Science-Based Stability and Packaging Development Under The Umbrella of QbD
Rey T Chern
Global Pharmaceutical Commercialization
Merck Sharp & Dohme
A systematic approach for characterization of product stability risks, selection of primary packages and utilization of first-principle modeling to manage stability outcomes is presented. The overarching framework of this approach focuses on three areas. First, controlled Product Characterization Studies (PCS) are performed to gain quantitative understanding of the impact of the factors including environmental conditions (e.g. temperature, relative humidity, oxygen, and light), formulation ingredients (e.g. API form, critical excipient impurities, etc.), and processing parameters (e.g. mechanical stress, drying, etc.) on the stability of the product.
Second, the primary containers under consideration are characterized quantitatively for their protective performance, specifically relevant to the stability drivers (e.g. moisture or oxygen transmission rate). Often, the critical environmental factors controlling the stability of oral products are temperature & water moisture. A model for quantitatively describing the time-course of water activity that the product is exposed to over the expected shelf life at the ICH testing conditions has been developed. This model, labeled as ?Simulation of Headspace Moisture Activity in Packages (SHMAP)?, is derived from the first principles of thermodynamics, mass balance, and mass transport dynamics. It has been verified by experimental data collected for >20 development projects in the past 10 years.
Third, the knowledge gained from PCS and SHMAP is combined to predict stability performance of the various product/primary-container combinations intended for registration. This approach allows for improved design of registration stability studies and enables projection of the stability-performance of new product-packaging configurations with a high degree of assurance since all needed scientific data input are available and controlled independently.
This approach for stability & primary package development is a good example of the application of Quality by Design principles.
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