Table of Contents

目錄

 

CHAPTER 1 PHARMACEUTICAL QUALITY SYSTEM

 

第1章 藥品質(zhì)量體系

 

CHAPTER 2 PERSONNEL

 

第2章 人員

 

CHAPTER 3 PREMISES AND EQUIPMENT

 

第3章 廠房設(shè)施和設(shè)備

 

CHAPTER 4 DOCUMENTATION

 

第4章 文件

 

CHAPTER 5 PRODUCTION

 

第5章 生產(chǎn)

 

CHAPTER 6 QUALITY CONTROL

 

第六章 質(zhì)量控制

 

CHAPTER 7 OUTSOURCED ACTIVITIES

 

第七章 外包活動(dòng)

 

CHAPTER 8 COMPLAINTS AND PRODUCT RECALL

 

第八章 投訴和產(chǎn)品召回

 

CHAPTER 9 SELF INSPECTION

 

第9章 自檢

 

CHAPTER 1 PHARMACEUTICAL QUALITY SYSTEM

第1章 藥品質(zhì)量體系

 

PRINCIPLE 原則

 

The holder of a Manufacturing Authorisation must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorisation or Clinical Trial Authorisation, as appropriate, and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company’s suppliers and by its distributors. To achieve this quality objective reliably there must be a comprehensively designed and correctly implemented Pharmaceutical Quality System incorporating Good Manufacturing Practice and Quality Risk Management. It should be fully documented and its effectiveness monitored. All parts of the Pharmaceutical Quality System should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the holder of the Manufacturing Authorisation and for the Authorised Person(s).

 

藥品生產(chǎn)許可持有人（MAH）必須確保生產(chǎn)的藥品符合其預(yù)期用途，符合注冊(cè)要求或臨床試驗(yàn)要求，且不會(huì)因安全性、質(zhì)量或有效性不足而使患者處于風(fēng)險(xiǎn)之中。上述質(zhì)量目標(biāo)的實(shí)現(xiàn)是企業(yè)高級(jí)管理人員的責(zé)任，同時(shí)需要公司內(nèi)部、供應(yīng)商和分銷商各部門和各級(jí)員工的參與和承諾。為了可靠地實(shí)現(xiàn)上述質(zhì)量目標(biāo)，必須有一個(gè)全面設(shè)計(jì)的，并正確實(shí)施藥品生產(chǎn)質(zhì)量管理規(guī)范（GMP）和質(zhì)量風(fēng)險(xiǎn)管理的藥品質(zhì)量體系。藥品質(zhì)量體系應(yīng)該完全文件化，并監(jiān)測(cè)其有效性。藥品質(zhì)量體系的所有部分都應(yīng)配備足夠的合格人員，以及適當(dāng)和充足的廠房、設(shè)備和設(shè)施。藥品生產(chǎn)許可持有人（MAH）和受權(quán)人員（AP）需承擔(dān)這些額外的法律責(zé)任。

 

The basic concepts of Quality Management, Good Manufacturing Practice (GMP) and Quality Risk Management are inter-related. They are described here in order to emphasise their relationships and their fundamental importance to the production and control of medicinal products.

 

質(zhì)量管理、良好制造規(guī)范(GMP)和質(zhì)量風(fēng)險(xiǎn)管理三者是相互關(guān)聯(lián)的。描述它們是為了強(qiáng)調(diào)它們的關(guān)系，以及它們對(duì)藥品生產(chǎn)和控制的重要性。

 

PHARMACEUTICAL QUALITY SYSTEM 1 藥品質(zhì)量體系

 

（1 National requirements require manufacturers to establish and implement an effective pharmaceutical quality assurance system. The term Pharmaceutical Quality System is used in this chapter in the interests of consistency with ICH Q10 terminology. For the purposes of this chapter these terms can be considered interchangeable. 

 

1 國(guó)家要求制藥企業(yè)建立和實(shí)施一個(gè)有效的藥品質(zhì)量保證體系。本章使用的藥品質(zhì)量體系相關(guān)術(shù)語與ICHQ10的術(shù)語是一致的，就本章而言，這些術(shù)語可以被認(rèn)為是可互換的。

 

1.1 Quality Management is a wide-ranging concept, which covers all matters, which individually or collectively influence the quality of a product. It is the sum total of the organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use. Quality Management therefore incorporates Good Manufacturing Practice.

 

1.1質(zhì)量管理是一個(gè)寬泛的概念，它涵蓋單獨(dú)或共同影響產(chǎn)品質(zhì)量的所有問題。質(zhì)量管理是確保藥品質(zhì)量達(dá)到其預(yù)期用途所作的有組織安排的總和。因此，質(zhì)量管理包含藥品生產(chǎn)質(zhì)量管理規(guī)范（GMP）。

 

1.2 GMP applies to the lifecycle stages from the manufacture of investigational medicinal products, technology transfer, commercial manufacturing through to product discontinuation. However the Pharmaceutical Quality System can extend to the pharmaceutical development lifecycle stage as described in ICH Q10, which while optional, should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities.

