以建立测定方法的片剂外，溶出度、释放度、含量均匀度等应符合要求。
ⅥG黏度测定法
ⅦA电位滴定法与永停滴定法 ⅦB非水溶液滴定法
0800 0900
编号
0801 0821 0831 0832 0861
0901 0902 0903 0904 0921 0923 0931 0941 0942 0982
通则名称限量检查法氯化物检查法重金属检查法干燥失重测定法水分测定法残留溶剂测定法特性检查法溶液颜色检查法澄清度检查法不溶性微粒检查法可见异物检查法崩解时限检查法片剂脆碎度检查法溶出度与释放度测定法含量均匀度检查法最低装量检查法粒度和粒度分布测定法

中国药典制剂通则

附录ⅠA 片剂增修概况介绍（二）
缓释片定义：系指在（水中或）规定的释放介质中缓慢地非恒速释放
药物的片剂。
控释片定义：系指在（水中或）规定的释放介质中缓慢地恒速（或接
近恒速）释放药物的片剂。
附录ⅠA 片剂增修概况介绍（三）
片剂在生产与贮藏期间应符合下列规定（一般要求）
1. 第五点：为增加稳定性、掩盖药物不良臭味、改善片剂外观等，可对片剂进行包衣。必要时，薄膜包衣片剂应检查残留溶剂。（把原第七点部分内容归类）
缓释颗粒与控释颗粒参照缓控释片剂修订一般要求项下：第二点：颗粒剂应干燥，颗粒均匀，色泽
一致… 【粒度】除另有规定外，照粒度和粒度分布测定法〔附
录Ⅸ E第二法（2）双筛分法〕检查，不能通过一号筛（ 2000μm）与能通过五号筛（180μm）的总和不得超过供试量的15%。【溶化性】泡腾颗粒因一般装量较大，测定数由6袋修订
第二点：注射剂所用的原辅料应从来源及工艺等生产环节进行严格控制并应符合注射用的质量要求。注射剂所用溶剂必须安全无害，并不得影响疗效和质量。一般分为水性溶剂和非水性溶剂。
（2）非水性溶剂：常用的为植物油，…等溶剂。供注射用的非水性溶剂，应严格限制其用量，并应在品种项下进行相应的检查。
附录ⅠB注射剂增修概况介绍（三）
生产与贮藏期间（一般要求）：
第四点：…供口服的滴丸或小丸可包糖衣或薄膜衣。必要时，薄膜包衣丸应检查残留溶剂（物与适宜的辅料制成具有一定粒度的干燥颗粒状制剂。供口服用。
基本分类：可溶颗粒（通称为颗粒）、混悬颗粒、泡腾颗粒、肠溶颗粒、缓释颗粒和控释颗粒等。
附录ⅠA 片剂
定义：片剂系指药物与适宜的辅料混匀压制而
成的圆片状或异形片状的固体制剂。

