药品生产企业s管理办法

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药品生产质量管理规范2010年修订-英

Good Manufacturing Practice for Pharmaceutical Products(Amended in 2010) SDA Order #79Order by Ministry of Health of the People’s Republic of ChinaPublished on February 12, 2011No. 79Good Manufacturing Practice for Pharmaceutical Products (Amended in 2010) has passed by Affairs Meeting o n October 19, 2010. This Regulation is now published and shall be effective from March 1, 2011.Director Zhu CHENJanuary 17, 2011Chapter 1 General ProvisionsArticle 1 In order to standardize good manufacturing for pharmaceutical products, this Regulation is enacted in accordance with the “Drug Administration Law of the People’s Republic of China” and “The Regulation on the Implementation of D rug Administration Law of the People’s Republic of China”.Article 2 A pharmaceutical enterprise shall establish pharmaceutical goods’ quality control system. The system shall contain all factors which may affect the quality of pharmaceutical goods, including all organized and planned activities ensuring pharmaceutical goods’ quality in accordance with intending purpose.Article 3 This Regulation is part of quality control system, is basic requirement for manufacturing and quality control of pharmaceutical products. This Regulation aims to reduce the risks in pharmaceutical goods’ manufacturing process at its maximum,such as pollution, cross pollution and confusion, mistake, ensure for continuous stably manufacturing pharmaceutical goods in accordance with intending purpose and registered requirements.Article 4 The enterprise shall obey this Regulation strictly,insist on honesty and keep faith,prohibit any ostensible and spurious activities.Chapter 2 Quality ControlSection 1 PrincipleArticle 5 The enterprise shall establish quality targe t in accordance with pharmaceutical goods’ quality control requirements,carry out all requirements related to safety, effective and quality control into the process of phar maceutical goods’ manufacturing, control and products’discharging, storage, delivering, ensure all pharmaceutical goods are produced in accordance with intending purpose and registered requirements.Article 6 Senior administrator in enterprise shall ensure the achievement of intending quality target. Personnel in different levels and provider, dealer shall participate in and take each responsibility.Article 7 The enterprise shall equip adequate personnel, workshop, establishment and equipment in accordance with requirements, and provide essential condition for achieving quality target.Section 2 Quality GuaranteeArticle 8 Quality guarantee is a part of quality control system.The enterprise must establish quality guarantee system, and establish integrate document system at the same time, in order to ensure the system’s effective running.Article 9 Quality guarantee system shall ensure the following:I. Represent the requirements of this Regulation in pharmaceutical goods’design and development.II. In accordance with the requirements of this Regulation in manufacturing management and quality control activities;III. Specific management responsibility;IV. Exact stocked and used raw material and wrapper;V. Effective control in semifinished product;VI. Implement of confirmation and validation;VII. Manufacture, examine, inspect and double examined according to rules strictly;VIII. Each batch of products shall only discharge after quality authorizing person’s approval;IX. Applicable measures to ensure pharmaceutical goods’quality during the process of storage, delivering and all succedent operation process;X. According to self-examine rules, examine and evaluate the validity and applicability of the quality guarantee system quality.Article 10 Basic requirements of pharmaceutical goods’ manufacture quality management:I. Frame manufacturing technique, systemic review and demonstrate it couldcontinuous stably manufacturing products in accordance with requirements;II. Manufacturing technique and its important changes shall be validated; III. Equip all required resources, include, but not limited the following:1. Hold applicable qualification and the eligible trained personnel;2. Adequate workshop and space;3. Applicable equipment and maintain guarantee;4. Accurate raw material, wrapper and label;5. Approved technique rules and operate rules;6. Applicable storage and freight condition.IV. Use accurate and easy understand language to frame operate rules;V. The operate person could accurate operate according to operate rules after training;VI. The whole manufacture process shall be recorded. The windage shall be researched and be recorded;VII. Batch record and delivering record shall be traced back to the whole history of the batch of products, and the records shall be saved appropriately and be easy consult;VIII. Reduce the quality risk during the pharmaceutical goods’ delivering process;IX. Establish pharmaceutical goods’ recall system, and ensure any batch delivered and sold products could be recalled;X. Survey the reasons leading to pharmaceutical goods’complaints and quality objections, take measures to prevent similar quality objections.Section 3 Quality ControlArticle 11 Quality control includes corresponding organization, document system and sampling, test and so on, to ensure material or products finish necessary examination before delivering, and to verify its quality is in accordance with the requirements.Article 12 Basic requirements of quality control:I. Equip applicable establishment, equipment, instrument and trained personnel to effective and reliable finish all related quality control activities;II. Have approved operate rules, which used to sampling, examine, inspect raw material, wrapper, semifinished product, bulk product and finished product and products’ stability, monitor environment when necessary, to ensure the products is in accordance with the requirements of this Regulation;III. Authorized person shall sampling to raw material, wrapper, semifinished product, bulk product and finished product according to stated methods;IV. Inspect methods shall be confirmed and validated;V. Sampling, check, inspect shall be recorded, the windage shall be researched and be recorded;VI. Material, semifinished product, bulk product and finished product shall be checked and inspected according to quality standard and be recorded;VII. Material and packaged finished product shall have enough reserved samples so that necessary check or inspect shall be taken; except the finished product with too large package container, the reserved sample s’package shall be the same with the final package of the finished product.Section 4 Quality Risk ManagementArticle 13 Quality risk management is evaluate, control, communicate, audit system process to quality risk during the whole product life period, via the manner of foresee or review.Article 14 Quality risk shall evaluate according to science knowledge and experience in order to ensure products’ quality.Article 15 The method, measure, form take during the quality risk management process and the documents formed in the said process shall accommodate to the level of the existent risk.Chapter 3 Organization and PersonnelSection 1 PrincipleArticle 16 An enterprise shall establish management organization which accommodate to the pharmaceutical goods’ product and have its organization framework chart.The enterprise shall set up independent quality management department, which carries out the responsibilities of quality guarantee and quality control. The quality management department could set up quality guarantee department and quality control department respectively.Article 17 Quality management department shall take part in all activities relating to quality, and take responsibility to audit all documents relating to this Regulation. The personnel in quality management department shall not relegate his responsibility to the personnel in other department.Article 18 The enterprise shall be staffed by an appropriate number of management and technical personnel with appropriate qualification (including education background, training and practice experience), and the responsibilities of each department and each station shall be clarified. Station’s responsibility shall not be missed and cross responsibility shall be prescribed specifically. Responsibility taken by each person shall not be overfull.Every person shall clear and understand his own responsibilities, be familiar with the requirements related to his responsibilities, and accept necessary training, including pre-job training and on-job training.Article 19 Generally, one shall not relegate his responsibility to other person. If the responsibilities do need to be relegated, the one should relegate his responsibility to the designated person who has equivalent qualification.Section 2 Important PersonArticle 20 The important person shall be the full-time person of the enterprise, at least including the director of the enterprise, director of manufacturing management, director of and authorized person of quality. Director of quality management and director of manufacturing management shall be independent of each other. Director of quality management and authorized person of quality shall not be independent of each other.Operation proceduress shall be established so that authorized person of quality could take his responsibility independently, with no interference from director