1 / 6

Linking Drug Stability to Manufacturing Risk Assessment Approaches

Linking Drug Stability to Manufacturing Risk Assessment Approaches. L. E. Kirsch Stability team leader. Stability in Design Space. L t End of Expiry. Post-Manuf. Kinetic Model. Manuf. Design Space Model. L 0 D 0. Manufacturing stability measurements: criteria and uses

princess-osborn
Download Presentation

Linking Drug Stability to Manufacturing Risk Assessment Approaches

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Linking Drug Stability to ManufacturingRisk Assessment Approaches L. E. Kirsch Stability team leader

  2. Stability in Design Space Lt End of Expiry Post-Manuf. Kinetic Model Manuf. Design Space Model L0 D0 • Manufacturing stability measurements: criteria and uses • Rationality based on understanding of instability • Correlates to shelf-life • Correlates to risk: failure to reach desired shelf-life without exceeding critical instability target

  3. Correlation between Shelf-life and Manufacturing-stability Measurements(preliminary long term stability studies) Shelf-life estimated from linear extrapolation of room temperature stability data

  4. 1.00 1 0.75 failure prob 0.50 0 0.25 0.00 .175 .200 .225 .250 .275 .300 D0 + L0 Logistical Regression Model for Stability Risk Assessment • Shelf-life = Time to 0.4 % lactam(linear extrapolation of long-term stability data) • Stability failure: Shelf-life < Desired target dating (e.g. 2 years) • Logistical Regression model: • probability of stability failure as a function of the manufacturing-stability measurements (L0 and D0, mole %)

  5. Estimated Stability Risk application of logistical regression model Lab Pilot Lots Lab Bench Lots

  6. Long-term stability • Objectives • Demonstrate relationship between Manufacturing-related stability measurement (MSM: D0 and L0) and shelf-life • Demonstrate/validate solid state degradation model • Construct definitive “Risk-based” Design Space Models • Current state • Studies underway

More Related