Microsoft Word - M4QR1 The Common Technical Document Quality Part Module 2 Module 3

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1 INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality M4Q(R1) Quality Overall Summary of Module 2 Module 3: Quality Current Step 4 version dated 12 September 2002 This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA. 1

2 M4Q(R1) Document History First Codification M4Q M4Q History Date New Codification November 2005 Approval by the Steering Committee under 20 July M4Q Step 2 and release for public consultation 2000 Approval by the Steering Committee under 8 M4Q Step 4 and recommendation for adoption November to the three ICH regulatory bodies Current Step 4 version M4Q Approval by the Steering Committee of 12 M4Q(R1) Numbering and Section Headers changes September for consistency directly under Step without further public consultation. In order to facilitate the implementation of the M4Q guideline, the ICH Experts have developed a series of Q&As which can be downloaded from the ICH web site: M4Q Questions & Answers History M4Q Q&As Approval by the Steering Committee. 12 September 2002 M4Q Q&As Current M4Q Questions & Answers posted on the web site M4Q Q&As Approval by the Steering Committee of the 18 July M4Q Q&As newly added questions (R1) 2

3 THE COMMON TECHNICAL DOCUMENT FOR THE REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE: QUALITY QUALITY OVERALL SUMMARY OF MODULE 2 MODULE 3: QUALITY ICH Harmonised Tripartite Guideline Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 9 November 2000, this guideline is recommended for adoption to the three regulatory parties to ICH. (Numbering and Section Headers have been edited for consistency and use in e- CTD as agreed at the Washington DC Meeting, September 11-12, 2002) 목차 MODULE 2: COMMON TECHNICAL DOCUMENTS SUMMARIES 2.3: QUALITY OVERALL SUMMARY(QOS) 서론 (INTRODUCTION) 2.3.S 원료의약품 (DRUG SUBSTANCE)(NAME, MANUFACTURER) 2.3.S.1 일반정보 (General Information)(name, manufacturer) 2.3.S.2 제조 (Manufacture)(name, manufacturer) 2.3.S.3 특성분석 (Characterisation)(name, manufacturer) 2.3.S.4 원료의약품관리 (Control of Drug Substance)(name, manufacturer) 2.3.S.5 참조표준품또는물품 (Reference Standards or Materials)(name, manufacturer) 2.3.S.6 용기마개시스템 (Container Closure System)(name, manufacturer) 2.3.S.7 안정성 (Stability)(name, manufacturer) 2.3.P 완제의약품 (DRUG PRODUCT)(NAME, DOSAGE FORM) 2.3.P.1 완제의약품기본정보및조성 (Description and Composition of the Drug Product)(name, dosage form) 2.3.P.2 개발경위 (Pharmaceutical Development)(name, dosage form) 2.3.P.3 제조 (Manufacture)(name, dosage form) 2.3.P.4 첨가제관리 (Control of Excipients)(name, dosage form) 2.3.P.5 완제의약품관리 (Control of Drug Product)(name, dosage form) 2.3.P.6 참조표준품또는물품 (Reference Standards or Materials)(name, dosage form) 3

4 2.3.P.7 용기마개시스템 (Container Closure System)(name, dosage form) 2.3.P.8 안정성 (Stability)(name, dosage form) 2.3.A 부록 (APPENDICES) 2.3.A.1 시설및설비 (Facilities and Equipment)(name, manufacturer) 2.3.A.2 외래성 인자 안전성 평가 (Adventitious Agents Safety Evaluation)(name, dosage form, manufacturer) 2.3.A.3 첨가제 (Excipients) 2.3.R 지역별정보 (REGIONAL INFORMATION) MODULE 3: QUALITY 3.1. 모듈 3 목차 (TABLE OF CONTENTS OF MODULE 3) 3.2. BOD(BODY OF DATA) 3.2.S 원료의약품 (DRUG SUBSTANCE)(NAME, MANUFACTURER) 3.2.S.1 일반정보 (General Information)(name, manufacturer) 3.2.S.1.1 명칭 (Nomenclature)(name, manufacturer) 3.2.S.1.2 구조 (Structure)(name, manufacturer) 3.2.S.1.3 일반특징 (General Properties)(name, manufacturer) 3.2.S.2 제조 (Manufacture)(name, manufacturer) 3.2.S.2.1 제조업체 (Manufacturer(s))(name, manufacturer) 3.2.S.2.2 제조공정및공정관리 (Description of Manufacturing Process and Process Controls)(name, manufacturer) 3.2.S.2.3 물품관리 (Control of Materials)(name, manufacturer) 3.2.S.2.4 핵심단계및중간제품관리 (Controls of Critical Steps and Intermediates)(name, manufacturer) 3.2.S.2.5 공정밸리데이션및 / 또는평가 (Process Validation and/or Evaluation)(name, manufacturer) 3.2.S.2.6 제조공정개발 (Manufacturing Process Development)(name, manufacturer) 3.2.S.3 특성분석 (Characterisation)(name, manufacturer) 3.2.S.3.1 구조및기타특성 (Elucidation of Structure and other Characteristics)(name, manufacturer) 3.2.S.3.2 불순물 (Impurities)(name, manufacturer) 3.2.S.4 원료의약품관리 (Control of Drug Substance)(name, manufacturer) 3.2.S.4.1 규격 (Specification)(name, manufacturer) 3.2.S.4.2 분석절차 (Analytical Procedures)(name, manufacturer) 4

5 3.2.S.4.3 분석 절차 밸리데이션 (Validation of Analytical Procedures)(name, manufacturer) 3.2.S.4.4 배치분석 (Batch Analyses)(name, manufacturer) 3.2.S.4.5 규격의 타당성 (Justification of Specification)(name, manufacturer) 3.2.S.5 참조표준품또는물품 (Reference Standards or Materials)(name, manufacturer) 3.2.S.6 용기마개시스템 (Container Closure System)(name, manufacturer) 3.2.S.7 안정성 (Stability)(name, manufacturer) 3.2.S.7.1 안정성 요약 및 결론 (Stability Summary and Conclusions)(name, manufacturer) 3.2.S.7.2 승인이후안정성시험프로토콜및안정성이행약속 (Postapproval Stability Protocol and Stability Commitment)(name, manufacturer) 3.2.S.7.3 안정성데이터 (Stability Data)(name, manufacturer) 3.2.P 완제의약품 (DRUG PRODUCT)(NAME, DOSAGE FORM) 3.2.P.1 완제의약품기본정보및조성 (Description and Composition of the Drug Product)(name, dosage form) 3.2.P.2 개발경위 (Pharmaceutical Development)(name, dosage form) 3.2.P.2.1 완제의약품원료 (Components of the Drug Product)(name, dosage form) 3.2.P 원료의약품 (Drug Substance)(name, dosage form) 3.2.P 첨가제 (Excipients)(name, dosage form) 3.2.P.2.2 완제의약품 (Drug Product)(name, dosage form) 3.2.P 조성 개발 (Formulation Development)(name, dosage form) 3.2.P 과량 (Overages)(name, dosage form) 3.2.P 이화학적및생물학적특징 (Physicochemical and Biological Properties)(name, dosage form) 3.2.P.2.3 제조공정개발 (Manufacturing Process Development)(name, dosage form) 3.2.P.2.4 용기마개시스템 (Container Closure System)(name, dosage form) 3.2.P.2.5 미생물학적특성 (Microbiological Attributes)(name, dosage form) 5

