红字部分为本次有修订的条款。
Certification of Substances Division
HB/CB
PUBLIC DOCUMENT
(Level 1)
English only/Anglais seulement
PA/PH/CEP (08) 17, R4
Strasbourg, June 2014
Certification of suitability to Monographs of the European Pharmacopoeia
欧洲药典各论适用性证书
SUSPENSION OR WITHDRAWAL OF
A CERTIFICATE OF SUITABILITY, CLOSURE OF AN APPLICATION
CEP的搁置或撤消，CEP申请的关闭
Address: 7 allée Kastner CS 30026 - F 67081 Strasbourg
Telephone: 33 (0) 3 88 41 30 30 - E-mail:cep@edqm.eu - Fax: 33 (0) 3 88 41 27 71
For implementation 实施时间 | July 2014 2014年7月 |
This document describes the policy of the EDQM for suspension or withdrawal of a certificate of suitability (CEP) and for closure of a CEP application in accordance with the provisions of Resolution AP-CSP (07) 1 of the Council of Europe.
本文说明了根据欧洲理事会AP-CSP(07)1法规，EDQM对CEP搁置或撤消、CEP申请关闭的政策。
1. DEFINITIONS 定义
? CEP: Certificate of suitability to the monographs of the European Pharmacopoeia, granted by the EDQM.
CEP：欧洲药典适用性证书，由EDQM颁发。
? Suspension: Temporary cancellation of a granted CEP made either upon request by the holder of the CEP or by a decision of the EDQM. Under certain conditions, the CEP may be restored.
搁置：根据CEP持有人要求，或EDQM的决定对已颁发的CEP进行临时取消的行为。在某些情况下，CEP可以恢复。
? Withdrawal: Definitive cancellation of a granted CEP made either upon request by the holder of the CEP or by a decision of the EDQM.
撤消：根据CEP持有人要求或EDQM的决定，对已颁发的CEP进行永久取消的行为。
? Closure: Cancellation of an on-going CEP application made either upon request of the holder of the CEP or by a decision of the EDQM.
关闭：根据CEP持有人的要求，或EDQM的决定，对在申请或审评过程中的CEP申请进行取消的行为。
? Hearing A hearing provides an opportunity for the applicant or the holder of a CEP to submit a written request for re-consideration of a decision taken by the EDQM Ad hoc Committee (Terms of Reference section 2.6.) regarding the validity of a CEP or an application for a CEP, either in the context of the EDQM inspection programme or in the context of the evaluation of a CEP application.
听证会：听证会提供给CEP申请者或持有者一个机会，如果他们对EDQM关于CEP有效性、CEP申请有效性、EDQM检查程序或CEP申请的评价所作出的决定有异议，可以进行申诉。
2. SCOPE 范围
This policy is applicable, but not limited to, the following situations:
本政策适用于但不限于下列情形
2.1. Suspension of a CEP: 搁置
2.1.1 The Ad hoc Committee may decide to suspend a CEP in the following situations: 下列情况下EDQM可能决定搁置一个CEP
— Inspection of a company, carried out in the framework of the EDQM Certification scheme, shows critical and/or major deficiencies leading to the conclusion that the company does not operate in compliance with EU GMP and, therefore, presents a potential risk for public health, and/or the inspection shows that the manufacturing process does not comply with the dossier submitted for the CEP.
— 根据EDQM认证计划的要求对公司进行检查中发现严重和/或主要缺陷，得到结论公司未执行欧洲GMP，和/或表明未按CEP文件内容进行生产
— Inspection of a company carried out by an inspectorate of a European Economic Area (EEA) member state or a country with which the EU has a Mutual Recognition Agreement on GMP inspections of APIs (MRA) shows that the company does not operate in compliance with GMP and, where the company has submitted CEP application(s), their validity is likely to be affected by the conclusions of the inspection.
— 由EEA（欧洲经济区）成员国，或与欧盟具有GMP检查共认协议（MRA）的国家对公司实施检查，得到结论公司未执行GMP，并且公司向该国提交CEP的，则CEP有效性可能会受到检查结果的影响
— A CEP dossier is not in compliance with the requirements of the Certification procedure and the holder has not submitted suitable information to maintain it.