of enterprise and other person.Article 21 Director of enterpriseDirector of enterprise is the main responsible person of pharmaceutical goods’quality, who comprehensive responsible to the daily management of the enterprise. In order to ensure the enterprise complete quality target and manufacture pharmaceutical goods according to this Regulation, the director of enterprise shall take responsible for providing necessary resources, reasonable plan, organize and correspond to ensure the quality management department could take its responsibility independently.Article 22 Director of manufacturing managementI. Qualification:Director of manufacturing management shall at least have pharmacology or related specialty undergraduate education background (or secondary professional technical title or licensed pharmacist qualification), have at least three years’pharmaceutical goods’manufacturing and quality management experience, including at least one year’s pharmaceutical goods’manufacturing management experience, have taken part in professional knowledge training related to manufacturing products.II. Main responsibility:1. Manufacture and storage the pharmaceutical goods according to approvedtechnology procedure in order to ensure the quality of the pharmaceutical goods;2. Ensure every operation proceduress related to manufacturing operationare performed strictly;3. Ensure batch production record and batch package record are audited bydesignated person and submitted to quality management department;4. Ensure the maintenance of workshop and equipment in order to preserveits good working condition;5. Ensure all kind of necessary validation work is completed;6. Ensure person related to manufacturing have been trained by pre-jobtraining and on-job training, adjust training content according to actual demands.Article 23 Director of quality managementI. Qualification:Director of quality management shall at least have pharmacology or related specialty undergraduate education background (or secondary professional technical title or licensed pharmacist qualification), have at least five years’pharmaceutical goods’manufacturing and quality management experience, including at least one year’s pharmaceutical goods’quality management experience, have taken part in professional knowledge training related to manufacturing products.II. Main responsibility:1. Ensure the raw material, wrapper, semifinished product, bulk product andfinished product are in accordance with the registered approved requirements and quality standard;2. Ensure the products are audited to batch record before delivering;3. Ensure necessary inspection is finished;4. Approve quality standard, sampling method, inspection method and otheroperation proceduress of quality management;5. Audit and approve all changes related to quality;6. Ensure all important windage and exceed criterion inspection results havebeen researched and been dealt with in time;7. Approve and supervise consigned inspection;8. Supervise the maintenance of workshop and equipment in order to maintainits good working condition;9. Ensure to finish every necessary confirmation and validation work,checking and approving confirmation or validation scheme and report;10. Ensure to finish self-check;11. Evaluate and approve material supplier;12. Ensure all complaints related to product quality have been researched,and have been dealt with in time and accurately;13. Ensure to finish products’persistent stability review plan, providethe data of persistent stability review;14. Ensure to finish product quality review analysis;15. Ensure quality control and quality guarantee person have been trainedby pre-job training and on-job training, adjust training content according to actual demands.Article 24 Director of manufacturing management and director of quality management often have the following common responsibility:I. Audit and approve the documents of products’ technology procedure, operation proceduress;II. Supervise the sanitation condition of factory;III. Ensure the key equipment have been confirmed;IV. Ensure to finish the validation of production technology;V. Ensure all related person in enterprise been trained by pre-job training and on-job training, adjust training content according to actual demands; VI. Approve and supervise consigned manufacture;VII. Ensure and monitor the storage condition of material and goods; VIII. Save the record;IX. Supervise the implement condition of this Regulation;X. Monitor the factors influence the quality of the products.Article 25 Authorized person of qualityI. Qualification:Authorized person of quality shall at least have pharmacology or related specialty undergraduate education background (or secondary professional technical title or licensed pharmacist qualification), have at least five years’pharmaceutical goods’manufacturing and quality management experience, have the experience of manufacturing process control and quality check work. Authorized person of quality shall have necessary professional theory knowledge, have taken part in the train about product delivering, and could take his responsibility independently.II. Main responsibility:1. Take part in the establishment of enterprise quality system, interiorself-check, exterior quality audit, validate and pharmaceutical goods’bad reaction report, product recall and other quality management activities;2. Take the responsibility of product delivering, to ensure themanufacturing, checking of every batch of delivered products are all in accordance with corresponding code, pharmaceutical goods’ registered requirements and quality standard;3. Before delivering the products, authorized person of quality must issueproduct delivering audit record according to the said item 2 and bring it into batch record.Section 3 TrainingArticle 26 The enterprise shall designate department or person to take responsible for training management work, and shall have the training scheme or plan audited or approved by director of manufacture management or director of quality management. The training record shall be preserved.Article 27 All personnel related to pharmaceutical goods’manufacturing, quality shall be trained, the training content shall accommodate to the post. Except the training of theory and practice of this Regulation, responsibility, skill training about the related code,relevant post shall also be trained, and actual effect shall be periodic evaluated.Article 28 The working person in high risk operating area (such as: manufacture area of high activity, high toxic, infective, high sensitive material) shall take expert training.Section 4 Personnel SanitationArticle 29 All personnel shall take sanitation requirements training, the enterprise shall establish personnel sanitation operation proceduress,so that to reduce the pollution risk to pharmaceutical goods taken by person at its maximum.Article 30 Personnel sanitation operation procedures shall include the content related to health, sanitation practice and personnel dress. Personnel in manufacturing area and quality control area shall correctly understand related personnel sanitation operation procedures. The enterprise shall take measures to ensure the implement of personnel sanitation operation procedures.Article 31 The enterprise shall manage personnel’s health and establish health file. The manufacture personnel contact pharmaceutical goods directly shall receive physical check, and take at least one physical check per year.Article 32 The enterprise shall take appropriate measure to avoid the person have wound in body surface, have infection disease or other person may pollute pharmaceutical goods to take the manufacture work which directly contact pharmaceutical goods.Article 33 Visiting person and untrained person shall not enter manufacture area and quality control area, if the persons need to enter in special conditions, the items of their individual sanitation, clothes changing and so on shall be instructed.Article 34 Any person enters into manufacturing area shall change clothes according to prescription. The material, style and dressing method of work clothes shall be accommodate to the work engaged and the level of air clean degree.Article 35 The person enters into clean manufacturing area shall not make up and adorn with accouterment.Article 36 Manufacturing area, storage area shall forbid smoking and having meals, forbid to store food, beverage, cigarette and individual pharmaceutical goods and other non-manufacturing goods.Article 37 Operation person shall avoid to touch the surface of pharmaceutical goods, wrapper material contact pharmaceutical goods directly and equipment by hand.Chapter 4 Workshop and EstablishmentSection 1 PrincipleArticle 38 The workshop location’s choice, design, overall arrangement, construct, reconstruct and maintenance must in accordance with the pharmaceutical goods’ manufacturing requirements, which may avoid pollution, cross pollution, confusion and mistake at its maximum, and may convenient for clean, operate and maintenance.Article 39 The workshop’s location shall consider according to the workshop and manufacturing safety measures. The environment of the workshop shall reduce the pollution risk to material or products at its maximum.Article 40 The enterprise shall have tidy manufacturing environment. The floor, road surface of the workshop and transport shall not pollute the pharmaceutical goods’manufacturing. The overall