Microsoft Word - M4Q Implementation Working Group Questions and Answers R1

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE M4Q Implementation Working Group Questions & (R1) Current version dated July 17, 2003 www..co.kr 1

In order to facilitate the implementation of the CTD Quality (M4Q) guideline, the ICH Experts have developed a series of Q&As: M4Q Q&As Document History First Codification History Date New Codification November 2005 M4Q Q&As Approval by the Steering Committee. 12 September 2002 M4Q Q&As Current M4Q Questions & posted on the web site M4Q Q&As Approval by the Steering Committee of the 18 July M4 Q&As newly added questions. 2003 (R1) In November 2005, the ICH Steering Committee adopted a new codification system for ICH Guidelines. The purpose of this new codification is to ensure that the numbering / coding of ICH Guidelines is more logical, consistent and clearer. Because the new system applies to existing as well as new ICH Guidelines a history box has been added to the beginning of all Guidelines to explain how the Guideline was developed and what is the latest version. With the new codification revisions to an ICH Guideline are shown as (R1), (R2), (R3) depending on the number of revisions. Annexes or Addenda to Guidelines have now been incorporated into the core Guidelines and are indicated as revisions to the core Guideline (e.g., R1). For better comprehension of the M4Q references within the text, please see below the document change history for M4Q guideline. www..co.kr 2

M4Q 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 2000 Current Step 4 version M4Q Approval by the Steering Committee of 12 M4(R1) Numbering and Section Headers changes September for consistency directly under Step 4 2002 without further public consultation www..co.kr 3

Common Technical Document - Quality Questions and / Location Issues Step 4- version 7- July 17, 2003 목차 (Table of Contents) 1. 서론 (Introduction) 2. 공통이슈 (General Issues) 3. 서로다른섹션에위치한관련정보 (Associated Information Located in Different Sections) 4. 원료의약품부분의위치이슈 : 3.2.S(Location Issues in Drug Substance: 3.2.S) 5. 완제의약품부분의위치이슈 : 3.2.P(Location Issues in Drug Product: 3.2.P) 6. 부록부분의위치이슈 : 3.2.A(Location Issues in Appendices: 3.2.A) www..co.kr 4

1. 서론 (Introduction) This document is intended to provide additional guidance for the preparation of an application file in the CTD-Q format (see section 2: General Issues). It should be read in conjunction with the CTD-Q guideline (Modules 2 and 3). The document also addresses the relationship between linked CTD-Q sections for certain parameters, such as polymorphism, impurities, or particle size (see section 3: Associated Information Located in Different Sections). This document also clarifies location issues; that is, it indicates in which CTD-Q section(s), requested information should be placed (see section 4: Location Issues in Drug Substance, section 5: Location Issues in Drug Product, and section 6: Location Issues in Appendices). 이문서는 CTD-Q 형식 ( 섹션 2: 공통이슈참조 ) 으로신청문서파일을작성하는방법에대한추가적인가이드라인을제공하기위한것이다. CTD-Q 가이드라인 ( 모듈 2, 3) 와연계하여읽어야한다. 또한다형체, 불순물, 입자크기등일부파라미터에대하여 CTD-Q 섹션사이의관계도살펴본다 ( 섹션 3: 여러섹션에위치한연관정보참조 ). 이외에도위치이슈를명확히설명한다. 즉필수적인정보를 CTD-Q의어느섹션에배치해야하는지설명한다 ( 섹션 4: 원료의약품부분의위치이슈, 섹션 5: 완제의약품부분의위치이슈, 섹션 6: 부록부분의위치이슈 ). This document does not address the content of an application file. For content questions, refer to regional guidance. 신청문서파일의내용에대한부분은다루지않는다. 내용에대한사항은지역별가이드라인을참조한다. www..co.kr 5

2. 공통이슈 (General Issues) 2.1 별도섹션또는반복섹션 (Separate or Repeated Sections) There can be a number of instances where repeated sections can be considered appropriate. Whenever a section is repeated, it should be made clear what the section refers to by creating a distinguishing title in parentheses following the CTD- Q heading, for example, 2.3.S Drug Substance (Name, Manufacturer A). 섹션을반복하는편이적절하다고생각되는경우가많을수있다. 특정섹션을반복하고자한다면, CTD-Q 제목옆에괄호로뚜렷하게구분되는제목을표시하여그섹션에기술된정보가무엇인지명확히제시한다. 예 ) 2.3.S 원료의약품 ( 명칭, 제조업체 A). 원료의약품 (Drug Substance) When more than one drug substance is used in a drug product, information should be presented separately as one complete Drug Substance section followed by other complete Drug Substance sections. In some cases, for a single drug substance, it could be considered appropriate and logical to have information presented in multiple Drug Substance sections. For example, separate sections can be warranted when a single drug substance is made at two different manufacturing sites with differences in the manufacturing processes. However, despite these differences, it is likely that these different processes will be described within the same relevant subsection of 3.2.S. If, on the other hand, the differences result in, for example, different specifications, then adding an additional Drug Substance section is recommended (see also regional guidance). 하나이상의원료의약품을완제의약품에사용하면, 원료의약품섹션하나를다작성한다음에다른원료의약품섹션을배치하는식으로분리하여작성한다. 단일원료의약품에대한정보를여러원료의약품섹션에서기술하는편이더적절하고논리적인경우도있다. 예를들어특정원료의약품을 2개제조사업장에서만들고제조공정도다른경우에는별도로만들어야할것이다. 하지만이런차이에도불구하고, 3.2.S의동일한세부섹션에서로다른제조공정을기술할수있다. 반면공정차이때문에예를들어규격이다르다면, 원료의약품섹션을별도로만들어추가하는방법을권장한다 ( 지역별가이드라인참조 ). 완제의약품 (Drug Product) www..co.kr 6

Depending upon regional requirements, different drug product presentations (e.g., strengths, container closure types and configurations, formulations) and/ or manufacturing schemes (e.g., aseptic and terminal sterilization) can be submitted in the same dossier. In general, when a single dossier can be submitted, information for each of the product presentations and manufacturing schemes should be combined and presented together in one Drug Product section, with information for each of the product presentations and manufacturing schemes provided in the Appendices and Regional Information sections, as warranted. For example, if 100 milligram (mg) tablets will be marketed in a bottle and a unit-dose blister package, the information should be presented in one Drug Product section. Where most of the quality information would be identical for the two drug products, the data common to both presentations should appear only once. The information that differs between the two should be presented as separate documents under the appropriate subsections (e.g., 3.2.P.7 Container Closure System, 3.2.P.8 Stability). 지역별기준에따라, 서로다른완제의약품프레젠테이션 ( 예, 함량, 용기마개유형과구성, 조성 ) 및 / 또는제조방법 ( 예, 무균공정, 사후멸균 ) 을동일한신청문서에포함시켜제출할수있다. 일반적으로단일문서를제출할수있는경우에는제품프레젠테이션과제조공정각각에대한정보를하나의완제의약품섹션에통합시켜기술하고, 제품프레젠테이션과제조공정각각에대한정보를부록과지역별정보섹션에배치한다. 예를들어 100 mg 정제를병과단일용량블리스터포장으로판매한다면, 1개완제의약품섹션에정보를기술한다. 2개완제의약품의품질정보대부분이동일하다면, 두프레젠테이션에공통적인데이터는한번만기술한다. 두프레젠테이션사이에차이나는정보는해당세부섹션에서별개문서로작성한다 ( 예, 3.2.P.7 용기마개시스템, 3.2.P.8 안정성 ). In some cases, however, for product presentations or manufacturing schemes that can be included in a single dossier, it is considered more appropriate and logical to have information presented separately. Information presented separately means one complete Drug Product section followed by other complete Drug Product sections. One such example is that information on a drug product supplied with a reconstitution diluent should be presented in separate Drug Product sections for the drug product and the reconstitution diluent. These could be titled 3.2.P (Drug Product) and 3.2.P (Diluent). 하지만하나의신청문서에여러제품프레젠테이션이나제조공정을포함시키더라도, 정보를별도로기술하는편이더적절하고논리적인경우가있다. 정보를별도로 www..co.kr 7