— 申请过程不符合程序要求，持有者未能提交适当的信息维护
2.1.2 The suspension of a CEP may also be requested by the holder of a CEP, e.g. if the CEP holder is not able to fulfil the commitments of the submitted CEP dossier. Typical examples are temporary cessation of production, upgrades or a partial destruction of the production site, or a temporary inability to meet the requirements of a revised Ph. Eur. monograph. CEP可以由持有者申请搁置，例如，如果CEP持有人不能履行提交的CEP文件的承诺。典型的例子是生产暂停、升级，或生产厂区部分改造，或暂时不能满足修订后的EP各论。
A suspension is limited to a period of 2 years. Failure to meet the conditions to lift a suspension leads to the withdrawal of the CEP if no justified extension to the suspension has been requested by the CEP holder and accepted by the EDQM.
搁置为期2年。如果2年内CEP持有人未向EDQM提出合理的延期申请，并由EDQM接受，2年内不能满足条件取消搁置的，CEP将会被撤消。
2.2. Withdrawal of a CEP: CEP的撤消
2.2.1 A CEP may be withdrawn by the EDQM Ad hoc Committee, for example, in the following situations: 在下列情况下，CEP可能会由EDQM特设委员会撤消，例如
— After an EDQM inspection, in cases where urgent action needs to be taken (a public health issue) and no corrective actions are considered possible.
— 在EDQM检查后，如果需要采取紧急措施（公共健康因素），或者不可能有适当的整改措施
— When an EDQM inspection has revealed that the CEP dossier consists of falsified data or when there is evidence of massive and systematic falsification of documents on site.
— EDQM检查中发现CEP文件包括造假数据，或有证据显示工厂文件大量系统性造假
— After a CEP suspension, when the company is not able to fulfil the requirements of the Certification procedure with regards to the updating of the CEP dossier and compliance with GMP (e.g. repeated GMP non-compliance).
— 在CEP搁置后，工厂未能满足认证程序的要求进行CEP文件更新，及符合GMP要求（例如，重复GMP缺陷）
— If a CEP dossier is not in compliance with the requirements of the Certification procedure and the holder is not able to provide suitable information to maintain it.
— 如果CEP文件与认证程序要求不符合，持有人无法提供适当的信息来维持CEP
— If the CEP holder no longer exists or has definitively ceased production of the substance without informing the EDQM.
— 如果CEP持有人不再存在，或完全停止该产品的生产而未通知EDQM
— When a company refuses to be inspected, either at receipt of the EDQM notification, at the arrival of inspectors on site, or during the inspection. This includes any oral or written request from the company to discontinue an inspection, or delaying or restricting access to documents or areas which are considered part of the inspection scope.
— 公司在收到EDQM通知时，或在检查团到达现场时，或在检查期间拒绝接受检查，其中包括公司以口头或书面方式要求中断检查，或延误或拒绝提供文件或拒绝让检查官进入被认为是检查覆盖范围的区域
2.2.2 A CEP may be withdrawn by the holder of the CEP due to, for example, cessation of production, closure of the site, or because the holder no longer wishes to retain the CEP. 在以下情况下，CEP可以由CEP的持有人进行撤消，例如，生产停止、工厂关闭、持有人不再希望持有该CEP。
A CEP that has been withdrawn cannot be restored. A new CEP application has to be submitted and will be treated as such.
CEP一经撤消，无法恢复。只能通过程序申请新的CEP。
2.3. Closure of a CEP application: CEP申请的关闭
2.3.1 The EDQM Ad Hoc Committee may decide to close a CEP application in the following situations: 在下述情况下，EDQM特设委员会可能会决定关闭CEP申请
— Inspection of a company carried out in the framework of the EDQM Certification scheme shows critical and/or major deficiencies leading to the conclusion that the company does not operate in compliance with EU GMP and, therefore, presents a potential risk for public health, and/or the inspection shows that the manufacturing process does not comply with the dossier submitted for the CEP application.
— EDQM根据认证计划对公司进行检查过程中发现，工厂存在关键和/主要缺陷，结论为工厂未按照EU GMP运作，从而对公众健康形成潜在风险，和/或检查显示生产工艺与提交CEP文件不符合
— Inspection of a company carried out by an inspectorate of a European Economic Area (EEA) member state or a country with which the EU has a Mutual Recognition Agreement on GMP inspections of APIs (MRA) shows that the company does not operate in compliance with GMP and, where the company has submitted CEP application(s), their validity is likely to be affected by the conclusions of the inspection.
— 欧洲经济区（EEA）的任一成员国，或与欧盟存在原料药GMP检查互认协议（MRA）的国家对公司的检查表明工厂操作不符合GMP要求，如果工厂已提交CEP申请，其有效性可能会受到检查结论的影响。
— Refusal by a company to be inspected in the framework of the EDQM Certification scheme, i.e. the CEP applicant does not fulfil its commitment of willingness to be subject to an inspection.
