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1 INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE III 및 IV 기후지역에서의등록신청을위한안정성데이터패키지 (Stability Data Package for Registration Applications ) Current Step 4 version dated 6 February 2003 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 Document History First Codification History Date New Codification November 2005 Approval by the Steering Committee under 76 Step 2 and release for public consultation February 2002 Current Step 4 version Approval by the Steering Committee under 6 Step 4 and recommendation for adoption February to the three ICH regulatory bodies

3 STABILITY DATA PACKAGE FOR REGISTRATION APPLICATIONS IN CLIMATIC ZONES III & IV ICH Harmonised Tripartite Guideline Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 6 February 2003, this guideline is recommended for adoption to the three regulatory parties to ICH. 목차 1. 서론 (INTRODUCTION) 1.1 목표 (Objectives of the Guideline) 1.2 배경 (Background) 1.3 적용범위 (Scope of the Guideline) 2. 가이드라인 (GUIDELINES) 2.1 모가이드라인과의연속성 (Continuity with the Parent Guideline) 2.2 보관조건 (Storage Conditions) 일반기준 (General Case) 반투성용기에포장한액체성의약품 (Aqueous-based drug products packaged in semi-permeable containers) 고온및 / 또는극한습도조건에서의시험 (Tests at elevated temperature and/or extremes of humidity) 2.3 추가고려사항 (Additional Considerations) 3. 참고문헌 (REFERENCES) 3

4 STABILITY DATA PACKAGE FOR REGISTRATION APPLICATIONS IN CLIMATIC ZONES III & IV 1. 서론 (INTRODUCTION) 1.1 목표 (Objectives of the Guideline) This guideline describes an approach to broader use of the ICH guideline Q1A(R) Stability Testing of New Drug Substances and Products (hereafter referred to as the parent guideline) and outlines the stability data package for a new drug substance or drug product that is considered sufficient for a registration application in territories in Climatic Zones III and IV 1,2. 이가이드라인은 ICH 가이드라인 "Q1A(R) 신규약효성분및제품의안정성시험 "( 이하 " 모가이드라인 ") 의활용방식을설명하고, III 및 IV 기후지역에서의등록신청서류에포함시켜야할약효성분또는의약품의안정성데이터패키지를기술한다. 1.2 배경 (Background) The parent guideline describes the stability data package for the ICH tripartite regions (EC, Japan, and the United States), which are in Climatic Zones I and II. The parent guideline can be followed to generate stability data packages for registration applications in other countries or regions in Zones I and II. For territories in Climatic Zones III and IV, the data package as described in the parent guideline can be considered applicable except for certain storage conditions. An approach for classification of countries according to Climatic Zones I, II, III, and IV can be found in the literature 3,4. 모가이드라인은 I 및 II 기후지역에해당되는 ICH 3개지역 (EC, 일본, 미국 ) 의안정성데이터패키지를설명하고있다. 모가이드라인에의거하여 I 및 II 기후지역에속하는다른국가또는지역에서의등록신청서류를위한안정성데이터패키지를만들수있다. III 및 IV 기후지역인경우, 일부보관조건을제외하면모가이드라인에기술된데이터패키지도적용가능한것으로생각할수있다. I, II, III, IV 기후지역별국가분류방법은참고문헌을참조한다. The World Health Organization (WHO) has published a guideline Stability testing of pharmaceutical products containing well established drug substances in 4

5 conventional dosage forms (WHO Technical Report Series, No 863, Annex 5), updated in the Report of the thirty-seventh meeting of the WHO Expert Committee on Specifications for Pharmaceutical Preparations, Geneva, October The WHO guideline describes stability testing recommendations, including storage conditions for all four climatic zones. WHO는 " 확립된약효성분을함유하는기존제형의약품의안정성시험 "(WHO TRS No. 863, Annex 5) 가이드라인을발행했다. 2001년 10월 22일-26일제네바에서열린 WHO 의약품규격전문위원회 37차회의보고서를통해이가이드라인이업데이트되었다. WHO 가이드라인은 4개기후지역의보관조건을포함하여안정성시험관련권고사항을기술하고있다. The stability testing recommendations in this guideline are based on the parent guideline and the WHO guideline. To harmonise with the long-term storage condition for Zones III and IV, the intermediate storage condition in the General Case for Zones I and II in the parent guideline is changed to 30 C ± 2 C/65% RH ± 5% RH. This condition of 30 C ± 2 C/65% RH ± 5% RH can also be a suitable alternative to 25 C ± 2 C/60% RH ± 5% RH as the long-term storage condition for Zones I and II. 이가이드라인의안정성시험권고사항은모가이드라인과 WHO 가이드라인에근거하고있다. III 및 IV 기후지역의장기보관조건과일치시키기위하여, 모가이드라인의 I 및 II 기후지역일반기준에서중간보관조건을 30 C ± 2 C/65%RH ± 5%RH로변경한다. 이조건 (30 C ± 2 C/65%RH ± 5%RH) 은또한 I 및 II 기후지역장기보관조건으로 25 C ± 2 C/60%RH ± 5%RH의적합한대체조건이될수있다. 1.3 적용범위 (Scope of the Guideline) This document is an annex to the parent guideline and recommends the long-term storage condition for stability testing of a new drug substance or drug product for a registration application in territories in Climatic Zones III and IV. 이문서는모가이드라인의부록에해당되며, III 및 IV 기후지역에서의등록신청을위한신규약효성분또는의약품의안정성시험에있어서장기보관조건을권고한다. 2. 가이드라인 (GUIDELINES) 5

