Validation of National Standard and Application of Quality Control Methods for Japanese Encephalitis Vaccine
일본뇌염백신의 국가표준품 밸리데이션 및 품질관리방법 적용 연구
- 주제(키워드) 일본뇌염백신 , 국가표준품 , 품질관리 , 역가시험
- 발행기관 고려대학교 대학원
- 지도교수 박용근
- 발행년도 2019
- 학위수여년월 2019. 2
- 학위구분 박사
- 학과 대학원 생명공학과
- 세부전공 생물법제학
- 원문페이지 107 p
- 실제URI http://www.dcollection.net/handler/korea/000000083034
- UCI I804:11009-000000083034
- DOI 10.23186/korea.000000083034.11009.0000930
- 본문언어 영어
- 제출원본 000045978973
초록/요약
Japanese encephalitis vaccine is one of the preventive vaccines listed in National Immunization Program in Korea. In order to conduct the routine tests of the quality control such as the potency test, it is necessary to establish a reliable reference standard assuring the robustness of the analytical method and improving the precision of the test result. In Korea, the 1st national standard of the Japanese encephalitis vaccine was established in 2002. The 2nd national standard which was established in 2007 is currently used for Japanese encephalitis vaccine (Nakayama-NIH strain) potency test. However, the supply of the 2nd national standard was anticipated to be exhausted by 2015, necessitating the supply of a new national reference standard with quality equivalent to the existing standard. The 3rd national standard candidate material was subjected to the quality control testing and proved its appropriateness in the potency testing of Japanese encephalitis vaccine. A collaborative study, which was performed by 4 institutions including the Ministry of Food and Drug Safety and three manufacturers, was carried out to assign the in vivo and in vitro potencies against the new standard candidate material. Based on the results of the collaborative study, the in vivo potency of the new national standard was determined to be 2.69 neutralizing-antibody titer (log10) per vial. The new national standard will continue to support the quality control testing of Japanese encephalitis vaccine in Korea. Upon the recent global movement in pharmaceutical industry, which now encourages the in vitro assays replacing animal tests in routine quality control, the collaboratvie study was also performed to establish the in vitro potency of the 3rd national standard using the enzyme-linked immunosorbent assay which was validated in the previous study. The in vitro relative potency of the 3rd national standard was set to be as 0.97 relative to the 2nd national standard. Due to the initiatives of the study planning to introduce the in vitro test method into the vaccine manufacturers, I conducted the additional collaborative study to establish the criteria for the in vitro potency test against two Japanese encephalitis vaccien products manufactured in Korea. The test criteria were newly determined to be 2.04 ~ 4.39 E-antigen units per vial for the Product I and 2.99 ~ 6.01 E-antigen units per vial for the Product II, respectively, using 20 lots for each product. The integrated specification of 40 lots was set to be as 1.50 ~ 6.22 E-antigen units per vial. In summary, I established the 3rd national standard which was assigned for both in vivo and in vitro potencies, and will support the quality control tests of Japanese encephalitis vaccine derived from Nakayama-NIH strain. In addition, I suggested the new test specification of the in vitro potency correspondingly promoting the revision of the manufacturer's dossiers for their Japanese encephalitis vaccine products. Whereas, the integrated test specification will be registed in the Minimum Requirement for Biological Products for future application such the area as the research and development of the inactivated Japanese encephalitis vaccine, offering common specification representative for the in vitro potency test.
more목차
Abstract i
Contents iv
List of Tables v
List of Figures vi
List of Abbreviations viii
1. Introduction 1
2. Materials and Methods 33
3. Results and Discussion 40
4. Conclusion 82
References 84
Abstract in Korean 90
Acknowledgements 94