기술한다는말은, 완제의약품섹션하나를완성한다음에다른완제의약품섹션을배치하는방식을의미한다. 예를들어재구성을위한희석액이완제의약품과함께제공되는경우에, 완제의약품과재구성용희석액에대하여별도의완제의약품섹션을만든다. 그리고제목을 3.2.P( 완제의약품 ), 3.2.P( 희석액 ) 으로표기할수있다. 첨가제 (Excipients) If appropriate, where a novel, or noncompendial nonnovel excipient is proposed and a significant amount of data is provided for the excipient, this information should be provided in 3.2.A.3 Excipients, which follows the same format and level of subsections as the Drug Substance section. There should be a complete section of 3.2.A.3 Excipients for each novel excipient, or noncompendial nonnovel excipient. 새로운첨가제또는새로운것은아니나공정서에수재되어있지않은첨가제를사용하고그첨가제에대하여상당한양의데이터를기술하는경우, 이정보를 3.2.A.3 " 첨가제 " 부분에배치하며, 원료의약품섹션과동일한형식과수준으로작성한다. 새로운첨가제또는새로운것은아니나공정서에수재되어있지않은첨가제각각에대하여 3.2.A.3 " 첨가제 " 섹션전체를작성한다. 부록 (Appendices) There can be occasions where it is appropriate to repeat an Appendix. For example, where a sponsor registers more than one manufacturing facility for the manufacture of a Biotech drug, the Appendix 3.2.A.1 should then be repeated. 특정부록을반복해야하는경우도있다. 예를들어 " 생명공학 " 의약품제조를위해하나이상의제조시설을등록하고자한다면, 부록 3.2.A.1를반복해야한다. 지역별정보 (Regional Information) The content of the Regional Information section (3.2.R) is not harmonised. In this section the documents, their titling, and their order should be consistent with the requirements of the relevant region. 지역별정보섹션 (3.2.R) 의내용은조화되어있지않다. 이섹션의문서, 문서제목, 순서는해당지역의기준에따른다. 2.2 여러용기에포장하는경우 (Multiple Containers) www..co.kr 8

When there are two containers (e.g., PVC blister and PE bottle) for one drug product, the documents for the drug product part in Module 3 should generally be common. In this case, one set of documentation, 3.2.P.1 through 3.2.P.8, should be provided. The information for the blister and the bottle should be presented in the corresponding sections of the single drug product part in Module 3 (e.g., 3.2.P.7, 3.2.P.8), divided by subsections for each type of container and identified by the type of container. 1개완제의약품을 2종류의용기로포장하는경우 ( 예, PVC 블리스터와 PE 병 ), 모듈 3의완제의약품부분에해당되는문서가전반적으로공통적일것이다. 이런경우에 3.2.P.1 부터 3.2.P.8 까지한세트를제공한다. 그리고모듈 3의단일완제의약품부분에서해당섹션 ( 예, 3.2.P.7, 3.2.P.8) 에블리스터와병에대한정보를기술한다. 용기유형별로세부항목을나누고용기종류별로표기하여구분한다. 2.3 생물분석방법 (Bioanalytical Methods) In the Common Technical Document, under what section should bioanalytical methods and their associated validation reports be included? 생물분석방법과관련밸리데이션보고서를 CTD 의어느섹션에포함시켜야하는가? In this context, bioanalytical methods are understood to mean analytical procedures used in clinical studies (human clinical pharmacology/ bioavailability/ bioequivalence) and/or nonclinical studies (nonhuman pharm./ tox. studies). 여기서생물분석방법은임상시험 ( 인체임상약리학 / 생체이용율 / 생물학적동등성시험 ) 이나비임상시험 ( 동물약리학 / 독성학시험 ) 에사용하는분석방법을의미한다. The description of analytical procedures and associated validation reports should be submitted in those modules where the corresponding studies are described (i.e., in Module 4, section 4.2.2.1 for analytical procedures and associated validation reports for nonclinical studies and in Module 5, section 5.3.1.4 for analytical procedures and associated validation reports used in clinical studies). 분석방법과관련밸리데이션보고서는해당시험을설명한모듈에포함시켜제출한다 ( 즉, 비임상시험과관련된분석방법과관련밸리데이션보고서는모듈 4의섹션 4.2.2.1, 임상시험과관련된분석방법과관련밸리데이션보고서는모듈 5의섹션 5.3.1.4). www..co.kr 9

2.4 DMF(Drug Master Files) Can the Drug Master File use the CTD format? DMF를 CTD 형식으로만들수있는가? Since the DMF systems differ in the three regions, ICH does not address this issue. Consequently, the applicant should check with the relevant competent authority in the region(s). 3개지역이서로다른 DMF 시스템을갖고있으므로, ICH가이이슈에대해뭐라말할수없다. 그러므로신청업체는해당지역의관계기관에문의하도록한다. 2.5 첨가제를함유한원료의약품 (Drug Substance Containing Additives) If a drug substance is used in the form of a preparation (e.g. a [commercially available] vitamin trituration) in which module/ section should the excipient(s) included in the preparation be described? Should the relevant information be given for example in Section 3.2.S Drug Substance or in Section 3.2.P.4 Drug Product - Control of Excipients? 원료의약품이조제물형태이면 ( 예, [ 상업적으로구입가능한 ] 비타민분쇄물 ), 이조제물에포함된첨가제를어떤모듈 / 섹션에서설명해야하는가? 예를들어섹션 3.2.S 원료의약품이나섹션 3.2.P.4 완제의약품 첨가제관리가운데어떤부분에서관련정보를기술해야하는가? If the drug substance is defined as two or more materials, the manufacturing information would be described in 3.2.S.2.2 and the control of the additional material(s) (e.g., excipient(s)) would be described in 3.2.S.2.3. 원료의약품이 2개이상의물질로구성되면, 제조정보를 3.2.S.2.2에기술하고추가물질 ( 예, 첨가제 ) 의관리에관한정보는 3.2.S.2.3에기술할수있다. 3. 서로다른섹션에위치한관련정보 (Associated Information Located in Different Sections) Below, examples of multiple references in CTD-Q are proposed for polymorphism, particle size, and impurities. They indicate for some parameters that the information should not necessarily be located in one section, but should be split into www..co.kr 10

different sections. 다형성, 입자크기, 불순물에대한정보를아래의예와같이 CTD-Q의여러곳에기술한다. 일부파라미터의정보는 1개섹션에만위치시켜야하는것이아니라, 여러섹션에나누어기술해야함을의미한다. 3.1 다형성 (Polymorphism) 3.2.S.1.3 If called for, list the polymorphic form(s) present in the proposed active as a characteristic of the drug substance. 필요한경우에는원료의약품의특성에해당되는활성상태의다형체를나열한다. 3.2.S.2.2 Description of Manufacturing Process and Process Controls should indicate which polymorphic form is synthesised. " 제조공정및공정관리 " 부분에서어떤다형체가합성되는지기술한다. 3.2.S.3.1 Studies performed to identify the potential polymorphic forms of the drug substance, including study results. Total number of polymorphs should be listed here and those intended to form the active should be summarised in 3.2.S.1.3. 원료의약품의다형체를파악하기위해실시한실험정보 ( 결과포함 ). 전체다형체수를나열하고활성성분이되는것을 3.2.S.1.3에요약한다. 3.2.S.4.1 Specification. If a polymorph is to be defined or limited, it should be discussed here. 규격. 어떤다형체의범위나한도를정하여적용한다면, 이곳에서관련정보를기술한다. 3.2.S.4.2 Analytical Procedures. 분석절차 3.2.S.4.3 Validation of Analytical Procedures. 분석절차밸리데이션 3.2.S.4.4 Results of batch analyses. 배치분석결과 3.2.S.4.5 Justification of Specification (if appropriate). Reasons why a particular limit on form is appropriate (should also probably refer to 3.2.P.2). 규격의타당성 ( 적절한경우 ). 다형체에특별하게한도기준을설정하는이유 (3.2.P.2도참조 ) www..co.kr 11