6 3.2.P.2.6 조화성 (Compatibility)(name, dosage form) 3.2.P.3 제조 (Manufacture)(name, dosage form) 3.2.P.3.1 제조업체 (Manufacturer(s))(name, dosage form) 3.2.P.3.2 배치조성 (Batch Formula)(name, dosage form) 3.2.P.3.3 제조공정및공정관리 (Description of Manufacturing Process and Process Controls)(name, dosage form) 3.2.P.3.4 핵심단계및중간제품관리 (Controls of Critical Steps and Intermediates)(name, dosage form) 3.2.P.3.5 공정밸리데이션및 / 또는평가 (Process Validation and/or Evaluation)(name, dosage form) 3.2.P.4 첨가제관리 (Control of Excipients)(name, dosage form) 3.2.P.4.1 규격 (Specifications)(name, dosage form) 3.2.P.4.2 분석절차 (Analytical Procedures)(name, dosage form) 3.2.P.4.3 분석 절차 밸리데이션 (Validation of Analytical Procedures)(name, dosage form) 3.2.P.4.4 규격의타당성 (Justification of Specifications)(name, dosage form) 3.2.P.4.5 사람또는동물유래첨가제 (Excipients of Human or Animal Origin)(name, dosage form) 3.2.P.4.6 신규첨가제 (Novel Excipients)(name, dosage form) 3.2.P.5 완제의약품관리 (Control of Drug Product)(name, dosage form) 3.2.P.5.1 규격 (Specification(s))(name, dosage form) 3.2.P.5.2 분석절차 (Analytical Procedures)(name, dosage form) 3.2.P.5.3 분석 절차 밸리데이션 (Validation of Analytical Procedures)(name, dosage form) 3.2.P.5.4 배치분석 (Batch Analyses)(name, dosage form) 3.2.P.5.5 불순물 특성 분석 (Characterisation of Impurities)(name, dosage form) 3.2.P.5.6 규격의타당성 (Justification of Specification(s))(name, dosage form) 3.2.P.6 참조표준품또는물품 (Reference Standards or Materials)(name, dosage form) 3.2.P.7 용기마개시스템 (Container Closure System)(name, dosage form) 3.2.P.8 안정성 (Stability)(name, dosage form) 6

7 3.2.P.8.1 안정성 요약 및 결론 (Stability Summary and Conclusion)(name, dosage form) 3.2.P.8.2 승인이후안정성시험프로토콜및안정성이행약속 (Postapproval Stability Protocol and Stability Commitment)(name, dosage form) 3.2.P.8.3 안정성데이터 (Stability Data)(name, dosage form) 3.2.A 부록 (APPENDICES) 3.2.A.1 시설및설비 (Facilities and Equipment)(name, manufacturer) 3.2.A.2 외래성 인자 안전성 평가 (Adventitious Agents Safety Evaluation)(name, dosage form, manufacturer) 3.2.A.3 첨가제 (Excipients) 3.2.R 지역별정보 (REGIONAL INFORMATION) 3.3 참고문헌 (LITERATURE REFERENCES) 7

8 MODULE 2: COMMON TECHNICAL DOCUMENTS SUMMARIES 2.3: QUALITY OVERALL SUMMARY(QOS) The Quality Overall Summary (QOS) is a summary that follows the scope and the outline of the Body of Data in Module 3. The QOS should not include information, data or justification that was not already included in Module 3 or in other parts of the CTD. QOS는모듈 3 BOD(Body of Data) 의범위와개요에따른요약문서이다. 모듈 3 또는다른 CTD 부분에포함되지않은정보, 데이터, 타당성증명자료를 QOS에포함시키지않는다. The QOS should include sufficient information from each section to provide the Quality reviewer with an overview of Module 3. The QOS should also emphasise critical key parameters of the product and provide, for instance, justification in cases where guidelines were not followed. The QOS should include a discussion of key issues that integrates information from sections in the Quality Module and supporting information from other Modules (e.g. qualification of impurities via toxicological studies discussed under the CTD-S module), including crossreferencing to volume and page number in other Modules. 각섹션의충분한정보를 QOS에포함시켜, 품질심사자에게모듈 3의전반적인내용을제공한다. 또한 QOS에서는제품의핵심파라미터를강조하여설명하고, 예를들어가이드라인을따르지않은경우에는그타당성에관한정보를제공한다. 품질모듈에제시된정보와다른모듈의근거정보를포괄하는핵심사항도 QOS에서기술한다 ( 예, CTD-S 모듈에설명된독성실험을인용한불순물적격성평가정보 ). 이때다른모듈의해당볼륨및페이지번호도기재하여상호참조가가능하게한다. This QOS normally should not exceed 40 pages of text, excluding tables and figures. For biotech products and products manufactured using more complex processes, the document could be longer but normally should not exceed 80 pages of text (excluding tables and figures). QOS는일반적으로표와그림을제외한본문이 40페이지를넘지않게작성한다. 복잡한공정으로제조되는제품과생명공학제품인경우, QOS가더길수도있으나일반적으로본문 ( 표와그림제외 ) 이 80페이지를넘지않게한다. The italicised text below indicates where tables, figures, or other items can be 8

9 imported directly from Module 3. 아래에서 " 이탤릭체 " 로표시한부분은, 표, 그림, 기타항목을모듈 3에서바로갖고올수 있는것에해당된다. 서론 (INTRODUCTION) The introduction should include proprietary name, non-proprietary name or common name of the drug substance, company name, dosage form(s), strength(s), route of administration, and proposed indication(s). 서론에는상품명, 원료의약품일반명, 회사명칭, 제형, 함량, 투여경로, 예정적응증정보를기술한다. 2.3.S 원료의약품 (DRUG SUBSTANCE)(NAME, MANUFACTURER) 2.3.S.1 일반정보 (General Information)(name, manufacturer) Information from 3.2.S.1 should be included. 3.2.S.1의정보를기재한다. 2.3.S.2 제조 (Manufacture)(name, manufacturer) Information from 3.2.S.2 should be included: 3.2.S.2의정보를기재한다. Information on the manufacturer; 제조업체관련정보 A brief description of the manufacturing process (including, for example, reference to starting materials, critical steps, and reprocessing) and the controls that are intended to result in the routine and consistent production of material(s) of appropriate quality; 적정품질수준의물품을일상적으로일관되게생산하기위한제조공정 ( 예를들어출발물품, 핵심단계, 재가공정보포함 ) 과관리에관한간단한설명 A flow diagram, as provided in 3.2.S.2.2; 9

10 3.2.S.2.2 의흐름도 A description of the Source and Starting Material and raw materials of biological origin used in the manufacture of the drug substance, as described in 3.2.S.2.3; 3.2.S.2.3에기술된바와같이, 원료의약품제조에사용되는생물학적유래의원료및출발물품, 기원물품에대한설명. A discussion of the selection and justification of critical manufacturing steps, process controls, and acceptance criteria. Highlight critical process intermediates, as described in 3.2.S.2.4; 핵심제조단계, 공정관리, 허용기준의선정및그타당성에대한설명. 3.2.S.2.4에기술된핵심공정중간제품을중심으로기술한다. A description of process validation and/or evaluation, as described in 3.2.S S.2.5에기술된바와같이, 공정밸리데이션및 / 또는평가에대한설명. A brief summary of major manufacturing changes made throughout development and conclusions from the assessment used to evaluate product consistency, as described in 3.2.S.2.6. The QOS should also crossrefer to the non-clinical and clinical studies that used batches affected by these manufacturing changes, as provided in the CTD-S and CTD-E modules of the dossier. 3.2.S.2.6에기술된바와같이, 제품일관성평가결론과개발도중에발생한주요제조변경사항의요약. 또한이러한제조변경으로영향을받은배치가사용된전임상및임상실험정보 (CTD-S 및 CTD-E 모듈에포함된정보 ) 도 QOS에서언급한다. 2.3.S.3 특성분석 (Characterisation)(name, manufacturer) NCE(For NCE): A summary of the interpretation of evidence of structure and isomerism, as described in 3.2.S.3.1, should be included. 10

