1. Accurate Shelf-Life Predictions Using ‘ASAP’ (Accelerated Stability Assessment Program) Garry Scrivens, Ph.D. Pfizer Global R&D, Sandwich, UK [email_address] http://www.linkedin.com/pub/garry-scrivens/17/8a0/4a1
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4. ASAP: How Well Does it Work? Check predictions against real-time results
5. Prediction of Packaged Product Stability 2 tablets 15 tablets 15 tablets + desiccant open bottle Drug Product ‘A’ in 60-cc HDPE Bottles (40 C/75%RH) Lines: stability prediction Datapoints: Actual results
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7. Interpretation of E a Values E a = 13 Kcal/mol, degradation rate 2x between 25ºC and 35ºC E a = 25 Kcal/mol, degradation rate 4x between 25ºC and 35ºC E a = 38 Kcal/mol, degradation rate 8x between 25ºC and 35ºC E a = 16 Kcal/mol, degradation rate 2x between 65ºC and 75ºC E a = 32 Kcal/mol, degradation rate 4x between 65ºC and 75ºC E a = 49 Kcal/mol, degradation rate 8x between 65ºC and 75ºC (at constant RH) E a Term: a measure of the temperature dependence of the degradation 22 days 149 days 3 years 36 81 days 290 days 3 years 24 299 days 1.5 years 3 years 12 40 C 30 C 20 C E a (KCal/mol) Shelf-Life at Different Temperatures (Constant RH)
8. Interpretation of B Values B = 0.07, degradation rate doubles for every 10% RH increase B = 0.035, degradation rate doubles for every 20% RH increase (at a constant temp) B Term: a measure of the moisture dependence of the degradation 3 years 3 years 3 years 0.00 121 days 81 days 3 years 0.04 8 days 3 days 3 years 0.09 65%RH open bottle 75%RH open bottle bottle/desiccant B Shelf-Life at Different %RH Values (Constant T)
9. Example B-Values in Drug Products 0 1 2 3 0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.1 B-Value Number in Range Oxidation Cyclization Hydrolysis
10. Typical E a and B values (n=60 ASAP Studies) 29.8 0.043 (temperature-dependence) (moisture-dependence)
11. The formulation that performs best under traditional accelerated conditions may not perform the best under long-term stability conditions: Ln k (1/T) 25ºC 30ºC 40ºC 50ºC 60ºC ICH Formulation A Formulation B The ASAP approach can detect when this is the case
12. The main degradation product in traditional accelerated studies is not necessarily the shelf life limiting one in real-time: Ln k (1/T) 25ºC 30ºC 40ºC 50ºC 60ºC ICH Deg Prod A Deg Prod B The ASAP approach can detect when this is the case
![Accurate Shelf-Life Predictions Using ‘ASAP’ (Accelerated Stability Assessment Program) Garry Scrivens, Ph.D. Pfizer Global R&D, Sandwich, UK [email_address] http://www.linkedin.com/pub/garry-scrivens/17/8a0/4a1](https://image.slidesharecdn.com/asapgarryscrivenslinkedin-13056485103936-phpapp01-110517111044-phpapp01/85/stability-predictions-by-asap-1-320.jpg)
![Stability Prediction by ASAP ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)