DEVELOPMENT OF QUALITY BY DESIGN QBD GUIDANCE ELEMENTS
DEVELOPMENT OF QUALITY BY DESIGN (QBD) GUIDANCE ELEMENTS ON DESIGN SPACE SPECIFICATIONS ACROSS SCALES WITH STABILITY CONSIDERATIONS Scale up consideration – NIR calibration Benoit Igne, Sameer Talwar, Brian Zacour, Carl Anderson, James Drennen Duquesne University Center for Pharmaceutical Technology
Blend Scale up issues • • • Volume of powder sampled decreased Differences in fill volume Blending dynamics changed Blender shape changed Different NIR sensors – Thermo. Fisher Spectral Probe to Expo. Tech e. PAT 601 Blend monitor
Efficient calibration approach • Used limited number of levels – 0%, 100%, nominal, granule • Classical least squares based method – Regression vector is based on the pure components • Consequently, the differences in regression vector from scale to scale, from NIR sensor to NIR sensor was mainly a function of the instrument differences
Efficient calibration approach • No unique samples • No degradation of sample • No transfer set / standardization method • Reduced time and effort for calibration model development: “calibration in hours”
Calibration comparison Laboratory scale RMSEC (%) = RMSECnom (%) = API MCC HPC Starch 1. 40 0. 95 1. 08 0. 70 1. 66 1. 09 1. 25 0. 75 Scale-up RMSEC (%) = RMSECnom (%) = API MCC HPC Starch 1. 56 0. 81 0. 98 0. 41 1. 93 1. 58 1. 38 0. 50
Blend point • At laboratory scale 1. Both instruments gave similar outputs 2. RMSNV under error of validation • At scale up 1. RMSNV under error of validation • Blend was stopped in a similar manner, based on similar criteria – – Similar definition of homogeneity Differences in scales of scrutiny
- Slides: 6