 

1.2 GMP適用于從臨床藥品生產(chǎn)、技術(shù)轉(zhuǎn)移、商業(yè)生產(chǎn)到產(chǎn)品退市的全生命周期階段，而藥品質(zhì)量體系可以拓展到ICHQ10所述的藥物開發(fā)生命周期階段，這一拓展是非強(qiáng)制的，但應(yīng)有助于創(chuàng)新和持續(xù)改進(jìn)，并能加強(qiáng)藥品開發(fā)和生產(chǎn)活動(dòng)之間的聯(lián)系。

 

1.3 The size and complexity of the company’s activities should be taken into consideration when developing a new Pharmaceutical Quality System or modifying an existing one. The design of the system should incorporate appropriate risk management principles including the use of appropriate tools. While some aspects of the system can be company-wide and others site-specific, the effectiveness of the system is normally demonstrated at the site level.

 

1.3在建立新的藥品質(zhì)量體系或調(diào)整現(xiàn)有的藥品質(zhì)量體系時(shí)，應(yīng)考慮到公司活動(dòng)的規(guī)模和復(fù)雜性。質(zhì)量體系的設(shè)計(jì)應(yīng)運(yùn)用適當(dāng)?shù)娘L(fēng)險(xiǎn)管理原則，包括使用適當(dāng)?shù)墓ぞ摺ｋm然質(zhì)量體系的某些方面適用于全公司，也有些方面適用于特定廠房，但質(zhì)量體系的有效性通常需在廠房層面證實(shí)。

 

1.4 A Pharmaceutical Quality System appropriate for the manufacture of medicinal products should ensure that:

 

1.4適用于藥品生產(chǎn)的藥品質(zhì)量體系應(yīng)確保：

 

(i) Product  is achieved by designing, planning, implementing, maintaining and continuously improving a system that allows the consistent delivery of products with appropriate quality attributes;

 

(i) 設(shè)計(jì)、規(guī)劃、實(shí)施、維護(hù)和持續(xù)改進(jìn)藥品質(zhì)量體系，以持續(xù)交付具有適當(dāng)質(zhì)量屬性的產(chǎn)品；

 

(ii) Product and process knowledge is managed throughout all lifecycle stages;

 

(ii)產(chǎn)品和工藝知識(shí)的管理應(yīng)貫穿所有生命周期階段；

 

(iii) Medicinal products are designed and developed in a way that takes account of the requirements of Good Manufacturing Practice;

 

(iii)藥品的設(shè)計(jì)和開發(fā)應(yīng)考慮藥品生產(chǎn)質(zhì)量管理規(guī)范（GMP）的要求

 

(iv) Production and control operations are clearly specified and Good Manufacturing Practice adopted;

 

(iv) 生產(chǎn)和控制操作應(yīng)有明確規(guī)定并符合良好生產(chǎn)規(guī)范；

 

(v) Managerial responsibilities are clearly specified;

 

(v) 應(yīng)明確規(guī)定管理責(zé)任；

 

(vi) Arrangements are made for the manufacture, supply and use of the correct starting and packaging materials, the selection and monitoring of suppliers and for verifying that each delivery is from the approved supply chain;

 

(vi)應(yīng)采取措施確保制造、供應(yīng)和使用正確的原材料和包裝材料，篩選和監(jiān)控供應(yīng)商，以及確認(rèn)每次交付是來自經(jīng)批準(zhǔn)的供應(yīng)鏈；

 

(vii) Processes are in place to assure the management of outsourced activities;

 

(vii)明確外包活動(dòng)的管理；

 

(viii) A state of control is established and maintained by developing and using effective monitoring and control systems for process performance and product quality;

 

(viii)通過開發(fā)和使用有效的監(jiān)控和生產(chǎn)、產(chǎn)品質(zhì)量系統(tǒng)，來建立和維護(hù)控制狀態(tài)；

 

(ix) The results of product and processes monitoring are taken into account in batch release, in the investigation of deviations, and, with a view to taking preventive action to avoid potential deviations occurring in the future;

 

(ix)在產(chǎn)品批放行、調(diào)查偏差時(shí)考慮到產(chǎn)品和過程監(jiān)測(cè)結(jié)果，并采取預(yù)防措施，避免未來可能發(fā)生的潛在偏差；

 

(x) All necessary controls on intermediate products, and any other in-process controls and validations are carried out;

 

(x)對(duì)中間產(chǎn)品進(jìn)行所有必要的控制以及任何其他過程控制和驗(yàn)證；

 

(xi) Continual improvement is facilitated through the implementation of quality improvements appropriate to the current level of process and product knowledge;

 

(xi) 通過實(shí)施符合當(dāng)前工藝和產(chǎn)品知識(shí)水平的質(zhì)量改進(jìn)，促進(jìn)持續(xù)改進(jìn)；

 

(xii) Arrangements are in place for the prospective evaluation of planned changes and their approval prior to implementation taking into account regulatory notification and approval where required;

 