arrangement of the manufacturing area, administration area, living area and assistant area shall be reasonable arranged and do not interfere each other. Stream of people and material in factory area and workshop shall reasonable.Article 41 The workshop shall take appropriate maintenance, and ensure the maintenance activity may not influence the quality of pharmaceutical goods. Clean or take necessary sterilization to workshop according to detailed written operation procedures.Article 42 The workshop shall have appropriate illumination, temperature, humidity and aeration, to ensure the quality of produced and reserved products and the performance of related equipment shall not be influenced directly or indirectly.Article 43 The design and installation of workshop, establishment shall effective prevent insect or other animal to enter in. Necessary measures shall be taken to prevent of using raticide, insecticide, smoke fumigant and so on which may pollute equipment, material, goods.Article 44 Necessary measures shall be taken to prevent unauthorized person to enter in. Manufacturing, storage and quality control area shall not be the direct gate for staffs not in this area.Article 45 Complete drawing of constructed or reconstructed workshop, public service, fixed pipeline shall be saved.Section 2 Manufacturing AreaArticle 46 In order to reduce pollution and cross pollution risk, workshop, manufacturing establishment and equipment shall reasonable designed, overall arranged and used according to the characteristic, technique process and corresponding clean level, and in accordance with the following requirements: I. Comprehensive considering the pharmaceutical goods’ characteristic,technique and intending purpose and other factors, to confirm feasibility of using workshop, manufacturing establishment and equipment together, and hing related evaluating report;II. Special and independent workshop, manufacturing establishment and equipment must be used when manufacturing special character pharmaceutical goods, such as high sensitive pharmaceutical goods (i.e.Penicillin) or biologics goods (i.e. bcg vaccine or other pharmaceutical goods prepared by active microorganism). The operating area with large quantity of dust forpenicillin species pharmaceutical goods shall keep comparatively negative pressure, the exhaust gas discharged to outdoor shall carry cleanse management and make it be up to the mustard. Air outlet shall be away from air inlet of other air cleanse system;III. Special establishment (i.e. independent air cleanse system) and equipment must be used when manufacturing β-lactam structure species pharmaceutical goods, sex hormone species prophylactic pharmaceutical goods, and shall be detached with other pharmaceutical goods’ manufacturing area strictly;IV. Special establishment (i.e. independent air cleanse system) and equipment shall be used when manufacturing some hormone species, cell toxicity species, high active chemical pharmaceutical goods; under special circumstance, if necessary validation shall be take before taking special protection measures, the above said pharmaceutical goods preparation could use the same establishment and equipment via manufacturing modes in different phases;V. Ventilation of air cleanse system in the above said item II, III, IV shall take cleanse management;VI. Pharmaceutical goods’ manufacturing workshop shall no t used for manufacturing non-officinal used products which may have bad influence to pharmaceutical goods’ quality.Article 47 Manufacturing area and storage area shall have enough space to ensure equipment, material, semifinished product, bulk product and finished product could storage in order, to prevent the confusion, cross pollution of different products or material, to prevent missing or mistake during the operation of manufacturing or quality control.Article 48 Air condition cleanse system shall be equipped according to pharmaceutical goods’ variety, manufacturing operation’s requirement and exterior environment condition which let the manufacturing area can effective aeration, and have temperature,humidity control and atmosphere cleanse filtration, to ensure the manufacturing environment of pharmaceutical goods is in accordance with the requirements.The pressure difference between clean area and non-clean area, clean areas in different level shall not lower than 10 Pascal. When necessary, appropriate pressure difference grads shall also be kept in different functional areas (operation area) with same clean level.Exposure working procedure area for oral liquid and solid preparation, chamber use pharmaceutical goods (including rectal pharmaceutical goods), surface external use pharmaceutical goods and other non-asepsis preparation manufacturing and exposure working procedure area for wrapper material directly contact pharmaceutical goods shall equip according to the requirements of “Asepsis Pharmaceutical Goods” D level clean area in Annex. The enterprise could take appropriate microorganism monitor measures according to product s’standard and characteristic.Article 49 Inner surface of clean area (wall, floor, sunshade) shall be slick, non-crack,narrow joint, non granule fell off, prevent stored dust, convenient for effective clean, and take sterilization when necessary.Article 50 The design and installation of every kind of pipeline, lighting establishment, place with a draught and other public establishment shall prevent having the part of not easy to clean, and shall try best to maintain outside the manufacturing area.Article 51 Sewerage shall have appropriate size and install the device of reversing flow. Try best to prevent drain in clear channel, if it is inevitably, the clear channel shall be flat so that it is convenient to clean and sterilize.Article 52 Quantify of preparation’s raw material often carry on in the metage room special designed.Article 53 Operation rooms which produce dust (such as sampling, metage, mix, package of dry material or products rooms and other operation rooms) shall keep comparatively negative pressure or take special measure, so as to prevent the diffusion of powder dust, avoid cross pollution and easy to keep clean.Article 54 Pharmaceutical goods’packaging workshop or area shall be reasonable designed and arranged, to prevent confusion or cross pollution. If there are several packaging lines in one area, isolation measures shall be taken.Article 55 Manufacturing area shall have appropriate light, the light in contact manufacturing area shall satisfy the operation requirements.Article 56 Manufacturing area could set middle control area. However, middle control operation shall not bring quality risk to pharmaceutical goods.Section 3 Storage AreaArticle 57Storage area shall have enough space, which ensure the under-examined, qualified, disqualified, withdrew or recalled raw materia l,wrapper, semifinished product, bulk product and finished product and all kinds of material and products could store in order.Article 58 The design and construct of storage area shall ensure good storage condition, and have aeration and lighting establishment. Storage area shall satisfy material or products’storage condition (such as temperature, humidity, avoid of light) and safety storage requirements, and check and monitor shall be taken.Article 59 High active material or product and printing package material shall storage in safe area.Article 60 Receiving, extending and delivering area shall protect material, product out of influence of weather outside(such as rain, snow). The arrangement and establishment of receiving area shall ensure taking necessary cleaning to the received material’s outside packaging.Article 61 If the under-examined material is stored in separate isolate area, the under-examine area shall have distinct mark, and only authorized person could in and out.Disqualified, withdrew or recalled material or product shall be stored isolated. If other method is used for replacing physics isolation, this method shall have equal security.Article 62 Separate material sampling area is often set up. Air cleaning level of sampling area is the same with the manufacturing requirements. If sample is taken in other area or use other method, pollution or cross pollution shall prevent.Section 4 Quality Control AreaArticle 63 Quality control laboratory is often divided from manufacturing area. Biology examine,microorganism and radioactivity isotope laboratory shall also divided from each other.Article 64 The design of laboratory shall ensure for applying it’s intending purpose, and prevent confusion and cross pollution, enough area shall have for disposing samples, reserved samples and samples for reviewing stability and keeping the records.Article 65 When necessary, set a special instrument room to prevent static, shaking, humid or other outside factors’ disturbance to instrument with high sensitivity.Article 66 The laboratory disposing special goods such as biology samples or radioactivity samples shall in accordance with the related requirements of the country.Article 67 Experiment animal room shall be strictly divided from other area. Its design, construct shall in accordance with the related requirements of the country and have independent air disposing establishment and animal’s special channel.Section 5 Assistant AreaArticle 68 Retiring room shall not take bad influence to manufacturing area, storage area and quality control area.。