— EDQM根据认证计划对公司发出的检查要求被公司拒绝，即CEP申请者不履行其愿意接受检查的承诺。
2.3.2 The assessors of the Certification procedure may decide to close a CEP application in the following situations: 在下列情形下，认证评审官可能决定关闭CEP申请
— If, after assessment of the initial application and the reply to a deficiency letter, the information provided by the CEP applicant does not demonstrate compliance with the requirements of the Certification procedure, leading to the conclusion that a CEP cannot be granted.
— 如果在经过初次审核后，对缺陷信的回复中，CEP申请者所提供的信息未能证明其符合认证程序的要求，则会导致不能签发CEP决定
— If the CEP applicant failed to provide an answer to a request for information in time.
— 如果CEP申请人未能及时提供所要求的信息
2.3.3 A CEP applicant may also request the closure of a CEP application. A letter should be sent by the applicant to EDQM asking for the closure. Fees are not refunded. CEP申请者也可以要求关闭CEP申请。申请人应向EDQM以信件形式提交申请关闭，已缴费用不退。
Note: 注
? A CEP that reaches the 5-year validity period and for which the holder has not submitted a request for renewal expires automatically and is, therefore, invalid at the date of expiry. This case is considered outside of the scope of this procedure.
? CEP有效期为5年，如果持有人未能提交更新申请，则到期自动失效。该情形不属于本程序的讨论范围。
? In cases where several manufacturing sites are covered by a CEP and when an inspection of one site shows critical and/or major deficiencies leading to the conclusion that it does not operate in compliance with EU GMP or does not comply with the dossier submitted for the CEP, the EDQM requires that the CEP holder initiates a revision of the respective CEP deleting the concerned manufacturing site from the scope of the CEP.
? 如果一个CEP中有几个生产场所，对其中一个场所的检查发现关键和/或重大缺陷，导致检查结论为不符合EU GMP，或与申报的CEP资料不符，则EDQM会要求该CEP持有人对相应的CEP进行修订，从CEP的范围中删除该生产场所。
3. DECISION-MAKING PROCESS AND COMMUNICATION TO THE CEP HOLDER 决定过程及与CEP持有人的沟通
3.1. Suspension of a CEP CEP搁置
Any suspension of a CEP must be justified: 所有CEP搁置必须进行说明
— When advised by the EDQM Certification of Substances Division in the situations described in point 2 (Scope No 2.1.1) above, by a justified recommendation from the relevant scientific officer (assessor or inspector).
— 如果是由EDQM认证中心根据上述第2点（范围2.1.1）提出，由相关的科学管理人员（评审员或现场检查官）填写建议表说明
— When requested by the CEP holder: By a letter sent to the EDQM asking for a suspension, explaining the reasons for the request and proposing a timetable for its restoration (Scope No 2.1.2).
— 如果是由CEP持有人提出，则由持有人向EDQM提交一份要求搁置的申请函，说明原因及恢复时间表（范围2.1.2）
In both cases, the Internal Decision Board (see Terms of Reference) reviews the recommendation for suspension and any supportive information and submits proposals to the Ad hoc Committee on the actions to be taken. The Ad hoc Committee decides on the suspension of the relevant CEP(s), as well as on the conditions for restoration and the information to be forwarded to the relevant authorities. The Ad hoc Committee renders its decision generally within two weeks after the end of the inspection campaign or the receipt of the request by the holder of the CEP(s). The detailed reasons (e.g. a list of critical and major deficiencies), the length of the suspension and the conditions for its restoration are given in the decision and communicated to the CEP holder.
上述两种情况下，内部决定委员会（见参考术语）将对搁置建议和支持性信息进行审核，将需要采取的措施提案上交特设委员会。特设委员会决定是否对相关CEP进行搁置，决定恢复的条件和需要送达各相关药监部门的信息。特设委员会一般会在一个检查周期结束后，或收到CEP持有人申请后两周内做出决定。具体原因（例如，关键和主要缺陷的清单）、搁置的时限、恢复的条件会在决定书中一并给出，并通知CEP持有人。
3.2. Withdrawal of a CEP CEP的撤消
Any withdrawal of a CEP must be justified: 对CEP的撤消必须进行说明
— When advised by the EDQM Certification of Substances Division in the situations described in point 2 (Scope No. 2.2.1) above, by a justified recommendation from the relevant scientific officer (assessor or inspector).