3.2.P.2.1.1 and 3.2.P.2.2.3 Identifies the influence of polymorphism on the drug substance and dosage form. 다형성이원료의약품과제제에미치는영향을기술한다. 3.2.P.5.1 Specification. If polymorphs are to be controlled in the drug product, they should appear here. 규격 : 완제의약품에존재하는다형체를관리하는경우에는규격정보를이곳에기술한다. 3.2.P.5.6 Justification of Specification (if called for). 규격의타당성 ( 필요한경우 ) 3.2 입자크기 (Particle Size) 3.2.S.2.2 Description of Manufacturing Process and Process Controls. 제조공정및공정관리 3.2.S.3.1 Studies performed to identify the particle size distribution of the drug substance. 원료의약품의입자크기분포를파악하기위해실시한실험 3.2.S.4.1 Specification. 규격 3.2.S.4.2 Analytical Procedures. 분석절차 3.2.S.4.3 Validation of Analytical Procedures. 분석절차밸리데이션 3.2.S.4.4 Results of batch analyses. 배치분석결과 3.2.S.4.5 Justification of Specification. 규격의타당성 3.2.P.2.1.1 and 3.2.P.2.2.1 Identification of the influence of particle size on, for instance, dissolution performance (consult the ICH Q6A decision tree). 입자크기가예를들어용출성능에미치는영향 (ICH Q6A 의사결정도참조 ). 3.3 불순물 (Impurities) www..co.kr 12

3.2.S.3.2 Here the discussion on impurities and information on their qualification should take place (reference to pre-clinical and clinical studies): e.g., absolute amount at which the impurities can be considered as qualified. 불순물과불순물의적격성에관한정보를기술한다 ( 전임상및임상시험참조 )( 예, 적격수준이라고볼수있는불순물의절대량 ). 3.2.S.4.1 Specification. 규격 3.2.S.4.2 Analytical Procedures. 분석절차 3.2.S.4.3 Validation of Analytical Procedures. 분석절차밸리데이션 3.2.S.4.4 Results of batch analyses (all batches including development, clinical, stability). 배치분석결과 ( 개발, 임상, 안정성배치를포함한모든배치 ) 3.2.S.4.5 Justification of Specification. 규격의타당성 3.2.P.5.1 Specification. 규격 3.2.P.5.2 Analytical Procedures. 분석절차 3.2.P.5.3 Validation of Analytical Procedures. 분석절차밸리데이션 3.2.P.5.4 Results of batch analyses (all batches including development, clinical, stability). 배치분석결과 ( 개발, 임상, 안정성배치를포함한모든배치 ) 3.2.P.5.5 Characterisation of Impurities (for those impurities not already discussed under 3.2.S). 불순물특성분석 (3.2.S에서기술하지않은불순물 ) 3.2.P.5.6 Justification of Specification. 규격의타당성 3.4 임상시험제제의품질정보위치 (New Location of Quality Information for Investigational Formulations) www..co.kr 13

How does the CTD link information on drug substance batch numbers, drug product batch numbers, nonclinical and clinical study numbers, the levels of impurities, history of formulation development, and any other relevant information? Please clarify the assignment of this information to the nonclinical and clinical sections. 원료의약품배치번호, 완제의약품배치번호, 비임상 / 임상시험번호, 불순물수준, 조성개발이력, 기타관련정보를 CTD에서어떻게연계시키나? 이정보를비임상 / 임상섹션과연계하여기술하는방법을명확히해주기바란다. The history of development for the drug substance should be included in 3.2.S.2.6. A description of batches and the result of batch analyses should be included in 3.2.S.4.4. The history of formulation development should be included in 3.2.P.2.2.1. A description (including a summary table) of batches and the results of batch analyses for the drug product should be included in 3.2.P.5.4. This information on the history of development and description of batches can also be linked to the impurity levels of batches described in 3.2.S.3.2 and 3.2.P.5.5. 원료의약품개발이력에관한정보는 3.2.S.2.6에기술한다. 배치에관한정보와배치분석결과는 3.2.S.4.4에배치한다. 조성개발이력에관한정보는 3.2.P.2.2.1에포함시킨다. 완제의약품배치에관한정보와배치분석결과 ( 요약표포함 ) 를 3.2.P.5.4에배치한다. 개발이력과배치에관한정보는 3.2.S.3.2와 3.2.P.5.5에기술된배치의불순물수준과연계시켜설명할수있다. Appropriate references to Modules 4 and 5 for the nonclinical and clinical studies can also be made. 비임상시험과임상시험에관한모듈 4와 5의정보를적절하게참조시킬수있다. 3.5 비바이러스외래성인자와관련된정보를모듈 3.2 의어디에배치하는가 (Where would the information related to non-viral adventitious agents be placed within Module 3.2?) The following guidance supersedes the first sentence under 3.2.A.2 for non-viral adventitious agents: 다음가이드라인이비바이러스외래성인자에대한 3.2.A.2의첫문장을대체한다. The detailed information regarding the routine manufacturing control of www..co.kr 14

adventitious agents, such as bacteria, mycoplasma, and fungi, typically using wellestablished (e.g., pharmacopoeial) analytical procedures, should be provided in the appropriate sections within Module 3.2.S and 3.2.P. If well-established (e.g., pharmacopoeial) analytical procedures are not used, more detailed information regarding the analytical procedure(s) used should also be included in 3.2.S and 3.2.P. 일반적으로충분히확립된 ( 예, 약전 ) 분석절차에의거한일상제조시의외래성인자 ( 예, 세균, 마이코플라즈마, 진균 ) 관리에관한세부정보를모듈 3.2.S와 3.2.P에기술한다. 확립된 ( 예, 약전 ) 분석절차를사용하지않는다면, 분석절차에대한보다자세한정보를 3.2.S와 3.2.P에포함시킨다. With respect to other non-viral adventitious agents, such as transmissible spongiform encephalopathy agents and prions, the detailed information, should be placed in 3.2.A.2. 다른비바이러스외래성인자 ( 예, TSE(transmissible spongiform encephalopathy) 인자와프리온 ) 와관련된자세한정보는 3.2.A.2에서기술한다. www..co.kr 15

4. 원료의약품부분의위치이슈 : 3.2.S(Location Issues in Drug Substance: 3.2.S) The to the Issues/ Questions recommend locations for information. 정보의위치에관한 " 이슈 / 질문 " 에대한답변 CTD-Q Section 3.2. Issues/ Questions S.1 General Information S.1.1 Nomenclature S 1.2 Structure S.1.3 General Properties www..co.kr Should drawings to show secondary and tertiary structures and, if applicable, quaternary structures of proteins be provided in 3.2.S.1.2? 이차 / 삼차구조, 그리고해당되는경우에는단백질의사차구조를보여주는그림을 3.2.S.1.2에포함시켜야하는가? How much detailed information on the general properties of the drug substance should be included in 3.2.S.1.3? 3.2.S.1.3에원료의약품의일반특징에관하여얼마나구체적인정보를기술해야하는가? 16 Drawings to show secondary and tertiary structures and, if applicable, quaternary structures should be provided in 3.2.S.3.1. 이차 / 삼차구조와해당되는경우에는사차구조를보여주는그림을 3.2.S.3.1에포함시킨다. As stated in CTD-Q, a list of physicochemical and other relevant properties of the drug substance, including biological activity, should be included in 3.2.S.1.3. The information on general properties should be provided only for the form of the drug substance used in the drug product, not possible alternative forms (e.g., polymorphs). More detailed information on the