2020版药典制剂通则之注射剂

2020版药典制剂通则之注射剂注射剂系指原料药物或与适宜的辅料制成的供注入体内的无菌制剂。

注射剂可分为注射液、注射用无菌粉末与注射用浓溶液等。

注射液系指原料药物或与适宜的辅料制成的供注入体内的无菌液体制剂，包括溶液型、乳状液型和混悬型等注射液。

可用于皮下注射、皮内注射、肌内注射、静脉注射、静脉滴注、鞘内注射、椎管内注射等。

其中，供静脉滴注用的大容量注射液（除另有规定外，一般不小于100ml，生物制品一般不小于50ml）也可称为输液。

中药注射剂一般不宜制成混悬型注射液。

乳状液型注射液，不得用于椎管内注射。

混悬型注射液不得用于静脉注射或椎管内注射。

注射用无菌粉末系指原料药物或与适宜辅料制成的供临用前用无菌溶液配制成注射液的无菌粉末或无菌块状物，可用适宜的注射用溶剂配制后注射，也可用静脉输液配制后静脉滴注。

以冷冻干燥法制备的注射用无菌粉末，也可称为注射用冻干制剂。

注射用无菌粉末配制成注射液后应符合注射剂的要求。

注射用浓溶液系指原料药物与适宜辅料制成的供临用前稀释后注射的无菌浓溶液。

注射用浓溶液稀释后应符合注射剂的要求。

注射剂在生产与贮藏期间应符合下列规定。

一、注射剂所用的原辅料应从来源及生产工艺等环节进行严格控制并应符合注射用的质量要求。

除另有规定外，制备中药注射剂的饮片等原料药物应严格按各品种项下规定的方法提取、纯化，制成半成品、成品，并应进行相应的质量控制。

生物制品原液、半成品和成品的生产及质量控制应符合相关品种要求。

二、注射剂所用溶剂应安全无害，并与其他药用成分兼容性良好，不得影响活性成分的疗效和质量。

一般分为水性溶剂和非水性溶剂。

（1）水性溶剂最常用的为注射用水，也可用0.9%氯化钠溶液或其他适宜的水溶液。

（2）非水性溶剂常用植物油，主要为供注射用的大豆油，其他还有乙醇、丙二醇和聚乙二醇等。

供注射用的非水性溶剂，应严格限制其用量，并应在各品种项下进行相应的检查。

三、配制注射剂时，可根据需要加入适宜的附加剂，如渗透压调节剂、pH调节剂、增溶剂、助溶剂、抗氧剂、抑菌剂、乳化剂、助悬剂等。

2010年中国药典制剂通则

（二）无菌与灭菌制剂无菌与灭菌制剂与灭菌
基本定义：基本定义：系指直接注射于体内或直接用于创伤面、
粘膜等的一大类制剂。
灭菌制剂：系指采用物理、化学方法杀灭或除去所

有活的微生物繁殖体和芽孢的一类制剂。
无菌制剂：系指采用无菌操作方法或制备技术的不
含任何活的微生物繁殖体和芽孢的一类制剂。
基本分类：注射制剂（注射剂、粉针等）、眼用
注射用浓溶液
附录ⅠB注射剂增修概况介绍（附录ⅠB注射剂增修概况介绍（二） ⅠB注射剂增修概况介绍
注射剂在生产与贮藏期间（一般要求）注射剂在生产与贮藏期间（一般要求）
第一点：除另有规定外混悬型注射液中药物粒度应控制在15μm 除另有规定外，第一点：…除另有规定外，混悬型注射液中药物粒度应控制在15μm 以下， 15～20μm（间有个别20 50μm） 20～不应超过10 10％。以下，含15～20μm（间有个别20～50μm）者，不应超过10％…。混悬型注射液不得用于静脉注射或椎管注射乳状液型注射液应稳定，不得用于静脉注射或椎管注射；悬型注射液不得用于静脉注射或椎管注射；乳状液型注射液应稳定，不得有相分离现象，不得用于椎管注射。静脉用乳状液型注射液中乳不得有相分离现象，不得用于椎管注射。静脉用乳状液型注射液中乳分散相球粒）的粒度90%应在1μm以下，不得有大于5μm 90%应在1μm以下 5μm的滴（分散相球粒）的粒度90%应在1μm以下，不得有大于5μm的乳滴球粒）除另有规定外，静脉输液应尽可能与血液等渗。（球粒）。除另有规定外，静脉输液应尽可能与血液等渗。第二点：第二点：注射剂所用的原辅料应从来源及工艺等生产环节进行严格控制并应符合注射用的质量要求。注射剂所用溶剂必须安全无害，制并应符合注射用的质量要求。注射剂所用溶剂必须安全无害，并不得影响疗效和质量。一般分为水性溶剂和非水性溶剂。得影响疗效和质量。一般分为水性溶剂和非水性溶剂。非水性溶剂：常用的为植物油，等溶剂等溶剂。（2）非水性溶剂：常用的为植物油，…等溶剂。供注射用的非水性溶剂，应严格限制其用量，并应在品种项下进行相应的检查。溶剂，应严格限制其用量，并应在品种项下进行相应的检查。

2020年版《中国药典》凡例和通则学习(1)

2015版《中国药典》概况
2015版《中国药典》主要变化
主要变化包括以下七个方面：（一）收载品种大幅增加（二）药典标准更加系统化、规范化（三）健全了药品标准体系（四）附录（通则）、辅料独立成卷 —— 四部（五）药用辅料品种收载数量显著增加，标准水平明显提高（六）安全性控制项目大幅提升（七）进一步加强有效性控制
项目与要求
4、贮藏：
药品标准中“贮藏”项下的规定：系为避免污染和降解而对药品贮存与保管的基本要求。除另有规定外，贮藏项下未规定贮藏温度的一般系指常温。药品应按质量标准中规定的条件贮藏，以免因贮藏不当而影响质量。
项目与要求
4、贮藏：
遮光系指用不透光的容器包装，例如棕色容器或黑纸包裹的无色透明、半透明容器；避光系指避免日光直射；密闭系指将容器密闭，以防止尘土及异物进入；密封系指将容器密封以防止风化、吸潮、挥发或异物进人；熔封或严封系指将容器熔封或用适宜的材料严封，以防止空气与水分的侵入并防止污染；阴凉处系指不超过20°C; 凉暗处系指避光并不超过20°C; 冷处系指2〜1(TC; 常温系指 10〜30°C。
2015版《中国药典》概况
四部：1、制剂通则、检验方法、标准物质、试剂试液和指导原则。制剂通则38个、检验方法240个、指导原则30个、标准物质和试液试药相关通则9个，共计317个。 2、药用辅料新增137个、修订97个、不收载2种，共计270个。
总则
2、明确了凡例与通则的地位；
总则
3、明确中国药典的各项规定仅针对符合GMP的产品而言。
任何违反GMP或有未经批准添加物质所生产的药品，即使符合《中国药典》或按照《中国药典》没有检出其添加物质或相关杂质，亦不能认为其符合规定。

