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公布工夫:2018-07-17 接见次数:

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PIC/S六月更新文件

2018年6月20日,PIC/S官网公布系列订正文件,包孕新订正的GMP和四篇指点文件。


 

新公布的GMP重要对第三章“厂房取设备”、第五章“消费”、第八章“赞扬取产物召回”和关于“及时放行测试及参数放行”的附件17停止了订正。订正后的PIC/S GMP指南第三章、第五章、第八章取欧盟GMP指南的响应内容根基同等,仅正在语言表达方面略有差别。


 

别的更新的四篇指点文件分别是关于共用设备交织净化的PIC/S备忘录(PI 043-1)、关于肯定用于人用药所用辅料的GMP程度肯定用正式风险评价指南(PI 045-1)、关于设定基于康健的袒露限值的指南,用于正在共用设备中制造差别药品的风险辨认(PI 046-1)、关于人用药物有效成分优越分派范例原则的指南(PI 047-1)。


 

现在这些文件均正在连续翻译中。以下为关于肯定用于人用药所用辅料的GMP程度肯定用正式风险评价指南(PI 045-1)中英对照文件。


 


 

GUIDELINES ON THE FORMALISED RISK ASSESSMENT FOR ASCERTAINING THE APPROPRIATE GOOD MANUFACTURING PRACTICE FOR EXCIPIENTS OF MEDICINAL PRODUCTS FOR HUMAN USE


人用药所用辅料的GMP程度肯定用正式风险评价指南


 

TABLE OF CONTENTS

目次

 

Section 1. Document history 

文件纪录

Section 2. Introduction 

引见

Section 3. Scope 

局限

Section 4. Determination of appropriate GMP based on type and use of excipient 

基于辅料范例和用处的恰当的GMP决议计划

Section 5. Determinationof excipient manufacturer’s risk profile 

肯定辅料消费的风险概略

Section 6. Confirmation of application of appropriate GMP 

恰当GMP申请确认

Section 7. Revision History 

订正纪录 


 


 

1. DOCUMENT HISTORY     文件纪录

详情请点击楚天人官微检察 


 


 

2. INTRODUCTION    引见


 


 

The present PIC/S Guidelines are based on EC document 2015/C 95/02, which has been drafted by the EMA GMDP IWG and transposed for PIC/S purpose by the PIC/S Sub-Committee on the Harmonisation of GM(D)P.


 

本PIC / S指南是基于EC文件2015 / C 95/02,由EMA GMDP IWG草拟、由PIC / S小组委员会和谐GM(D)P的PIC/S用处。

 

These guidelines have been adopted by PIC/S as a guidance document. It is up to each PIC/S Participating Authority to decide whether it should become a legally- binding standard.


 

这些原则已被PIC / S作为指导性文件。由每一个PIC / S到场机构决意是不是应成为具有法律约束力的尺度。

 

The manufacturing authorisation holder is required to ensure that the excipients are suitable for use in medicinal products by ascertaining what the appropriate good manufacturing practice (GMP) is. The appropriate GMP for excipients of medicinal products for human use shall be ascertained on the basis of a formalised risk assessment in accordance with these guidelines. The risk assessment shall take into account requirements under other appropriate quality systems as well as the source and intended use of the excipients and previous instances of quality defects. The manufacturing authorisation holder shall ensure that the appropriate GMP ascertained is applied. The manufacturing authorisation holder shall document the measures taken.


 

消费允许持有人应经由过程确认恰当的GMP包管辅料适用于正在药品中的用处。人药用药辅料恰当的GMP应凭据这些指南,基于正式的风险评价停止肯定。风险评价应思索其他恰当质量体系的要求,和辅料的泉源和用处,和之前的质量缺点状况。 消费允许持有人应包管所肯定的GMP是实用的。消费允许持有人应纪录所接纳的步伐。

 

The excipient risk assessment/risk management procedure should be incorporated in the pharmaceutical quality system of the manufacturing authorisation holder.


 

辅料风险评价/风险管理程序应联合消费允许持有人的药品质量体系中。


Manufacturing authorisation holders should have the risk assessment/management documentation for appropriate GMP for excipients available on site for review by GMP inspectors. Consideration should be given to sharing relevant information from the risk assessment with the excipient manufacturer to facilitate continuous improvement.