11 구조와이성질에관한증거를요약하여설명한다 (3.2.S.3.1). When a drug substance is chiral, it should be specified whether specific stereoisomers or a mixture of stereoisomers have been used in the nonclinical and clinical studies, and information should be given as to the stereoisomer of the drug substance that is to be used in the final product intended for marketing. 원료의약품이키랄성이라면, 전임상및임상실험에특정입체이성질체가사용되었는지, 아니면입체이성질체혼합물이사용되었는지명기한다. 또한시판용최종제품에투입될원료의약품의입체이성질체에관한사항도기술한다. 생명공학제품 (For Biotech): A description of the desired product and product-related substances and a summary of general properties, characteristic features and characterisation data (for example, primary and higher order structure and biological activity), as described in 3.2.S.3.1, should be included. 목적제품및제품관련성분에대한설명과일반특징, 독특한특성, 특성분석데이터 ( 예, 일차및고차구조와생물학적활성 ) 요약을포함시킨다 (3.2.S.3.1). NCE 및생명공학제품 (For NCE and Biotech): The QOS should summarise the data on potential and actual impurities arising from the synthesis, manufacture and/or degradation, and should summarise the basis for setting the acceptance criteria for individual and total impurities. The QOS should also summarise the impurity levels in batches of the drug substance used in the non-clinical studies, in the clinical trials, and in typical batches manufactured by the proposed commercial process. The QOS should state how the proposed impurity limits are qualified. 합성, 제조및 / 또는분해과정에서발생하는잠재 / 실제불순물데이터를요약하여기술한다. 또한불순물각각과전체에대한허용기준설정의근거를요약한다. 이외에도전임상, 임상실험에사용된원료의약품과예정상업적공정으로제조한대표배치에투입된원료의약품배치의불순물수준도정리한다. 예정불순물한도기준의적격성을어떻게평가했는지기술한다. 11

12 A tabulated summary of the data provided in 3.2.S.3.2, with graphical representation, where appropriate should be included. 3.2.S.3.2의데이터를도표와적절한경우에는그래프로정리하여포함시킨다. 2.3.S.4 원료의약품관리 (Control of Drug Substance)(name, manufacturer) A brief summary of the justification of the specification(s), the analytical procedures, and validation should be included. 규격의타당성, 분석방법, 밸리데이션에관해요약한다. Specification from 3.2.S.4.1 should be provided. 3.2.S.4.1의규격을제공한다. A tabulated summary of the batch analyses from 3.2.S.4.4, with graphical representation where appropriate, should be provided. 3.2.S.4.4의배치분석요약표와적절한경우에는그래프를제공한다. 2.3.S.5 참조표준품또는물품 (Reference Standards or Materials)(name, manufacturer) Information from 3.2.S.5 (tabulated presentation, where appropriate) should be included. 3.2.S.5의정보 ( 적절한경우에도표로정리 ) 를포함시킨다. 2.3.S.6 용기마개시스템 (Container Closure System)(name, manufacturer) A brief description and discussion of the information, from 3.2.S.6 should be included. 3.2.S.6의정보를간단하게정리하고설명한다. 2.3.S.7 안정성 (Stability)(name, manufacturer) This section should include a summary of the studies undertaken (conditions, batches, analytical procedures) and a brief discussion of the results and conclusions, 12

13 the proposed storage conditions, retest date or shelf-life, where relevant, as described in 3.2.S.7.1. 안정성시험을요약하고 ( 조건, 배치, 분석방법 ), 그결과와결론, 예정보관조건, 재시험일자또는유효기간을정리한다 (3.2.S.7.1). The post-approval stability protocol, as described in 3.2.S.7.2, should be included. 승인이후에실시할안정성시험프로토콜 (3.2.S.7.2) 도포함시킨다. A tabulated summary of the stability results from 3.2.S.7.3, with graphical representation where appropriate, should be provided. 3.2.S.7.3의안정성시험결과를도표로요약하고적절한경우에는그래프로정리한다. 2.3.P 완제의약품 (DRUG PRODUCT)(NAME, DOSAGE FORM) 2.3.P.1 완제의약품기본정보및조성 (Description and Composition of the Drug Product)(name, dosage form) Information from 3.2.P.1 should be provided. 3.2.P.1 의정보를정리한다. Composition from 3.2.P.1 should be provided. 3.2.P.1의조성정보를기술한다. 2.3.P.2 개발경위 (Pharmaceutical Development)(name, dosage form) A discussion of the information and data from 3.2.P.2 should be presented. 3.2.P.2 의정보와데이터를정리하여설명한다. A tabulated summary of the composition of the formulations used in clinical trials and a presentation of dissolution profiles should be provided, where relevant. 임상시험에사용된제제의조성을도표로정리하고관련성이있는경우에는용출프로파일을제공한다. 2.3.P.3 제조 (Manufacture)(name, dosage form) 13

14 Information from 3.2.P.3 should include: 다음을포함하여 3.2.P.3 의정보를요약한다. Information on the manufacturer. 제조업체관련정보 A brief description of the manufacturing process and the controls that are intended to result in the routine and consistent production of product of appropriate quality. 적정품질수준의물품을일상적으로일관되게생산하기위한제조공정및관리에관한간단한설명 A flow diagram, as provided under 3.2.P P.3.3의흐름도 A brief description of the process validation and/or evaluation, as described in 3.2.P P.3.5 에기술된바와같이, 공정밸리데이션및 / 또는평가에대한설명. 2.3.P.4 첨가제관리 (Control of Excipients)(name, dosage form) A brief summary on the quality of excipients, as described in 3.2.P.4, should be included. 3.2.P.4 의첨가제품질에관한정보를간단히요약한다. 2.3.P.5 완제의약품관리 (Control of Drug Product)(name, dosage form) A brief summary of the justification of the specification(s), a summary of the analytical procedures and validation, and characterisation of impurities should be provided. 규격의타당성, 분석방법과밸리데이션사항요약, 불순물특성분석에관한정보를정리한다. Specification(s) from 3.2.P.5.1 should be provided. 3.2.P.5.1의규격을제공한다. 14

15 A tabulated summary of the batch analyses provided under 3.2.P.5.4, with graphical representation where appropriate should be included. 3.2.P.5.4의배치분석요약표와적절한경우에는그래프를제공한다. 2.3.P.6 참조표준품또는물품 (Reference Standards or Materials)(name, dosage form) Information from 3.2.P.6 (tabulated presentation, where appropriate) should be included. 3.2.P.6 의정보 ( 적절한경우에도표로정리 ) 를포함시킨다. 2.3.P.7 용기마개시스템 (Container Closure System)(name, dosage form) A brief description and discussion of the information in 3.2.P.7 should be included. 3.2.P.7 의정보를간단하게정리하고설명한다. 2.3.P.8 안정성 (Stability)(name, dosage form) A summary of the studies undertaken (conditions, batches, analytical procedures) and a brief discussion of the results and conclusions of the stability studies and analysis of data should be included. Conclusions with respect to storage conditions and shelf-life and, if applicable, in-use storage conditions and shelf-life should be given. 안정성시험을요약하고 ( 조건, 배치, 분석방법 ), 안정성시험및데이터분석결과와결론을정리한다. 보관조건및유효기간, 그리고해당되는경우에는사용시의보관조건및유효기간에관한결론을제시한다. A tabulated summary of the stability results from 3.2.P.8.3, with graphical representation where appropriate, should be included. 3.2.P.8.3의안정성시험결과를도표로요약하고적절한경우에는그래프로정리한다. The post-approval stability protocol, as described in 3.2.P.8.2, should be provided. 승인이후에실시할안정성시험프로토콜 (3.2.P.8.2) 도포함시킨다. 15