CTD-Q Section 3.2. Issues/ Questions S.2 Manufacture S.2.1 Manufacturers S.2.2 Description of the Manufacturing Process and Process Controls S.2.3 Control of Materials www..co.kr Should information on process controls be provided in section 3.2.S.2.2 or 3.2.S.2.4? 공정관리정보를섹션 3.2.S.2.2나 3.2.S.2.4 가운데어디에기술해야하는가? Should the discussion and justification of starting materials be included in 3.2.S.2.3? 출발물품의타당성에대한정보를 3.2.S.2.3에기술해야하는가? Where should analytical procedures for materials described in 3.2.S.2.3 be included? 17 properties of the drug substance, including possible alternative forms, should be included in 3.2.S.3.1. CTD-Q 문서에서도설명한바와같이, 생물학적활성을포함하여원료의약품의이화학적특징과기타관련특징을정리하여 3.2.S.1.3에기술한다. 완제의약품에사용하는원료의약품형태에대해서만기술한다 ( 다형체의경우처럼다른형태에대해서는기술하지않는다 ). 다른형태를포함하여원료의약품의특징에관한보다자세한정보를 3.2.S.3.1에포함시킨다. All process controls should be identified in 3.2.S.2.2. For critical controls, additional information should be provided in 3.2.S.2.4. 모든공정관리정보를 3.2.S.2.2에기술한다. 핵심관리항목인경우에는추가적인정보를 3.2.S.2.4에기술한다. The discussion and justification of starting materials should be included in 3.2.S.2.3. 출발물품의타당성에관한정보는 3.2.S.2.3에포함시킨다. The analytical procedures for the control of materials (e.g., starting materials, reagents, raw materials, solvents) should be

CTD-Q Section 3.2. Issues/ Questions 3.2.S.2.3에기술한물품에대한분석절차를어디에기술하는가? presented in section 3.2.S.2.3. For materials of biological origin, analytical procedures related to adventitious agent safety evaluation, if applicable, should be presented in 3.2.A.2. 물품 ( 예, 출발물품, 시약, 원료, 용매 ) 의관리를위한분석절차를 섹션 3.2.S.2.3에서기술한다. 생물학적유래물품인경우에외래성 인자안전성평가와관련된분석절차는 3.2.A.2에서기술한다. S.2.4 Control of Critical Steps and Intermediates www..co.kr Since the addition of new headings is not an option, where in the CTD should one locate (Quality Section) information regarding a reagent used in the production of the drug substance when the reagent is manufactured via recombinant DNA technology? 새로운제목을추가할수없는데, 재조합 DNA 기술로만든시약을원료의약품생산에사용하는경우에는그시약에관한정보를 CTD의어디에배치해야하는가 ( 품질섹션 )? Should batch data for intermediates or critical steps be included in 3.2.S.2.4? 중간제품이나핵심단계의배치데이터를 3.2.S.2.4에배치해야하는가? 18 The information should be located in 3.2.S.2.3: Control of Materials. 이정보는 3.2.S.2.3 " 물품관리 " 에배치한다. Batch data, together with analytical procedures and acceptance criteria for intermediates or critical steps, would be presented in 3.2.S.2.4. 중간제품이나핵심단계의분석절차와허용기준, 그리고배치

CTD-Q Section 3.2. Issues/ Questions 데이터를 3.2.S.2.4에기술한다. If release tests are performed on Acceptance criteria should be referred to in 3.2.S.4.1 and intermediates and at critical steps instead of analytical procedures should be referred to in 3.2.S.4.2. on drug substance, where would the 허용기준은 3.2.S.4.1의정보를인용하고, 분석절차는 3.2.S.4.2의 information on the analytical procedures and 정보를인용한다. acceptance criteria be presented in 3.2.S.4? 원료의약품이 아니라 중간 제품이나 핵심 단계에서출하승인시험을실시한다면, 분석절차와허용기준정보를 3.2.S.4에기술하는가? S.2.5 Process Where should justification for reprocessing If justification for reprocessing is warranted by a regional Validation and/or be included? authority, the information would be included as part of the Evaluation 재가공의 타당성에 관한 정보를 어디에서 description of the manufacturing process in 3.2.S.2.2. If there 기술하는가? are critical controls associated with the reprocessing operation, the critical controls should be included in 3.2.S.2.4. If validation information is warranted, the validation information should be included in 3.2.S.2.5. 재가공의타당성정보를규제기관이요구하는경우, 그정보를 3.2.S.2.2의제조공정부분에서기술한다. 재가공과관련하여 핵심적인관리항목이있으면, 3.2.S.2.4에포함시킨다. 밸리데이션 정보가필요한경우에는 3.2.S.2.5에서밸리데이션정보를기술한다. S.2.6 Manufacturing Should bioavailability/ bioequivalence study Reports of Bioavailability/ Bioequivalence studies that www..co.kr 19

CTD-Q Section 3.2. Issues/ Questions Process Development S.3 Characterisation S.3.1 Elucidation of Structure and Other Characteristics www..co.kr results that demonstrate product comparability following process changes be described in 3.2.S.2.6? 공정변경이후에제품동등성을증명하는생체이용율 / 생물학적동등성시험결과를 3.2.S.2.6에포함시켜야하는가? Where should studies conducted to determine the physicochemical characteristics of the drug substance be included? 원료의약품의이화학적특성을파악하기위해실시한시험내용을어디에기술해야하는가? 20 demonstrate comparability/ equivalence after formulation or process changes should be presented in Module 5. Crossreferences to these reports should be placed in section 3.2.S.2.6 (for drug substance process changes), 3.2.P.2.2.1 (for drug product formulation changes) or 3.2.P.2.3 (for drug product process changes). A brief summary of the reports can be placed in these sections when considered appropriate. 조성이나공정변경이후동등성을증명하는생체이용율 / 생물학적동등성시험보고서를모듈 5에포함시킨다. 3.2.S.2.6( 원료의약품공정변경인경우 ), 3.2.P.2.2.1( 완제의약품조성변경인경우 ), 3.2.P.2.3( 완제의약품공정변경인경우 ) 에서해당보고서를참조시킨다. 적절하다고생각되는경우에는해당섹션에서보고서내용을간략히요약하여설명할수있다. Information on the studies conducted to determine the physicochemical characteristics of the drug substance should be included in 3.2.S.3.1. Only a list of the general properties of the drug substance should be included in 3.2.S.1.3. 원료의약품의이화학적특성을파악하기위해실시한시험에관한정보를 3.2.S.3.1에포함시킨다. 3.2.S.1.3에는원료의약품의일반특징을간단히정리한다.

CTD-Q Section 3.2. Issues/ Questions S.3.2 Impurities Should structural characterisation data and a summary of the method of preparation of impurities be included in 3.2.S.3.2? 구조적특성분석데이터와불순물조제방법을 3.2.S.3.2에포함시켜야하는가? Where should chromatograms be provided for impurities? 불순물의크로마토그램은어디에배치하는가? Where should nonclinical and clinical data supporting impurity levels be summarised? 불순물수준을뒷받침하는비임상 / 임상데이터를어디에기술하는가? This information should be included in 3.2.S.3.2. Characterisation of impurity reference standards should be provided in 3.2.S.5. See also Q&A under 3.3. 이정보는 3.2.S.3.2에포함시킨다. 불순물참조표준품의특성분석정보는 3.2.S.5에기술한다. 3.3의 Q&A 참조. ICH Q3A identifies the chromatograms as part of the analytical validation studies. Therefore, relevant chromatograms should be included in 3.2.S.4.3. ICH Q3A에분석방법밸리데이션실험의한부분으로크로마토그램이명시되어있다. 그러므로관련크로마토그램을 3.2.S.4.3에포함시킨다. The qualified level of each impurity with cross-reference to the supporting nonclinical/ clinical studies should be included in 3.2.S.3.2. 각불순물의적격수준을해당비임상 / 임상시험자료의상호참조정보와함께 3.2.S.3.2에기술한다. www..co.kr Should data on impurities reported in batch analyses be included in 3.2.S.3.2 or 3.2.S.4.4? 배치 분석 시에 얻은 불순물 데이터를 21 Data on observed impurities for relevant batches (e.g., clinical, nonclinical, stability) should be provided in 3.2.S.3.2. The data should be provided whether or not the impurity is included in the specification. This information can be cross-referenced to

