Course Detail

  This course will introduce students to downstream processes for development of biopharmaceutical products. Increasing scope of biotechnology derived products has been taken into consideration in designing this course that will provide knowledge and skills necessary for obtaining a thorough understanding of downstream processing of protein and peptide based biologics, including vaccine products. Comprehensive understanding of purification techniques, formulation design, recent advances in analytical methods for characterization, stability analysis and delivery of protein and peptide based drugs will be provided based on case studies of commercial products. The course consists of lectures, case studies, literature review, student presentations/group discussions and laboratory excercises.

Recommended Reading:
Published articles relevant to individual topics taught will be provided.

• Instability of liquid protein pharmaceuticals: stabilization and formulation.
• Formulation considerations for proteins susceptible to asparagine deamidation and aspartate isomerization.
• Role of formulations in insulin comparability assessments - Eli Lilly's experience.
• Stability of insulin Lispro (Eli Lilly) in insulin infusion systems.
• Antibody structure, instability and formulation.
• Comparative study of biological activities of intravenous immunoglobulin preparations manufactured by different processes.
• Characterization, formulation and stability of Amgen's Neupogen.
• Development and shelf-life determination of Immunex's Leukine.
• Stability characterization and formulation development of Genentech's Pulmozyme.
• Development of Wyeth's manufacturing process for commercial production of Benefix: bioprocessing, biochemical characterization, formulation and viral safety.
• Novel adjuvants and formulation of vaccines.
• Choice of product specific analytical methods for product characterization for quality control and regulatory submission.
• Preparation of dossier for regulatory submission of analytical data for biological products.
• Novel delivery technologies for protein and peptide therapeutics, important factors for a successful delivery system for proteins, emerging strategies for delivery of peptide and protein drugs and commercial challenges of protein drug delivery.
• Development of a novel product Exubera (Pfizer and Nektar Therapeutics) for pulmonary delivery of insulin.
• Biophysical comparability of the same protein from different manufacturers: Epoetin alfa from Epogen (Amgen) and Eprex (Ortho Biotech).

Laboratory Exercises:

• Purification of antibody by Protein A affinity chromatography and characterization of the product.
• Characterization and quality control of proteins in a product development environment: Analysis and batch consistency studies using various analytical techniques such as SDS-PAGE, analytical HPLC and mass spectrometry.
• HPLC and mass spectrometric analysis of a peptide based dietary supplement.
• Formulation of a protein antigen with an adjuvant for vaccination/immunization.

Optional Field Trips:

• Visit a protein or peptide drug manufacturer.

Students will gain specific knowledge about downstream processes for the production of proteins and peptide based biologics at development/production scale. Students will gain expertise in procedures for purification and formulation of the products as well as analytical tools to evaluate the purity, structure and biological activity of protein and peptide products. They will acquire a clear understanding about presentation of technical data for regulatory submission. They will gain hands on experience on a number of protein/peptide preparative and analytical techniques. They will also learn what the real issues are in downstream processes for production of biologics, and what techniques can be used to improve product quality and efficacy.

Classroom attendance and participation in discussion   20%
Oral presentations   20%
Written reports   20%
Laboratory Exercises 20%
Quizzes on Lecture and Practical 20%