16 2.3.A 부록 (APPENDICES) 2.3.A.1 시설및설비 (Facilities and Equipment)(name, manufacturer) 생명공학제품 (Biotech): A summary of facility information described under 3.2.A.1 should be included. 3.2.A.1의시설정보를요약한다. 2.3.A.2 외래성인자안전성평가 (Adventitious Agents Safety Evaluation)(name, dosage form, manufacturer) A discussion on measures implemented to control endogenous and adventitious agents in production should be included. 생산시의내인성및외인성인자관리대책을설명한다. A tabulated summary of the reduction factors for viral clearance from 3.2.A.2, should be provided. 3.2.A.2의바이러스클리어런스감소율을도표로정리한다. 2.3.A.3 첨가제 (Excipients) 2.3.R 지역별정보 (REGIONAL INFORMATION) A brief description of the information specific for the region, as provided under 3.2.R should be included, where appropriate. "3.2.R" 의지역별로지정된정보를요약하여기술한다. 16

17 MODULE 3: QUALITY 적용범위 (SCOPE OF THE GUIDELINE) This document is intended to provide guidance on the format of a registration application for drug substances and their corresponding drug products as defined in the scope of the ICH Guidelines Q6A ("NCE") and ICH Guideline Q6B ("Biotech"). This format may also be appropriate for certain other categories of products. To determine the applicability of this format for a particular type of product, applicants should consult with the appropriate regulatory authorities. 이문서는 ICH 가이드라인 Q6A("NCE") 와 Q6B(" 생명공학제품 ") 의적용범위에규정된원료의약품및그에해당되는완제의약품의등록신청서류형식에관한가이드라인을제시한다. 또한이형식은일부다른카테고리의제품에도적용할수있다. 이형식을특정유형의제품에적용하기로결정하기전에, 신청업체는해당규제당국과협의하는것이좋다. The text following the section titles is intended to be explanatory and illustrative only. The content of these sections should include relevant information described in existing ICH guidelines, but harmonised content is not available for all sections. The "Body of Data" in this guideline merely indicates where the information should be located. Neither the type nor extent of specific supporting data has been addressed in this guideline, and both may depend upon regional guidance. 섹션별제목아래의본문은일종의예를제시하기위한것이다. 섹션별내용에관한사항은기존의다른 ICH 가이드라인을참고한다. 하지만모든섹션에적용할수있는합의된내용은없다. 이가이드라인의 "BOD(Body of Data)" 는해당정보가어디에있어야하는지를표시하기위한것이다. 구체적인근거데이터의정도나유형은이가이드라인에서제시하지않으며, 지역별가이드라인에따라결정된다. The section titles of Part 3.2.R (Regional Information) represent examples of typical topics of information that are not common to all ICH regions. Hence, the information to be provided in these sections should be based on the relevant regional guidelines. 파트 3.2.R( 지역별정보 ) 의섹션제목은모든 ICH 지역에공통적으로적용되지않는대표적인사항의예에해당된다. 그러므로이섹션에포함시켜야할정보는해당지역의가이드라인을따른다. 17

18 3.1. 모듈 3 목차 (TABLE OF CONTENTS OF MODULE 3) A Table of Contents for the filed application should be provided. 신청서류의목차를정리한다 BOD(BODY OF DATA) 3.2.S 원료의약품 (DRUG SUBSTANCE) 1 (NAME, MANUFACTURER) 3.2.S.1 일반정보 (General Information)(name, manufacturer) 3.2.S.1.1 명칭 (Nomenclature)(name, manufacturer) Information on the nomenclature of the drug substance should be provided. For example: 원료의약품의명칭에관한정보를다음의예와같이기재한다. Recommended International Nonproprietary Name (INN); 권장 INN Compendial name if relevant; 공정서수재명칭 Chemical name(s); 화학명 Company or laboratory code; 회사또는실험실자체코드 Other non-proprietary name(s), e.g., national name, United States Adopted Name (USAN), Japanese Accepted Name (JAN); British Approved Name (BAN), and 1 For a drug product containing more than one drug substance, the information requested for part S should be provided in its entirety for each drug substance. 하나이상의원료의약품을함유하는완제의약품인경우, 원료의약품각각에대하여 "S" 파트에서요구하는정보전체를제공해야한다. 18

19 기타일반명 ( 예, 국가별명칭, USAN, JAN, BAN) Chemical Abstracts Service (CAS) registry number. CAS 등록번호 3.2.S.1.2 구조 (Structure)(name, manufacturer) NCE: The structural formula, including relative and absolute stereochemistry, the molecular formula, and the relative molecular mass should be provided. 상대및절대입체화학을포함한구조식, 분자식, 상대분자량을기재한다. 생명공학제품 (Biotech): The schematic amino acid sequence indicating glycosylation sites or other post-translational modifications and relative molecular mass should be provided, as appropriate. 적절한경우에당화부위또는기타번역이후변형을표시한대략적인아미노산서열과상대분자량을기재한다. 3.2.S.1.3 일반특징 (General Properties)(name, manufacturer) A list should be provided of physicochemical and other relevant properties of the drug substance, including biological activity for Biotech. 생명공학제품인경우에생물학적활성을포함하여, 원료의약품의이화학적특징과기타관련특징을표로정리한다. Reference ICH Guidelines: Q6A and Q6B 참고 ICH 가이드라인 : Q6A, Q6B 3.2.S.2 제조 (Manufacture)(name, manufacturer) 3.2.S.2.1 제조업체 (Manufacturer(s))(name, manufacturer) The name, address, and responsibility of each manufacturer, including contractors, and each proposed production site or facility involved in manufacturing and testing should be provided. 19

20 계약업체를포함한제조업체와제조및시험업무를수행할예정생산사업장또는시설 각각의명칭, 주소, 책임사항을기술한다. 3.2.S.2.2 제조공정및공정관리 (Description of Manufacturing Process and Process Controls)(name, manufacturer) The description of the drug substance manufacturing process represents the applicant s commitment for the manufacture of the drug substance. Information should be provided to adequately describe the manufacturing process and process controls. For example: 원료의약품제조공정에대한정보는, 원료의약품제조에대한신청업체의약속을의미한다. 다음의예와같이제조공정과공정관리에관한정보를적절하게기술한다. NCE: A flow diagram of the synthetic process(es) should be provided that includes molecular formulae, weights, yield ranges, chemical structures of starting materials, intermediates, reagents and drug substance reflecting stereochemistry, and identifies operating conditions and solvents. 분자식, 중량, 수율범위, 출발물품의화학구조, 중간제품, 시약, 그리고입체화학을반영한원료의약품을포함하여, 공정조건과용매를명기한합성공정흐름도를제공한다. A sequential procedural narrative of the manufacturing process should be submitted. The narrative should include, for example, quantities of raw materials, solvents, catalysts and reagents reflecting the representative batch scale for commercial manufacture, identification of critical steps, process controls, equipment and operating conditions (e.g., temperature, pressure, ph, time). 제조공정을순차적으로설명한다. 이때예를들어원료, 용매, 촉매제, 시약의양 ( 상업적제조를위한대표배치스케일반영 ) 을기재하고, 핵심공정단계와공정관리, 설비, 공정조건 ( 예, 온도, 압력, ph, 시간 ) 을명시한다. Alternate processes should be explained and described with the same level of detail as the primary process. Reprocessing steps should be identified 20

