In this presentation, LCM exercise for post-approval change of liquid drug substance into frozen platform will be discussed. Development efforts, engineering solutions, and filing strategy will be described.

Donnan and volume exclusion effects during ultrafiltration and diafiltration of highly concentrated proteins can cause a large shift of pH and composition from the target formulation. In order to predict and compensate for those effects, a mechanistic model is developed and example applications of the model will be given. The model can be used to understand the extent of Donnan and volume exclusion effect as a function of the protein characteristics and formulation conditions, and as a tool to design the process and control strategy to achieve target formulation in UF/DF operation. 

Protein-based therapies hold an enormous potential for treating many terminal diseases. Nevertheless, the lack of universal technological approaches that enable development of protein formulations with the targeted attributes significantly impedes clinical translation of these advanced therapies. This presentation will overview the use of droplet-based microfluidic technology for developing protein formulations with pre-programmed functional characteristics, including size and internal morphology, encapsulation efficiency, and protein release profile. In addition, an overview of microfluidic devices offering accurate and cost-effective measuring antibodies in blood samples will be provided. 

Biologics drug development has experienced rapid growth in recent years. To meet the need, biologics formulation development has quickly acquired a set of automation tools and analytical techniques to provide robust drug products for patients. The push for more effective therapeutics and better patient care options has demanded higher concentrations. This has motivated adaptation of our tools to meet the increases in process complexity for the benefit of patients globally.

Conversion of tedious, manual assays into automated highthroughput workflows typically consists of large capital expenditures on hardware that also require a significant investment in training of personnel and equipment. By strategically leveraging and refitting existing instruments, we efficiently converted commodity assays that focused on sample preparation and analysis into a robust, high throughput approach. Advancements in digital sample management and data capture were required to keep pace with increased sample throughput.

Forced degradation of proteins are carried out to understand degradation pathways, the effect of exposure to conditions other than those proposed for storage and manufacturing, demonstrate specificity of stability indicating assays, and understand critical quality attributes. This presentation describes the development of an automated forced degradation workflow of therapeutic proteins. This workflow has significantly reduced scientist in-lab time, increased efficiency of our process, and reduced time to complete each study.