1 EUROPEAN COMMISSION HEALTH AND CONSUMERS DIRECTORATE-GENERAL 브뤼셀 SANCO/C8/AM/sl/ares(2010) EudraLex The Rules Governing Medicinal in the European Union Volume 4 Good Manufacturing Practice Medicinal for Human and Veterinary Use Explanatory Notes on the Preparation of a Site Master File These notes are intended to provide guidance on the recommended content of the Site Master File. A requirement for a Site Master File is referred to in Chapter 4 of the GMP Guide. SMF(Site Master File) 의작성방법에관한가이드라인을제시하기위한문서이다. SMF에대한기준은 GMP 가이드의 4장을참조한다. Status of the document: New 1

2 1. 서론 (INTRODUCTION) 1.1 The Site Master File is prepared by the pharmaceutical manufacturer and should contain specific information about the quality management policies and activities of the site, the production and/or quality control of pharmaceutical manufacturing operations carried out at the named site and any closely integrated operations at adjacent and nearby buildings. If only part of a pharmaceutical operation is carried out on the site, a Site Master File need only describe those operations, e.g. analysis, packaging, etc. SMF는의약품제조업체가작성하는문서이며, 해당사업장의품질경영방침과활동, 지정사업장에서수행하는의약품제조공정의생산및 / 또는품질관리, 그리고인접건물과인근건물에서수행되는밀접하게통합된작업에관한구체적인정보를제시하는것이다. 의약품제조작업가운데일부만수행한다면, 그부분 ( 예, 분석, 포장등 ) 만 SMF에기술한다. 1.2 When submitted to a regulatory authority, the Site Master File should provide clear information on the manufacturer s GMP related activities that can be useful in general supervision and in the efficient planning and undertaking of GMP inspections. 규제기관에 SMF를제출할때는, GMP 실사의효율적인계획및실시와전반적인관리 / 감독활동에도움이되는, 해당제조업체의 GMP 관련활동에관한정보를명확히포함시켜 SMF를작성한다. 1.3 A Site Master File should contain adequate information but, as far as possible, not exceed pages plus appendices. Simple plans outline drawings or schematic layouts are preferred instead of narratives. The Site Master File, including appendices, should be readable when printed on A4 paper sheets. 적절한정보를포함시켜 SMF를작성하되, 가능하면본문을 25~30페이지로하고부록을포함하여 SMF를만든다. 자세한서술적표현보다는간단한평면도나개략도가바람직하다. 부록을포함한 SMF는 A4 용지에인쇄하여읽을수있어야한다. 1.4 The Site Master File should be a part of documentation belonging to the quality management system of the manufacturer and kept updated accordingly. The Site Master File should have an edition number, the date it 2

3 becomes effective and the date by which it has to be reviewed. It should be subject to regular review to ensure that it is up to date and representative of current activities. Each Appendix can have an individual effective date, allowing for independent updating. SMF는제조업체의품질경영시스템에속하는문서의일부여야하며, 그에맞게최신상태로유지해야한다. SMF에개정번호와시행일자, 다음검토일자를표기한다. 주기적으로검토하여최신정보를포함하며현재의활동을잘반영하고있는지확인한다. 부록마다시행일자를표기하여독립적으로업데이트를할수있게운영하는방법도가능하다. 2. 목적 (PURPOSE) The aim of these Explanatory Notes is to guide the manufacturer of medicinal products in the preparation of a Site Master File that is useful to the regulatory authority in planning and conducting GMP inspections. 이문서의목적은규제기관이 GMP 실사를계획하고수행하는데도움이되는 SMF 문서를의약품제조업체가작성하는데도움이되는가이드라인을제시하는데있다. 3. 적용범위 (SCOPE) These Explanatory Notes apply to the preparation and content of the Site Master File. Manufacturers should refer to regional / national regulatory requirements to establish whether it is mandatory for manufacturers of medicinal products to prepare a Site Master File. 이문서는 SMF의작성방법과내용에적용된다. 제조업체는지역 / 국가규제기준을참고하여, SMF의작성이필수기준인지확인할필요가있다. These Explanatory Notes apply for all kind of manufacturing operations such as production, packaging and labelling, testing, relabeling and repackaging of all types of medicinal products. The outlines of this guide could also be used in the preparation of a Site Master File or corresponding document by Blood and Tissue Establishments and manufacturers of Active Pharmaceutical Ingredients. 이문서는각종의약품의생산, 포장및라벨작업, 시험, 재라벨 / 재포장작업등모든종류의제조활동에적용된다. 또한혈액및조직시설과 API 제조업체가 SMF나이와유사한문서를만들때도이문서에제시된사항을참조할수있다. 3