(完整版)2015年版《中国药典》凡例和通则学习(1)

项目与要求
制剂中使用的原料药和药用辅料，均应符合本版药典的规定；本版药典未收载者，必须制定符合药用要求的标准，并需经国务院药品监督管理部门批准。同一原料药用于不同制剂（特别是给药途径不同的制剂）时，需根据临床用药要求制定相应的质量控制项目。
制剂生产企业使用的药用辅料即使符合本版药典药用辅料标准，也应进行药用辅料标准的适用性验证。药用辅料标准适用性验证应充分考虑药用辅料的来源、工艺，以及制备制剂的特点、给药途径、使用人群以及使用剂量等相关因素的影响。
明显提高（六）安全性控制项目大幅提升（七）进一步加强有效性控制
凡例
一、总则二、正文三、通则四、名称与编排五、项目与要求六、检查方法和限度七、标准品与对照品八、计量九、精确度十、试药、试液、指示剂十一、动物实验十二、说明书、包装、标签
总则
1、明确了药典的组成、内容、英文名；
2018年10月
目录
➢ 药典概况 ➢ 凡例 ➢ 通则（注射剂）
2015版《中国药典》概况
国家法典质量准绳技术标准行业必备
《中国药典》由国家药品监督管理部门颁布，是国家为保证药品质量、确保民众用药安全有效、质量可控而制定的药品法典。可以说是药企药品研制、生产、经营、使用和管理都必须严格遵守的法定依据，是国家药品标准的核心组成部分，是最具严肃性和权威性的药品标准。
中国药典2015年版：由一部、二部、三部、四部及其增补本组成
一部二部三部四部
• 中药 • 化学药 • 生物制品 • 通则和药用辅料
总则
2、明确了凡例与通则的地位；
凡例是制定和执行药典必须了解和遵循的法则，是解释和说明《中国药典》概念，正确进行质量检验提供指导原则。将正文、通则及质量检定有关的共性问题加以规定，避免全书中重复说明。其内容同样具有法定约束力。

