Microsoft Word - In Use Stability Testing.doc

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1 2001년 3월 1일런던 CPMP/QWP/2934/99 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) 사람의약품의사용시안정성실험에관한가이드라인 (NOTE FOR GUIDANCE ON IN-USE STABILITY TESTING OF HUMAN MEDICINAL PRODUCTS) Discussion in the Quality Working Party (QWP) January/October 1999 Transmission to the CPMP December 1999 Release for Consultation December 1999 Deadline for Comments June 2000 Adoption by CPMP February 2001 Date for Coming into Operation September

2 NOTE FOR GUIDANCE ON IN-USE STABILITY TESTING OF HUMAN MEDICINAL PRODUCTS 목적 (Objective) The purpose of in-use stability testing is to establish - where applicable - a period of time during which a multidose product can be used whilst retaining quality within an accepted specification once the container is opened. 사용시안정성실험의목적은해당되는경우에다회용량의약품의용기개봉이후품질이허용규격이내로유지되는사용가능기한을설정하는데있다. 적용범위 (Scope) This guideline refers to medicinal products in multidose containers which - by nature of their physical form and chemical composition - due to repeated opening and closing, may pose a risk to its content with regard to microbiological contamination, proliferation and/or physicochemical degradation once the closure system has been breached. 이가이드라인은다용량의약품을대상으로한다. 다용량의약품은반복적으로개봉하고닫기때문에그의물리적상태와화학적조성의특성으로인하여일단밀폐상태가훼손된다음에는미생물학적오염, 증식, 및 / 또는이화학적품질저하등의위험이발생할수있다. 서론 (Introduction) The continued integrity of products in multidose containers after the first opening is an important quality issue. While this principle is acknowledged in the Ph. Eur. and EU Guidelines, no specific guidance is available on defining test design and conduct of studies to be undertaken to define in-use shelf life in a uniform fashion. Therefore, this document attempts to define a framework for selection of batches, test design, test storage conditions, test parameters, test procedures etc., taking into consideration the broad range of products concerned. 다용량제품의첫개봉이후완전성의지속여부는매우중요한품질이슈이다. 유럽약전과 EU 가이드라인이이원칙을수용하고있으나, 사용기한 (in-use shelf life) 을 2

3 정하기위한통일된실험디자인과수행방법에관한구체적인가이드라인은없다. 그러므로이문서는각종제품들을고려하여배치의선정, 테스트디자인, 테스트보관 조건, 테스트변수, 테스트절차등에대한전반적인틀을제시하고자한다. Nevertheless should this Note for guidance also be read in connection with the Notes for guidance on Development pharmaceutics (CPMP/QWP/155/96), Stability testing of existing active substances and related finished products (CPMP/QWP/556/96) and Stability testing of new drug substances and products (CPMP/ICH/2736/99). 하지만 " 의약품개발 (CPMP/QWP/155/96)", " 기존활성성분및관련최종제품의안정성실험 (CPMP/QWP/556/96)", " 신규약효성분및제품의안정성실험 (CPMP/ICH/2736/99)" 과연계하여이문서를읽고적용해야한다. The registration dossier for a multi-dose product should include either the in-use stability data on which the in-use shelf life is based or a justification why no in-use shelf life is established. This justification can also be based on experimental results. 다용량제품의등록신청서류에는사용기한 (in-use shelf life) 을뒷받침하는안정성데이터나사용기한을설정하지않은이유에대한타당한설명을포함해야한다. 이때실험적결과에근거하여타당성을제시할수도있다. 배치의선정 (Selection of batches) A minimum of two batches, at least pilot scale batches, should be subjected to the test. At least one of the batches should be chosen towards the end of its shelf life. If such results are not available, one batch should be tested at the final point of the submitted stability studies. The batch number, date of manufacture and size of each batch should be stated. The container and closure of the product and, if present, the medicinal device should be equivalent to that proposed for marketing. 최소 2개배치 ( 최소한파일럿규모배치 ) 를테스트한다. 적어도 1개배치는유효기간말기시점의것으로선택한다. 이런배치를상대로한실험결과가없다면, 제출한안정성실험의최종시점에 1개배치를테스트해야한다. 각배치의배치번호, 제조일자, 제조규모를명시한다. 제품의용기와마개, 그리고해당되는경우에투약장치는판매용과동등해야한다. 3