4 4. SMF 의내용 (CONTENT OF SITE MASTER FILE) Refer to the Annex for the format to be used. SMF 의형식은부록을참조한다. 4

5 ANNEX: SMF 의내용 (CONTENT OF SITE MASTER FILE) 1. 제조업체일반정보 (GENERAL INFORMATION ON THE MANUFACTURER) 1.1 제조업체의연락처정보 (Contact information on the manufacturer) - Name and official address of the manufacturer; 제조업체의명칭과공식주소 - Names and street addresses of the site, buildings and production units located on the site; 사업장의명칭과주소, 해당사업장에있는건물과생산조직 - Contact information of the manufacturer including 24 hrs telephone number of the contact personnel in the case of product defects or recalls. 제품결함이나리콜상황발생시에연락할담당자의전화번호 (24시간연락가능한전화번호 ) 를포함하여제조업체의연락처정보 - Identification number of the site as e.g. GPS details, or any other geographic location system, D-U-N-S (Data Universal Numbering System) Number (a unique identification number provided by Dun & Bradstreet) of the site 1 사업장의식별번호, 예를들어 GPS 정보또는다른지리적위치파악시스템, D-U-N-S(Data Universal Numbering System) 번호 (Dun & Bradstreet가제공하는고유식별번호 ) 1.2 사업장의허가받은의약품제조활동 (Authorised pharmaceutical manufacturing activities of the site) - Copy of the valid manufacturing authorisation issued by the relevant Competent Authority in Appendix 1; or when applicable, reference to the EudraGMP database. If the Competent Authority does not issue manufacturing authorizations, this should be stated. 1 A D-U-N-S reference is required for Site Master Files submitted to EU/EEA authorities for manufacturing sites located outside of the EU/EEA. EU/EEA 역외에위치한제조사업장인경우, EU/EEA 기관에 SMF를제출할때는 D- U-N-S 코드가필요하다. 5

6 관계기관이발행한제조허가서사본 ( 부록 1) 또는해당되는경우에는 EudraGMP 데이터베이스정보. 관계기관이제조허가서를발행하지않는다면, 이사실을기술한다. - Brief description of manufacture, import, export, distribution and other activities as authorized by the relevant Competent Authorities including foreign authorities with authorized dosage forms/activities, respectively; where not covered by the manufacturing authorization; 허가받은제형 / 활동과해외규제기관을포함하여관련규제기관이허가한제조, 수입, 수출, 유통, 기타활동에대한간략한설명 ; 제조허가서에기술되어있지않은경우. - Type of products currently manufactured on-site (list in Appendix 2) where not covered by Appendix 1 or EudraGMP entry; 부록 1이나 EudraGMP 데이터베이스에없는경우, 해당사업장에서현재제조하고있는제품의유형 ( 부록 2의리스트 ). - List of GMP inspections of the site within the last 5 years; including dates and name/country of the Competent Authority having performed the inspection. A copy of current GMP certificate (Appendix 3) or reference to the EudraGMP database, should be included, if available. 최근 5년동안의 GMP 실사리스트 : 실사를수행한규제기관의명칭 / 국가와일자포함. 가능한경우에는현행 GMP 증명서사본 ( 부록 3) 또는 EudraGMP 데이터베이스정보를포함시킨다. 1.3 사업장에서수행하는기타제조활동 (Any other manufacturing activities carried out on the site) - Description of non-pharmaceutical activities on-site, if any. 해당사업장에서수행하는비의약품관련활동에대한설명 2. 제조업체의품질경영시스템 (QUALITY MANAGEMENT SYSTEM OF THE MANUFACTURER) 2.1 제조업체의품질경영시스템 (The quality management system of the manufacturer) - Brief description of the quality management systems run by the company and reference to the standards used; 6