美国药典注射剂通则

Designation as a Pharmacy bulk package is limited to prepara-〈1〉 INJECTIONStions from Nomenclature categories 1, 2, or 3 as defined above.Pharmacy bulk packages, although containing more than one single dose, are exempt from the multiple-dose container volume limit of 30 mL and the requirement that they contain a substance or suitable mixture of substances to prevent the growth of microorganisms.Where a container is offered as a Pharmacy bulk package, the INTRODUCTIONlabel shall (a) state prominently “Pharmacy Bulk Package—Not for direct infusion,” (b) contain or refer to information on proper tech-Parenteral articles are preparations intended for injection through niques to help assure safe use of the product, and (c) bear a state-the skin or other external boundary tissue, rather than through the ment limiting the time frame in which the container may be used alimentary canal, so that the active substances they contain are ad-once it has been entered, provided it is held under the labeled stor-ministered, using gravity or force, directly into a blood vessel, or-age conditions.gan, tissue, or lesion. Parenteral articles are prepared scrupulously by methods designed to ensure that they meet Pharmacopeial re-quirements for sterility, pyrogens, particulate matter, and other con-LARGE - AND SMALL -VOLUME INJECTIONStaminants, and, where appropriate, contain inhibitors of the growth of microorganisms. An Injection is a preparation intended for par-Where used in this Pharmacopeia, the designation Large-volume enteral administration and/or for constituting or diluting a parenteral intravenous solution applies to a single-dose injection that is in-article prior to administration.tended for intravenous use and is packaged in containers labeled as containing more than 100 mL. The designation Small-volume Injec-tion applies to an Injection that is packaged in containers labeled as NOMENCLATURE AND DEFINITIONScontaining 100 mL or less.BIOLOGICSNomenclature *The following nomenclature pertains to five general types of The Pharmacopeial definitions for sterile preparations for paren-preparations, all of which are suitable for, and intended for, paren-teral use generally do not apply in the case of the biologics because teral administration. They may contain buffers, preservatives, or of their special nature and licensing requirements (see Biologics other added substances.〈1041〉).1.[DRUG] Injection—Liquid preparations that are drug sub-stances or solutions thereof.2.[DRUG] for Injection—Dry solids that, upon the addition ofINGREDIENTSsuitable vehicles, yield solutions conforming in all respects to the requirements for Injections.3.[DRUG] Injectable Emulsion—Liquid preparations of drugVehicles and Added Substancessubstances dissolved or dispersed in a suitable emulsion medium.Aqueous Vehicles—The vehicles for aqueous Injections meet 4.[DRUG] Injectable Suspension—Liquid preparations of sol-the requirements of the Pyrogen Test 〈151〉 or the Bacterial Endo-ids suspended in a suitable liquid medium.toxins Test 〈85〉, whichever is specified. Water for Injection gener-5.[DRUG] for Injectable Suspension—Dry solids that, upon theally is used as the vehicle, unless otherwise specified in the individ-addition of suitable vehicles, yield preparations conforming ual monograph. Sodium chloride may be added in amounts in all respects to the requirements for Injectable Suspensions.sufficient to render the resulting solution isotonic; and Sodium Chloride Injection, or Ringer’s Injection, may be used in whole or in part instead of Water for Injection, unless otherwise specified in Definitionsthe individual monograph. For conditions applying to other ad-juvants, see Added Substances in this chapter.Other Vehicles—Fixed oils used as vehicles for nonaqueous In-jections are of vegetable origin, are odorless or nearly so, and have PHARMACY BULK PACKAGEno odor suggesting rancidity. They meet the requirements of the test for Solid paraffin under Mineral Oil, the cooling bath being main-A Pharmacy bulk package is a container of a sterile preparation tained at 10°, have a Saponification Value between 185 and 200for parenteral use that contains many single doses. The contents are (see Fats and Fixed Oils 〈401〉), have an Iodine Value between 79intended for use in a pharmacy admixture program and are re-and 141 (see Fats and Fixed Oils 〈401〉), and meet the requirements stricted to the preparation of admixtures for infusion or, through a of the following tests.sterile transfer device, for the filling of empty sterile syringes.Unsaponifiable Matter—Reflux on a steam bath 10 mL of the oil The closure shall be penetrated only one time after constitution with 15 mL of sodium hydroxide solution (1 in 6) and 30 mL of with a suitable sterile transfer device or dispensing set which allows alcohol, with occasional shaking until the mixture becomes clear.measured dispensing of the contents. The Pharmacy bulk package Transfer the solution to a shallow dish, evaporate the alcohol on a is to be used only in a suitable work area such as a laminar flow steam bath, and mix the residue with 100 mL of water: a clear solu-hood (or an equivalent clean air compounding area).tion results.*This nomenclature has been adopted by the USP Drug Nomenclature Committee for Free Fatty Acids—The free fatty acids in 10g of oil require for implementation by supplemental revisions of USP 23-NF 18. For currently official neutralization not more than 2.0 mL of 0.020N sodium hydroxide monograph titles in the form Sterile [DRUG] that have not yet been revised, the following nomenclature continues in use in this Pharmacopeia:(1) medicaments or (see Fats and Fixed Oils 〈401〉).solutions or emulsions thereof suitable for injection, bearing titles of the form [DRUG]Synthetic mono- or diglycerides of fatty acids may be used as Injection; (2) dry solids or liquid concentrates containing no buffers, diluents, or other vehicles, provided they are liquid and remain clear when cooled to added substances, and which, upon the addition of suitable solvents, yield solutions conforming in all respects to the requirements for Injections, and which are 10° and have an Iodine Value of not more than 140 (see Fats and distinguished by titles of the form Sterile [DRUG]; (3) preparations the same as those Fixed Oils 〈401〉).described under (2) except that they contain one or more buffers, diluents, or other These and other nonaqueous vehicles may be used, provided they added substances, and which are distinguished by titles of the form [DRUG] for are safe, in the volume of Injection administered, and also provided Injection; (4) solids which are suspended in a suitable fluid medium and which are not to be injected intravenously or into the spinal canal, distinguished by titles of the form they do not interfere with the therapeutic efficacy of the preparation Sterile [DRUG] Suspension; and (5) dry solids which, upon the addition of suitable or with its response to prescribed assays and tests.vehicles, yield preparations conforming in all respects to the requirements for Sterile Added Substances—Suitable substances may be added to prepa-Suspensions, and which are distinguished by titles of the form Sterile [DRUG] for Suspension.rations intended for injection to increase stability or usefulness, un-less proscribed in the individual monograph, provided they are Containers for Injections that are intended for use as dialysis, harmless in the amounts administered and do not interfere with the hemofiltration, or irrigation solutions and that contain a volume of therapeutic efficacy or with