6 2.1 모가이드라인과의연속성 (Continuity with the Parent Guideline) This guideline should be used in conjunction with the parent guideline and subsequently published annexes (Q1B, Q1C, Q1D, Q1E, Q5C). The recommendations in the parent guideline and annexes should be followed unless specific alternatives are described within this guideline. The following sections of the parent guideline can be considered common to any territory in the world and are not reproduced here: 이가이드라인은모가이드라인및이후발행된부록가이드라인 (Q1B, Q1C, Q1D, Q1E, Q5C) 과연계하여활용해야한다. 이가이드라인에구체적으로다른방안이설명되어있지않으면, 모가이드라인및부록문서의권고사항을따라야한다. 모가이드라인의다음섹션은세계어느지역에서나적용되는공통적인것으로생각할수있으며, 그러므로여기서다시반복하지않는다. Stress testing 가혹시험 Selection of batches 배치선정 Container closure system 용기마개시스템 Specification 규격 Testing frequency 시험주기 Storage conditions for drug substance or product in a refrigerator 냉장보관약효성분또는제품의보관조건 Storage conditions for drug substance or product in a freezer 냉동보관약효성분또는제품의보관조건 Stability commitment 안정성이행약속 Evaluation 평가 Statements/labelling 표시사항 6

7 2.2 보관조건 (Storage Conditions) 일반기준 (General Case) For the General case (as described in the parent guideline), the recommended long-term and accelerated storage conditions for Climatic Zones III and IV are shown below: " 일반기준 "( 모가이드라인에기술된바에따른 ) 에대하여 III 및 IV 기후지역의권장장기및가속보관조건은아래와같다. 시험조건 (Study) 보관조건 (Storage Condition) 최소제출자료 (Minimum time period covered by data at submission) 장기 (long term) 30 C ± 2 C/65%RH ± 5%RH 12 개월 가속 (accelerated) 40 C ± 2 C/75%RH ± 5%RH 6 개월 No intermediate storage condition for stability studies is recommended for Climatic Zones III and IV. Therefore, the intermediate storage condition is not relevant when the principles of retest period or shelf life extrapolation described in Q1E are applied. III 및 IV 기후지역에서의안정성시험에대해서는중간보관조건을권고하지않는다. 그러므로 Q1E의재시험기간또는유효기간외삽원칙을적용하는데있어서, 중간보관조건은관련성이없다 반투성용기에포장한액체성의약품 (Aqueous-based drug products packaged in semi-permeable containers) For aqueous-based drug products packaged in semi-permeable containers (as described in the parent guideline), the recommended long-term and accelerated storage conditions for Climatic Zones III and IV are shown below: 반투성용기에포장한액체성의약품 ( 모가이드라인에기술된바에따른 ) 인경우에 III 및 IV 기후지역의권장장기및가속보관조건은아래와같다. 시험조건 (Study) 보관조건 (Storage Condition) 최소제출 7