7 품질경영시스템에대한간략한설명과적용표준에관한정보 - Responsibilities related to the maintaining of quality system including senior management; 고위경영자를포함하여품질시스템의유지와관련된업무분장 - Information of activities for which the site is accredited and certified, including dates and contents of accreditations, names of accrediting bodies. 증명 / 인증받은활동에관한정보 : 인증기구의명칭, 인증일자와인증내용포함 2.2. 최종제품의출하승인절차 (Release procedure of finished products) - Detailed description of qualification requirements (education and work experience) of the Authorised Person(s) / Qualified Person(s) responsible for batch certification and releasing procedures; 배치의증명및출하승인절차를책임지는 AP/QP의자격기준 ( 교육, 업무경험 ) 에관한자세한설명 - General description of batch certification and releasing procedure; 배치증명및출하승인절차에관한일반적인설명 - Role of Authorised Person / Qualified Person in quarantine and release of finished products and in assessment of compliance with the Marketing Authorisation; 최종제품의격리보관및출하승인과판매허가준수여부평가에있어서 AP/QP의역할 - The arrangements between Authorised Persons / Qualified Persons when several Authorised Persons / Qualified Persons are involved; AP/QP가다수관련된경우에는 AP/QP 사이의관계 - Statement on whether the control strategy employs Process Analytical Technology (PAT) and/or Real Time Release or Parametric Release; PAT 및 / 또는 RTR 또는파라미터기반출하승인방법을관리전략으로채택하고있는지여부에대한설명 2.3 공급업체및계약업체관리 (Management of suppliers and contractors) - A brief summary of the establishment/knowledge of supply chain and the external audit program; 7

8 공급체인정보와외부감사프로그램의간략한요약 - Brief description of the qualification system of contractors, manufacturers of active pharmaceutical ingredients (API) and other critical materials suppliers; 계약업체, API 제조업체, 기타핵심물품공급업체의적격성평가시스템에관한간략한설명 - Measures taken to ensure that products manufactured are compliant with TSE (Transmitting animal spongiform encephalopathy) guidelines. 제조제품이 TSE 가이드라인에부합하도록하기위한대책 - Measures adopted where counterfeit/falsified products, bulk products (i.e. unpacked tablets), active pharmaceutical ingredients or excipients are suspected or identified. 위조 / 허위물품 ( 제품, 벌크제품 ( 즉, 미포장정제 ), API 또는첨가제 ) 으로의심되거나확인된경우의대책 - Use of outside scientific, analytical or other technical assistance in relation to manufacture and analysis; 제조및분석과관련하여과학적, 분석적, 또는기타기술적외부지원의활용에관한정보 - List of contract manufacturers and laboratories including the addresses and contact information and flow charts of supply-chains for outsourced manufacturing and Quality Control activities; e.g. sterilization of primary packaging material for aseptic processes, testing of starting raw-materials etc, should be presented in Appendix 4; 계약제조업체및시험시설리스트 : 주소와연락처정보, 아웃소싱대상인제조및품질관리활동의업무흐름도 : 예 ) 무균공정에사용할일차포장자재의멸균, 출발물질등의시험을부록 4에정리한다. - Brief overview of the responsibility sharing between the contract giver and acceptor with respect to compliance with the Marketing Authorization (where not included under 2.2). 판매허가사항의준수와관련하여위탁업체와수탁업체사이의업무분장에관한설명 (2.2에서다루지않은경우 ) 2.4 QRM(Quality Risk Management) - Brief description of QRM methodologies used by the manufacturer; 8

9 제조업체가활용하는 QRM 방법에관한간략한설명 - Scope and focus of QRM including brief description of any activities which are performed at corporate level, and those which are performed locally. Any application of the QRM system to assess continuity of supply should be mentioned; QRM의범위와중점 : 회사전체차원에서실시하는활동과부서차원에서실시하는것을간략하게설명한다. QRM 시스템을적용하여공급의연속성을평가한부분을기술한다. 2.5 제품품질검토 (Product Quality Reviews) - Brief description of methodologies used 제품품질검토방법에관한간략한설명 3. 작업자 (PERSONNEL) - Organisation chart showing the arrangements for quality management, production and quality control positions/titles in Appendix 5, including senior management and Qualified Person(s); 고위경영자와 QP를포함하여, 품질경영, 생산, 품질관리직책 / 직위를보여주는조직도 ( 부록 5) - Number of employees engaged in the quality management, production, quality control, storage and distribution respectively; 품질경영, 생산, 품질관리, 보관, 유통등에관련된작업자의수 4. 시설및설비 (PREMISES AND EQUIPMENT) 4.1 시설 (Premises) - Short description of plant; size of the site and list of buildings. If the production for different markets, i.e. for local, EU, USA etc takes place in different buildings on the site, the buildings should be listed with destined markets identified (if not identified under 1.1); 공장에대한간략한설명 : 사업장크기와건물리스트. 해당사업장의여러건물에서서로다른시장 ( 예, 국내, EU, 미국등 ) 을대상으로제품을생산하고있다면, 해당건물과판매예정시장을정리한다 (1.1에서명확히 9