 

消费允许持有人应针对辅料所用的恰当的GMP要求的风险评价/管理文件纪录,并能提供给GMP检查员搜检。 应思索取辅料生产商同享风险评价所发生的相干信息,以增进连续革新。

 

A risk assessment as set out in these guidelines should be carried out for excipients for authorised medicinal products for human use in accordance with provisions established by applicable national competent authorities.


 

凭据国度有关主管部门的划定,应对人用药品中辅料便这些列出的指南停止风险评价。

 


 

3. SCOPE    局限


 

3.1 These guidelines apply to the risk assessment for ascertaining the appropriate GMP for excipients for medicinal products for human use. An excipient is any constituent of a medicinal product other than the active substance and the packaging material

 

这些指南适用于风险评价,去评价运用恰当的GMP于人用药所用辅料管理。 辅料是药品中不包括活性身分和包装材料在内的别的组成部分。

 

 

3.2 These guidelines do not cover substances added to stabilise active substances that cannot exist on their own.


 

这些指南不涵盖增加入药品中那些不克不及零丁存在、而需求正在活性物质中增加稳定剂使活性物资稳固的身分。


 

 

4. DETERMINATION OF APPROPRIATE 

GMP BASED ON TYPE AND USE OF 

EXCIPIENT  

 基于辅料范例和用处的恰当的GMP决议计划


 

 

4.1 In PIC/S PE 009 Guide to Good Manufacturing Practice for Medicinal Products Annex 20, principles and examples of tools for quality risk management that can  be applied to different aspects of pharmaceutical  quality,  including excipients, can be found.


 

正在PIC / S PE 009 GMP指南附录20中,能够找到能应用于药品质量,包孕辅料,差别方面的质量风险管理原则和东西实例。


 

4.2 These quality risk management principles should be used to assess the risks presented to the quality, safety and function of each excipient and to classify the excipient in question, e.g. as low risk, medium risk or high risk. Quality risk management tools such as those listed in Annex 20 (e.g. hazard analysisand critical controlpoints — HACCP) should be used for this purpose.


 

这些质量风险管理原则应用于评价每种辅料所显现的质量、平安和功用方面的风险,并对所述辅料风险品级停止分类,如低风险、中等风险或下风险。 质量风险管理工具,如附件20中列出的《风险剖析和要害掌握点—HACCP》运用于此目标。


4.3 For each excipient from each manufacturer used, the manufacturing authorisation holder should identify the risks presented to the quality, safety and function of each excipient from its source — be that animal, mineral, vegetable, synthetic, etc. — through to its incorporation in the finished pharmaceutical dose form. Areas for consideration should include, but are not limited to:

 

来自于每一个死厂商的每种辅料,消费允许持有人应从其泉源—植物、矿物、动物、合成物等—辨认每种辅料的质量、平安和功用风险,直至其终究构成制剂制品。 要思索的内容应包孕但不限于:


(a) transmissible spongiform encephalopathy;

TSE风险

 

(b) potential for viral contamination;

病毒净化的可能性

 

(c) potential for microbiological or endotoxin/pyrogen contamination;

微生物或内毒素/热源净化的可能性

 

(d) potential, in general, for any impurity originating from the raw materials, e.g. aflatoxins or pesticides, or generated as part of the process and carried over, e.g. residual solvents and catalysts;
 


 

质料中发生的任何杂质存在的可能性,比方,黄曲霉素或杀虫剂,或工艺消费中发生或带入的杂质,比方,残留溶剂和催化剂。

 

(e) sterility assurance for excipients claimed to be sterile;

无菌包管用于证实辅料的无菌性

 

(f) potential for any impurities carried over from other processes, in absence of dedicated equipment and/or  facilities;

非专用设备/或设备中其他工艺带入杂质的可能性

 

(g) environmental control and storage/transportation conditions including cold chain management, if appropriate;

情况掌握和存贮运输前提,恰当时包孕热链管理

 

(h) supply chain complexity;

供给链庞大水平

 

(i) stability of excipient;

辅料的稳定性

 

(j) packaging integrity evidence.