21 and justified. Any data to support this justification should be either referenced or filed in 3.2.S.2.5. 주된공정과마찬가지수준으로대체공정을자세하게설명한다. 재가공단계를명시하고그타당성을제시한다. 이와관련된근거데이터를 3.2.S.2.5에포함시키거나참고정보를기재한다. 생명공학제품 (Biotech): Information should be provided on the manufacturing process, which typically starts with a vial(s) of the cell bank, and includes cell culture, harvest(s), purification and modification reactions, filling, storage and shipping conditions. 제조공정에대한정보를기술한다. 일반적으로세포뱅크바이알부터시작하며, 세포배양, 세포수득, 정제및변형반응, 충전, 보관및운송조건을포함한다. 배치및배치스케일 (Batch(es) and scale definition) An explanation of the batch numbering system, including information regarding any pooling of harvests or intermediates and batch size or scale should be provided. 배치번호부여시스템을설명한다. 이때수득물또는중간제품의혼합 (pooling) 과배치크기또는스케일에대한정보도기술한다. 세포배양및수득 (Cell culture and harvest) A flow diagram should be provided that illustrates the manufacturing route from the original inoculum (e.g. cells contained in one or more vials(s) of the Working Cell Bank up to the last harvesting operation. The diagram should include all steps (i.e., unit operations) and intermediates. Relevant information for each stage, such as population doubling levels, cell concentration, volumes, ph, cultivation times, holding times, and temperature, should be included. Critical steps and critical intermediates for which specifications are established (as mentioned in 3.2.S.2.4) should be identified. 최초접종물 ( 예, 1개이상의 WCB 바이알에들어있는세포 ) 부터마지막수득 21

22 작업까지의제조경로를정리한흐름도를제공한다. 이흐름도에모든단계 ( 즉, 단위공정 ) 와중간제품을포함시킨다. 단계별관련정보 ( 예, 집단배증수준, 세포농도, 볼륨, ph, 배양시간, 유지시간, 온도 ) 를기술한다. 규격이확립된 (3.2.S.2.4) 핵심중간제품과핵심단계를표기한다. A description of each process step in the flow diagram should be provided. Information should be included on, for example, scale; culture media and other additives (details provided in 3.2.S.2.3); major equipment (details provided in 3.2.A.1); and process controls, including in-process tests and operational parameters, process steps, equipment and intermediates with acceptance criteria (details provided in 3.2.S.2.4). Information on procedures used to transfer material between steps, equipment, areas, and buildings, as appropriate, and shipping and storage conditions should be provided. (Details on shipping and storage provided in 3.2.S.2.4.) 흐름도의공정단계별로설명한다. 예를들어스케일, 배양배지및기타첨가제 ( 세부사항은 3.2.S.2.3에기술 ), 주요설비 ( 세부시항은 3.2.A.1에기술 ), IPT(in-process test) 와공정파라미터, 공정단계, 설비및중간제품을포함한공정관리와허용기준 ( 세부사항은 3.2.S.2.4에기술 ) 에관한정보를기술한다. 공정단계, 설비, 지역, 건물사이의물품이송절차와운반및보관조건에관한정보도제공한다. ( 운반및보관에관한세부사항은 3.2.S.2.4에기술.) 정제및변형반응 (Purification and modification reactions) A flow diagram should be provided that illustrates the purification steps (i.e., unit operations) from the crude harvest(s) up to the step preceding filling of the drug substance. All steps and intermediates and relevant information for each stage (e.g., volumes, ph, critical processing time, holding times, temperatures and elution profiles and selection of fraction, storage of intermediate, if applicable) should be included. Critical steps for which specifications are established as mentioned in 3.2.S.2.4 should be identified. 배양수득물부터원료의약품충전이전단계까지, 정제단계 ( 즉, 단위공정 ) 를보여주는흐름도를작성한다. 모든단계와중간제품, 그리고단계별관련정보 ( 예, 볼륨, ph, 가공시간, 유지시간, 온도및용출프로파일, 분획물의선택, 중간제품보관 ) 를기술한다. 규격이확립된 (3.2.S.2.4) 핵심단계를표기한다. 22

23 A description of each process step (as identified in the flow diagram) should be provided. The description should include information on, for example, scale, buffers and other reagents (details provided in 3.2.S.2.3, major equipment (details provided in 3.2.A.1), and materials. For materials such as membranes and chromatography resins, information for conditions of use and reuse also should be provided. (Equipment details in 3.2.A.1; validation studies for the reuse and regeneration of columns and membranes in 3.2.S.2.5.) The description should include process controls (including in-process tests and operational parameters) with acceptance criteria for process steps, equipment and intermediates. (Details in 3.2.S.2.4.) 공정단계별로 ( 흐름도에기재된바에따라 ) 설명한다. 이때예를들어스케일, 완충액및기타시약 ( 세부사항은 3.2.S.2.3에기술 ), 주요설비 ( 세부사항은 3.2.A.1에기술 ), 물품에관한정보를포함한다. 멤브레인과크로마토그래피수지등에대해서는, 사용및재사용조건에대한정보를제공한다. ( 설비세부사항은 3.2.A.1에기술하고, 칼럼과멤브레인재사용및재생에관한밸리데이션실험사항은 3.2.S.2.5에기술한다.) 공정관리 (IPT(in-process test) 및공정파라미터포함 ) 와공정단계, 설비, 중간제품의허용기준도기술한다 ( 세부사항은 3.2.S.2.4에기술 ). Reprocessing procedures with criteria for reprocessing of any intermediate or the drug substance should be described. (Details should be given in 3.2.S.2.5.) 재가공절차와중간제품또는원료의약품의재가공기준을기술한다. ( 세부사항은 3.2.S.2.5에기술.) Information on procedures used to transfer material between steps, equipment, areas, and buildings, as appropriate, and shipping and storage conditions should be provided (details on shipping and storage provided in 3.2.S.2.4.). 공정단계, 설비, 지역, 건물사이의물품이송절차와운반 / 보관조건에관한정보를기술한다. ( 운반및보관에관한세부사항은 3.2.S.2.4에기술.) 충전, 보관, 운반 (Filling, storage and transportation (shipping)) 23

24 A description of the filling procedure for the drug substance, process controls (including in-process tests and operational parameters), and acceptance criteria should be provided. (Details in 3.2.S.2.4.) The container closure system(s) used for storage of the drug substance (details in 3.2.S.6.) and storage and shipping conditions for the drug substance should be described. 원료의약품충전절차와공정관리 (IPT(in-process test) 와공정파라미터포함 ), 그리고허용기준을기술한다. ( 세부사항은 3.2.S.2.4에기술.) 원료의약품보관용용기마개시스템 ( 세부사항은 3.2.S.6에기술 ) 과원료의약품보관및운반조건을기술한다. Reference ICH Guidelines: Q5A, Q5B, and Q6B 참고 ICH 가이드라인 : Q5A, Q5B, Q6B 3.2.S.2.3 물품관리 (Control of Materials)(name, manufacturer) Materials used in the manufacture of the drug substance (e.g., raw materials, starting materials, solvents, reagents, catalysts) should be listed identifying where each material is used in the process. Information on the quality and control of these materials should be provided. Information demonstrating that materials (including biologically-sourced materials, e.g., media components, monoclonal antibodies, enzymes) meet standards appropriate for their intended use (including the clearance or control of adventitious agents) should be provided, as appropriate. For biologically-sourced materials, this can include information regarding the source, manufacture, and characterisation. (Details in 3.2.A.2 for both NCE and Biotech) 원료의약품제조에사용되는물품 ( 예, 원료, 출발물품, 용매, 시약, 촉매제 ) 을정리하고, 각물품이어느공정에사용되는지기술한다. 이들물품의품질과관리에관한정보를기술한다. 물품 ( 생물학적기원물품포함, 예 : 배지성분, 단클론항체, 효소 ) 의목적용도에비추어적절한표준에부합함 ( 외래성인자의관리또는클리어런스 ) 을증명하는정보도기술한다. 생물학적기원물품인경우에는, 그기원, 제조, 특성분석에관한정보를포함시킬수있다. (NCE와생명공학제품모두, 세부사항은 3.2.A.2에기술.) Reference ICH Guidelines: Q6A and Q6B 참고 ICH 가이드라인 : Q6A, Q6B 24

