Analytical Science and Technology (분석과학)

The Korean Society of Analytical Sciences (한국분석과학회)
권호 표지
DOI QR코드

DOI QR Code

Process analytical technology (PAT): field applications and current status in pharmaceutical industries

공정분석기술: 제약산업에서의 기술개발 사례 및 현황

  • 우영아 ((주) 한국유나이티드제약 제제연구소) ;
  • 김종윤 (한국원자력연구원 원자력화학연구부) ;
  • 박용준 (한국원자력연구원 원자력화학연구부) ;
  • 연제원 (한국원자력연구원 원자력화학연구부) ;
  • 송규석 (한국원자력연구원 원자력화학연구부) ;
  • 김효진 (동덕여자대학교 약학과)
  • Received : 2008.11.03
  • Accepted : 2009.01.29
  • Published : 2009.02.25
Download PDF
⟨ Previous Next ⟩

Abstract

The goal of PAT (Process Analytical Technology) is to build quality into products through better understanding and control of manufacturing processes, rather than merely testing the quality of the end product. Pharmaceutical manufacturers are trying to develop and implement new technologies in pharmaceutical production and quality control for real-time measurements of critical product and process parameters. Characterization of manufacturing process through experimental design, for evaluation of the effect of product and process variables, represents an integral part of the PAT framework. However, the publications regarding real PAT application to pharmaceutical process are very limited and the technologies are confidential as well. In this review, the case studies related to PAT are shown with real applications from a pharmaceutical company. Additionally, various applications of PAT on the developing stage are introduced with high analytical technologies for the improvement of quality control on manufacturing process.

단순히 완제품만을 평가하는 기존의 방법에서 제조 공정의 보다 깊은 이해와 공정 제어를 통한 품질 확보가 PAT (공정분석기술, process analytical technology)가 지향하고 있는 핵심이다. 생산 상 위험 요소가 많이 발생하는 공정을 제어할 수 있는 목적으로 새로운 실시간 공정 제어 기술을 개발하는 것이 PAT 연구 내용이다. 공정 단계에 대한 이해, 공정에 필요한 여러 가지 변수 및 공정 생산품의 평가 기술은 PAT를 수행하기 위한 기술적 핵심 요소이다. 이에 관련하여 다국적 제약회사의 실제 공정에서의 실시간 품질관리 사례는 상당히 많은 것으로 알려져 있으나, 제조공정 및 분석 기술 자체가 기업 비밀인 경우가 많아 관련 정보는 극히 제한되어 있다. 본 총설을 통하여 실제 제약 산업 현장에서 활용되고 있는 적용사례를 소개하고, 각 제조 공정 및 완제품 실시간 품질 관리를 위한 PAT 연구 사례 및 기술개발 현황에 대하여 언급하고자 한다.

