翻译稿-European%2BMedicines%2BAgency%2Bconfirms

European Medicines AgencyInspectionsLondon, 21 September 2005Doc. Ref: EMEA/INS/GMP/318222/2005/Correction GMP Annex 1: Proposals for amendment to the environmental classification table for particles and associated text, amendment to section 42 concerning acceptance criteria for media simulations, amendment to section 52 concerning bio-burden monitoring, and additional guidance in section 88 on the sealing ofvials.The existing text of clause 3 remains unchanged up to and including the following: Grade C and D: Clean areas for carrying out less critical stages in the manufacture of sterile products.The remaining text of clause 3 up to but not including the following:Other characteristics such as temperature and relative humidity depend on the product and nature of the operations carried out. These parameters should not interfere with the defined cleanliness standard.and clause 4 is replaced by:Clean room and clean air device classificationClean rooms and clean air devices should be classified in accordance with EN ISO 14644-1. Classification should be clearly differentiated from operationalprocess environmental monitoring. The maximum permitted airborne particleconcentration for each grade is given in the following table.at rest in operationGrade Maximum permitted number of particles/m3 equal to or aboveµm 5.0µm0.5 µm 5.0µm 0.5A 3 500 1* 3 500 1*B 3 500 1* 350 000 2 000C 350 000 2 000 3 5000 000 20 000D 3 500 000 20 000 Not defined Not defined * The maximum permitted number of particles at ≥5.0µm is established at 1/ m but for reasons related to false counts associated with electronic noise, stray light, etc. a limit of 20/m3 could be considered.For classification purposes, in Grade A zones, a minimum sample volume of1m 3 should be taken. Grade A and Grade B (at rest) is similar to EN ISOClass 5 for particles ≥0.5 µm. For classification purposes EN/ISO 14644-1methodology defines both the minimum number of sample locations and thesample size based on the class limit of the largest considered particle size. Itshould be noted that this will give rise to a sampling time of about 35 minutesat each location when using a particle counter with a sample rate of 28.3litre/minute (one cubic-feet per minute).Portable particle counters with a short length of sample tubing should be used for classification purposes because of the relatively higher rate of precipitation of particles ≥5.0µm particles in remote sampling systems with long lengths of tubing. Isokinetic sample heads shall be used in unidirectional airflowsystems.“In operation” classification may be demonstrated during media fills becauseof the worst-case simulation required for this.EN ISO 14644-2 provides information on testing to demonstrate continuedcompliance with the assigned cleanliness classifications.5.Clean room and clean air device monitoringClean rooms and clean air devices should be routinely monitored in operation and the monitoring locations based on formal risk analysis study and resultsobtained during the initial classification of rooms and/or devices.For Grade A zones a continuous or frequent sampling particle monitoringsystem should be used, except where justified, e.g. the filling of live virusvaccines. It is recommended that a similar system be used for Grade B zonesalthough the sample frequency may be decreased. Such systems may consistof independent particle counters; or have one particle counter that is linked toa number of sampling ports sequentially via a tubing manifold system. Whereremote sampling systems are used, the length of tubing and the radii of anybends in the tubing must be validated. The Grade A zone should be monitored at such a frequency that all interventions and other transient events would becaptured and alarms triggered if excursions from defined operating normsoccur.The sample sizes taken for monitoring purposes using automated systems will usually be a function of the sampling rate of the system used. It is notnecessary for the sample volume to be the same as that used for formalclassification of clean rooms and clean air devices.6. In Grade A and B zones, the monitoring of the 5.0 µm particle concentrationcount takes on a particular significance as it is an important diagnostic tool for early detection of failure. The occasional indication of µm particle counts≥5.µmay be false counts due to electronic noise, stray light, coincidence, etc.However consecutive or regular counting of low levels is an indicator of apossible contamination event and should be investigated. Such events mayindicate early failure of the HVAC system, filling equipment failure or mayalso be diagnosis of poor practices during machine set-up and routineoperation.7. The particle limits given in the table for the “at rest” state should be achievedafter a short “clean up” period of 15-20 minutes (guidance value) in anunmanned state after completion of operations. It is accepted that it may notalways be possible to demonstrate low levels of particles ≥5 µm at the point of fill when filling is in progress, due to the generation of particles or dropletsfrom the product itself.8. For Grade D areas in operation, the requirements and limits will depend on thenature of the operations carried out, but the recommended “clean up period”should be attained.The new clause 9 takes up the existing text of clause 3 at the following point:Other characteristics such as temperature and relative humidity depend on the product and nature of the operations carried out. These parameters should notinterfere with the defined cleanliness standard.The existing clauses from 5 to 41 are unchanged but re-numbered as 10-46.Clause 47 (formerly clause 42) is changed as follows:47. Validation of aseptic processing should include a process simulation test usinga nutrient medium (media fill). Selection of the nutrient medium should bemade based on dosage form of the product and selectivity, clarity,concentration and suitability for sterilisation of the nutrient medium. Theprocess simulation test should imitate as closely as possible the routine aseptic manufacturing process and include all the critical subsequent manufacturingsteps. It should also take into account various interventions known to occurduring normal production as well as worst-case situations. Process simulation tests should be performed as initial validation with three consecutivesatisfactory simulation tests per shift and repeated at defined intervals andafter any significant modification to the HVAC-system, equipment, processand number of shifts. Normally process simulation tests should be repeatedtwice a year per shift and process. The number of containers used for mediafills should be sufficient to enable a valid evaluation. For small batches, thenumber of containers for media fills should at least equal the size of theproduct batch. The target should be zero growth and the followingrecommendations apply:i W hen filling fewer than 5000 units, no contaminated units should bedetected.ii When filling 5,000 to 10,000 units:1 contaminated unit should result in an investigation, includingconsideration of a repeat media fill.2 contaminated units are considered cause for revalidation, followinginvestigation.iii When filling more than 10,000 units:1 contaminated unit should result in an investigation.2 contaminated units are considered cause for revalidation, followinginvestigation.Investigation of gross failures should include the potential impact on thesterility assurance of batches manufactured since the last successful media fill.Clauses 43 to 51 are unchanged but re-numbered as 48-56. Clause 57 (formerly clause 52) is changed as follows:57. The bioburden should be monitored before sterilisation. There should beworking limits on contamination immediately before sterilisation, which arerelated to the efficiency of the method to be used. Bioburden assay should beperformed on each batch for both aseptically filled product and terminallysterilised products. Where overkill sterilisation parameters are set forterminally sterilised products, bioburden might be monitored only at suitablescheduled intervals. For parametric release systems, bioburden assay should be performed on each batch and considered as an in-process test. Whereappropriate the level of endotoxins should be monitored. All solutions, inparticular large volume infusion fluids, should be passed through a micro-organism-retaining filter, if possible sited immediately before filling. Clauses 53 to 87 are unchanged but re-numbered as 58-92. Clause 93 (formerly clause 88) is changed as follows:93. Containers should be closed by appropriately validated methods. Containersclosed by fusion, e.g. glass or plastic ampoules should be subject to 100%integrity testing. Samples of other containers should be checked for integrityaccording to appropriate procedures.Partially stoppered freeze drying vials should be maintained under Grade Aconditions at all times, from the time of partial stoppering to capping.The container closure system for aseptically filled vials is not fully integraluntil the aluminium cap has been crimped into place. Vials should bemaintained in Grade A environment until the cap has bee crimped. As theequipment used to crimp vial caps can generate large quantities of non-viableparticulates, the equipment should be located at a separate station equippedwith adequate air extraction. The capping station may not be able to meetGrade A conditions for non-viable particles in the “in operation” condition but should meet the microbiological requirements.Clauses 89 to 93 are unchanged but re-numbered as 94-98.。