— 如果撤消要求由EDQM认证中心根据上述第2点（范围2.2.1）中情节做出，则由相关科学管理人员（评审员或现场检查官）提交建议表格进行说明
— Or by a letter from the CEP holder to the EDQM asking for the withdrawal of the CEP and explaining the reasons for the request (Scope No. 2.2.2).
— 也可以由CEP持有人通过向EDQM递交申请函，要求撤消CEP，并说明撤消的原因（范围2.2.2）
In certain cases when a CEP holder requests a withdrawal of a CEP, the Internal Decision Board may review the request and any supportive information (e.g. public health risk or GMP non-compliance). If necessary the Ad hoc Committee endorses the actions to be taken.
在某些情况下，如果CEP持有人要求撤消CEP，内部决定委员会可能会对要求和支持性信息进行审核（例如，公众健康风险或GMP不符合性）。必要时，特设委员会会对需要采取的措施进行评论。
When the withdrawal of a CEP is proposed by the EDQM Certification of Substances Division, the Internal Decision Board reviews the relevant recommendations for withdrawal, together with the supporting information. If there is a potential risk for public health or GMP non-compliance, proposals are submitted to the Ad hoc Committee on the actions to be taken. The Ad hoc Committee then decides on the withdrawal of the relevant CEP(s) and the information to be forwarded to the relevant authorities. The Ad hoc Committee renders its decision generally within two weeks after the end of the inspection campaign or receipt of the withdrawal request by the CEP holder.
如果CEP的撤消要求由EDQM认证中心提出，则内部决定委员会会对相关撤消建议与支持性文件进行审核。如果对公众健康存在风险，或有GMP不符合风险，则委员会向特设委员会提交需采取措施的提案。特设委员会作出是否对相关CEP撤消的决定，并将相关信息送达相关的药监机构。特设委员会一般会在检查周期结束后，或收到CEP持有人申请的两周后做出决定。
The detailed reasons for withdrawal (e.g. a list of critical and major deficiencies) are given in the decision and communicated to the CEP holder.
撤消的具体原因（例如，关键或主要缺陷的清单）会在决定中列出，并通知CEP持有人。
3.3. Closure of an Application 申请的关闭
Any closure of a CEP application must be justified: 所有CEP申请的关闭均需要说明。
— When advised by the EDQM Certification of Substances Division in the situations described in point 2 (Scope No. 2.3.1) above, by a justified recommendation from the relevant scientific officer (assessor or inspector).
— 如果申请关闭是由EDQM认证中心根据第2点（范围2.3.1）描述的情形提出，则由相关科学人员（审评员或检查官）填写建议表格进行说明
— When advised by the assessors of the Certification procedure in the situations described in point 2 (Scope No. 2.3.2) above and where supported by a justified rationale.
— 如果申请关闭是由认证过程中的评审员根据上述第2点（范围2.3.2）中描述的情形提出，则应说明要求关闭的理由
— By a letter from the CEP applicant to the EDQM asking for the closure of the application and explaining the reasons for the request (Scope No. 2.3.3).
— 如果由CEP申请人提出，则CEP申请人应向EDQM提交一封信函，要求关闭申请，并说明原因（范围2.3.3）
In certain cases when a CEP applicant requests the closure of their CEP application, the Internal Decision Board may review the request and any supportive information (e.g. public health risk or GMP non-compliance). If necessary the Ad hoc Committee endorses the actions to be taken.
在某些情况下，如果CEP申请人要求关闭CEP申请，内部决定委员会可能对该要求及支持性信息（例如公众健康风险和GMP不符合性）进行审核。必要时，特设委员会可能会对要采取的行动进行评论。
When the closure of an application is proposed by the EDQM Certification of Substances Division, the Internal Decision Board reviews the request together with the supporting information. If there is any potential risk for public health or GMP non-compliance, proposals are submitted to the Ad hoc Committee on the actions to be taken.
如果是由EDQM认证中心提出关闭申请，则内部决定委员会将对要求和支持性信息进行审核。如果涉及到任何潜在公众健康风险或GMP不符合性，则向特设委员会提交提案说明要求采取的措施。
The Ad hoc Committee then decides on the closure of the relevant CEP application(s) and the information to be forwarded to the relevant authorities. The Ad hoc Committee renders its decision generally within two weeks after the end of the inspection campaign or receipt of the request by the CEP applicant.