(xii)在實(shí)施計(jì)劃變更的預(yù)期評(píng)估及其批準(zhǔn)前，考慮是否需要告知監(jiān)管當(dāng)局和得到監(jiān)管當(dāng)局的批準(zhǔn)；

 

(xiii) After implementation of any change, an evaluation is undertaken to confirm the quality objectives were achieved and that there was no unintended deleterious impact on product quality;

 

(xiii)實(shí)施任何變更后，進(jìn)行評(píng)估以確認(rèn)質(zhì)量目標(biāo)已達(dá)到以及變更對(duì)產(chǎn)品質(zhì)量沒有潛在的影響；

 

(xiv) An appropriate level of root cause analysis should be applied during the investigation of deviations, suspected product defects and other problems. This can be determined using Quality Risk Management principles. In cases where the true root cause(s) of the issue cannot be determined, consideration should be given to identifying the most likely root cause(s) and to addressing those. Where human error is suspected or identified as the cause, this should be justified having taken care to ensure that process, procedural or system based errors or problems have not been overlooked, if present. Appropriate corrective actions and/or preventive actions (CAPAs) should be identified and taken in response to investigations. The effectiveness of such actions should be monitored and assessed, in line with Quality Risk Management principles;

 

(1iv)在調(diào)查偏差、可疑產(chǎn)品缺陷等問題時(shí)，應(yīng)采用適當(dāng)水平的根本原因分析。這可以通過質(zhì)量風(fēng)險(xiǎn)管理原則來確定。在無法確定問題的真正根本原因的情況下，應(yīng)考慮確定最可能的根本原因并解決這些原因。如果懷疑或確定為人為錯(cuò)誤，則應(yīng)謹(jǐn)慎處理，應(yīng)確保不會(huì)忽視過程、程序或系統(tǒng)的錯(cuò)誤或問題。調(diào)查后應(yīng)確定并采取適當(dāng)?shù)募m正措施和/或預(yù)防措施(CAPAs)。根據(jù)質(zhì)量風(fēng)險(xiǎn)管理原則，監(jiān)測(cè)和評(píng)估這些措施的有效性；

 

(xv) Medicinal products are not sold or supplied before an Authorised Person has certified that each production batch has been produced and controlled in accordance with the requirements of the Marketing Authorisation and any other regulations relevant to the production, control and release of medicinal products;

 

(xv)在授權(quán)人員證明每批生產(chǎn)已按照藥品生產(chǎn)、控制和放行相關(guān)的要求生產(chǎn)和控制之前，不得銷售或供應(yīng)藥品；

 

(xvi) Satisfactory arrangements exist to ensure, as far as possible, that the medicinal products are stored, distributed and subsequently handled so that quality is maintained throughout their shelf life;

 

(xvi) 應(yīng)采取適當(dāng)?shù)拇胧M可能保證藥品在有效期內(nèi)儲(chǔ)存、分發(fā)和后續(xù)處理過程中的質(zhì)量；

 

(xvii) There is a process for self-inspection and/or quality audit, which regularly appraises the effectiveness and applicability of the Pharmaceutical Quality System.

 

(xvii)應(yīng)有自檢和/或質(zhì)量審計(jì)的程序，定期評(píng)估藥品質(zhì)量體系的有效性和適用性。

 

1.5 Senior management has the ultimate responsibility to ensure an effective Pharmaceutical Quality System is in place, adequately resourced and that roles, responsibilities, and authorities are defined, communicated and implemented throughout the organisation. Senior management’s leadership and active participation in the Pharmaceutical Quality System is essential. This leadership should ensure the support and commitment of staff at all levels and sites within the organisation to the Pharmaceutical Quality System.

 

1.5高級(jí)管理人員有責(zé)任確保藥品質(zhì)量體系的有效實(shí)施，確保體系配備充足的資源，并定義、溝通和實(shí)施整個(gè)組織中的角色、職責(zé)和權(quán)力分配。高級(jí)管理人員必須領(lǐng)導(dǎo)并積極參與到藥品質(zhì)量體系中。其領(lǐng)導(dǎo)方式應(yīng)確保組織內(nèi)各級(jí)和現(xiàn)場(chǎng)的工作人員對(duì)藥品質(zhì)量體系的支持和承諾。

 

1.6 There should be periodic management review, with the involvement of senior management, of the operation of the Pharmaceutical Quality System to identify opportunities for continual improvement of products, processes and the system itself.

 

1.6應(yīng)在高級(jí)管理人員的參與下，對(duì)藥品質(zhì)量體系的運(yùn)行進(jìn)行定期的管理評(píng)審，以確定產(chǎn)品、過程和體系本身的持續(xù)改進(jìn)。

 

1.7 The Pharmaceutical Quality System should be defined and documented. A Quality Manual or equivalent documentation should be established and should contain a description of the quality management system including management responsibilities.

 

1.7應(yīng)對(duì)藥品質(zhì)量體系進(jìn)行定義并文件化。建立質(zhì)量手冊(cè)或同等文件，并應(yīng)包含對(duì)質(zhì)量管理體系的描述，包括管理職責(zé)。