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2009年EMA内部再次改组，以适应日益复杂的 业务。 目前，EMA有超过3500名的专家，500多名的 员工 经费来自会员国的 国家主管机关(National Competent Authority, NCA)。
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2004年起草新的路线 从欧盟内至全球
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2007.7
儿科委员会（PDCO）
2007.11.13
欧洲议会和理事会条例（EC）No 1394/2007 (生效时间2008.12.30) 设立先进疗法委员会（CAT）
• 至此，EMA下属科学委员会为6个
– – – – – – 人用药品委员会（CHMP） 兽用药品委员会（CVMP） 孤儿药品委员会（COMP） 草药药品委员会（HMPC） 儿科药品委员会（PDCO） 先进疗法委员会（CAT）
2004.4.30（EC）No.2004/726法规
盟内药品上市许可程序 行政管理
• EMEA及其科学委员会机构和成员的变化
为了简化起见 EMEA更名为EMA（2004.6）
2004.9
药草草品委员会(HMPC) 2004/24/EC指令 第16h条（2004.3)
职能变化
1993年通过，1995.1.1正式实施
一项法规（EEC NO.2309/93） 三项法令（93/39/EEC,93/40/EEC,93/41/EEC）。
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EMEA (European Medicines Evaluation Agency)成立
1995.2.1正式投入运转 原欧盟药品化妆品部（Pharmaceuticals &Cosmetics）负责对其指导 总部：位于伦敦最东头的金丝雀码头地区 EMEA正式受理欧盟各成员国人用和兽用 专卖药品的上市申请