the responses to the specified assays more than 1 L are labeled to indicate that the contents are not in-and tests. No coloring agent may be added, solely for the purpose of tended for use by intravenous infusion.coloring the finished preparation, to a solution intended for paren-Injections intended for veterinary use are labeled to that effect. teral administration (see also Added Substances under General No-The container is so labeled that a sufficient area of the container tices and Antimicrobial Effectiveness Testing 〈51〉).remains uncovered for its full length or circumference to permit in-spection of the contents.Observe special care in the choice and use of added substances inpreparations for injection that are administered in a volume exceed-ing 5 mL. The following maximum limits prevail unless otherwiseSTRENGTH AND TOTAL VOLUME FOR SINGLE- AND directed: for agents containing mercury and the cationic, surface-active compounds, 0.01%; for chlorobutanol, cresol, phenol, and MULTIPLE-DOSE INJECTABLE DRUG PRODUCTS similar types of substances, 0.5%; and for sulfur dioxide, or anequivalent amount of the sulfite, bisulfite, or metabisulfite of potas-For single-dose and multiple-dose injectable drug products, the sium or sodium, 0.2%.strength per total volume should be the primary and prominent ex-pression on the principal display panel of the label, followed in A suitable substance or mixture of substances to prevent theclose proximity by strength per mL enclosed by parentheses. For growth of microorganisms must be added to preparations intendedcontainers holding a volume of less than 1 mL, the strength per for injection that are packaged in multiple-dose containers, regard-fraction of a mL should be the only expression of strength. Strength less of the method of sterilization employed, unless one of the fol-per single mL should be expressed as mg/mL, not mg/1 mL. lowing conditions prevails: (1) there are different directions in theThe following formats are acceptable for contents of greater individual monograph; (2) the substance contains a radionuclidethan 1 mL:with a physical half-life of less than 24 hours; and (3) the activeTotal strength/total volume: 500 mg/10 mLingredients are themselves antimicrobial. Such substances are usedStrength/mL: 50 mg/mLin concentrations that will prevent the growth of or kill microorgan-orisms in the preparations for injection. Such substances also meet theTotal strength/total volume: 25,000 Units/5 mL requirements of Antimicrobial Effectiveness Testing 〈51〉 and Anti-Strength/mL: 5,000 Units/mLmicrobial Agents—Content 〈341〉. Sterilization processes are em-The following format is acceptable for contents of less than 1 ployed even though such substances are used (see also SterilizationmL: 12.5 mg/0.625 mLand Sterility Assurance of Compendial Articles 〈1211〉). The air inThere are, however, some exceptions to expressing strength per the container may be evacuated or be displaced by a chemically in-total volume. In certain cases, the primary and prominent expres-ert gas. Where specified in a monograph, information regardingsion of the total drug content per container would not be effective in sensitivity of the article to oxygen is to be provided in the labeling.preventing medication errors (e.g., insulin). An example is the useof lidocaine or other similar drugs used as a local anesthetic wherethe product is ordered and administered by percentage (e.g., 1%, LABELS AND LABELING2%) or a local anesthetic in combination with epinephrine that isexpressed as a ratio (e.g., 1:100,000). In such cases, the totalstrength should be expressed: for example, 1% (100 mg/10 mL).Dry solids, which need to be reconstituted, should follow the same Labeling format, with the exception that only the total strength of the drugshould be listed, not the strength/total volume or strength/mL. NOTE—See definitions of “label” and “labeling” in Labeling in(Official February 1, 2009) the section Preservation, Packaging, Storage, and Labeling of theGeneral Notices and Requirements.The label states the name of the preparation; in the case of a liq-Aluminum in Large-Volume Parenterals (LVPs), uid preparation, the percentage content of drug or amount of drug in Small-Volume Parenterals (SVPs), and Pharmacy a specified volume; in the case of a dry preparation, the amount ofBulk Packages (PBPs) Used in Total Parenteral active ingredient; the route of administration; a statement of storageconditions and an expiration date; the name and place of business of Nutrition (TPN) Therapythe manufacturer, packer, or distributor; and an identifying lot num-ber. The lot number is capable of yielding the complete manufactur-(a)The aluminum content of LVPs used in TPN therapy must ing history of the specific package, including all manufacturing,not exceed 25 µg per L (µg/L).filling, sterilizing, and labeling operations.(b)The package insert of LVPs used in TPN therapy must state Where the individual monograph permits varying concentrations that the drug product contains no more than 25 µg of alumi-of active ingredients in the large-volume parenteral, the concentra-num per L. This information must be contained in the “Pre-tion of each ingredient named in the official title is stated as if part cautions” section of the labeling of all LVPs used in TPN of the official title, e.g., Dextrose Injection 5%, or Dextrose (5%)therapy.and Sodium Chloride (0.2%) Injection.(c)If the maximum amount of aluminum in SVPs and PBPs is The labeling includes the following information if the complete25 µg per L (µg/L) or less, instead of stating the exact formula is not specified in the individual monograph: (1) In the case amount of aluminum that each contains, as in paragraph (d), of a liquid preparation, the percentage content of each ingredient or the immediate container label for SVPs and PBPs used in the the amount of each ingredient in a specified volume, except that preparation of TPN parenterals (with exceptions as noted be-ingredients added to adjust to a given pH or to make the solution low) may state: “Contains no more than 25 µg/L of alumi-isotonic may be declared by name and a statement of their effect;num”. If the SVP or PBP is a lyophilized powder, the im-and (2) in the case of a dry preparation or other preparation to mediate container label may state the following: “When which a diluent is intended to be added before use, the amount of reconstituted in accordance with the package insert instruc-each ingredient, the composition of recommended diluent(s) [the tions, the concentration of aluminum will be no more than 25 name(s) alone, if the formula is specified in the individual mono-µg/L”.graph], the amount to be used to attain a specific concentration of(d)The maximum level of aluminum at expiry must be stated on active ingredient and the final volume of solution so obtained, a the immediate container label of all SVPs and PBPs used in brief description of the physical appearance of the constituted solu-the preparation of TPN parenterals and injectable emulsions. tion, directions for proper storage of the constituted solution, and an The aluminum content must be stated as follows: “Contains expiration date limiting the period during which the constituted no more than __ µg/L of aluminum”. The immediate con-solution may be expected to have the required or labeled potency if tainer label of all SVPs and PBPs that are lyophilized powder it has been stored as ed in the preparation of TPN solutions must contain the fol-lowing statement: “When reconstituted in accordance with pul is prohibited, except for Potassium