Formulation and Stabilization of Biotherapeutics

Biotherapeutics are complex molecular species with numerous routes of both chemical and physical instability, which can manifest from discovery through development and manufacturing. Addressing these instabilities presents a sizable challenge, because of the complexity of the biotherapeutics themselves and the multiplicity of degradation mechanisms.

This course addresses those challenges, with a focus on mechanistic understanding leading to rational strategies for formulation and stabilization. Numerous modalities are addressed, from globular proteins and monoclonal antibodies to peptides, vaccines, antibody-drug conjugates, oligonucleotides, cell therapy, and gene therapy. Formulations can include liquid dosage forms that range from low to high concentration along with frozen and lyophilized compositions. Stability and drug delivery issues are presented including their association with packaging, devices, and bioprocessing. Cutting-edge approaches are also included, such as physico-chemical-based predictive methods and machine learning.

Certificate of Completion from MIT Professional Education

• Understand the fundamentals of stabilization of biotherapeutics or biologics, including degradation mechanisms, rational design, and formulation
• Incorporate approaches to streamline stabilization during discovery, development, and manufacturing in your company
• Determine analytical approaches needed to solve various problems
• Understand the potential for cutting-edge approaches and technologies for a variety of modalities from antibodies to globular proteins, from peptides to vaccines and antibody-drug conjugates

Program Outline

Please note that the course schedule is subject to change.

Day One

Session 1--1.5 hours
Introduction, Overview of Instability Issues and Their Relevance to Discovery and Product, Process, and Clinical Development; Physical Instability 

Session 2--1.5 hours
Chemical Instability: Analytics, Mechanism, and Control 

Session 3--1.5 hours
Physical Instability: Conformational, Colloidal, and Interfacial Mechanisms in Aggregation and Viscosity 

Session 4--1.5 hours
Instability Issues in Context, Break-out groups with problems, Report back, Initial Discussion of Projects 

Day Two

Session 5--1.5 hours
Overview of Analytical Methods: Methods to Characterize Aggregates and Particulates 

Session 6--1.5 hours
Rational Development of Low and High Concentration Liquid Formulations 

Session 7--1.5 hours
Regulatory Considerations for Biotherapeutics 

Session 8--1.5 hours
Formulation challenge, Break-out Groups, Report

Day Three

Session 9--1.5 hours
Rational Development of Frozen and Dried Formulations 

Session 10--1.5 hours
Case Studies in Addressing Formulation Challenges 

Session 11--1.5 hours
Addressing Stability Problems as they Relate to Biopharmaceutical Manufacturing and Packaging 

Session 12--1.5 hours
Break-out groups, Work on project, Report

Day Four

Session 13--1.5 hours
Special Formulation Challenges: Peptides, Vaccines, ADCs, RNA Products, PEGylated Products

Session 14--1.5 hours
Final Project Reports and Final Discussion

Links & Resources

News/Articles:

• Continuous drug manufacturing offers speed, lower costs - Professor Trout's other research developing a prototype continuous-manufacturing system
• Inside an innovation ecosystem - History, proximity, and serendipity make Kendall Square fertile ground for the next big idea.
• American made? - MIT forum examines the role of manufacturing in rebuilding the economy.
• Predictive tools for stabilization of therapeutic proteins

This course is targeted for scientists and engineers in biopharmaceutical discovery, development, and manufacturing. The course will be of particular benefit to those who wish to enhance their skills in rational approaches for stabilizing biotherapeutics. Those who should attend include:

• Formulation scientists from beginning to advanced
• Scientists and engineers who are interested in or need to understand stability issues
• Bioprocessing scientists and engineers
• Biotherapeutic discovery scientists and engineers who want to incorporate developability and manufacturability into biotherapeutic design
• Scientists and engineers interested in physical and chemical processes that occur with biomolecules
• Managers responsible for pharmaceutical development, manufacturing, and regulatory affairs