10 기술하지않은경우 ) - Simple plan or description of manufacturing areas with indication of scale (architectural or engineering drawings are not required); 제조지역에대한설명또는간단한도면과축척표시 ( 건축도면이나엔지니어링도면을요구하는것은아님 ) - Lay outs and flow charts of the production areas (in Appendix 6) showing the room classification and pressure differentials between adjoining areas and indicating the production activities (i.e. compounding, filling, storage, packaging, etc.) in the rooms.; 인접지역사이의차압과청정도등급을보여주며, 작업실의생산활동 ( 예, 혼합, 충전, 보관, 포장등 ) 을나타낸, 생산지역의레이아웃과흐름도 ( 부록 6). - Lay-outs of warehouses and storage areas, with special areas for the storage and handling of highly toxic, hazardous and sensitising materials indicated, if applicable; 보관지역의레이아웃, 고독성물질, 위험물질, 감작성물질등의보관과취급이이루어지는특수지역포함. - Brief description of specific storage conditions if applicable, but not indicated on the lay-outs; 해당되는경우에는레이아웃에표시되지않은구체적인보관조건에관한간략한설명 Brief description of heating, ventilation and air conditioning (HVAC) systems HVAC 시스템에관한간략한설명 - Principles for defining the air supply, temperature, humidity, pressure differentials and air change rates, policy of air recirculation (%); 공기공급, 온도, 습도, 차압, 환기횟수, 공기순환원칙 (%) Brief description of water systems 용수시스템에관한간략한설명 - Quality references of water produced 생산된용수의품질기준 - Schematic drawings of the systems in Appendix 7 용수시스템의개략도 ( 부록 7) 10

11 Brief description of other relevant utilities, such as steam, compressed air, nitrogen, etc. 기타관련유틸리티 ( 예, 스팀, 압축공기, 질소등 ) 에관한간략한설명 4.2 설비 (Equipment) Listing of major production and control laboratory equipment with critical pieces of equipment identified should be provided in Appendix 8. 생산및품질관리시험에사용되는주요설비리스트를부록 8에정리한다. 핵심설비를표시한다 세척및소독 (Cleaning and sanitation) - Brief description of cleaning and sanitation methods of product contact surfaces (i.e. manual cleaning, automatic Clean-in-Place, etc). 제품접촉표면세척및위생처리방법에관한간략한설명 ( 예, 수동세척, 자동 CIP 등 ) GMP 핵심컴퓨터화시스템 (GMP critical computerised systems) - Description of GMP critical computerised systems (excluding equipment specific Programmable Logic Controllers (PLCs) GMP 핵심컴퓨터화시스템에대한설명 ( 설비특이적 PLC 제외 ) 5. 문서 (DOCUMENTATION) - Description of documentation system (i.e. electronic, manual); 문서시스템에관한설명 ( 예, 전자, 수동 ) - When documents and records are stored or archived off-site (including pharmacovigilance data, when applicable): List of types of documents/records; Name and address of storage site and an estimate of time required retrieving documents from the off-site archive. 문서와기록서를사업장외부에보관또는아카이브하는경우 ( 해당되는경우에는약물감시데이터포함 ), 문서 / 기록서의유형과보관장소의명칭및주소, 그리고외부아카이브장소에서문서를찾아오는데걸리는시간. 11

12 6. 생산 (PRODUCTION) 6.1. 제품의종류 (Type of products) (References to Appendix 1 or 2 can be made): ( 부록 1 또는 2 를참조하게할수있다.) - Type of products manufactured including 다음을포함하여제조제품의종류 list of dosage forms of both human and veterinary products which are manufactured on the site 해당사업장에서제조하는사람의약품과동물의약품제형리스트 list of dosage forms of investigational medicinal products (IMP) manufactured for any clinical trials on the site, and when different from the commercial manufacturing, information of production areas and personnel 해당사업장에서임상시험용도로제조하는임상시험용의약품 (IMP) 제형리스트, 그리고상업적제조공정과다른경우에는생산지역및작업자에관한정보 - Toxic or hazardous substances handled (e.g. with high pharmacological activity and/or with sensitising properties); 해당사업장에서취급하는독성또는위해성분 ( 예, 약리학적활성이크거나감작성특징이있는성분 ) - Product types manufactured in a dedicated facility or on a campaign basis, if applicable; 전용시설에서제조하거나캠페인방식으로제조하는제품 - Process Analytical Technology (PAT) applications, if applicable: general statement of the relevant technology, and associated computerized systems; 해당되는경우에는 PAT 정보 : 해당기술과관련컴퓨터화시스템에관한일반적인설명 6.2 공정밸리데이션 (Process validation) - Brief description of general policy for process validation; 공정밸리데이션방침에관한간략한설명 12