4 If the product is to be supplied in more than one container size or in different strengths, the in-use stability test should be applied to the product which presents the greatest susceptibility to change. The choice of the tested product should always be justified. 제품을여러함량이나하나이상의용기크기로제공한다면, 변화에대한민감성이가장큰제품을대상으로사용중의안정성실험을실시한다. 제품선정의타당성을제시해야한다. 테스트디자인 (Test design) As far as possible the test should be designed to simulate the use of the product in practice taking into consideration the filling volume of the container and any dilution/reconstitution before use. At intervals comparable to those which occur in practice appropriate quantities should be removed by the withdrawal methods normally used and described in the product literature. Sampling should take place under normal environmental conditions of use. 사용전의희석 / 재구성과용기의충전량을고려하여, 실제제품사용상황을최대한시뮬레이션해테스트방법을설계한다. 실제투약상황을감안한주기에따라적절한양을제품설명서에기술된정해진투약방법에따라제거한다. 정상적인사용환경조건에서검체를채취한다. The appropriate physical, chemical and microbial properties of the product susceptible to change during storage should be determined over the period of the proposed in-use shelf life. 보관중의변화에민감한제품의이화학적 / 미생물학적특성을예정사용기간동안분석한다. If possible, testing should be performed at intermediate time points and at the end of the proposed in-use shelf life on the final remaining amount of the product in the container. 가능하면중간시점과예정사용기간말기에남은제품잔량을상대로테스트를실시한다. 테스트보관조건 (Test storage conditions) 4

5 The product should be stored under the conditions as recommended in the product literature (SPC and PIL) throughout the in-use stability test period. 사용안정성실험기간동안제품설명서 (SPC와 PIL) 에제시된조건에서제품을보관한다. Any other storage conditions should be justified. 다른보관조건을적용한다면, 그타당성을제시해야한다. 테스트변수 (Test parameters) The appropriate physical, chemical and microbial properties of the product susceptible to change during use should be monitored. The tests used must be appropriate to individual dosage forms, however, examples of parameter types which may need to be studied are given below: 사용과정에서변화에민감한이화학적 / 미생물학적특징을모니터한다. 제품에따라적절한항목을테스트해야하지만, 조사가필요할수있는변수유형의예가아래에제시되어있다. Physical: colour, clarity, closure integrity, particulate matter, particle size Chemical: active substance assay(s), antimicrobial preservative and antioxidant content(s), degradation product level(s), ph Microbial: Total viable count, sterility 분석방법 (Analytical procedures) The analytical procedures used in the study should be described and fully validated. Stability indicating assays should be employed. 분석방법을설명해야하며, 충분하게밸리데이션되어야한다. 안정성지시방법을사용한다. 결과 (Presentation of the results) The results should be summarized and tabulated. 결과를요약하고도표로정리한다. 5

6 If relevant, the results should be presented graphically. 관련성이있을때는그래프로결과를정리한다. 평가 (Evaluation) Conclusions reached based on the data provided should be stated. In the case of anomalous results these should be explained. 데이터를토대로도출한결론을명시한다. 결과가일관성을보이지않는경우에는그에대해설명한다. Where applicable and justified an in-use shelf life specification should be given. 타당한이유가있는경우에는사용기간규격을제시한다. In-use stability data should be used to determine whether or not a declaration of an in-use shelf life and additional storage conditions are necessary. 사용안정성데이터를바탕으로사용기간과추가적인보관조건의고지가필요한지결정한다. 일차용기의표시 (Labelling of the primary container) The in-use shelf life should be stated on the label. In addition (if space allows) there should be a space for the user to write the date of opening or the "use-by" date. 사용기간을라벨에표시한다. 또한 ( 공간이있으면 ) 사용자가개봉일자또는 " 사용기한 " 을적을수있는공간을두어야한다. SPC, 설명서, 이차용기의표시사항 (SPC, leaflet and labelling of the secondary container) The in-use shelf life and in-use storage recommendations - if applicable - should be included in SPC, leaflet and outer carton text. 사용기간과사용보관조건 ( 해당되는경우 ) 을 SPC, 설명서, 외부카톤문구에 포함시킨다. 6

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