药品生产监督管理办法 (中英文)

药品生产监督管理办法Measures for the Supervision over and Administration ofPharmaceutical Production国家食品药品监督管理总局State Food and Drug Administration药品生产监督管理办法Measures for the Supervision over and Administration of Pharmaceutical Production （2004年8月5日国家食品药品监督管理局令第14号公布根据2017年11月7日国家食品药品监督管理总局局务会议《关于修改部分规章的决定》修正）The Measures for the Supervision over and Administration of Pharmaceutical Production, which were deliberated and adopted at the executive meeting of the State Food and Drug Administration, are hereby promulgated, and shall come into force as of the date of promulgation.第一章总则Chapter I General Provisions第一条为加强药品生产的监督管理，根据《中华人民共和国药品管理法》、《中华人民共和国药品管理法实施条例》（以下简称《药品管理法》、《药品管理法实施条例》），制定本办法。

Article 1 With a view to strengthening the supervision over and administration of pharmaceutical production, the present Measures are formulated in accordance with the Pharmaceutical Administration Law of the People's Republic of China, Regulation on the Implementation of the Pharmaceutical Administration Law of the People's Republic of China (hereinafter referred to as the Pharmaceutical Administration Law, Regulation on the Implementation of the Pharmaceutical Administration Law).第二条药品生产监督管理是指食品药品监督管理部门依法对药品生产条件和生产过程进行审查、许可、监督检查等管理活动。