各国药监局网站U.S.：Food and Drug Administration（美国：食品和药品管理局）UK: Medicines and Healthcare Products Regulatory Agency（英国：药物和保健产品监管署）UK: Medical Devices Agency（英国：医疗器械署）Ukraine: Ministry of Health（乌克兰：卫生部）Sweden: Medical Products Agency（瑞典：药品署）Spain: Spanish Drug Agency（西班牙：西班牙药物署）India: Agricultural and Processed Food Products Export Development Authority（印度：农产和加工食品出口发展局）India: Ministry of Health and Family Welfare（印度：卫生和家庭福利部）India: Ministry of Food Processing Industries（印度：食品加工产业部）India: Ministry of Consumer Affairs, Food & Public Distribution（印度：消费者事务、食品和公共分配部）UK: National Institute for Biological Standards and Control（英国：国家生物学标准和管制所）UK: Department of Health（英国：卫生部）Turkey: Ministry of Health（土耳其：卫生部）Switzerland: Federal Veterinary Office（瑞士：联邦兽医办公室）Switzerland: Agency for Therapeutic Products（瑞士：治疗产品署）Switzerland: Federal Office of Public Health（瑞士：联邦公共卫生办公室）Sweden: National Board of Health and Welfare（瑞典：国家卫生与福利委员会）Spain: Ministry of Health and Consumption（西班牙：卫生与消费部）Slovenia: Institute of Public Health（斯洛文尼亚：公共卫生所）Slovenia: Ministry of Public Health（斯洛文尼亚：公共卫生部）Slovak Republic: State Institute for Drug Control（斯洛伐克共和国：国家药物管制所）San Marino: Ministry of Health and Social Security（圣马力诺：卫生与社会保障部）UK: Food Standards Agency（英国：食品标准署）UK: Veterinary Medicines Directorate（英国：兽药理事会）Papua New Guinea: Department of Health（巴布亚新几内亚：卫生部）Philippines: Department of Health（菲律宾：卫生部）Philippines: National Food Authority（菲律宾：国家食品局）Singapore: Ministry of Health（新加坡：卫生部）Singapore: Health Sciences Authority（新加坡：卫生科学局）Singapore: Ministry of Environment（food control）（新加坡：环境部［食品管制］）Singapore: Agri-food and Veterinary Authority（新加坡：农产食品和兽医局）Sri Lanka: Ministry of Health ,Nutrition & Welfare（斯里兰卡：卫生、营养和福利部）Thailand: Ministry of Public Health（泰国：公共卫生部）Thailand: Food and Drug Administration（泰国：食品药品管理局）New Zealand: Medicines and Medical Devices Safety Authority（新西兰: 药物和医疗器械安全局）New Zealand: Ministry of Health（新西兰：卫生部）Korea: Food and Drug Administration（韩国：食品药品管理局）Malaysia: National Pharmaceutical Control Bureau（马来西亚：国家药品管制局）Japan: Pharmaceuticals and Medical Devices Evaluation Center（日本：药品和医疗器械评价中心）Indonesia: Ministry of Health（印尼：卫生部）Russian Federation: Ministry of Public Health（俄罗斯：公共卫生部）Romania: Ministry of Health and the Family（in Romanian）（罗马尼亚：卫生与家庭部）Portugal: Ministry of Health（葡萄牙：卫生部）Poland: Drug Institute（波兰：药物所）Poland: Ministry of Health and Social Security（波兰：卫生与社会保障部）Norway: Norwegian Medicines Agency（挪威：挪威药物署）Norway: Norwegian Board of Health（挪威：挪威卫生委员会）Norway: Ministry of Health and Social Affairs（挪威：卫生与社会事务部）Netherlands: Inspectorate for Health Protection and Veterinary Public Health（荷兰：健康保护和兽医公共卫生检查处）Netherlands: Medicines Evaluation Board（荷兰：药物评价委员会）Netherlands: Ministry of Health, Welfare and Sport（荷兰：卫生、福利与体育部）Malta: Ministry of Health（马耳他：卫生部）Luxembourg: Ministry of Health（卢森堡：卫生部）Lithuania: State Medicines Control Agency（立陶宛：国家药物管制署）Lithuania: Ministry of Health（立陶宛：卫生部）Latvia: State Agency of Medicines（拉脱维亚：国家药物署）Italy: National Institute of Health（意大利：国家卫生所）Italy: Ministry of Health（意大利：卫生部）Ireland: Medicines Board（爱尔兰：药物委员会）Ireland: Department of Health and Children（爱尔兰：卫生与儿童部）Iceland: Environmental and Food Agency（冰岛：环境与食品署）Iceland: Medicines Control Agency（冰岛：药物管制署）Hungary: National Institute of Pharmacy（匈牙利：国家药房所）Hungary: Ministry of Health, Social and Family Affairs（匈牙利：卫生、社会与家庭事务部）Greece: Hellenic Food Authority（希腊：希腊食品局）Greece: National Organization for Medicines（希腊：国家药物组织）Greece: Ministry of Health and Welfare（希腊：卫生与福利部）Germany: Federal Institute for Drugs and Medical Devices（德国：联邦药物与医疗器械所）Germany: Ministry of Health（德国：卫生部）Georgia: Ministry of Labor, Health and Social Security（格鲁吉亚：劳动、卫生和社会保障部）France: National Agency for Veterinary Medicinal Products（法国：国家兽用药品署）France: General Directorate of Competition, Consumption and Repression of Fraud（food control）（法国：竞争、消费和抑制欺诈总理事会［食品管制］）France: Sanitary Safety of Health Products Agency（法国：健康产品卫生安全署）France: Ministry of Health（法国：卫生部）Finland: National Food Agency（芬兰：国家食品署）Finland: National Agency for Medicines（芬兰：国家药物署）Finland: Ministry of Social Affairs and Health（芬兰：社会事务和卫生部）Denmark: Veterinary and Food Administration（丹麦：兽医和食品管理局）Estonia: State Agency of Medicines（爱沙尼亚：国家药物署）Denmark: Medicines Agency（丹麦：药物署）Denmark: Ministry of Health（丹麦：卫生部）Czech Republic: State Institute for Drug Control（捷克共和国：国家药物管制所）Czech Republic: Ministry of Health（捷克共和国：卫生部）Croatia: Ministry of Health（克罗地亚：卫生部）Bulgaria: Drug Agency（保加利亚：药物署）Bulgaria: Ministry of Health（保加利亚：卫生部）Belgium: Federal Agency for the Safety of the Food Chain（比利时：联邦食物链安全署）Belgium: Pharmaceutical Inspectorate（比利时：药品检查处）Armenia: Drug and Medical Technology Agency（亚美尼亚：药物和医学技术署）Armenia: Ministry of Health（亚美尼亚：卫生部）Andorra: Ministry of Health and Welfare （安道尔：卫生与福利部）European Commission: DG Fisheries（欧洲委员会：DG渔业）European Commission: DG Agriculture（欧洲委员会：DG农业）European Commission: DG Enterprise: Pharmaceuticals and Cosmetics（欧洲委员会：DG企业：药品和化妆品）European Commission: DG Enterprise（欧洲委员会：DG企业）European Agency for the Evaluation of Medicinal Products（欧洲药品评价署）United Arab Emirates: Federal Department of Pharmacies（阿拉伯联合酋长国：联邦药房部）United Arab Emirates: Ministry of Health（阿拉伯联合酋长国：卫生部）Saudi Arabia: Ministry of Health（沙特阿拉伯：卫生部）Palestinian Authority: Ministry of Health（巴勒斯坦：卫生部）Lebanon: Ministry of Health（黎巴嫩：卫生部）Jordan: Ministry of Health（约旦：卫生部）Israel: Ministry of Health（以色列：卫生部）Zimbabwe: Ministry of Health and Child Welfare（津巴布韦：卫生与儿童福利部）Uganda: Ministry of Health（乌干达：卫生部）Tunisia: Office of Pharmacy and Medicines（突尼斯：药房与药物办公室）Tunisia: Ministry of Public Health（突尼斯：公共卫生部）Swaziland: Ministry of Health and Social Welfare（斯威士兰：卫生与社会福利部）South Africa: Department of Health（南非：卫生部）Morocco: Ministry of Public Health（摩洛哥：公共卫生部）Mauritius: Ministry of Health & Quality of Life（毛里求斯：卫生和生活质量部）Kenya: Ministry of Health（肯尼亚：卫生部）Botswana: Ministry of Health（博茨瓦纳：卫生部）Benin: Ministry of Health（贝宁：卫生部）Venezuela: Ministry of Health and Social Development（委内瑞拉：卫生与社会发展部）U.S.：Substance Abuse Prevention, Addictions Treatment and Mental Health Services（美国：药物滥用防止、毒瘾治疗与精神卫生局）U.S.：National Institutes of Health（美国：国家健康研究所）U.S.：National Agricultural Library USDA/FDA Foodborne Illness Education Information Center（美国：国家农业图书馆的USDA/FDA食源性疾病教育信息中心）Joint Institute for Food Safety and Applied Nutrition（食品安全和应用营养联合研究所）National Center for Toxicological Research（国家毒理学研究中心）Center for Veterinary Medicine（兽药中心）Center for Food Safety and Applied Nutrition（食品安全和应用营养中心）Center for Drug Evaluation and Research（药品评价和研究中心）Center for Devices and Radiological Health（器械和辐射健康中心）Center for Biologics Evaluation and Research（生物制品评价和研究中心）U.S.：Drug Enforcement Administration（美国：毒品强制执法管理局）U.S.：Department of Health and Human Services（美国：健康和人类服务部）U.S.：Centers for Disease Control and Prevention 美国：疾病控制与预防中心Uruguay: Ministry of Public Health（乌拉圭：公共卫生部）Trinidad & Tobago: Bureau of Standards（特立尼达和多巴共和国：标准局）Trinidad and Tobago: Ministry of Health（特立尼达和多巴共和国：卫生部）Peru: General Directorate of Pharmaceuticals, Devices and Drugs（秘鲁：药品，器械与药物理事会）Peru: Ministry of Health（秘鲁：卫生部）Panama: Ministry of Health（巴拿马：卫生部）Nicaragua: Ministry of Health（尼加拉瓜：卫生部）Netherlands Antilles: Department of Public Health and Environmental Protection（荷兰安的列斯群岛：公共卫生与环境保护部）Jamaica: Ministry of Health（牙买加：卫生部）Guyana: National Bureau of Standards（圭亚那：国家标准局）Guyana: Ministry of Health（圭亚那：卫生部）Guatemala: Ministry of Health（危地马拉：卫生部）El Salvador: Ministry of Public Health and Social Assistance（萨尔瓦多：公共卫生与社会援助部）Ecuador: Ministry of Public Health（厄瓜多尔：公共卫生部）Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos（哥伦比亚：INVIMA国家药物和营养警戒所）Colombia: Ministry of Health（哥伦比亚：卫生部）Brazil: National Health Surveillance Agency（巴西：国家卫生监督署）Brazil: Ministry of Health（巴西：卫生部）Bolivia: Ministry of Health and Social Welfare（玻利维亚：卫生与社会福利部）Belize: Ministry of Health（洪都拉斯：卫生部）Argentina: Ministry of Health（阿根廷：卫生部）Argentina: National Administration of Drugs, Foods and Medical Technology（阿根廷：国家药物、食品与医疗技术管理局）美国疾病控制中心。