25 생명공학제품 (Biotech): 생물학적유래기원물품과출발물품의관리 (Control of Source and Starting Materials of Biological Origin) Summaries of viral safety information for biologically-sourced materials should be provided. (Details in 3.2.A.2.) 생물학적기원물품의바이러스안전성정보를요약한다. ( 세부사항은 3.2.A.2에기술 ) 세포기질의기원, 이력, 세대 (Source, history, and generation of the cell substrate) Information on the source of the cell substrate and analysis of the expression construct used to genetically modify cells and incorporated in the initial cell clone used to develop the Master Cell Bank should be provided as described in Q5B and Q5D. 세포기질의기원과세포의유전적변형을위해초기세포클론에통합되어 MCB를만드는데사용된발현구성물의분석에관한정보를 Q5B와 Q5D에의거하여기술한다. 세포뱅크시스템, 특성분석, 시험 (Cell banking system, characterisation, and testing) Information on the cell banking system, quality control activities, and cell line stability during production and storage (including procedures used to generate the Master and Working Cell Bank(s)) should be provided as described in Q5B and Q5D. 세포뱅크시스템, 품질관리활동, 생산및보관시의세포주안정성에관한정보 (MCB와 WCB 생산방법포함 ) 를 Q5B와 Q5D에의거하여기술한다. Reference ICH Guidelines: Q5A, Q5B, Q5C and Q5D 참고 ICH 가이드라인 : Q5A, Q5B, Q5D 25

26 3.2.S.2.4 핵심단계및중간제품관리 (Controls of Critical Steps and Intermediates)(name, manufacturer) Critical Steps: Tests and acceptance criteria (with justification including experimental data) performed at critical steps identified in 3.2.S.2.2 of the manufacturing process to ensure that the process is controlled should be provided. 핵심단계 : 3.2.S.2.2의제조공정핵심단계에서공정이관리상태에있음을확인하기위해실시하는시험과허용기준 ( 실험데이터를포함한타당성입증정보포함 ) 을기술한다. Intermediates: Information on the quality and control of intermediates isolated during the process should be provided. 중간제품 : 공정도중에분리되는중간제품의품질과관리에관한정보를기술한다. Reference ICH Guidelines: Q6A and Q6B 참고 ICH 가이드라인 : Q6A, Q6B Additionally for Biotech: Stability data supporting storage conditions should be provided. 생명공학제품 ( 추가사항 ): 보관조건을뒷받침하는안정성데이터를제공한다. Reference ICH Guideline: Q5C 참고 ICH 가이드라인 : Q5C 3.2.S.2.5 공정밸리데이션및 / 또는평가 (Process Validation and/or Evaluation)(name, manufacturer) Process validation and/or evaluation studies for aseptic processing and sterilisation should be included. 무균공정및멸균공정의밸리데이션및 / 또는평가실험정보를기술한다. 생명공학제품 (Biotech): Sufficient information should be provided on validation and evaluation studies to demonstrate that the manufacturing process (including reprocessing steps) is suitable for its intended purpose and to substantiate 26

27 selection of critical process controls (operational parameters and inprocess tests) and their limits for critical manufacturing steps (e.g., cell culture, harvesting, purification, and modification). 제조공정 ( 재가공단계포함 ) 이예정목적에적합함을증명하고, 핵심제조단계 ( 예, 세포배양, 수득, 정제, 변형 ) 의주요공정관리 ( 공정파라미터및 IPT(in-process tests)) 와그기준설정의근거를제시하는, 밸리데이션및평가실험에관한정보를충분히기술한다. The plan for conducting the study should be described and the results, analysis and conclusions from the executed study(ies) should be provided. The analytical procedures and corresponding validation should be crossreferenced (e.g., 3.2.S.2.4, 3.2.S.4.3) or provided as part of justifying the selection of critical process controls and acceptance criteria. 실험계획과실험결과, 분석, 결론을기술한다. 핵심공정관리및허용기준설정의타당성을증명하는일환으로, 분석방법과그의밸리데이션에관한정보를기술하거나상호참조 ( 예, 3.2.S.2.4, 3.2.S.4.3) 정보를기술한다. For manufacturing steps intended to remove or inactivate viral contaminants, the information from evaluation studies should be provided in 3.2.A.2. 바이러스오염물의제거또는불활화를목적으로하는제조단계인경우에는, 평가실험정보를 3.2.A.2에기술한다. 3.2.S.2.6 제조공정개발 (Manufacturing Process Development)(name, manufacturer) NCE: A description and discussion should be provided of the significant changes made to the manufacturing process and/or manufacturing site of the drug substance used in producing nonclinical, clinical, scale-up, pilot, and, if available, production scale batches. 전임상, 임상, 스케일업, 파일럿, 그리고가능한경우에는생산스케일배치생산에사용된원료의약품의제조공정및 / 또는제조사업장과관련된중요변경사항을설명한다. 27

28 Reference should be made to the drug substance data provided in section 3.2.S.4.4. 섹션 3.2.S.4.4 의원료의약품데이터를인용한다. Reference ICH Guideline: Q3A 참고 ICH 가이드라인 : Q3A 생명공학제품 (Biotech): The developmental history of the manufacturing process, as described in 3.2.S.2.2, should be provided. The description of change(s) made to the manufacture of drug substance batches used in support of the marketing application (e.g., nonclinical or clinical studies) should include, for example, changes to the process or to critical equipment. The reason for the change should be explained. Relevant information on drug substance batches manufactured during development, such as the batch number, manufacturing scale, and use (e.g., stability, nonclinical, reference material) in relation to the change, should be provided. 3.2.S.2.2에기술한제조공정의개발내역을기술한다. 판매신청서류를뒷받침하는데 ( 예, 전임상또는임상시험 ) 사용된원료의약품배치제조와관련된변경사항을기술하며, 이때공정이나핵심설비의변경사항도포함한다. 변경이유를기술한다. 개발과정에서제조된원료의약품배치에관한관련정보 ( 예, 변경과관련된배치번호, 제조규모, 용도 ( 예, 안정성, 전임상, 참조물품 )) 를기술한다. The significance of the change should be assessed by evaluating its potential to impact the quality of the drug substance (and/or intermediate, if appropriate). For manufacturing changes that are considered significant, data from comparative analytical testing on relevant drug substance batches should be provided to determine the impact on quality of the drug substance (see Q6B for additional guidance). A discussion of the data, including a justification for selection of the tests and assessment of results, should be included. 변경의의미를평가한다. 원료의약품 ( 및 / 또는중간제품 ) 품질에미칠파급효과를 28

29 평가한다. 중대한제조변경인경우에는, 관련원료의약품배치와의비교분석 데이터를통해원료의약품의품질에미치는파급영향을파악한다 (Q6B 참조 ). 시험항목선정의타당성과결과평가를포함하여, 데이터를제시하고설명한다. Testing used to assess the impact of manufacturing changes on the drug substance(s) and the corresponding drug product(s) can also include nonclinical and clinical studies. Cross-reference to the location of these studies in other modules of the submission should be included. 제조변경이원료의약품과완제의약품에미치는파급영향을평가하기위한시험에는전임상및임상실험도포함될수있다. 제출서류중의다른모듈에포함된이런실험데이터의상호참조정보도포함시킨다. Reference should be made to the drug substance data provided in section 3.2.S.4.4. 섹션 3.2.S.4.4 의원료의약품데이터도인용한다. Reference ICH Guideline: Q6B 참고 ICH 가이드라인 : Q6B 3.2.S.3 특성분석 (Characterisation)(name, manufacturer) 3.2.S.3.1 구조및기타특성 (Elucidation of Structure and other Characteristics)(name, manufacturer) NCE: Confirmation of structure based on e.g., synthetic route and spectral analyses should be provided. Information such as the potential for isomerism, the identification of stereochemistry, or the potential for forming polymorphs should also be included. 예를들어합성경로와스펙트럼분석에근거하여구조정보를기술한다. 이성질현상가능성, 입체화학, 또는다형체형성가능성에관한정보도포함시킨다. Reference ICH Guideline: Q6A 참고 ICH 가이드라인 : Q6A 29