药品生产公司文件管理制度

药品生产公司文件管理制度一、目的本文件管理制度旨在建立和维护一个有序的文件控制体系，确保药品生产和质量控制活动的所有文件都能够被正确编写、审核、批准、分发和维护。

通过这一体系，公司能够确保文件的准确性、完整性和可追溯性，满足法规要求和客户要求。

二、适用范围本制度适用于本公司所有涉及药品生产和质量控制的文件，包括但不限于工艺规程、操作标准、记录表格、检验报告、培训资料等。

所有员工必须遵守本制度的规定，对文件进行妥善管理。

三、责任1. 质量管理部门负责本制度的制定、修订和监督执行。

2. 各部门负责人负责本部门文件的编写、审核和更新。

3. 所有员工负责遵守文件管理规定，确保文件的正确使用和保管。

四、文件分类和编码1. 文件应根据其性质和用途进行分类，如技术文件、质量管理文件、记录文件等。

2. 每个文件应有唯一的编码，以便识别和追溯。

编码规则应简单明了，易于理解。

五、文件编写和审核1. 文件编写应遵循公司规定的格式和内容要求，确保信息的准确性和完整性。

2. 文件编写完成后，应由相关部门负责人进行审核，必要时还应进行专业评审。

3. 审核通过后，文件应由授权人员签字批准，方可正式发布。

六、文件发布和分发1. 经批准的文件应由质量管理部门统一发布，并记录发布日期和版本号。

2. 文件应分发到所有相关部门和使用场所，确保相关人员能够获取最新版本的文件。

七、文件变更和更新1. 文件如有变更需求，应按照文件编写和审核程序进行。

2. 变更后的文件应及时更新版本号，并通知所有持有旧版文件的人员更换新文件。

八、文件存档和保管1. 所有文件应妥善存档，电子文件应备份在安全的服务器上，纸质文件应存放在指定的档案室内。

2. 文件的存档期限应符合法规要求和公司政策，过期文件应按照规定程序销毁。

九、文件访问和复制1. 文件的访问应限制在授权人员范围内，防止未授权的访问和修改。

2. 文件的复制应得到相关部门负责人的批准，并记录复制的日期和数量。

药品生产企业需要遵循哪些法律规定？

It’s not easy to push me away as a stubborn gangster and become dusty as a diamond.悉心整理助您一臂（页眉可删）药品生产企业需要遵循哪些法律规定？导读：随着我国改革的不断深化，对外开放逐步放大，药品的需求也越来越大，维护人民身体健康和用药的合法权益是《药品管理法》的根本目的，加强药品企业的管理，保证药品质量，从源头控制药品问题，切实做好药品的生产工作，让药品能够真正发挥其有效的作用。

随着我国改革的不断深化，对外开放逐步放大，药品的需求也越来越大，维护人民身体健康和用药的合法权益是《药品管理法》的根本目的，加强药品企业的管理，保证药品质量，从源头控制药品问题，切实做好药品的生产工作，让药品能够真正发挥其有效的作用。

第二章药品生产企业管理第七条开办药品生产企业，须经企业所在地省、自治区、直辖市人民政府药品监督管理部门批准并发给《药品生产许可证》。

无《药品生产许可证》的，不得生产药品。

《药品生产许可证》应当标明有效期和生产范围，到期重新审查发证。

药品监督管理部门批准开办药品生产企业，除依据本法第八条规定的条件外，还应当符合国家制定的药品行业发展规划和产业政策，防止重复建设。

第八条开办药品生产企业，必须具备以下条件：(一)具有依法经过资格认定的药学技术人员、工程技术人员及相应的技术工人;(二)具有与其药品生产相适应的厂房、设施和卫生环境;(三)具有能对所生产药品进行质量管理和质量检验的机构、人员以及必要的仪器设备;(四)具有保证药品质量的规章制度。

第九条药品生产企业必须按照国务院药品监督管理部门依据本法制定的《药品生产质量管理规范》组织生产。

药品监督管理部门按照规定对药品生产企业是否符合《药品生产质量管理规范》的要求进行认证;对认证合格的，发给认证证书。

《药品生产质量管理规范》的具体实施办法、实施步骤由国务院药品监督管理部门规定。

药品生产企业授权管理制度

药品生产企业授权管理制度一、总则为了加强对药品生产企业的管理，维护药品生产企业的法定权益，促进药品生产企业合法合规经营，保障人民群众用药安全和合理用药，根据《药品生产企业管理规范》和相关法律法规，制定本制度。

