Senior Principal Scientist Pfizer Inc. Chesterfield, Missouri
Despite the rapid transition of Adeno-associated Virus-based (AAV) gene therapy (GTx) products to clinic, there are unique challenges that still remain to be overcome by pharmaceutical engineers/scientists to realize the full potential of gene therapy. Some of the challenges include limited understanding of product quality attributes, lack of platform formulation and a flexible drug product fill-finish process to support small batches of incoming drug substance, and scarcity of representative material for product development. Due to the complex and delicate nature of AAV, an ideal formulation should preserve not only the physical and chemical stability of the capsid and transgene of interest, but most importantly promote infectivity/expression and enhanced transduction of target cells/tissues. A systematic screening of formulation attributes (pH, buffer and excipients) using the current Pfizer GTx candidates provides valuable information towards development of a platform formulation for GTx. To facilitate this process, a biophysical characterization tool kit was assembled to retrospectively assess the biophysical attributes that drives the biological function of AAV. In addition to the update on the formulation development, this presentation will also cover the current challenges and capabilities for early and late stage drug product manufacturing.
Describe advances and gaps in formulation and manufacturing of novel modalities
Describe the formulation tools and strategies applied for novel modalities
Demonstrate various analytical and regulatory challenges during formulation development and manufacturing