30 생명공학제품 (Biotech): For desired product and product-related substances, details should be provided on primary, secondary and higher-order structure, posttranslational forms (e.g., glycoforms), biological activity, purity, and immunochemical properties, when relevant. 목적제품과제품관련성분에대하여, 일차, 이차, 고차구조, 번역이후의형태 ( 예, 단백당형 ), 생물학적활성, 순도, 면역화학적특징등에관한세부정보를기술한다. Reference ICH Guideline: Q6B 참고 ICH 가이드라인 : Q6B 3.2.S.3.2 불순물 (Impurities)(name, manufacturer) Information on impurities should be provided. 불순물관련정보를제공한다. Reference ICH Guidelines: Q3A, Q3C, Q5C, Q6A, and Q6B 참고 ICH 가이드라인 : Q3A, Q3C, Q5C, Q6A, Q6B 3.2.S.4 원료의약품관리 (Control of Drug Substance)(name, manufacturer) 3.2.S.4.1 규격 (Specification)(name, manufacturer) The specification for the drug substance should be provided. 원료의약품의규격을기술한다. Reference ICH Guidelines: Q6A and Q6B 참고 ICH 가이드라인 : Q6A, Q6B 3.2.S.4.2 분석절차 (Analytical Procedures)(name, manufacturer) The analytical procedures used for testing the drug substance should be provided. 30

31 원료의약품시험에적용할분석절차를기술한다. Reference ICH Guidelines: Q2A and Q6B 참고 ICH 가이드라인 : Q2A, Q6B 3.2.S.4.3 분석절차밸리데이션 (Validation of Analytical Procedures)(name, manufacturer) Analytical validation information, including experimental data for the analytical procedures used for testing the drug substance, should be provided. 분석절차밸리데이션정보 ( 원료의약품시험절차에대한실험적데이터포함 ) 를기술한다. Reference ICH Guidelines: Q2A, Q2B, and Q6B 참고 ICH 가이드라인 : Q2A, Q2B, Q6B 3.2.S.4.4 배치분석 (Batch Analyses)(name, manufacturer) Description of batches and results of batch analyses should be provided. 배치에대한정보와배치분석결과를기술한다. Reference ICH Guidelines: Q3A, Q3C, Q6A, and Q6B 참고 ICH 가이드라인 : Q3A, Q3C, Q6A, Q6B 3.2.S.4.5 규격의타당성 (Justification of Specification)(name, manufacturer) Justification for the drug substance specification should be provided. 원료의약품규격의타당성을제시한다. Reference ICH Guidelines: Q3A, Q3C, Q6A and Q6B 참고 ICH 가이드라인 : Q3A, Q3C, Q6A, Q6B 3.2.S.5 참조표준품또는물품 (Reference Standards or Materials)(name, manufacturer) Information on the reference standards or reference materials used for testing of 31

32 the drug substance should be provided. 원료의약품시험에사용하는참조표준품또는참조물품에관한정보를기술한다. Reference ICH Guidelines: Q6A and Q6B 참고 ICH 가이드라인 : Q6A, Q6B 3.2.S.6 용기마개시스템 (Container Closure System)(name, manufacturer) A description of the container closure system(s) should be provided, including the identity of materials of construction of each primary packaging component, and their specifications. The specifications should include description and identification (and critical dimensions with drawings, where appropriate). Non-compendial methods (with validation) should be included, where appropriate. 일차포장자재의구성재질과그규격을포함하여, 용기마개시스템에대해기술한다. 자재의성상과확인 ( 및적절한경우에는주요치수와도면 ) 항목이규격에포함되어야한다. 적절한경우에는비공정서방법 ( 밸리데이션포함 ) 도포함시킨다. For non-functional secondary packaging components (e.g., those that do not provide additional protection), only a brief description should be provided. For functional secondary packaging components, additional information should be provided. 비기능적이차포장자재 ( 예, 추가적인보호기능을제공하지않는자재 ) 에대해서는간략하게설명한다. 기능적이차포장자재에대해서는추가적인정보를기술한다. The suitability should be discussed with respect to, for example, choice of materials, protection from moisture and light, compatibility of the materials of construction with the drug substance, including sorption to container and leaching, and/or safety of materials of construction. 예를들어물품선택, 습기및빛으로부터보호, 구성재질과원료의약품의조화성 ( 용기흡착및유출포함 ), 구성재질의안전성측면에서적합성을설명한다. 3.2.S.7 안정성 (Stability)(name, manufacturer) 3.2.S.7.1 안정성요약및결론 (Stability Summary and Conclusions)(name, manufacturer) 32

33 The types of studies conducted, protocols used, and the results of the studies should be summarized. The summary should include results, for example, from forced degradation studies and stress conditions, as well as conclusions with respect to storage conditions and retest date or shelf-life, as appropriate. 안정성시험유형, 프로토콜, 시험결과를요약한다. 이때예를들어강제분해실험및스트레스조건에서실시한실험결과, 그리고보관조건및재시험일자또는유효기간과관련한결론이있어야한다. Reference ICH Guidelines: Q1A, Q1B, and Q5C 참고 ICH 가이드라인 : Q1A, Q1B, Q5C 3.2.S.7.2 승인이후안정성시험프로토콜및안정성이행약속 (Post-approval Stability Protocol and Stability Commitment)(name, manufacturer) The post-approval stability protocol and stability commitment should be provided. 승인이후안정성시험프로토콜및안정성시험이행에관한정보를기술한다. Reference ICH Guidelines: Q1A and Q5C 참고 ICH 가이드라인 : Q1A, Q5C 3.2.S.7.3 안정성데이터 (Stability Data)(name, manufacturer) Results of the stability studies (e.g., forced degradation studies and stress conditions) should be presented in an appropriate format such as tabular, graphical, or narrative. Information on the analytical procedures used to generate the data and validation of these procedures should be included. 안정성시험결과 ( 예, 강제분해실험및스트레스조건 ) 를적절한형식 ( 예, 도표, 그래프, 서술식 ) 으로제시한다. 데이터생성에활용한분석절차와이분석절차의밸리데이션관련정보도포함시킨다. Reference ICH Guidelines: Q1A, Q1B, Q2A, Q2B, and Q5C 참고 ICH 가이드라인 : Q1A, Q1B, Q2A, Q2B, Q5C 33

34 3.2.P 완제의약품 (DRUG PRODUCT)(NAME, DOSAGE FORM) 3.2.P.1 완제의약품기본정보및조성 (Description and Composition of the Drug Product)(name, dosage form) A description of the drug product and its composition should be provided. The information provided should include, for example: 완제의약품에대한기본정보와조성을기술한다. 예를들어다음정보를기술한다. Description 2 of the dosage form; 제형 Composition, i.e., list of all components of the dosage form, and their amount on a per-unit basis (including overages, if any) the function of the components, and a reference to their quality standards (e.g., compendial monographs or manufacturer s specifications) 조성 : 완제의약품의모든원료리스트와단위용량별함량 ( 과량포함 ), 원료의기능, 품질표준참조정보 ( 예, 공정서모노그래프또는제조업체자체규격 ). Description of accompanying reconstitution diluent(s); and 동봉하는재구성용희석액에대한설명. Type of container and closure used for the dosage form and accompanying reconstitution diluent, if applicable. 완제의약품및동봉하는재구성용희석액의용기마개유형. Reference ICH Guidelines: Q6A and Q6B 참고 ICH 가이드라인 : Q6A, Q6B 3.2.P.2 개발경위 (Pharmaceutical Development)(name, dosage form) 2 For a drug product supplied with reconstitution diluent(s), the information on the diluent(s) should be provided in a separate part P, as appropriate 재구성용희석액과함께제공되는완제의약품인경우, 희석제정보도별도의파트 "P" 로하여제공한다. 34