二、授权管理的基本要求1. 授权合法合规药品生产企业在授权经营过程中，应严格遵循国家有关药品经营管理的法律法规，确保授权行为合法合规。

2. 授权范围合规药品生产企业应当将授权范围、授权时间、授权内容等明确规定在授权文件中，严格限定授权范围，并确保授权行为符合国家相关规定。

3. 授权机构合规药品生产企业应当选择具备相应资质的授权机构，确保授权机构的正当性和合规性。

4. 授权行为合规药品生产企业应当与授权机构签署书面授权协议，确保授权行为的合法性和合规性。

5. 授权管理规范药品生产企业应当建立健全授权管理的制度和流程，包括授权申请、授权审核、授权监督等环节，确保授权管理工作的规范化和制度化。

三、授权管理的基本程序1. 授权申请药品生产企业需要进行授权经营的，应当向具备相应资质的授权机构提交授权申请，并提供相关资料。

2. 授权审核授权机构应当对药品生产企业提交的授权申请进行审核，核实药品生产企业的资质和合规性，确定是否授予授权。

3. 授权协议签署经审核合格后，授权机构和药品生产企业应当签署书面授权协议，明确授权范围、授权时间、授权内容等。

4. 授权监督授权机构应当对药品生产企业进行授权活动的监督和检查，确保药品生产企业的授权行为合规合法。

四、授权管理的监督检查国家药品监督管理部门对药品生产企业的授权行为进行定期和不定期的监督检查，对发现的违法行为及时处理，确保药品生产企业的授权活动合法合规。

五、授权管理的处罚规定对药品生产企业违反授权管理制度的行为，国家药品监督管理部门会依法采取相应的处罚措施，包括警告、罚款、责令停产整顿等。

六、授权管理的信息公开国家药品监督管理部门将对药品生产企业的授权信息进行公开，提供给社会公众查询，确保授权活动的透明度和公开性。

药品生产企业化验室OOS处理指南

Page: 1of 6. SOP #A-195-02-0100S T A N D A R D O P E R A T I N GP R O C E D U R E SPROCEDURES FOR HANDLING OOS RESULTS1.PURPOSET he purpose of this Standard Operation Procedure is to establish a procedure for the routine handling of out-of-specification (OOS) laboratory results The investigation or ‘failure investigation’ should where ever possible identify the cause of the OOS and evaluate its impact.2.RESPONSIBILITYE ach Analyst or Researcher is responsible for the immediate analytical review of OOS results in cooperation with the laboratory head of supervisor/delegate. All solutions and standards must be preserved and properly stored.The laboratory head of supervisor is responsible for the final decision as to the disposition and use of the result.3.FREQUENCYI mmediately afterwards (where possible) or within 1 to 2 days of each completed analytical test (after being checked, audited and reviewed by the supervisor).4.PROCEDURE[a]. A nalysts may classify Out-of-Specification Test Results (OOS) as reversible or as non-reversible due to either a :-Ügenuine laboratory error orÜsampling errorNon-reversible classification may cover:-Ümanufacturing or processing errors (including manufacturing operator error) [b.] I nvestigation for Genuine Laboratory An alytical Error.A nalysts must investigate for laboratory errors which can occur when analysts make analytical mistakes. Check if samples were incorrectly prepared, diluted, injected or stored at inappropriate environmental temperatures or that containers not properly closed or possibly not sampled in the correct designated sampling container. [e.] S uspected laboratory error must be investigated and if a genuine error is found, then the OOS result must immediately be invalidated. The OOS result must be disregarded (after appropriate recording and filing).[c].E ach Analyst shall review for completeness the entire test procedure, equipment / calibration and calculation used in obtaining the test result using the attached guideline checklists.Edition Number:Effective Date:APPROVEDPROCEDURES FOR HANDLING OOS RESULTSPage: 2of 6 [d].T he supervisor shall review and discuss in depth with the analyst, theexecution of the entire analytical testing procedure, equipment and calculation used.[e.] O nce the nature of the OOS has been identified - as an laboratory error - a repeat test must be performed and the initial test totally discarded as a reversible laboratory error. (since the initial test result was proven invalid)[f.] T he analytical or analyst error must be thoroughly documented and properly invalidated - with written reasons, together with the supervisor and analyst signatures and date of the invalidation process.INCONCLUSIVE ERRORS RETEST[g.] A n inconclusive error is an OOS where the 'supervisor-analyst investigation' did not draw a firm conclusion and the reason for the error was not clearly identified.[h.] R etest with new aliquot (replicates, if required) from the same sample, if the sampling procedure was proven OK by investigation.[i.] I f the sampling procedure is found to be in error, then re-sample the target material is undertaken and a new duplicate analysis is performed.DECISION TREE5.LIMITATION[j.] A n overview of Out-of-Specification Results procedures is provided by a decision tree flowchart. The decision tree provides a logical set of procedural steps in order to standardize the investigative procedure for all analysts when performing an OOS investigation.[f.] R e-sampling the material for a new representative sample should take place only when the original procedure was found to be clearly non-representative of the whole.6.DOCUMENTATION[k.] Out-of-specification (OOS) Test Results Report or ‘failure investigation Test Result Report’ is prepared and filed.3[End of Document]•‚ƒ„…†‡Œ•ŽEdition Number:Effective Date:APPROVEDEdition Number:Effective Date:APPROVED ØC H E C K L I S T ×SOP # A -195-02-0100OUT-of-SPECIFICATION RESULTS‘…A v e r a g i n g p a s s i n g a n d O O S T e s t R e s u l t s t o g e t h e ri s n o t p e r m i t t e d a s i t c o n c e a l s t h e f u l l a n a l y t i c a l p i c t u r e …’IDENTIFYING OOS TEST RESULTS1. Does the firms have a clear SOP spelling out the procedure and investigations required when ever an OOS result is obtained?q Yes q No 2. Are all firm's 'rejected batch' OOS results investigated as well?q Yes q No 3. Are the previous (or related) batches associated with the failed batch specification reviewed and the overall impact (on quality) evaluated?q Yes q No 4. Are written investigations undertaken and then follow-up procedures recommended in writing?q Yes q No 5. Are the investigations performed in a timely manner and follow a defensible scientific logic (see attached Decision Tree)?q Yes q No 6. Does the companies 'Investigation SOP' include the three key tenants i.e.TO INVESTIGATE - TO CONCLUDE - TO FOLLOW-UP?q Yes q No 7. Have the laboratory analysts been instructed to keep the original 'suspect test solutions' for possible reanalysis (Ref. Decision Tree)?q Yes q No 8. When an OOS has been detected does the initial review, before the investigation, check for instrument or system suitability malfunction, faulty reagents, calculation, documentation or transcribing errors?q Yes q No 9. If no clear analytical errors are detected in a 'suspect result' does a comprehensive 'failure investigation' ALWAYS follow?q Yes q No 10. Where malfunctions are identified and detected are all prior 'suspect data'evaluated and reviewed for a possible related (or similar) errors?q Yes q No 11. Are analytical failures tracked back to their original point of failure?q Yes q No 12. When a faulty lab procedure is detected, is the analytical test procedure immediately terminated (as a matter of routine)?q Yes q No 13. Have the analysts been trained to immediately report to their supervisors an obvious error or an analytical fault?q Yes q No 14. Are obvious errors (spilling, incorrect dilution, injection volume etc.)documented in the lab book and a brand new test restarted?q Yes q NoPage: 3 of 6Edition Number:Effective Date:APPROVED SOP # A -195-02-0100OUT-of-SPECIFICATION RESULTS‘…f a i l u r e i n v e s t i g a t i o n s a r e c o n d u c t e d t o d e t e r m i n ew h a t c a u s e d t h e u n e x p e c t e d O O S r e s u l t …’INVESTIGATING OOS TEST RESULTS15. Does the supervisor's 'initial assessment' follow a written in-house 'SOP procedure '?q Yes q No16. Are the retained 'suspect' sample preparations examined during the 'initialassessment' and then retested promptly on initiating the 'failure investigation'?q Yes q No 17. Where a clear error is identified, is the result immediately invalidated?q Yes q No 18.Where clear error is NOT identified, is a failure investigation conducted immediately?q Yes q No 19. Is the firm's full scale failure investigation fully predefined in writing?q Yes q No 20. Does the firm's own QC Unit perform the 'full scale failure investigation'?q Yes q No 21. Does the general review include a list of related batches which may be impacted?q Yes q No 22. Does the full scale failure investigation include the production side and the laboratory side?q Yes q No 23. Does the laboratory protocol include the two key steps - retesting the original sample and testing a new sample from the batch lot?q Yes q No 24. Retesting the original sample with a new analyst, is generally the first step after the 'initial assessment' is completed?q Yes q No 25. Are the number of re-tests (usually duplicates) specified and not exceeded? Averaging 'original suspect' and retest results is forbidden.q Yes q No 26. When improperly prepared samples are proven as faulty, then the original test results may be immediately invalidated?q Yes q No 27. The firm may re-sample when the investigation highlights that the original sample was unrepresentative?q Yes q No 28. Where the investigation concludes that the sampling method is in error a new sampling method must be developed and qualified?q Yes q No 29. To prove the original aliquot is faulty, the analyst prepares two additional aliquots and compares the three sets of results?q Yes q NoPage: 4 of 6Edition Number:Effective Date:APPROVED SOP # A -195-02-0100OUT-of-SPECIFICATION RESULTS ‘…B a t c h e s m u s t b e f o r m u l a t e d w i t h t h e i n t e n t t o p r o v i d e 100%o f t h e l a b e l e d a m o u n t …'AVERAGING IN OOS RESULTS30. Averaging results from a standard solution or a test aliquot is acceptable (i.e. averaging replicate results).q Yes q No31. Averaging results from microbial count plates are quite acceptable.q Yes q No32. Averaging a set of results, where some are OOS is not acceptable.q Yes q No33. Hiding an OOS result in any average is not acceptable.q Yes q No34. When the intent is to highlight variability within the product then averagingisnot acceptable, but RSD (CV) values are generally reported to show statistical significance.q Yes q No 35. Replicate peak responses whether test or standard should be averages as one result.q Yes q No 36. Are analysts trained, so not to average passing and OOS results together in order to hide the failing results?q Yes q No 37. Composite assays, require only one assay result and are in fact average assay values, as opposed to individual content uniformity values.q Yes q No 38.OUTLIER USE IN OOS RESULTS39. Where 'control' and 'specification' lower and upper limits are used in QC criteria an OUTLIER may be outside the control limits but inside the specifications limits? [i.e. an example of OUTLIER use.]q Yes q No 40. Analyst are trained not to assume OUTLIERS as testing errors but inherent variability in the sample.q Yes q No 41. The firm has an OUTLIERS SOP detailing the use of OUTLIER TESTS.q Yes q No 42. OUTLIERS are not permissible in Content Uniformity and Dissolution tests.q Yes q No 43. Where the intent is to measure the variability, OUTLIERS should not be used.q Yes q NoPage: 5 of 6DECISIONTREE . (IJGD Vol. 02 #07 1998)。