特设委员会将决定是否对相关CEP申请进行关闭，并将相关信息送到各相关药监机构。特设委员会一般在一个检查周期结束后或收到CEP申请人的请求后两周内做出决定。
When proposed by the assessors of the Certification procedure, the responsibility for approving a request for the closure of a CEP application and informing the relevant authorities rests with the Head of the Certification of Substances Division (EDQM).
如果提议是由认证程序的审评员提出，则批准关闭CEP申请和通知相关药监机构的责任由认证中心（EDQM）承担。
The detailed reasons for closure shall be given in the decision and communicated to the applicant.
关闭申请的详细理由应在决定中给出，并通知申请人。
4. Hearing 听证会
When the Ad hoc Committee or the EDQM has made a decision to withdraw or suspend a CEP, or to close a CEP application, the holder/applicant is given the possibility to submit a written request for re-consideration of the decision(s) (request for hearing) within two weeks of receiving the decision if they consider that the decision was not justified. The request for re-consideration should include information (supported by facts or figures) that demonstrates that the decision was unjustified.
如果特设委员会或EDQM已做出决定要撤消、搁置某CEP，或关闭某CEP申请，持有人/申请人如有异议，可以在收到决定的两周内提交书面申请，要求对该决定进行重审（要求召开听证会）。提出再审请求时，应同时提交相关信息（有事实或数据支持）证明决定不公。
Within two weeks of receipt of the request for re-consideration, the Ad hoc Committee reviews the request of the CEP holder/applicant and either rejects the request (i.e. maintains the original decision), or issues a new decision based on the written justification provided by the CEP holder/applicant.
在收到再审请求的两周内，特设委员会应对CEP持有人/申请人的请求进行审核，驳回要求（即维持原判），或根据CEP持有人/申请人提交的书面证据签署新的决定。
5. INFORMING CUSTOMERS AND AUTHORITIES 通知客户和药监当局
Once a CEP has been suspended or withdrawn, the CEP holder must immediately inform its customers of the situation to allow them to take responsibility with regard to the substance concerned and any related marketing authorisation or marketing authorisation application.
一旦CEP被搁置或撤消，CEP持有人必须立即通知其客户，告知目前现状，以便客户对被牵涉的物质、所有相关上市许可或上市许可申请采取必要措施。
Details on decisions to suspend or to withdraw a CEP, or to close a CEP application are communicated, in confidence, to the relevant authorities of the member states of the Convention on the Elaboration of a European Pharmacopoeia, as well as to the countries/organisations with which special agreements have been made, to enable them to take appropriate actions regarding the marketing authorisations or marketing authorisation applications concerned.
关于CEP搁置、CEP申请关闭的决定细节将以保密方式送到EP起草委员会成员国相关药监机构、签署特殊协议的国家/组织，以使其对相关上市许可或上市许可申请采取适当措施。
When confirmed, any change in the status of a CEP becomes publicly available on the EDQM website.
决定一经确认，CEP的状态会在EDQM官网上公布。
6. EXTENSION OF A SUSPENSION 搁置延期
A CEP is generally suspended for 2 years. In exceptional cases, the suspension may be extended, provided that the CEP holder submits a justified request for the extension for review by the Internal Decision Board before the end of the 2-year period.
CEP搁置期限一般为2年。在例外情况下，如果CEP持有人在2年结束前提交有理由的申请，并由内部决定委员会审核通过，搁置可以延期。
The extension to the suspension may be accepted, but if the situation cannot be positively resolved, the EDQM may decide to withdraw the CEP as described in point 3 above.
延期可能会被接受，但如果情形仍未能改善，EDQM可能会根据上述第3点所述决定撤消CEP。
7. RESTORATION OF A SUSPENDED CEP搁置CEP的恢复
After a suspension, a CEP may be restored as soon as the conditions for lifting the suspension are met by the CEP holder. The CEP restoration follows the same decision-making process as that for the suspension of the related CEP(s). In this case, a revised CEP is granted, which supersedes the suspended one. The CEP appears as valid in the public Certification database, together with its new revision number.
CEP在搁置后，一旦CEP持有人改善消除搁置因素，CEP即可能被恢复。CEP恢复的程序与决定其搁置的程序相同。在此情况下，会颁发一份修订过的CEP，取代被搁置的CEP。CEP在公开证书数据库中显示为新的版本编号。
8. RELATED DOCUMENTS 相关文件
4 Resolution AP-CSP (07) 1 / Certification of suitability to the monographs of the European Pharmacopoeia 欧洲药典各论适用性证书
5 PA/PH/CEP (01) 1 Terms of Reference 参考术语
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