CTD-Q Section 3.2. Issues/ Questions 3.2.S.3.2나 3.2.S.4.4에포함시켜야하는가? support other sections of the dossier as appropriate. 관련배치 ( 예, 임상, 비임상, 안정성배치 ) 의불순물데이터를 3.2.S.3.2에정리한다. 불순물항목이규격에포함되어있건아니건, 데이터를기술한다. 이정보를상호참조시켜신청문서의다른섹션을뒷받침할수있다. S.4 Control of Drug Substance S.4.1 Specification If there are different specifications for a drug When appropriate, more than one specification should be substance manufacturer and/ or applicant, included in 3.2.S.4.1. should they all be provided in 3.2.S.4.1? 적절한경우에는하나이상의규격을 3.2.S.4.1에포함시킨다. 원료의약품제조업체와신청업체의규격이다른 경우에는 3.2.S.4.1에모두포함시켜야하는가? If alternative analytical procedures are used Any analytical procedure used to control the drug substance, to control the drug substance, should they and the associated acceptance criteria, should be listed in the also be listed in the specification (3.2.S.4.1)? 다른분석방법으로원료의약품의품질관리를 specification. 원료의약품의품질관리를위한분석방법과관련허용기준을 실시한다면, 이 정보도 규격에 포함시켜야 규격에포함시켜야한다. 하는가 (3.2.S.4.1)? S.4.2 Analytical Often an analytical procedure changes during Information on historical analytical procedures used to Procedures the development of the drug substance. If generate data included in the batch analyses should be this analytical procedure is submitted to included in 3.2.S.4.4. www..co.kr 22

CTD-Q Section 3.2. Issues/ Questions support the dossier, in which section should these analytical procedures be placed? 원료의약품개발시에분석절차가변경되기도한다. 등록서류를뒷받침하기위하여이분석절차에관한정보를포함시켜야하는경우, 어느섹션에배치해야하는가? Should an analytical procedure that is only used for stability studies be included in 3.2.S.4.2? 배치분석데이터를생산하는데사용한과거의분석절차에관한정보를 3.2.S.4.4에서설명한다. Information on analytical procedures that are used only for stability studies should be included in 3.2.S.7.3. 안정성시험에만사용하는분석절차에관한정보는 3.2.S.7.3에서 안정성 시험에만 사용하는 분석 절차를 설명한다. 3.2.S.4.2에서설명해야하는가? If the analytical methods for a drug The analytical methods should be placed in both the relevant substance and drug product are identical, sections of 3.2.S and 3.2.P because the sample preparation, at can these methods and corresponding least, will differ. validation, if applicable, be described in 적어도검체조제방법이다를것이므로, 3.2.S와 3.2.P 모두에서 either 3.2.S or 3.2.P, with a corresponding 분석방법을설명해야한다. reference (e.g., a reference from 3.2.S to 3.2.P)? 원료의약품과 완제의약품의 분석 방법이 동일하다면, 이 방법과 해당되는 경우에 밸리데이션 정보를 3.2.S나 3.2.P 가운데 www..co.kr 23

CTD-Q Section 3.2. Issues/ Questions 하나에서기술하고다른곳에서는참조정보만기재해도되는가 ( 예, 3.2.S에서 3.2.P를인용 )? S.4.3 Validation of Where should chromatograms be included? Relevant chromatograms should be included in 3.2.S.4.3. Analytical Procedures 크로마토그램을포함시켜야하는가? 관련크로마토그램을 3.2.S.4.3에포함시켜야한다. S.4.4 Batch Analyses Where should results from all relevant Results from all relevant batches (e.g., clinical, nonclinical, batches be provided? 모든관련배치의결과를제공해야하는가? stability), including those batches used to justify acceptance criteria should be provided in 3.2.S.4.4. 허용기준의타당성을입증하기위한배치를포함하여모든관련 배치 ( 예, 임상, 비임상, 안정성 배치 ) 의 결과를 3.2.S.4.4에 기술한다. If there are results from tests that are not listed in the specifications, where should they be provided? If results are submitted from tests that are not listed in the specification, they should be provided in 3.2.S.4. 규격에포함되지않은시험항목의결과는 3.2.S.4에포함시킨다. 규격에포함되지않은시험항목의시험결과가 있으면, 어디에배치해야하는가? Where should collated data for a test from multiple batch analyses be presented? If collated data from batch analyses is warranted, the data should be presented in 3.2.S.4.4. 여러배치의시험데이터를비교한자료는어디에 배치 분석 데이터를 비교하여 정리할 필요가 있는 경우에는 배치해야하는가? 3.2.S.4.4에서데이터를정리한다. S.4.5 Justification of Should justification for skip testing be If skip testing is considered appropriate, the justification should Specification included in 3.2.S.4.5? be included in 3.2.S.4.5. www..co.kr 24

CTD-Q Section 3.2. Issues/ Questions 스킵 시험 방식의 타당성을 3.2.S.4.5에서 스킵 시험이 적절하다고 판단되는 경우에는 그 타당성을 기술해야하는가? Rather than repeating information, can a summary of data from other sections with a 3.2.S.4.5에서설명한다. A summary of data from other sections with a cross-reference to the detailed information can be provided to support the cross-reference to the detailed information justification of specification. be provided to support the justification of 구체적인정보에대하여상호참조정보를표시하고다른섹션의 specification section of the dossier? 데이터를요약하여규격의타당성을뒷받침할수있다. 정보를 반복하여 기술하기보다는, 구체적인 정보에대하여상호참조정보를표시하고다른 섹션의데이터를요약함으로써규격의타당성을 뒷받침할수있는가? S.5 Reference Reference standards might be available for If information is warranted for a reference standard, the Standards or Materials the active moiety and impurities. Should information on all reference standards be included in 3.2.S.5? 활성부분과불순물에대한참조표준품이있을 information should be included in 3.2.S.5. 참조표준품에대한정보가필요한경우에는그정보를 3.2.S.5에기술한다. 수있다. 모든참조 표준품에대한정보를 3.2.S.5에서기술해야하는가? Where should characterisation data for a reference standard be placed in the CTD-Q? 참조표준품의특성분석데이터는 CTD-Q의 Characterisation data for the reference standard should be included in 3.2.S.5. Cross-reference to information in other sections (e.g., 3.2.S.3.2) can be included as considered www..co.kr 25

CTD-Q Section 3.2. Issues/ Questions 어디에배치해야하는가? appropriate. 참조 표준품의 특성 분석 데이터를 3.2.S.3.2에서 기술한다. 적절하다고판단되는경우에는다른섹션 ( 예, 3.2.S.3.2) 에있는 정보의상호참조정보도포함시킬수있다. S.6 Container Closure System S.7 Stability S.7.1 Stability Summary and Conclusions S.7.2 Post-approval Stability Protocol and Stability Commitment S.7.3 Stability Data Should stress studies be located in Stress studies should be located in 3.2.S.7.3. These data can 3.2.S.7.3? be referenced for validation of analytical procedures as 가혹 시험 데이터를 3.2.S.7.3에 배치해야 considered appropriate. 하는가? 가혹시험데이터를 3.2.S.7.3에배치한다. 적절하다고판단되는 경우에는분석방법밸리데이션에서이데이터를참조할수있다. Should information on any changes in analytical procedures over the course of Information on historical analytical procedures used to www..co.kr 26

CTD-Q Section 3.2. Issues/ Questions generating stability data be included in 3.2.S.7.3? 안정성시험도중에분석방법이변경되는경우에는그정보를 3.2.S.7.3에서기술해야하는가? Can data from supporting studies be included in 3.2.S.7.3? 근거시험데이터를 3.2.S.7.3에포함시킬수있는가? Should information on analytical procedures unique to the stability program be presented in 3.2.S.7.3? 안정성시험에만사용하는분석절차에관한정보를 3.2.S.7.3에포함시켜야하는가? generate the stability data should be included in 3.2.S.7.3. 안정성데이터를생산하는데사용했었던과거의분석절차에대한정보를 3.2.S.7.3에서기술한다. Data from supporting studies can be included in 3.2.S.7.3, if considered appropriate. 적절하다고생각되는경우에는근거시험데이터를 3.2.S.7.3에포함시킬수있다. Information on analytical procedures unique to the stability program should be included in 3.2.S.7.3. 안정성시험에만사용하는분석절차에관한정보를 3.2.S.7.3에포함시킨다. www..co.kr 27

