(160c) Science-Based Stability and Packaging Development Under the Umbrella of QbD

Abstract

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.