8 자료 (Minimum time period covered by data at submission) 장기 (long term) 30 C ± 2 C/35%RH ± 5%RH 12 개월 가속 (accelerated) 40 C ± 2 C/not more than 25%RH ± 5%RH 6 개월 As described in the parent guideline, an appropriate approach for deriving the water loss rate at the reference relative humidity is to multiply the water loss rate measured at an alternative relative humidity at the same temperature by a water loss rate ratio (see table below for examples). 모가이드라인에서설명하고있는바와같이, 참조상대습도에서의수분손실율을도출하는적절한방법은동일온도의다른상대습도에서측정한수분손실율을수분손실비율 ( 아래의표참조 ) 로곱하는것이다. The ratio of water loss rates at a given temperature is calculated by the general formula (100 reference % RH)/(100 alternative % RH). 특정온도에서수분손실비율은일반공식 (100 참조 %RH)/(100 대체 %RH) 로계산한다. 다른상대습도 (alternative relative humidity) 참조상대습도 (reference relative humidity) 특정온도에서의수분손실비율 (ratio of water loss rates at a given temperature) 65% RH 35% RH % RH 25% RH 3.0 Valid water loss rate ratios at relative humidity conditions other than those shown in the table above can be used. A linear water loss rate at the alternative relative humidity over the storage period should be demonstrated. 표에제시된것이외의상대습도조건에서의유효수분손실비율을활용할수도있다. 보관기간동안다른상대습도에서직선형수분손실율을증명해야한다 고온및 / 또는극한습도조건에서의시험 (Tests at elevated temperature and/or extremes of humidity) 8

9 Special transportation and climatic conditions outside the storage conditions recommended in this guideline should be supported by additional data. For example, these data can be obtained from studies on one batch of drug product conducted for up to 3 months at 50 C/ambient humidity to cover extremely hot and dry conditions and at 25 C/80% RH to cover extremely high humidity conditions 2. 이가이드라인에제시된보관조건을벗어나는특별운송및기후조건은추가데이터에의해뒷받침되어야한다. 예를들어극단적인고온건조조건을대상으로하는 50 C/ 외기습도조건과극단적인다습조건을대상으로하는 25 C/80%RH 조건에서의약품한배치를최대 3개월동안시험하여데이터를확보할수있다. Stability testing at a high humidity condition, e.g., 25 C/80% RH, is recommended for solid dosage forms in water-vapour permeable packaging, e.g., tablets in PVC/aluminum blisters, intended to be marketed in territories with extremely high humidity conditions in Zone IV. However, for solid dosage forms in primary containers designed to provide a barrier to water vapour, e.g. aluminum/aluminum blisters, stability testing at a storage condition of extremely high humidity is not considered necessary. 수증기침투성포장상태의고형제 ( 예, PVC/ 알루미늄블리스터포장정제 ) 로극단적인다습조건의 IV 지역에서시판할예정인경우에는다습조건 ( 예, 25 /80%RH) 에서의안정성시험이권장된다. 하지만수증기배리어를제공하도록설계된일차용기에고형제를포장하는경우에는 ( 예, 알루미늄 / 알루미늄블리스터 ), 극단적인다습조건에서의안정성시험은필요하지않다. 2.3 추가고려사항 (Additional Considerations) If it cannot be demonstrated that the drug substance or drug product will remain within its acceptance criteria when stored at 30 C ± 2 C/65 % RH ± 5 % RH for the duration of the proposed retest period or shelf life, the following options should be considered: (1) a reduced retest period or shelf life, (2) a more protective container closure system, or (3) additional cautionary statements in the labeling. 약효성분또는의약품을 30 C ± 2 C/65 % RH ± 5 % RH에서예정재시험기간또는유효기간동안보관할때허용기준이내에서품질이유지되리라는점을증명할수없는경우, (1) 재시험기간또는유효기간단축, (2) 보호성용기마개시스템추가, 또는 (3) 라벨에추가적인주의사항표시등의방안을고려해야한다. 9

10 3. 참고문헌 (REFERENCES) 1. Schumacher, P. Aktuelle Fragen zur Haltbarkeit von Arzneimitteln [Current questions on drug stability] Pharmazeutische Zeitung, 119: , Grimm, W. Storage Conditions for Stability Testing Long term testing and stress tests Drugs made in Germany, 28: , 1985 (Part I) and 29: 39-47, 1986 (Part II) 3. Dietz, R., Feilner, K., Gerst, F., Grimm, W. Drug Stability Testing Classification of countries according to climatic zone Drugs made in Germany, 36: , Grimm, W. Extension of the International Conference on Harmonization Tripartite Guideline for Stability Testing of New Drug Substances and Products to Countries of Climatic Zones III and IV Drug Development and Industrial Pharmacy, 24, ,

Microsoft Word - Q1AR2 stability testing of new drug substances and dproducts

Microsoft Word - Q1AR2 stability testing of new drug substances and dproducts INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE 새로운원료의약품과완제의약품의안정성시험 (Stability Testing of New