5. 완제의약품부분의위치이슈 : 3.2.P(Location Issues in Drug Product: 3.2.P) The to the Issues/ Questions recommend locations for information. 정보의위치에관한 " 이슈 / 질문 " 에대한답변 CTD-Q Section 3.2. Issues/ Questions P.1 Description and Composition of the Drug Product www..co.kr Where should information related to the composition of inks used on the drug product be placed? 완제의약품에사용하는잉크의조성에관한정보는어디에기술하는가? Where should information on reconstitution diluents be included? 재구성희석액에관한정보는어디에포함시키는가? 28 1. All drug product components should be listed in 3.2.P.1. The composition (e.g., components of the capsule shell, components of inks) should also be included in 3.2.P1. In some regions, the qualitative composition of proprietary components can be replaced with reference to appropriate DMFs. 모든완제의약품구성성분을 3.2.P.1에기술해야한다. 또한조성정보 ( 예, 캡슐구성성분, 잉크성분 ) 를 3.2.P.1에포함시킨다. 특정성분의정성적조성에관한자세한정보대신에관련 DMF 정보를기술해도되는지역이있다. 2. If the diluent is co-packaged with the drug product, the information on the diluent should be placed in a separate Drug Product section. The compatibility of the drug product with reconstitution diluents should be discussed in 3.2.P.2.6. 희석액과완제의약품을함께포장하여제공한다면, 희석액에관한

CTD-Q Section 3.2. Issues/ Questions 정보를별도의완제의약품섹션에기술한다. 완제의약품과재구성 희석액의조화성에관한정보는 3.2.P.2.6에기술한다. Should an over-fill be indicated in 3.2.P.1? " 오버필 " 을 3.2.P.1에기재해야하는가? 3. The use of an over-fill should be indicated in 3.2.P.1. The rationale for an overfill should be included in 3.2.P.2.2.1. 오버필 정보를 3.2.P.1에 기술한다. 오버필의 근거는 3.2.P.2.2.1에기술한다. P.2 Pharmaceutical Development P.2.1 Components of the Drug Product www..co.kr Can information on the composition of a drug product, other than what is listed in the CTD- Q guideline, be included in 3.2.P.1? CTD-Q 가이드라인에 기술된 것 이외의 완제의약품조성에관한다른정보를 3.2.P.1에 포함시킬수있는가? Where should information on the development of co-packaged diluents be placed? 29 4. When called for, additional information can be included to adequately describe the composition of the drug product, for example, (1) total weight, volume, etc., of unit, (2) tracers or markers, (3) composition statement for (purchased) mixtures, and (4) capsule shells. 필요한경우에는예를들어 (1) 개별제품의총중량, 총부피등, (2) 트레이서또는마커, (3) ( 구매 ) 혼합물의조성정보, (4) 캡슐등완제의약품의조성정보를적절하게제공하기위하여추가정보를포함시킬수있다. There should be a separate Drug Product (Diluent) section for co-packaged diluents. Choice and development of co-packaged diluents should be included in 3.2.P.2.2.1 and 3.2.P.2.6.

CTD-Q Section 3.2. Issues/ Questions 함께포장하는희석제의개발에관한정보는어디에배치하는가? 함께포장하는희석제에대하여별도의완제의약품 ( 희석제 ) 섹션을작성한다. 함께포장하는희석제의선택과개발에관한정보는 3.2.P.2.2.1과 3.2.P.2.6에포함시킨다. P.2.1.1 Drug Where should a discussion of the drug Drug substance stability data should be included in 3.2.S.7 and Substance substance stability or key physicochemical cross-referenced as needed in 3.2.P.2 as appropriate. characteristics that might influence the Discussion of key drug substance physicochemical manufacturing process of the drug product be provided? characteristics that can influence manufacturability of the drug product should be included in 3.2.P.2.1.1. 완제의약품제조공정에영향을미칠가능성이 원료의약품안정성데이터를 3.2.S.7에정리하고, 필요에따라 있는 원료의약품 안정성이나 주요 이화학적 3.2.P.2에서상호참조시킨다. 완제의약품의제조성에영향을미칠 특성에관한정보를어디에기술해야하는가? 수 있는 원료의약품의 주요 이화학적 특성에 관한 정보는 3.2.P.2.1.1에기술한다. Where should a discussion of the effect of modification of active moiety (e.g., salt) on Discussion of effect of modification of active moiety (e.g., salt) on key drug substance physicochemical characteristics should key drug substance physicochemical be included in 3.2.P.2.1.1. characteristics be provided? 활성부분의변형 ( 예, 염 ) 이원료의약품의주요 활성부분의변형 ( 예, 염 ) 이원료의약품의주요이화학적특성에미치는영향에관한정보는 3.2.P.2.1.1에기술한다. 이화학적특성이미치는영향에관한정보를 어디에기술해야하는가? Where should data from studies on drug product to evaluate the potential effect of Data from studies on drug product to evaluate the potential effect of key drug substance physicochemical characteristics www..co.kr 30

CTD-Q Section 3.2. Issues/ Questions P.2.1.2 Excipients www..co.kr key drug substance physicochemical characteristics be provided? 원료의약품의주요이화학적특성의영향을평가하기위해완제의약품을상대로실시한실험데이터를어디에정리해야하는가? Should justification for using an excipient if there is evidence of incompatibility be included in 3.2.P.2.1.1 or 3.2.P.2.1.2? 부조화성의증거가있는경우에첨가제사용의타당성에관한정보를 3.2.P.2.1.1과 3.2.P.2.1.2 가운데어디에포함시켜야하는가? Where should a discussion of an excipient s influence on the manufacturability of the drug product be included? 첨가제가완제의약품의제조성에미치는영향을어디에서설명해야하는가? Where should a discussion of the ability of a functional excipient to perform through shelf-life be included? 기능성첨가제가유효기간내내그기능을발휘할수있다는정보를어디에포함시켜야 31 should be provided in 3.2.P.2.1.1 (see ICH Q6A Decision Trees 3 and 4 (Part 2)). 원료의약품의주요이화학적특성의영향을평가하기위해완제의약품을상대로실시한실험데이터를 3.2.P.2.1.1에정리한다 (ICH Q6A 의사결정도 3과 4( 파트 2) 참조 ). Justification for using an excipient if there is evidence of incompatibility should be included in 3.2.P.2.1.1 부조화성의증거가있는경우에첨가제사용의타당성에관한정보를 3.2.P.2.1.1에기술한다. Discussion of excipients that can influence the manufacturability of the drug product should be included in 3.2.P.2.1.2. 완제의약품의제조성에영향을미칠수있는첨가제에관한정보를 3.2.P.2.1.2에기술한다. Discussion of the ability of functional excipients (e.g., antioxidants, penetration enhancers) to perform through shelflife should be included in 3.2.P.2.1.2. The effectiveness of antimicrobial preservatives should be discussed in 3.2.P.2.5. 기능성첨가제 ( 예, 항산화제, 침투촉진제 ) 가유효기간내내그

CTD-Q Section 3.2. Issues/ Questions 하는가? 기능을 발휘할 수 있다는 정보를 3.2.P.2.1.2에 포함시킨다. 항미생물보존제의효과는 3.2.P.2.5에서기술한다. P.2.2 Drug Product Where should tables that describe the Tables describing different development formulations should be composition of formulations used in included in 3.2.P.2.2.1. development studies be included? 여러가지개발제제를정리한표를 3.2.P.2.2.1에포함시킨다. 개발실험에사용한제제의조성을정리한표를 어디에포함시켜야하는가? P.2.2.1 Formulation Where should information on IV-IV Summarised information on the in vivo-in vitro (IV-IV) Development correlation be included in CTD-Q? IV-IV 상호관계에관한정보를 CTD-Q의어디에포함시켜야하는가? correlation should be included in 3.2.P.2.2.1 with a crossreference to the studies in Module 5. IV-IV 상호관계에관한요약정보를 3.2.P.2.2.1에기술하고, 모듈 5의해당시험을상호참조시킨다. Can cross-reference be made to Cross-referencing to both Modules 2 and 5 can be included to bioequivalence information in other Modules? facilitate the review process. 다른 모듈의 생물학적 동등성 정보를 상호 심사를원활히진행할수있게, 모듈 2와 5 모두의상호참조정보를 참조해도되는가? Where should information to justify a scoring of tablets be included? 정제의분할선에관한정보를어디에포함시켜야 포함시킬수있다. The rationale/ justification for scoring of tablets should be provided in 3.2.P.2.2.1. 정제분할선의근거 / 타당성정보를 3.2.P.2.2.1에기술한다. 하는가? Should the release mechanism of the dosage Description of the release mechanism in the dosage form for www..co.kr 32