Chloride for Injection the package insert instructions, the concentration of alumi-Concentrate.num will be no more than __ µg/L.” This maximum amount of aluminum must be stated as the highest one of the follow-Neuromuscular Blocking and Paralyzing Agentsing three levels:(1)The highest level for the batches produced during the lastAll injectable preparations of neuromuscular blocking agents and three yearsparalyzing agents must be packaged in vials with a cautionary state-(2)The highest level for the latest five batchesment printed on the ferrules or cap overseals. Both the container cap (3)The maximum level in terms of historical levels, but only un-ferrule and the cap overseal must bear in black or white print til completion of production of the first five batches after July (whichever provides the greatest color contrast with the ferrule or 26, 2004.cap color) the words: “Warning: Paralyzing Agent” or “Paralyzing The package insert for all LVPs, SVPs, and PBPs used in the Agent” (depending on the size of the closure system). Alternatively,preparation of TPN products must contain a warning statement.the overseal may be transparent and without words, allowing for This warning must be contained in the “Warning” section of the visualization of the warning labeling on the closure ferrule.labeling and must state the following: “WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is Containers for Sterile Solidsimpaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium Containers, including the closures, for dry solids intended for and phosphate solutions that contain aluminum. Research indicates parenteral use do not interact physically or chemically with the that patients with impaired kidney function, including premature preparation in any manner to alter the strength, quality, or purity neonates, who receive parenteral levels of aluminum at greater than beyond the official requirements under the ordinary or customary 4 to 5 µg per kg per day accumulate aluminum at levels associated conditions of handling, shipment, storage, sale, and use.with central nervous system and bone toxicity. Tissue loading may A container for a sterile solid permits the addition of a suitable occur at even lower rates of administration of TPN products.”solvent and withdrawal of portions of the resulting solution or sus-pension in such manner that the sterility of the product is maintained.PACKAGING Where the Assay in a monograph provides a procedure for the Assay preparation, in which the total withdrawable contents are to be withdrawn from a single-dose container with a hypodermic nee-dle and syringe, the contents are to be withdrawn as completely as Containers for Injectionspossible into a dry hypodermic syringe of a rated capacity not ex-ceeding three times the volume to be withdrawn and fitted with a Containers, including the closures, for preparations for injections 21-gauge needle not less than 2.5 cm (1 inch) in length, with care do not interact physically or chemically with the preparations in any being taken to expel any air bubbles, and discharged into a con-manner to alter the strength, quality, or purity beyond the official tainer for dilution and assay.requirements under the ordinary or customary conditions of han-dling, shipment, storage, sale, and use. The container is made of material that permits inspection of the contents. The type of glass Volume in Containerpreferable for each parenteral preparation is usually stated in the individual monograph. Unless otherwise specified in the individual Each container of an injection is filled with sufficient excess of monograph, plastic containers may be used for packaging injections the labeled “size” or that volume which is to be withdrawn. See (see Containers—Plastics 〈661〉).Injections under Pharmaceutical Dosage Forms 〈1151〉.For definitions of single-dose and multiple-dose containers, see Containers in the General Notices and Requirements. Containers meet the requirements under Containers—Glass 〈660〉 and Con-DETERMINATION OF VOLUME OF INJECTION INtainers—Plastics 〈661〉.Containers are closed or sealed in such a manner as to prevent CONTAINERS contamination or loss of contents. Validation of container integrity must demonstrate no penetration of microbial contamination or Suspensions and emulsions must be shaken before withdrawal of chemical or physical impurities. In addition, the solutes and the ve-the contents and before the determination of the density. Oily and hicle must maintain their specified total and relative quantities or viscous preparations may be warmed according to the instructions concentrations when exposed to anticipated extreme conditions of on the label, if necessary, and thoroughly shaken immediately be-manufacturing and processing, and storage, shipment, and distribu-fore removing the contents. The contents are then cooled to tion. Closures for multiple-dose containers permit the withdrawal of 20°–25°C before measuring the volume.the contents without removal or destruction of the closure. The clo-Single-Dose Containers—Select 1 container if the volume of the sure permits penetration by a needle and, upon withdrawal of the container is 10 mL or more, 3 containers if the nominal volume is needle, closes at once, protecting the container against contamina-more than 3 mL and less than 10 mL, or 5 containers if the nominal tion. Validation of the multiple-dose container integrity must in-volume is 3 mL or less. Take up individually the total contents of clude verification that such a package prevents microbial contami-each container selected into a dry syringe of a capacity not exceed-nation or loss of product contents under anticipated conditions of ing three times the volume to be measured and fitted with a 21-multiple entry and use.gauge needle not less than 2.5 cm (1 inch) in length. Expel any air Piggyback containers are usually intravenous infusion containers bubbles from the syringe and needle, and then discharge the con-used to administer a second infusion through a connector of some tents of the syringe, without emptying the needle, into a standard-type or an injection port on the administration set of the first fluid,ized, dry cylinder (graduated to contain rather than to deliver the thereby avoiding the need for another injection site on the patient’s designated volumes) of such size that the volume to be measured body. Piggyback containers are also known as secondary infusion occupies at least 40% of its graduated volume. Alternatively, the containers.volume of the contents in mL may be calculated as the mass, in g,divided by the density. For containers with a nominal volume of 2mL or less, the contents of a sufficient number of containers may be Potassium Chloride for Injection Concentratepooled to obtain the volume required for the measurement, provided that a separate, dry syringe assembly is used for each container. The The use of a black closure system on a vial (e.g., a black flip-off contents of containers holding 10 mL or more may be determined button and a black ferrule to hold the elastomeric closure) or the use by means of opening them and emptying the contents directly into of a black band or series of bands above the constriction on an am-the graduated cylinder or tared beaker.The volume is not less than the nominal volume in the case of Injections packaged for intravascular use that may be used for containers examined individually or, in the case of containers with a intermittent, continuous, or bolus replacement fluid administration nominal volume of 2 mL or less, is not less than the sum of the during