Keywords

References

  1. US FDA, http://www.fda.gov/oc/guidance/gmp.html
  2. US FDA, http://www.fda.gov/cder/guidance/6419fnl.pdf
  3. J.-Y. Kim, Y.-J. Park, J.-W. Yeon, Y.-A. Woo, H.-J. Kim and K. Song, Anal. Sci. Tech., 21, 345-363(2008)
  4. L. Abboud and S. Hensley, 'New Prescription for Drug Makers: Update the Plant', The Wall Street Journal, September 3(2003)
  5. Y.-A. Woo and H.-J. Kim, Microchem. J., 78, 167-173(2004) https://doi.org/10.1016/j.microc.2004.04.004
  6. Y.-A. Woo, H.-R. Lim, H.-J. Kim and H. Chung, J. Pharm. Biomed. Anal., 33, 1049-1057(2003) https://doi.org/10.1016/S0731-7085(03)00420-5
  7. Y.-A. Woo, J.-W. Ahn, I.-K. Chun and H.-J. Kim, Anal. Chem., 73, 4964-4971(2001) https://doi.org/10.1021/ac0102563
  8. M.-S. Hwang, S.-H. Cho, H. Chung and Y.-A. Woo, J. Pharm. Biomed. Anal., 38, 210-215(2005) https://doi.org/10.1016/j.jpba.2004.12.031
  9. M. J. Kim, H. Chung, Y.-A. Woo and M. S. Kemper, Anal. Chim. Acta., 587, 190-197(2007)
  10. J. Kim, J. Noh, H. Chung, Y.-A. Woo, M. S. Kemper and Y. Lee, Anal. Chim. Acta., 598, 280-285(2007) https://doi.org/10.1016/j.aca.2007.07.049
  11. M. J. Kim, H. Chung, Y.-A. Woo and M. S. Kemper, Anal. Chim. Acta., 579, 209-216(2006) https://doi.org/10.1016/j.aca.2006.07.036
  12. T. Norris, P. K. Aldridge and S. S. Sekulic, Analyst, 122, 549-552(1997) https://doi.org/10.1039/a700782e
  13. S. H. Scafi and C. Pasquini, Analyst, 126, 2218-2224(2001) https://doi.org/10.1039/b106744n
  14. M. Blanco and M. A. Romero, Analyst, 126, 2212-2217(2001) https://doi.org/10.1039/b105012p
  15. Y.-A. Woo, H.-J. Kim and J. Cho, Microchem. J., 63, 61-70(1999) https://doi.org/10.1006/mchj.1999.1768
  16. A. Candolfi, R. De Maesschalck, D. L. Massart, P. A. Hailey and A. C. E. Harrington, J. Pharm. Biomed. Anal., 19, 923-935(1999) https://doi.org/10.1016/S0731-7085(98)00234-9
  17. P. R. Khan, R. D. Jee, R. A. Watt and A. C. Moffat, J. Pharm. Sci., 3, 447-453(1997)
  18. V. W. Uhl and J. B. Gray, 'Mixing: Theory and Practice Academic Press', New York, 1967
  19. E. W. Ciurczak, Pharm. Tech., 15, 140-145(1991)
  20. D. J. Wargo and J. K. Drennen, J. Pharm. Biomed. Anal., 14, 1415-1423(1996) https://doi.org/10.1016/0731-7085(96)01739-6
  21. C. Van der Vlies, K. J. Kaffka and W. Plugge, Pharm. Technol. Eur., 7, 46-49(1995)
  22. P. Gemperline, G. Puxty, M. Maeder, D. Walker, F. Tarczynski and M. Bosserman, Anal. Chem., 76, 2575-2582(2004) https://doi.org/10.1021/ac035356i
  23. P. A. Hailey, P. Doherty, P. Tapsell, T. Oliver and P. K. Aldridge, J. Pharm. Biome. Anal., 14, 551-559(1996) https://doi.org/10.1016/0731-7085(95)01674-0
  24. S. S. Sekulic, H. W. Ward, D. R. Brannegan, E. D. Stanley, C. L. Evans, S. T. Sciavolino, P. A. Hailey and P. K. Aldridge, Anal. Chem., 68, 509-513(1996) https://doi.org/10.1021/ac950964m
  25. M. Blanco, R. Gonzalez and E. Bertran, Talanta, 56, 203-212(2002) https://doi.org/10.1016/S0039-9140(01)00559-8
  26. C.-K. Lai and C. C. Cooney, J. Pharm. Sci., 93, 60-70(2004) https://doi.org/10.1002/jps.10478