包装完整性证据


 

4.4 Additionally, with respect to the use and function of each excipient, the manufacturing authorisation holder should consider:

另外,关于每种辅料的运用和功用方面,消费允许持有人应思索:

 

(a) the pharmaceutical form and use of the medicinal product containing the excipient;

含有辅料的药品剂型和药品的用处

 

(b) the function of the excipient in the formulation, e.g. lubricant in a tablet product or preservative material in  a liquid formulation, etc.;

辅料正在制剂中的功用,比方,片剂中的润滑剂、液体制剂中的防腐剂等。

 

(c) the proportion of the excipient in  the  medicinal  product composition;

辅料正在药品身分中所占的比例

 

(d) daily patient intake of the excipient;

患者的日摄入辅料量

 

(e) any known quality defects/fraudulent adulterations, both globally and at a local company level related to the  excipient;

环球局限或本地公司局限取辅料有关的已知的质量缺点或造假状况

 

(f) whether the excipient is a composite;

辅料是不是是一种身分

 

(g) known or potential impact on the critical quality attributes of the medicinal product;

对药品要害质量属性的已知的或潜伏的影响

 

(h) other factors as identified or known to be relevant to assuring patient safety.

已辨认的或已知的取包管患者平安相干的其他身分

 

4.5Having established and documented the risk profile of the excipient, the manufacturing authorisation holder should establish and document the elements of the PIC/S PE 009 Guide to Good Manufacturing Practice for Medicinal Products that he/she believes are needed to be in place in order to control and maintain the quality of the excipient, e.g. Annex 1 or/and Annex 2; Guide to Good Manufacturing Practice for Medicinal Products Part II: Basic Requirements for Active Pharmaceutical Ingredients.


 

正在竖立或纪录辅料的风险概略以后,消费允许持有人应竖立和纪录PIC/S PE 009 GMP的要素,这些要素应是以为其为掌握和保护辅料质量所必需的,比方附录1和/或附录2,GMP第二局部用作肇端物料的活性物资的基本要求。

 

4.6 These elements will vary depending on the source, the supply chain and the subsequent use of the excipient, but as a minimum the following high level GMP elements should be considered by the manufacturing authorisation holder:


 

这些要素会凭据辅料的泉源、供给链和随后的运用而差别,但消费允许持有人最少应思索以下程度的GMP要素:

 

(a) establishment and implementation of an effective pharmaceutical quality system;

竖立和实行有用的药品质量体系

 

(b) sufficient competent and appropriately qualified personnel;

具有充足胜任力取天资适宜的职员

 

(c) defined job descriptions for managerial and supervisory staff responsible for manufacturing and quality activities;

肯定对消费和质量运动管理和主管职员的岗位职责

 

(d) training programmes for all staff involved in manufacturing and quality activities (included but not limited to cleaning, engineering, laboratory, maintenance, materials management, safety, and technical services);


 

所触及消费和质量运动的员工的培训项目(包孕但不只限于干净、工程、实验室、保护、质料管理、平安和技术服务)


 

(e) training  programmes  related to health, hygiene and clothing  as identified as necessary to the intended operations;


 

取康健、卫生和打扮相干的培训项目,并对其预估操纵是需要的; 

 

(f) provision and maintenance of premises and equipment appropriate to the intended operations;

设备和装备的构造和保护适合于其既定操纵

 

(g) documentation system(s) covering all processes and specifications for the various manufacturing and quality operations;

文件纪录系统掩盖一切差别消费和质量操纵的加工和质量标准

 

(h) systems for coding and identifying starting materials, intermediates and excipients to allow full traceability;

肇端物料、中间体、辅料的编码和辨认体系能够停止全程追踪

 

(i) qualification program of suppliers;

供应商确认顺序

 

(j) system for quality control of the excipient and a responsible person independent from production to release the batches;

对辅料停止体系的质量掌握,有一个责任人独立于消费以外来放行批次

 

(k) retention of records for incoming materials  and excipients  and retention of samples of excipients for the periods required by PIC/S Guide to Good Manufacturing Practice for Medicinal Products, Part II;

出场物料和辅料纪录应生存,辅料留样工夫应相符PIC/S GMP第二局部要求

 

(l) systems to ensure that any activity contracted out is subject to a written contract;

体系包管一切外包运动皆有书面条约

 

(m) maintenance  of  an  effective  system  whereby  complaints  are reviewed and excipients may be recalled;

有用体系的保护、客户赞扬停止考核,辅料能够被召回

 

(n) change management and deviation management system;

调换管理和偏向管理体系

 

(o) self-inspection program;

自检顺序


(p) environmental control and storage conditions.