浅谈药品生产OOS调查的实施

错误、生产工艺相关错误，这就确定了ＯＯＳ及其调查的基本框架。随着药品质量管理的发展，ＯＯＳ的定义也不断清微，＇ｂＯＯＳ偏差是指超出常规范围，超出警戒限度，但仍在纠偏限度和企业内控标准之内，不足以影响药品质量的偏差。只需记录，并说明原因即可。２．２一般ＯＯＳ偏差
ＯＯＳ的概念源于１９９３年美国新泽ＤＡ在对Ｂａｒｒ药厂进行现场检查时发现，
保证体系的缺陷诊断，既是保证药品质量的可靠手段，又是质量体系持续改进的原动力。
其生产工艺、清洁方法没有验证，年度回顾不完整，没
药品ＯＯＳ结果调查的行业指南，探讨了如何在药品生产企业进行ＯＯＳ的调查，以寻找药品生产过程中ＯＯＳ结果调查的有
效途径。
关键词：ＯＯＳ：调查；ｃＧＭＰ
ＢｒｉｅｆＣｏｍｍｅｎｔｏｎＩｍｐｌｅｍｅｎｔｉｎｇｉｎｖｅｓｔｉｇａｔｉｏｎｏｆＯＯＳＲｅｓｕｌｔｓｄｕｒｉｎｇＰｈａｒｍａｃｅｕｔｉｃａｌＰｒｏｄｕｃｉｏｔｎ
一
晰与深化，目前，只要是超出标准的所有检验结果的，违反药品注册申请审批文件，包括ＤＭＦ文件（药物主文件）、药典及企业标准（包括中控标准），以及所有违反ＧＭＰ标准的情况都是ＯＯＳ。