european journal of medicinal chemistry审稿状态欢迎来到我的专栏，今天的主题是关于《European Journal of Medicinal Chemistry》的审稿状态。

在这篇文章中，我将一步一步回答您关于这个期刊审稿状态的问题。

首先，我们需要了解《European Journal of Medicinal Chemistry》这本期刊。

该期刊是由欧洲药物化学协会（European Federation for Medicinal Chemistry）主办的国际期刊，专注于药物化学和医药领域的研究。

如果您的研究工作涉及到这些领域，那么将您的研究成果投稿到这本期刊是一个很好的选择。

接下来，我们来讨论一下审稿状态的定义。

审稿状态是指您的论文在投稿后经历的不同阶段和过程。

一般来说，审稿状态可以包括以下几种：已提交、待审阅、审稿中、修订中、待出版、已出版等。

不同的期刊可能有不同的审稿状态定义，所以具体的状态细节可能会有所不同。

那么，《European Journal of Medicinal Chemistry》的审稿状态是如何划分的呢？根据该期刊的官方网站上的信息，审稿状态可以分为以下几个阶段：1.已提交：在您的论文投稿后，该期刊将为您生成一个提交号，并在系统中显示为“已提交”状态。

这表示您的稿件已成功提交到该期刊，等待编辑的安排。

2.待审阅：一旦您的论文成功进入到编辑的系统中，它的状态将会变为“待审阅”。

编辑将对您的论文进行初步评估，并决定是否将其分配给专业领域内的审稿人进行评审。

3.审稿中：一旦您的论文被分配给审稿人进行评审，状态将会变为“审稿中”。

审稿人将会对您的论文进行详细评审，并提出建议和修改意见。

4.修订中：如果审稿人提出了一些修改意见或建议，您需要根据他们的意见进行修改。

一旦您完成了修订并提交给编辑，您的论文状态将会变为“修订中”。

审稿人将会重新评估您的修订稿，并决定是否接受您的修改。