CTD-Q Section 3.2. Issues/ Questions P.2.2.2 Overages P.2.2.3 Physicochemical and Biological Properties www..co.kr form for controlled release drug products be described in 3.2.P.2.2.1? 방출제어완제의약품의방출메커니즘을 3.2.P.2.2.1에기술해야하는가? Where should overages be justified? 과량투입의타당성을어디에서기술하는가? Where should any discussion on dissolution development be included? 용출개발정보를어디에기술하는가? Where should a discussion of the key drug product physicochemical or biological characteristics that might influence the manufacturing process of the drug product be provided? 완제의약품제조공정에영향을미칠가능성이있는완제의약품의주요이화학적 / 생물학적특성에관한정보를어디에기술하는가? 33 controlled release drug products should be included in 3.2.P.2.2.1. 방출제어완제의약품의방출메커니즘에관한정보를 3.2.P.2.2.1에기술한다. Justification for overages should be included in 3.2.P.2.2.2. 과량의타당성에관한정보를 3.2.P.2.2.2에기술한다. 1. A summary of dissolution development should be included in 3.2.P.2.2.3, with cross-reference to studies in Module 5, as considered appropriate. The justification for the dissolution test should be included in 3.2.P.5.6. 용출개발정보를 3.2.P.2.2.3에요약하여기술하고, 모듈 5의해당시험정보를상호참조시킨다. 용출시험의타당성에관한정보는 3.2.P.5.6에포함시킨다. 2. A discussion of key drug product physicochemical or biological characteristics that can influence manufacturability of the drug product should be included in 3.2.P.2.2.3. 완제의약품의제조성에영향을미칠가능성이있는완제의약품의주요이화학적 / 생물학적특성에관한정보를 3.2.P.2.2.3에기술한다.

CTD-Q Section 3.2. Issues/ Questions P.2.3 Manufacturing Process Development www..co.kr Where should data from studies on the potential effects of key drug substance physiochemical characteristics on the performance of the drug product be provided? 원료의약품의 주요 이화학적 특성이 완제의약품의성능에미치는영향에관한실험 데이터를어디에기술하는가? Where should justification of sterilisation be provided? 멸균의 타당성에 대한 정보를 어디에 기술하는가? What information on clinical trial formulations should be included in 3.2.P.2.3? 임상시험제제에관한정보를 3.2.P.2.3에 기술해야하는가? 34 3. Data from studies on drug product to evaluate the appropriateness of the drug product acceptance criteria for physicochemical/ biological properties should be included in 3.2.P.2.2.3 (see ICH Q6A Decision Trees 4 (Part 3) and 7 (Part 1)). 완제의약품의이화학적 / 생물학적특징에대한허용기준의적절성을평가하기위해실시한실험에서확보된데이터를 3.2.P.2.2.3에포함시킨다 (ICH Q6A 의사결정도 4( 파트 3) 와 7( 파트 1) 참조 ). 1. When called for, justification of sterilisation should be included in 3.2.P.2.3. 필요한경우에는멸균의타당성에관한정보를 3.2.P.2.3에포함시킨다. 2. Information on clinical trial formulations should be included in 3.2.P.2.2.1. Information on the differences in the manufacturing process among supporting batches (e.g., clinical, stability) and the proposed production process should be included in 3.2.P.2.3. 임상시험제제에관한정보를 3.2.P.2.2.1에기술한다. 근거배치 ( 예, 임상배치, 안정성배치 ) 의제조공정과예정생산

CTD-Q Section 3.2. Issues/ Questions 공정의차이에관한정보를 3.2.P.2.3에포함시킨다. P.2.4 Container 1. Should information on container closure 1. Information on both should be included in 3.2.P.2.4. When Closure System system leachables and extractables be warranted, information on leachables should also be included in 3.2.P.2.4? 용기마개시스템의유출물 / 추출물에관한정보를 3.2.P.2.4에기술해야하는가? included in 3.2.P.5.1 and 3.2.P.5.5. Also, if leachables are confirmed through shelf-life as part of the formal stability studies, the results would be reported in 3.2.P.8.3. 이정보를 3.2.P.2.4에기술한다. 필요한경우에는유출물에관한 정보를 3.2.P.5.1과 3.2.P.5.5에도포함시킨다. 또한공식안정성 시험 과정에서 유효기간 동안 유출물이 발생하는 것으로 확인되면, 그결과를 3.2.P.8.3에포함시킨다. 2. Where should performance characteristics of a container closure be provided? 2. Information on performance of the container closure system should be included in 3.2.P.2.4 (e.g., priming and repriming 용기 마개의 성능 특성 정보를 어디에 studies for metered dose inhalers). 기술해야하는가? 용기 마개 시스템의 성능에 관한 정보를 3.2.P.2.4에 3. Where should information on studies 기술한다 ( 예, MDI의프라이밍과재프라이밍시험 ). 3. Information on cleaning of metered dose inhalers should be relating to cleaning of metered dose inhalers be included? included in 3.2.P.2.4. MDI의세척에관한정보를 3.2.P.2.4에기술한다. MDI(metered dose inhaler) 의세척관련 실험정보를어디에기술해야하는가? 4. Where should information on the light 4. Suitability of the container closure system to protect from www..co.kr 35

CTD-Q Section 3.2. Issues/ Questions P.2.5 Microbiological Attributes P.2.6 Compatibility www..co.kr protection characteristics of the container closure be provided? 용기마개의차광특성에관한정보를어디에기술해야하는가? Should discussion of Decision Tree #6 from ICH Q6A be included in 3.2.P.2.5? ICH Q6A의의사결정도 #6에대한정보를 3.2.P.2.5에포함시켜야하는가? 1. Where should data from constitution or dilution studies performed as part of the formal stability studies to confirm product quality through shelf-life be provided? 유효기간동안제품품질을확인하기위해공식안정성시험의일환으로실시한구성또는희석실험데이터를어디에기술해야하는가? 2. Should compatibility of co-administered 36 light (e.g., light transmission data) should be discussed in 3.2.P.2.4. Photo-stability data should be provided in 3.2.P.8.3 (defined as a stress study in Q1A/ Q1B). 용기마개시스템의차광적합성 ( 예, 광투과데이터 ) 을 3.2.P.2.4에서설명한다. 광안정성데이터를 3.2.P.8.3에서정리한다 (Q1A/Q1B의가혹시험에해당 ). Discussions relating to ICH Q6A Decision Tree #6 (non-sterile drug substance and excipients) and Decision Tree #8 (nonsterile solid) should be provided in 3.2.P.2.5. ICH Q6A 의사결정도 #6( 비무균원료의약품과첨가제 ) 과의사결정도 #8( 비무균고형제 ) 와관련된사항을 3.2.P.2.5에기술한다. Information on the compatibility of reconstitution diluents to support claims on the label should be included in 3.2.P.2.6. Data from constitution or dilution studies that are performed as part of the formal stability studies to confirm product quality through shelf-life should be reported in 3.2.P.8.3. 라벨표시사항을뒷받침하는재구성희석제의조화성관련정보를 3.2.P.2.6에포함시킨다. 유효기간동안제품품질을확인하기위해공식안정성시험의일환으로실시한구성또는희석실험데이터를 3.2.P.8.3에기술한다. Compatibility with co-administered drugs should be included in

