The Application of Science- and Risk-Based Concepts to Drug Substance Stability Strategies

Lean Stability Approaches in Pharmaceutical Product Development, Registration, and Post-marketing CMC Change Management; Industry Survey Insights

“…The way forward in addressing the internal variabilities lies in enhanced knowledge-sharing across industry. Several case studies documenting successful adoption of lean stability approaches are available in the external literature [8][9][10][11][12][13][14][15][16]. These examples can drive change within industry as the strategies described become embedded in quality documentation and processes.…”

“…Pharmaceutical companies that responded to the IQ Consortium lean stability survey publications have described opportunities (case studies) for application of LSS during the clinical development lifecycle[8,[15][16][17]. Inspired by these success stories and based on greater product understanding during earlier stages of development and availability of predictive tools, pharmaceutical companies have increased the use of lean strategies in their regulatory submissions.Based on the survey conducted, 89% (17/19) of the companies surveyed have successfully utilized LSS in support of clinical trial application (CTA) submissions.…”

A Scientific and Statistical Analysis of Accelerated Aging for Pharmaceuticals. Part 1: Accuracy of Fitting Methods

“…Determining the stability of drug substances and drug products is one of the critical, and at times, gating elements in the drug development process. In recent years, new protocols and mathematical models have been applied to the use of accelerated processes for rapidly determining the chemical stability of APIs and drug products both in solution and solid state . With the increased use of these models, it is appropriate to consider the implications of different methodologies in terms of both the statistics and science involved.…”

“…In recent years, new protocols and mathematical models have been applied to the use of accelerated processes for rapidly determining the chemical stability of APIs and drug products both in solution and solid state. [1][2][3][4][5][6][7][8][9][10] With the increased use of these models, it is appropriate to consider the implications of different methodologies in terms of both the statistics and science involved. In Part 1 of this detailed examination, the ability of different models to accurately estimate shelf-life is determined on a theoretical basis.…”