바이오인

출처 : 식품의약품안전처

리포좀제제 품질평가 가이드라인(민원인 안내서)

[목 차]

Ⅰ. 서론 ········································································································· 1

Ⅱ. 품질평가 시 고려사항 ······································································ 2
1. 구성성분 및 조성 ············································································· 2
2. 제제개발 ································································································ 2
3. 품질특성 평가 ······················································································ 3
3.1. 입자크기분포 ················································································ 3
3.2. 형태 및 층 구조 ·········································································· 4
3.3. 표면전하 ························································································ 4
3.4. 상전이 온도 ·················································································· 4
3.5. 삼투압 ···························································································· 4
3.6. pH ·································································································· 4
3.7. 응집 ································································································ 5
3.8. 유효성분의 봉입률 ······································································ 5
3.9. 약물방출 특성 ·············································································· 5
3.10. 유연물질 ····················································································· 5
3.11. 기타 ····························································································· 6

4. 제조 특성 ······························································································ 6
4.1. 제조공정 ························································································ 6
4.2. 제조 변경 관리 ············································································ 7
5. 지질 및 구성성분 관리 ······································································ 8
5.1. 지질의 기원 ·················································································· 8
5.2. 구성 성분 및 종류 ···································································· 9
5.3. 불순물 프로파일 ·········································································· 9
5.4. 제조 공정 및 공정 관리 ···························································· 9
5.5. 규격 ································································································ 9
5.6. 안정성 ···························································································· 10
6. 리포좀제제의 기준규격 ······································································ 10
6.1. 확인시험 ························································································ 11
6.2. 시성치 ···························································································· 11
6.3. 유효성분의 in vitro 방출시험 ················································· 11
6.4. 유연물질 ························································································ 11
6.5. 함량 ································································································ 11
6.6. 엔도톡신 ························································································ 11
6.7. 잔류용매 ························································································ 12
7. 안정성 ···································································································· 12
7.1. 보관 조건에서의 안정성 ···························································· 12
7.2. 재분산 후 안정성 ········································································ 13

Ⅲ. 참고문헌 ································································································ 14

Ⅰ. 서론

1. 배경

리포좀(liposome)은 인지질과 같은 양친매성 지질분자가 동심원 형태의 이중층 또는 다중이중층을 이루는 미세소포(microvesicle)이며, 리포좀제제는 리포좀의 수상 또는 지질막에 유효성분을 봉입하여 제조한 의약품이다. 리포좀은 생체성분 중 하나인 지질로 구성되어 생체 적합성이 우수하고, 크기, 전하, 막 구성성분, 막 투과성 등의 조절이 가능하여 약물수송체로서 다양하게 활용할 수 있다. 따라서 최근에는 유효성분의 용해도 및 체내 안정성 등을 개선하고 유효성분이 치료부위에 정확히 전달되거나 약효가 지속될 수 있도록 하는 다양한 리포좀제제가 개발되고 있다.

리포좀제제는 일반제제와 비교하여 제제설계 또는 제조공정에 따라 투여 후 체내에 분포되는 양상이 다르고, 유사한 혈장 농도라도 치료효과와 연관되지 않을 수 있다. 즉, 리포좀제제는 원료약품의 구성과 분량이 동일하더라도 제조공정 및 제제 제어기술의 차이에 따라 서로 다른 치료 효과를 나타낼 수 있다. 따라서 리포좀제제의 품질특성에 대한 평가는 의약품의 효능·효과에 매우 중요한 영향을 미칠 수 있다.

본 가이드라인에서는 리포좀제제의 품질특성을 제시하고 주요품질특성(critical quality attributes, CQA1))에 근거한 과학적인 기준규격 설정 및 품질관리를 지원하고자 한다.

2. 적용범위

이 가이드라인은 합성 또는 반합성의 저분자 원료의약품을 봉입한 리포좀제제를 대상으로 하며, 제제개발, 제조방법, 기준 및 시험방법, 안정성시험에 대한 자료 작성 시 품질특성과 관련하여 고려해야 할 사항을 제시한다.

리포좀제제는 「의약품의 품목허가·신고·심사 규정」제25조제2항제5호에 따라 제제의 특수성이 인정되는 제제이며, 본 가이드라인에서는 리포좀제제의 특이적인 사항을 주로 제시하되, 그 외 일반적인 사항은 다른 품질관련 규정 및 가이드라인 등을 참고한다.

...................(계속)

☞ 자세한 내용은 내용바로가기 또는 첨부파일을 이용하시기 바랍니다.