hemodialysis or other procedures, unless excepted above,nominal volumes of the containers taken collectively.must conform to the 1-L restriction.Multi-Dose Containers—For Injections in multiple-dose con-Injections labeled for veterinary use are exempt from packaging tainers labeled to yield a specific number of doses of a stated vol-and storage requirements concerning the limitation to single-dose ume, select 1 container, and proceed as directed for single-dose containers and the limitation on the volume of multiple-dose containers, using the same number of separate syringe assemblies as containers.the number of doses specified. The volume is such that each syringe delivers not less than the stated dose.Injections in Cartridges or Prefilled Syringes—Select 1 con-FOREIGN AND PARTICULATE MATTERtainer if the volume is 10 mL or more, 3 containers if the nominal volume is more than 3 mL and less than 10 mL, or 5 containers if All articles intended for parenteral administration shall be pre-the nominal volume is 3 mL or less. If necessary, fit the containers pared in a manner designed to exclude particulate matter as defined with the accessories required for their use (needle, piston, syringe)in Particulate Matter in Injections 〈788〉 and other foreign matter.and transfer the entire contents of each container without emptying Each final container of all parenteral preparations shall be inspected the needle into a dry tared beaker by slowly and constantly depress-to the extent possible for the presence of observable foreign and ing the piston. Determine the volume in mL, calculated as the mass,particulate matter (hereafter termed “visible particulates”) in its in g, divided by the density.contents. The inspection process shall be designed and qualified to The volume measured for each of the containers is not less than ensure that every lot of all parenteral preparations is essentially free the nominal volume.from visible particulates. Qualification of the inspection process Large-Volume Intravenous Solutions—For intravenous solu-shall be performed with reference to particulates in the visible range tions, select 1 container. Transfer the contents into a dry measuring of a type that might emanate from the manufacturing or filling pro-cylinder of such a capacity that the volume to be determined occu-cess. Every container whose contents shows evidence of visible par-pies at least 40% of the nominal volume of the cylinder. Measure ticulates shall be rejected. The inspection for visible particulates the volume transferred.may take place when inspecting for other critical defects, such as The volume is not less than the nominal volume.cracked or defective containers or seals, or when characterizing the appearance of a lyophilized product.Where the nature of the contents or the container-closure system permits only limited capability for the inspection of the total con-Labeling on Ferrules and Cap Oversealstents, the 100% inspection of a lot shall be supplemented with the inspection of constituted (e.g., dried) or withdrawn (e.g., dark am-Only cautionary statements are to appear on the top (circle) sur-ber container) contents of a sample of containers from the lot.face of the ferrule or cap overseal of a vial containing an injectable All large-volume Injections for single-dose infusion and small-product. A cautionary statement is one intended to prevent an immi-volume Injections are subject to the light obscuration or micro-nent life-threatening situation if the injectable drug is used inappro-scopic procedures and limits for subvisible particulate matter set priately. Examples of such statements include but are not limited to forth in Particulate Matter In Injections 〈788〉, unless otherwise the following: “Warning”, “Dilute Before Using”, “Paralyzing specified in the individual monograph. An article packaged as both Agent”, “I.M. Use Only”, and “Chemotherapy”.a large-volume and a small-volume Injection meets the require-The text must be in contrasting color and conspicuous under ordi-ments set forth for small-volume Injections where the container is nary conditions of use. The cautionary statement may appear solely labeled as containing 100 mL or less, if the individual monograph on the ferrule, provided the cap overseal is constructed so as to al-states a test for Particulate Matter 〈788〉; it meets the requirements low the cautionary statement beneath the cap to be readily legible.set forth for large-volume Injections for single-dose infusion where Identifying numbers or letters, such as code numbers, lot num-the container is labeled as containing more than 100 mL. Injections bers, etc., may appear on the side (skirt) surface of the ferrule on administered exclusively by the intramuscular or subcutaneous vials containing injectable products. The appearance of such identi-route or packaged and labeled for use as irrigating solutions are ex-fying data on the skirt surface of the ferrule, placed where it does empt from requirements for Particulate Matter 〈788〉.not detract from, or interfere with, the cautionary statement on the top surface, should be considered to be a beneficial attribute of the in-process quality control of a product throughout the manufactur-ing process. Any anticounterfeiting scheme must not detract from or STERILITYinterfere with the cautionary statements.Under no circumstances would advertising such as company Sterility Tests—Preparations for injection meet the requirements names, logos, or product names be permitted to appear on the top under Sterility Tests 〈71〉.(circle) surface of any ferrule or cap overseal.(Official February 1, 2009)CONSTITUTED SOLUTIONSPackaging and StorageDry solids from which constituted solutions are prepared for in-jection bear titles of the form [DRUG] for Injection. Because these The volume of injection in single-dose containers provides the dosage forms are constituted at the time of use by the health care amount specified for parenteral administration at one time and in no practitioner, tests and standards pertaining to the solution as consti-case is more than sufficient to permit the withdrawal and adminis-tuted for administration are not included in the individual mono-tration of 1 L.graphs on sterile dry solids or liquid concentrates. However, in the Preparations intended for intraspinal, intracisternal, or peridural interest of assuring the quality of injection preparations as they are administration are packaged only in single-dose containers.actually administered, the following nondestructive tests are pro-Unless otherwise specified in the individual monograph, a multi-vided for demonstrating the suitability of constituted solutions when ple-dose container contains a volume of Injection sufficient to per-they are prepared just prior to use.mit the withdrawal of not more than 30 mL.Completeness and Clarity of Solution—Constitute the solution The following injections are exempt from the 1-L restriction of as directed in the labeling supplied by the manufacturer for the ster-the foregoing requirements relating to packaging:ile dry dosage form.1.Injections packaged for extravascular use as irrigation solu-A:The solid dissolves completely, leaving no visible residue tions or peritoneal dialysis solutions as undissolved matter.2.Injections packaged for intravascular use as parenteral nutri-B:The constituted solution is not significantly less clear than tion or as replacement or substitution fluid to be administeredan equal volume of the diluent or of Purified Water contained in a continuously during hemofiltrationsimilar vessel and examined similarly.。

