Impact of Dose Formulation on Stability
Impact of Dose Formulation on Stability Peter Bryan, Ph.D.
Topics/Questions for Discussion • Stability Recommendations (20 minutes)
• Acceptance Criteria (20 minutes) • Do these acceptance criteria make sense? • When Do You Need to Revalidate? (20 minutes)
Stability Recommendations • Preprocessed Stability • Compare to nominal concentration • In-life administration • Including dose delivery system • Sample analysis • Storage stability • Freeze/thaw stability
• Postprocessed Stability • Compare to nominal concentration • After dilution into STD curve range • Reinjection
• Stock Solution Stability • Compare to freshly prepared stock • Needed if stocks are prepared in a solvent different from dosing formulation
Acceptance Criteria • Different formulation types necessitate different acceptance criteria • Solutions • 100 ± 10% recovery; RSD ≥10% • Suspensions • 100 ± 15% recovery; RSD ≥10% • Solids • 100 ± 20% recovery; RSD ≥15%
• Do these acceptance criteria make sense?
When Do You Need to Revalidate? • How much of a “formulation/method” change necessitates a revalidation for formulation stability? • • • •
• • • • •
Reagent supplier pH change Buffering capacity Container • Plastic vs glass beaker • Amber bottle vs foil wrapped bottle Particle size • Change in granulation procedure API manufacture change • Different impurity profile Change in concentration Change in analytical procedure Change in analytical lab
Topics/Questions for Discussion • Stability Recommendations (20 minutes)
• Acceptance Criteria (20 minutes) • Do these acceptance criteria make sense? • When Do You Need to Revalidate? (20 minutes)
Stability Recommendations • Preprocessed Stability • Compare to nominal concentration • In-life administration • Including dose delivery system • Sample analysis • Storage stability • Freeze/thaw stability
• Postprocessed Stability • Compare to nominal concentration • After dilution into STD curve range • Reinjection
• Stock Solution Stability • Compare to freshly prepared stock • Needed if stocks are prepared in a solvent different from dosing formulation
Acceptance Criteria • Different formulation types necessitate different acceptance criteria • Solutions • 100 ± 10% recovery; RSD ≥10% • Suspensions • 100 ± 15% recovery; RSD ≥10% • Solids • 100 ± 20% recovery; RSD ≥15%
• Do these acceptance criteria make sense?
When Do You Need to Revalidate? • How much of a “formulation/method” change necessitates a revalidation for formulation stability? • • • •
• • • • •
Reagent supplier pH change Buffering capacity Container • Plastic vs glass beaker • Amber bottle vs foil wrapped bottle Particle size • Change in granulation procedure API manufacture change • Different impurity profile Change in concentration Change in analytical procedure Change in analytical lab