13 - Policy for reprocessing or reworking; 재가공또는재작업방침 6.3 물품관리및보관 (Material management and warehousing) - Arrangements for the handling of starting materials, packaging materials, bulk and finished products including sampling, quarantine, release and storage 출발물질, 포장자재, 벌크및완제품의취급절차 ( 검체채취, 격리보관, 사용 / 출하승인, 보관포함 ) - Arrangements for the handling of rejected materials and products 부적합물품및제품의취급방법 7. QC(QUALITY CONTROL) - Description of the Quality Control activities carried out on the site in terms of physical, chemical, and microbiological and biological testing. 이화학적시험과미생물학적 / 생물학적시험등해당사업장에서수행하는품질관리활동에관한정보 8. 유통, 불만, 제품결함, 리콜 (DISTRIBUTION, COMPLAINTS, PRODUCT DEFECTS AND RECALLS) 8.1 유통 (Distribution) (to the part under the responsibility of the manufacturer) ( 제조업체가책임지는부분 ) - Types (wholesale licence holders, manufacturing licence holders, etc) and locations (EU/EEA, USA, etc) of the companies to which the products are shipped from the site; 해당사업장에서제품을보내는회사의종류 ( 도매업허가보유업체, 제조허가보유업체등 ) 와위치 (EU/EEA, USA 등 ) - Description of the system used to verify that each customer / recipient is legally entitled to receive medicinal products from the manufacturer 각고객 / 수령인이해당제조업체로부터의약품을인수할법적권한을갖고있는지확인하기위한시스템 13

14 - Brief description of the system to ensure appropriate environmental conditions during transit, e.g. temperature monitoring/ control; 운반도중에적정환경조건을유지하기위한시스템에대한간략한설명 ( 예, 온도모니터 / 관리 ). - Arrangements for product distribution and methods by which product traceability is maintained; 제품유통방법과제품의추적성확보방법 - Measures taken to prevent manufacturers products to fall in the illegal supply chain. 제조업체의제품이불법적인공급체인으로유통되지않도록하기위한대책 8.2 불만, 제품결함, 리콜 (Complaints, product defects and recalls) - Brief description of the system for handling complains, product defects and recalls 불만, 제품결함, 리콜의처리시스템에관한간략한설명 9. 자체실사 (SELF INSPECTIONS) - Short description of the self inspection system with focus on criteria used for selection of the areas to be covered during planned inspections, practical arrangements and follow-up activities 자체실사시스템에관한간략한설명. 예정실사시의실사대상영역을선정하는데적용하는기준과실제실사절차, 사후관리활동에중점을두어설명한다 Appendix 1. 유효한제조허가서사본 (Copy of valid manufacturing authorisation) Appendix 2. API의 INN 명칭또는일반명 ( 가능한경우 ) 을포함하여, 제조제형리스트 (List of dosage forms manufactured including the INN-names or common name (as available) of active pharmaceutical ingredients (API) used) Appendix 3. 유효한 GMP 인증서사본 (Copy of valid GMP Certificate) Appendix 4. 계약제조업체및시험시설리스트 : 주소와연락처정보, 아웃소싱활동의업무흐름도포함 (List of contract manufacturers and laboratories 14

15 including the addresses and contact information, and flow-charts of the supply-chains for these outsourced activities) Appendix 5. 조직도 (Organisational charts) Appendix 6. 생산지역레이아웃 : 제품유형 ( 제제 ) 별제조공정흐름도, 작업자흐름, 물류 (Lay outs of production areas including material and personnel flows, general flow charts of manufacturing processes of each product type (dosage form)) Appendix 7. 수처리시스템개략도 (Schematic drawings of water systems) Appendix 8. 주요생산및시험설비리스트 (List of major production and laboratory equipment) 15

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