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1.目的：
建立整齐、洁净、舒适、安全的工厂场所，节省资源及能源浪费，降低成本，提高公司企业形象。

2.适用范围：
适用于公司所有区域(包括生产车间、办公室、食堂、厂区公共区域)。

3.权责：
3.1 5S推行委员会主任:
3.1.1负责委员会的运作,并指挥和监督所属委员。

3.1.2主任由总经理兼任。

3.1.3全程计划执行和管制。

3.2副主任:
3.2.1在主任领导下，负责委员会的运作，指挥和监督所属委员，并于主任授权时，代行其职务。

3.2.2副主任由相关副总经理兼任。

3.2.3协助主任负责全程计划执行和管制。

3.3 秘书:
3.3.1辅助主任、副主任处理委员会事务。

3.3.2全程计划执行和管制。

3.3.3召开会议的准备与资料的整理，会议记录。

3.3.4评比分数的统计和公布。

3.3.5 5S活动的宣传
3.4 委员:
3.4.1共同参与5S活动之计划，并确实执行。

根据主任的要求，平时为5S评比
委员。

3.4.2活动办法的拟定。

3.4.3活动的宣传教育和推动等。

3.4.4定期检讨、推动改善。

3.4.5活动的检讨与争议的处理。

3.4.6其它5S相关的活动
4.定义：
4.1 5S即整理(seiri)、整顿(seitor)、清扫(seiso)、清洁(seikei)、素养(shisuke)的简称.
4.1.1整理(seiri)将要与不要的物品分开管理：要的保留,不要的丢弃.
4.1.2整顿(seitor)物品要定位、定物、定量并标示易于寻找,减少时间上的浪费.
4.1.3清扫(seitor)打扫工作场所,保持干净的状态.
4.1.4清洁(seiket)将整理、整顿、清扫三项彻底执行的状态维持.
4.1.5素养(shisuke)养成守法纪的精神及良好的作业习惯,遵守作业标准教程.
5.作业内容:
5.1整理的推行方法:
5.1.1深切认识,建立共识.
5.1.2工作场所,全盘点检.
5.1.3各部门订定“需要”与“不需要”的基准.
5.1.4对不需要物品“大扫除”.
5.2整顿的推行方法:
5.2.1落实整理工作.
5.2.2决定置放场所,划放置线.
5.2.3实施广告牌作战(目视之整顿).
5.2.4知道(在哪里,有什么,有多少)拿取归还.
5.2.5三定管制(定位、定品、定量).
5.3清扫的推行方法：
5.3.1全员动手,上下班前后五分钟将不需要的东西加以清除.
5.3.2明确清扫对象,从天花板开始.
5.3.3调查其来源,彻底根除.
5.3.4建立清扫基准共同遵守.
5.4清洁的推行方法：
5.4.1用眼睛说话,贯彻落实5S推行执行状态.
5.4.2制订各区域查检表格.
5.4.3维护干净清爽的现场.
5.4.4标示.
5.5素养的推行方法：
5.5.1落实持续推行前4S活动(至定着化为止) 5.5.2建立共同遵守的规章至养成良好的习惯.
5.5.3实施各种教育训练.
5.5.4认识企业,参与管理.
5.5.5个人修养提升,为人处事原则.
5.5.6洁身自爱,思想端正,共同进步.
5.5.7接受指责纠正,立即改正.
5.5.8推行各种精神向上活动.
5.6推行步骤：
5.6.1 5S推行计划
(1)各部门主管担任5S推行委员，要有较强的5S意念和以身作则的作风.
(2)制订5S推行责任区域图.
(3)制订5S推行时间及计划:倡导、执行、改善、确认.
5.6.2倡导
(1)对各委员进行课程深入教育训练.
(2)制订相应的规章制度.
(3)成立5S管理广告牌倡导5S.
(4)确定各区域5S责任人,代理人.
5.6.3 5S落实全员化
(1)5S随时巡查登记并利用早晚机会教育指正.
(2)加强现场内死角实施状况.
5.6.4 5S检查
(1)5S推行委员会依“5S检查表”每周对各部门进行点检,除巡查各部门缺失外并须做成检查记录.
(2)对典型缺陷拍照公布,并依“5S监查不合格报告”改善后拍照比较.
5.6.5审查
办公室主管确认点检缺失,对有缺失的部门提出处置,并要求各部门主管改善.
5.6.6确认公布
点检成绩经审查后并将于每月5日前公布于公布栏中.
5.6.7奖惩对策
5S的管理办法设定为周评比,月总结
(1)每月总评比不得低于80分(不含),凡在每月评分中低于80分且为后三名的单位,将给予罚款；前三名的单位，将给予优秀流动红旗并奖励。

(2)连续两个月低于80分且为最低的单位,另外给予部门主管处罚100元。

(3)连续三个月低于80分且为最低的单位, 另外给予部门主管处罚300元。

(4)连续两个月高于95分,且在评比单位中评比分数最高的单位，另外给予该部门主管奖励
100元。

(5)连续三个月高于95分,且在评比单位中评比分数最高的单位,，另外给予该部门主管奖励300元。

（6）如检查人员不及时到位，部门扣5分。

（7）定期检查：每周四或周五下午15：00。

5.7推行效果评审
5.7.1 每个月各单位评分标准及评分查检表进行重新审核更正不适用的地方，或在推进过程中的某个单位申请后更改在评审过程中，推进中心为监督，稽核确认作用。

5.7.2 定期或不定期，由推行委员会对于5S推行结果召集推行小组进行检讨其效果，并分析原因后，采取纠正预防措施改善。

6.附件：
6.1 5S检查表
6.2 5S推行委员会架构图
6.3 5S区域划分图
6.4 5S追踪改善报告。