情况掌握和存贮前提


 


 


 

5. DETERMINATION OF EXCIPIENT MANUFACTURER’S RISK PROFILE       

肯定辅料消费的风险概略


 


 

5.1 After determination of the appropriate GMP, a gap analysis of the required GMP against the activities  and capabilities of the excipient manufacturer should be performed.


 

正在肯定了恰当的GMP后,应针对辅料生产商的运动和才能停止所要求的GMP差异剖析

 

5.2 Data/evidence to support the gap analysis should be obtained through audit or from information received from the excipient manufacturer.


 

用以支撑差异剖析的数据/证据应经由过程审计得到,或从辅料生产商处得到的信息。

 

5.3 Certification of quality systems and/or GMP held by the excipient manufacturer and the standards against which these have been granted should be considered as such certification may fulfill the requirements, subject to national legislation requirements.


 

质量体系的证书/或辅料生产商持有的GMP证书,和公布证书所根据的尺度应停止思索,由于该认证可能会知足这些要求,这些要求受国度立法要求的限定。

 

5.4 Any gaps identified between the required GMP and the activities and capabilities of the excipient manufacturer should be documented.


 

所辨认出的GMP要求取辅料生产商的运动及才能之间的差异应停止纪录。


 

Furthermore, the manufacturing authorisation holder should perform a further risk assessment to determine the risk profile, e.g. low risk, medium risk or high risk, for that excipient manufacturer. PIC/S PE 009 Guide to Good Manufacturing Practice for Medicinal Products Annex 20: Quality Risk Management should be used for that purpose. Quality risk management tools such as those listed there — HACCP etc. —should be used for this.


 

别的,消费允许持有人应实行进一步风险评价,以决意该辅料生产商的风险概略,比方,低风险、中等风险或下风险。PIC/S PE 009  GMP指南附件20:质量风险管理工具,比方列于其中的那些---HACCP—等逐一运用于此。

 

5.5 The manufacturing authorisation holder should have a series of strategies ranging from acceptance through control to unacceptable for the different risk profiles and based on these a control strategy, e.g. audit, document retrieval and testing, should be established.


 

消费允许持有人应制订一系列的战略,关于差别的风险概略从可接受到弗成接管,基于这些,应竖立一种掌握战略,比方,审计、文件规复和检测。

 


 


 

6. CONFIRMATION OF APPLICATION OF APPROPRIATE GMP   

恰当的GMP申请确认


 


 

6.1 Once the appropriate GMP for the  excipient  and the risk profile of the excipient manufacturer have been defined, ongoing risk review should be performed through mechanisms such as:


 

一旦界说了辅料实用的GMP,和辅料生产商的风险概略,后续经由过程肯定机制停止连续风险评价,如:

 

(a) numberof defects connected to batches of excipient received;

取收到的辅料批次相干的缺点数目

 

(b) type/severity of such defects;

这些缺点的范例和严峻水平

 

(c) monitoring and trend analysis of excipient quality;

辅料质量的监控和趋向剖析

 

(d) loss of relevant quality system and/or GMP certification by excipient manufacturer;

相干质量体系的缺失和/或辅料生产商持有的GMP证书

 

(d) observation of trends in drug product quality attributes;this will depend on the nature and role of excipient;

药品质量属性的趋向视察,这些将取决于辅料的属性和感化


 

(e) observed organisational, procedural or technical/process changes at the excipient manufacturer;

观察到的辅料生产商的有组织性的、程序性的或技术性的/工艺调换

 

(f) audit/re-audit of excipient manufacturer;

对辅料生产商停止审计/复审


 

(g) questionnaires.

问卷


 

Based on the outcome of the risk review, the established control strategy should be reviewed and revised if needed.

基于风险考核的效果,需要时应对已竖立的掌握战略停止考核取订正。

 

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