Risk-Based Predictive Stability for Pharmaceutical Development–A Proposed Regulatory Template

• Published in: Pharmaceutical Technology 2018-08, Vol.42 (8), p.42-47
• Main Authors: Stephens, Dennis, Williams, Helen, McMahon, Megan, Qiu, Fenghe, Hyzer, Cherokee Hoaglund, Debie, Elke, Wu, Yan, Li, Hanlin, Wang, Jin
• Format: Magazinearticle
• Language: English
• Subjects: Consortia; Drug dosages; Humidity; Pharmaceutical industry; Pharmaceutical sciences; Product development; Quality; R&D; Research & development; Risk assessment; Software; Temperature; Working groups
• ISSN: 1543-2521; 2150-7376

The resulting open-dish data were fit to a humidity-corrected Arrhenius equation using ASAPprime Version 5.0 [a lternative commercial or inhouse software may be used]: (ProQuest: ... denotes formula omitted.) [Eq. 1] Where k is the degradation rate, A is the Arrhenius collision frequency, Ea is the activation energy for the chemical reaction, R is the gas constant, T is the temperature in Kelvin, B is a humidity sensitivity constant, and RH is relative humidity. The stability understanding gained from a well-designed RBPS study generally exceeds knowledge gained from a three-month time point data at the long-term storage and traditional accelerated conditions (4 0 °C/75% RH). [...]shelf-life predictions supported by RBPS studies are considered conservative, because typically, the predicted shelf-life limiting attribute will not breach the acceptance limit until well beyond the assigned shelflife. Dennis Stephens is director, Combination Product Development at AbbVie; Helen Williams is associate principal scientist, Pharmaceutical Technology and Development at AstraZeneca; Megan McMahon is director at Pfizer, Inc.; Fenghe Qiu is senior research fellow at Boehringer Ingelheim; Cherokee Hoaglund Hyzer is senior research advisor at Eli Lilly & Company; Elke Debie is manager, CMC Regulatory Affairs at Janssen Pharmaceutica R&D, a division of Janssen Pharmaceutica NV; Yan Wu is principal scientist at Merck & Co., Inc.; Hanlin Li is associate director at Vertex Pharmaceuticals; and Jin Wang is regulatory program manager Pharma Technical Regulatory at Genentech. IQ is a not-for-profit organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators, and the broader research and development community.