製品開発： 例研究 の概要 - jpma.or.jp

1 Implementation of ICH Q8, Q9, Q10.. international conference on harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview . Quality by Design .. - QTPP .. - .. ICH, Tokyo, October 2010 slide 3. Quality by Design QbD . QTPP .. GMP .. CQA . CQA . CPP .. DOE CQA . DOE CPP . CQA . QRM .. PQS.. PQS & GMP. PQS QP, ..) .. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview .. - ICH Q8 Q9 Q10 .. - .. ICH, Tokyo, October 2010 slide 5.

2 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview . ICH, Tokyo, October 2010 slide 6. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview .. - .. - . - . ICH, Tokyo, October 2010 slide 7. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview . Quality Target Product Profile: QTPP).. Quality by Design QbD . ICH, Tokyo, October 2010 slide 8. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview.

3 - - . - - . - - .. ICH, Tokyo, October 2010 slide 9. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview .. - . - . - . - . - . - .. QRM .. ICH, Tokyo, October 2010 slide 10. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview QbD . QTPP.. & CQA.. ICH, Tokyo, October 2010 slide 11. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview . ICH, Tokyo, October 2010 slide 12. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview.

4 - . - Biopharmaceutics Classification System (BCS). 2 . - . - . In vitro-in vivo IVIVC .. ICH, Tokyo, October 2010 slide 13. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview .. - . - Biopharmaceutics Classification System (BCS) 2 .. - . - . - . - . - . - . In vitro-in vivo IVIVC .. ICH, Tokyo, October 2010 slide 14. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview QTPP .. QTPP . 30 mg .. , .. ICH .. PSD . ICH . 2 30 C .. QTPP .. ICH, Tokyo, October 2010 slide 15. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview.

5 ICH, Tokyo, October 2010 slide 16. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview .. ICH, Tokyo, October 2010 slide 17. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview .. D- .. 6000.. ICH, Tokyo, October 2010 slide 18. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview .. ICH, Tokyo, October 2010 slide 19. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview.

6 No impact to CQA. known or potential impact to CQA . current controls mitigate risk known or potential impact to CQA. additional study required Drug Substance Drug Product * includes bioperformace of API and safety Semi-Continuous Moisture Control (API purity). Solvent Switch Crystallization Rotary Drying Compression Manufacture Extractions Lubrication Centrifugal Packaging Distillative Coupling Reaction Aqueous Blending Filtration Coating CQA. in vivo performance*. Dissolution Assay Degradation Content Uniformity Appearance Friability Stability-chemical Stability-physical ICH, Tokyo, October 2010 slide 20. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview.

7 No impact to CQA. known or potential impact to CQA . current controls mitigate risk known or potential impact to CQA. additional study required Drug Substance Drug Product * includes bioperformace of API and safety Semi-Continuous Moisture Control (API purity). Solvent Switch Crystallization Rotary Drying Compression Manufacture Extractions Lubrication Centrifugal Packaging Distillative Coupling Reaction Aqueous Blending Filtration Coating CQA. in vivo performance*. Dissolution Assay Degradation Content Uniformity Appearance Friability Stability-chemical Stability-physical ICH, Tokyo, October 2010 slide 21. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview.

8 - . - FMEA. > . - .. - .. ICH, Tokyo, October 2010 slide 22. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview .. - DOE . - FMEA. > % . - DOE QTPP . 1/2 . - DOE .. PSD DOE . ICH, Tokyo, October 2010 slide 23. ICH Quality Implementation Working Group - Integrated Implementation Training Workshop Product Development: Case Study Overview . PSD . What is the Impact that ------------- will have on PSD? 1) minimal 5) moderate 9) significant What is the Probability that variations in ------------ will occur? 1) unlikely 5) moderately likely 9) highly likely What is our Ability to Detect a meaningful variation in --------------- at a meaningful control point?

9 1) certain 5) moderate 9) unlikely PR T. De . t C. OB. tec Unit Operation Parameter Comments PA. IM. RPN. Prior knowledge (slowness of crystallization kinetics) ensures that the hot crystallizer feed will be well dispersed and thermally equilibrated Crystallization Feed Temperature 1 5 1 5. DOE . before crystallizing. Hence no impact of feed temp variation on crystal size. Prior knowledge (solubility data) shows that small variations in water Crystallization Water content of Feed 1 5 5 25. do not affect crystalliation kinetics. Fast addition could result in uncontrolled crystallization. Detection of Crystallization Addition Time (Feed Rate) 9 5 9 405 short addition time could occur too late to prevent this uncontrolled crystallization, and thus impact final PSD.

10 Prior knowledge (Chemical Engineering theory) highlights seed wt Crystallization Seed wt percentage 9 5 5 225. percentage variations as a potential source of final PSD variation Yield loss to crystallization already low (< 5%), so reasonable Crystallization Antisolvent percentage 1 1 1 1 variations in antisolvent percentage (+/- 10%) will not affect the percent of batch crystallized, and will not affect PSD. Change in crystallization temperature is easily detected, but rated Crystallization Temperature 9 5 9 405 high since no possible corrective action (such as, if seed has been dissolved). Prior knowledge indicates that final PSD highly sensitive to Agitation, Crystallization Agitation (tip speed) 9 5 5 225.