CTD-Q Section 3.2. Issues/ Questions P.3 Manufacture P.3.1 Manufacturer(s) P.3.2 Batch Formula P.3.3 Description of Manufacturing Process and Process Controls www..co.kr drugs be provided in 3.2.P.2.6? 함께투여되는의약품의조화성을 3.2.P.2.6에서설명해야하는가? 3. Should information on incompatible diluents be provided in 3.2.P.2.6? 부조화성희석제에관한정보를 3.2.P.2.6에기술해야하는가? Should overages be included in 3.2.P.3.2? 과량정보를 3.2.P.3.2에포함시켜야하는가? 1. Where should reprocessing be described? 재가공정보를어디에기술해야하는가? 37 3.2.P.2.6. 함께투여되는의약품의조화성에관한정보를 3.2.P.2.6에포함시킨다. Information on incompatible diluents should be provided in 3.2.P.2.6. 부조화성희석제에관한정보를 3.2.P.2.6에포함시킨다. Overages should be included in the batch fomula in 3.2.P.3.2. 과량정보는 3.2.P.3.2의배치조성에포함시켜야한다. 1. Reprocessing should be included as part of the description of the manufacturing process in 3.2.P.3.3. If there are critical controls associated with the reprocessing operation, the critical controls should be included in 3.2.P.3.4. If validation information is warranted, the validation information should be included in 3.2.P.3.5. 3.2.P.3.3에제조공정을설명하면서재가공부분도기술한다. 재가공과관련하여핵심적인관리항목이있으면, 그정보를 3.2.P.3.4에서설명한다. 밸리데이션정보가필요하다면,

CTD-Q Section 3.2. Issues/ Questions 2. Should critical steps and intermediates be identified in P.3.3? 핵심단계와중간제품을 P.3.3에명기해야하는가? 3.2.P.3.5에밸리데이션정보를포함시킨다. 2. All process controls should be identified in 3.2.P.3.3. For critical controls, additional information should be provided in 3.2.P.3.4. 3.2.P.3.3에서모든공정관리사항을명기한다. 핵심관리항목인경우에는 3.2.P.3.4에서추가정보를기술한다. 3. Should an over-fill be identified in 3. An over-fill should be identified in 3.2.P.3.3. 3.2.P.3.3? 오버필을 3.2.P.3.3에명기한다. 오버필을 3.2.P.3.3에명기해야하는가? 4. Should a statement regarding 4. A statement regarding manipulation of ruminant-derived manipulation of ruminant-derived materials in the drug product manufacturing facility should materials in the drug product be included here (3.2.P.3.3). If a potential for crosscontamination manufacturing facility be included in with adventitious agents exists, additional 3.2.P.3.3? information should be provided in 3.2.A.1 and 3.2.A.2. 완제의약품제조시설에서반추동물유래 완제의약품제조시설에서반추동물유래물질을취급하는행위에 물질을 취급하는 행위와 관련한 정보를 대하여 3.2.P.3.3에서 설명한다. 외래성 인자의 교차 오염 3.2.P.3.3에포함시켜야하는가? 가능성이 존재하면, 3.2.A.1과 3.2.A.2에서 추가 정보를 기술한다. P.3.4 Controls of Should the detailed information on critical Detailed information should be provided in 3.2.P.3.4 for critical Critical Steps and steps and intermediates that have been steps and all intermediates that are controlled. Intermediates identified in 3.2.P.3.3 be included in 핵심 단계와 관리 대상 모든 중간제품에 관한 세부 정보를 www..co.kr 38

CTD-Q Section 3.2. Issues/ Questions 3.2.P.3.4? 3.2.P.3.4에서기술한다. 3.2.P.3.3에명기한핵심단계와중간제품에 관한정보를 3.2.P.3.4에서자세히기술해야 하는가? Should critical process control values from Critical process control values from relevant batches to support relevant batches be included in 3.2.P.3.4 to support numeric ranges, limits, etc., for the critical process controls? 핵심공정관리항목의허용범위나한도기준 numeric ranges, limits, etc., for critical process controls should be included in 3.2.P.3.4. 핵심공정관리항목의허용범위나한도기준등을뒷받침하는관련배치의핵심공정관리결과를 3.2.P.3.4에정리한다. 등을뒷받침하기위하여, 관련배치의핵심공정 관리결과를 3.2.P.3.4에서정리해야하는가? Where should information on the analytical In 3.2.P.3.4, the same information should be provided for an procedures for an in-process material test in-process material test performed in lieu of a finished product performed in lieu of a finished product test be included? 최종제품시험대신실시하는공정중물질시험항목의분석절차를어디에서설명해야하는가? test as that submitted for a finished product test (analytical procedure, methods validation information). 최종제품시험대신실시하는공정중물질시험인경우에, 최종제품시험과동일한정보 ( 분석절차, 분석방법밸리데이션정보 ) 를 3.2.P.3.4에기술한다. If a process test were to replace an endproduct test, where would it be mentioned in the specification? If a process test takes the place of an end-product test, it should be listed in the specification (3.2.P.5.1) and specified as a process test (see ICH Q6A). www..co.kr 39

CTD-Q Section 3.2. Issues/ Questions 최종제품시험대신공정시험을실시한다면, 최종 제품 시험 대신 공정 시험을 실시한다면, 그 항목을 규격정보를어디에기술해야하는가? 규격 (3.2.P.5.1) 에포함시키고공정시험으로표기한다 (ICH Q6A 참조 ). P.3.5 Process Validation and/or Evaluation P.4 Control of If a significant amount of data for an This information should be included in 3.2.A.3 Excipients, if Excipients excipient (e.g., a novel excipient or a required. If only a minimal amount of information was noncompendial nonnovel excipient) needs to be provided, where would it be placed? 첨가제에대하여상당한양의데이터를제공할 necessary for these excipients (e.g., pharmacopoeial), this information should be provided in 3.2.P.4.1 and/or 3.2.P.2.1.2. 이정보를 3.2.A.3에포함시킨다. 첨가제에대하여최소한의정보만 필요가있다면 ( 예, 새로운첨가제또는비공정서 필요한 경우 ( 예, 약전 수재 첨가제 ), 3.2.P.4.1 및 / 또는 비신규첨가제 ), 그정보를어디에배치해야 3.2.P.2.1.2에서기술한다. 하는가? P.4.1 Specifications P.4.2 Analytical Procedures P.4.3 Validation of Analytical Procedures P.4.4 Justification of Specifications Where should certificates of analysis or batch data for excipients be included? Certificates of analysis or batch data for excipients should be included in 3.2.P.4.4. www..co.kr 40

CTD-Q Section 3.2. Issues/ Questions 첨가제의 COA나 배치 데이터를 어디에 첨가제의 COA나배치데이터를 3.2.P.4.4에포함시킨다. 포함시켜야하는가? Can a summary of data from other sections A summary of data from other sections with a cross-reference with a cross-reference to the detailed to the detailed information can be provided to support the information be provided, rather than justification of specification. repeating this information to support the Justification of Specifications section of the 다른섹션의데이터를요약하고보다구체적인사항은상호참조표시를하여규격의타당성을뒷받침할수있다. dossier? 규격의 타당성을 뒷받침하는 정보를 자세히 반복하기보다는, 다른섹션의데이터를요약하고 보다구체적인사항은상호참조표시를해도 되는가? P.4.5 Excipients of Where should information on excipients of Information on excipients of human or animal origin should be Human or Animal Origin human or animal origin be located? 사람이나동물유래첨가제에관한정보를어디에배치해야하는가? included in 3.2.P.4.5. Information on adventitious agent safety evaluation should be included in 3.2.A.2. For the location of certifications relating to TSE/ BSE, see region specific guidance. 사람이나동물유래첨가제에관한정보를 3.2.P.4.5에포함시킨다. 외래성인자안전성평가정보는 3.2.A.2에배치한다. TS/BSE 관련증명문서의위치는지역별가이드라인을참조한다. P.4.6 Novel Excipients www..co.kr 41