  27. Z. Shi, R. P. Cogdill, S. M. Short and C. A. Anderson, J. Pharm. Biomed. Anal., 47, 738-745(2008) https://doi.org/10.1016/j.jpba.2008.03.013
  28. A. J. O'Neil, R. D. Jee and A. C. Moffat, Analyst, 123, 2297-2302(1998) https://doi.org/10.1039/a806001k
  29. A. J. O'Neil, R. D. Jee and A. C. Moffat, Analyst, 128, 1326-1330(2003) https://doi.org/10.1039/b307263k
  30. J. P. Higgins, S. M. Arrivo, G. Thurau, R. L. Green, W. Bowen, A. Lange, A. C. Templeton, D. L. Thomas and R. A. Reed, Anal. Chem., 75, 1777-1785 (2003) https://doi.org/10.1021/ac0207980
  31. J. J Schwegman, L. M. Hardwick and M. J. Akers, Pharm. Dev. Technol., 10, 151-173(2005) https://doi.org/10.1081/PDT-56308
  32. X. Tang and M. J. Pikal, Pharm. Res., 21, 191-200(2004) https://doi.org/10.1023/B:PHAM.0000016234.73023.75
  33. S. C. Tsinontides, P. Rajniak, D. Pham, W. A. Hunke, J. Placek and S. D. Reynolds, Int. J. Pharm.., 280, 1-16(2004) https://doi.org/10.1016/j.ijpharm.2004.04.018
  34. W. Y. Kuu, L. M. Hardwick and M. J. Akers, Int. J. Pharm., 302, 56-67(2005) https://doi.org/10.1016/j.ijpharm.2005.06.022
  35. J. A. Searles, Am Pharm. Rev., 7, 58-68(2004)
  36. M. Fransson and S. Folestad, Chemom. Intell. Lab. Syst., 84, 56-61(2006) https://doi.org/10.1016/j.chemolab.2006.04.020
  37. S. Kawai, Drying Tech., 11, 719-731(1993) https://doi.org/10.1080/07373939308916860
  38. S. Watano, H. Takashima and K. Miyanami, J. Chem. Eng. Japan., 30, 223-229(1997) https://doi.org/10.1252/jcej.30.223
  39. A. Y. Gore, D. W. McFarland and N. H. Batuyios, Pharm. Tech., 9, 114-122(1985)
  40. H. Gieseler, W. J. Kessler, M. Finson, S. J Davis, P. A. Mulhall, V. Bons, D. J. Debo and M. J. Pikal, J. Pharm. Sci., 96, 1776-1793(2007) https://doi.org/10.1002/jps.20827
  41. R. L. Green, G. Thurau, N. C. Pixley, A. Mateos, R. A. Reed and J. P. Higgins, Anal. Chem., 77, 4515-4522 (2005) https://doi.org/10.1021/ac050272q
  42. J. Burgbacher and J. Wiss, Org. Proc. Res. Dev., 12, 235-242(2008) https://doi.org/10.1021/op700293p
  43. P. F. Taday, I. V. Bradley, D. D. Arnone and M. Pepper, J. Pharm. Sci., 92, 831-838(2003) https://doi.org/10.1002/jps.10358
  44. C. J. Strachan, T. Rades, D. A. Newnham, K. C. Godron, M. Pepper and P. F. Taday, Chem. Phys. Lett., 390, 20-24(2004) https://doi.org/10.1016/j.cplett.2004.03.117
  45. A. J. Fitzgerald, B. E. Cole and P. F. Taday., J. Pharm. Sci., 94, 177-183(2005) https://doi.org/10.1002/jps.20225
  46. C. J. Strachan, P. F. Taday, D. A. Newnham, K. C. Gordon, J. A. Zeitler, M. Pepper and T. Rades, J. Pharm. Sci., 94, 837-846(2005) https://doi.org/10.1002/jps.20281
  47. H. Wu, E. J. Heilweil, A. S. Hussain and M. A. Khan, J. Pharm. Sci., 97, 958-971(2008)
  48. H. Wu, E. J. Heilweil, A. S. Hussain and M. A. Khan, J. Pharm. Sci., 97, 970-984(2008) https://doi.org/10.1002/jps.21004
  49. E. N. Lewis, J. W. Schoppelrei, E. Lee, L. H. Kidder, K. A. Bakeev (Eds.), 'Process Analytical Technology', Blackwell Publishing Ltd., Oxford, UK, 187-225, 2005
  50. E. Lee, W. X. Huang, P. Chen, E. N. Lewis and R. V. Vivilecchia, Spectroscopy, 21, 24-33(2006)
  51. E. N. Lewis, J. Schoppelrei and E. Lee, Spectroscopy, 19, 26-36(2004)