中国药品检验标准操作规——注射剂检验程序

文件内容：1、主题内容和适用范围⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯ 22、引用标准⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯ 23、定义⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯ 24、检查项目⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯ 25、更改信息⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯ 5颁发部门：质量管理部。

分发清单：QC办公室、化学室、微生物室、稳定性考察室1主题内容和适用范围本程序规定了注射剂的检查项目、操作方法和注意事项，使其规范化、标准化，并描述了更改信息。

本程序适用于注射剂的检验。

2引用标准中国药典2010 年版二部附录Ⅰ B“注射剂”、中国药品检验标准操作规范2010 年版P4“注射剂”。

3定义注射剂（中国药典2010 年版二部附录Ⅰ B）系指药物与适宜的溶剂或分散介质制成的供注入体内的溶液、乳状液或混悬液，以及供临用前配制或稀释成溶液或混悬液的粉末或浓溶液的无菌制剂。

注射剂可分注射液（其中供静脉滴注用的大体积注射液也称静脉输液）、注射用无菌粉末与注射用浓溶液。

4检查项目注射剂除应按药典品种项下规定的检验项目外，还应检查“装量”或“装量差异” “可见异物”和“无菌” 。

静脉用注射剂应加查“热原”或“细菌内毒素” ；溶液型静脉用注射液、溶液型静脉注射用粉末及注射用浓溶液应加查“不溶性微粒” 。

静脉输液及插管注射用注射液应加查“渗透压摩尔浓度” 。

4.1装量本法适用于50ml及50ml以下的单剂量注射液的装量检查，其目的在于保证单剂量注射液的注射用量不少于标示量，以达到临床用药剂量要求。

标示装量为50ml 以上的注射液和注射用浓溶液，按最低装量检查法标准操作规范检查，应符合规定。

凡规定检查含量均匀度的注射液（如塞替派注射液），可不进行“装量”检查。

4.1.1仪器与用具注射器及注射针头。

药典注射剂通则