35 The Pharmaceutical Development section should contain information on the development studies conducted to establish that the dosage form, the formulation, manufacturing process, container closure system, microbiological attributes and usage instructions are appropriate for the purpose specified in the application. The studies described here are distinguished from routine control tests conducted according to specifications. Additionally, this section should identify and describe the formulation and process attributes (critical parameters) that can influence batch reproducibility, product performance and drug product quality. Supportive data and results from specific studies or published literature can be included within or attached to the Pharmaceutical Development section. Additional supportive data can be referenced to the relevant nonclinical or clinical sections of the application. 개발경위섹션에는제형, 조성, 제조공정, 용기마개시스템, 미생물학적특성, 사용방법이신청서류에규정된목적에적절함을보여주기위해실시한개발실험정보를기술한다. 여기에기술하는실험은규격에의거하여정기적으로실시하는품질관리시험과는구분된다. 또한배치재현성, 제품성능, 완제의약품품질에영향을줄수있는조성및공정특성요소 ( 핵심파라미터 ) 를기술하고설명한다. 공표된참고문헌이나특정실험을통해확보한근거데이터와결과를개발경위섹션에포함시키거나첨부한다. 신청서류의관련전임상또는임상섹션을인용하여추가적인근거데이터를제시할수있다. Reference ICH Guidelines: Q6A and Q6B 참고 ICH 가이드라인 : Q6A, Q6B 3.2.P.2.1 완제의약품원료 (Components of the Drug Product)(name, dosage form) 3.2.P 원료의약품 (Drug Substance)(name, dosage form) The compatibility of the drug substance with excipients listed in 3.2.P.1 should be discussed. Additionally, key physicochemical characteristics (e.g., water content, solubility, particle size distribution, polymorphic or solid state form) of the drug substance that can influence the performance of the drug product should be discussed. 3.2.P.1 의첨가제와원료의약품의조화성에대해설명한다. 또한완제의약품의성능에영향을줄수있는원료의약품의주요이화학적특성 ( 예, 수분함량, 용해성, 입자크기 35

36 분포, 다형성또는고체상 ) 을설명한다. For combination products, the compatibility of drug substances with each other should be discussed. 복합제품인경우에는원료의약품상호간의조화성을설명한다. 3.2.P 첨가제 (Excipients)(name, dosage form) The choice of excipients listed in 3.2.P.1, their concentration, their characteristics that can influence the drug product performance should be discussed relative to their respective functions. 3.2.P.1 의첨가제선택, 그의농도, 완제의약품성능에영향을줄수있는특성을각각의기능과관련하여설명한다. 3.2.P.2.2 완제의약품 (Drug Product)(name, dosage form) 3.2.P 조성개발 (Formulation Development)(name, dosage form) A brief summary describing the development of the drug product should be provided, taking into consideration the proposed route of administration and usage. The differences between clinical formulations and the formulation (i.e. composition) described in 3.2.P.1 should be discussed. Results from comparative in vitro studies (e.g., dissolution) or comparative in vivo studies (e.g., bioequivalence) should be discussed when appropriate. 예정투여경로와용법을고려하여완제의약품개발과정을간략하게요약한다. 임상시험제품조성과 3.2.P.1 의제제 ( 즉, 조성 ) 사이에차이가있으면, 그에대해설명한다. 적절한경우에는비교체외실험 ( 예, 용출 ) 또는비교체내실험 ( 예, 생물학적동등성 ) 결과도기술한다. 3.2.P 과량 (Overages)(name, dosage form) Any overages in the formulation(s) described in 3.2.P.1 should be justified. 3.2.P.1 의조성가운데과량투입부분에대하여타당성을제시한다. 3.2.P 이화학적및생물학적특징 (Physicochemical and Biological 36

37 Properties)(name, dosage form) Parameters relevant to the performance of the drug product, such as ph, ionic strength, dissolution, redispersion, reconstitution, particle size distribution, aggregation, polymorphism, rheological properties, biological activity or potency, and/or immunological activity, should be addressed. 완제의약품성능관련변수 ( 예, ph, 이온강도, 용출, 재분산성, 재구성, 입자크기분포, 응집, 다형성, 유동성, 생물학적활성또는역가및 / 또는면역학적활성 ) 를설명한다. 3.2.P.2.3 제조공정개발 (Manufacturing Process Development)(name, dosage form) The selection and optimisation of the manufacturing process described in 3.2.P.3.3, in particular its critical aspects, should be explained. Where relevant, the method of sterilisation should be explained and justified. 3.2.P.3.3 에기술된제조공정의선정및최적화, 특히핵심부분을기술한다. 관련성이있는경우에는멸균방법을설명하고그타당성을제시한다. Differences between the manufacturing process(es) used to produce pivotal clinical batches and the process described in 3.2.P.3.3 that can influence the performance of the product should be discussed. 제품성능에영향을줄수있는 3.2.P.3.3 의공정과핵심임상배치제조공정사이의차이점을설명한다. 3.2.P.2.4 용기마개시스템 (Container Closure System)(name, dosage form) The suitability of the container closure system (described in 3.2.P.7) used for the storage, transportation (shipping) and use of the drug product should be discussed. This discussion should consider, e.g., choice of materials, protection from moisture and light, compatibility of the materials of construction with the dosage form (including sorption to container and leaching) safety of materials of construction, and performance (such as reproducibility of the dose delivery from the device when presented as part of the drug product). 완제의약품보관, 운반, 사용을위한용기마개시스템 (3.2.P.7에기술 ) 의적합성을설명한다. 이때예를들어물품선택, 습기및빛으로부터보호, 구성재질과제제와의 37

38 조화성 ( 용기흡착및유출포함 ), 구성재질의안전성, 성능 ( 예, 완제의약품의한부분으로 포함된장치의용량전달재현성 ) 측면에서적합성을설명한다. 3.2.P.2.5 미생물학적특성 (Microbiological Attributes)(name, dosage form) Where appropriate, the microbiological attributes of the dosage form should be discussed, including, for example, the rationale for not performing microbial limits testing for non-sterile products and the selection and effectiveness of preservative systems in products containing antimicrobial preservatives. For sterile products, the integrity of the container closure system to prevent microbial contamination should be addressed. 적절한경우에는완제의약품의미생물학적특성을설명한다. 이때예를들어비무균제품에대하여미생물한도시험을하지않는이유, 항미생물보존제를함유하는제품인경우에보존제시스템의선정및그효능에대해설명한다. 무균제품인경우에는미생물오염방지를위한용기마개시스템의완전성을설명한다. 3.2.P.2.6 조화성 (Compatibility)(name, dosage form) The compatibility of the drug product with reconstitution diluent(s) or dosage devices (e.g., precipitation of drug substance in solution, sorption on injection vessels, stability) should be addressed to provide appropriate and supportive information for the labeling. 완제의약품과재구성용희석액또는투약장치의조화성 ( 예, 용액상태인원료의약품의침전, 주사용기로의흡착, 안정성 ) 을설명하여, 적절하고충분한근거를갖춘표시사항정보를제공한다. 3.2.P.3 제조 (Manufacture)(name, dosage form) 3.2.P.3.1 제조업체 (Manufacturer(s))(name, dosage form) The name, address, and responsibility of each manufacturer, including contractors, and each proposed production site or facility involved in manufacturing and testing should be provided. 계약업체를포함한제조업체와제조및시험업무를수행하는예정생산사업장또는시설각각의명칭, 주소, 책임사항을기술한다. 38