Ongoing Challenges to Develop High Concentration Monoclonal Antibody-based Formulations for Subcutaneous...

Area of Science:

• Biopharmaceutical Formulation
• Drug Delivery Systems
• Monoclonal Antibody Therapeutics

Background:

• High-concentration antibody formulations (HCAF) delivered subcutaneously (s.c.) are commercially successful.
• Developing new mAb-based candidates for s.c. HCAF faces formulation challenges impacting stability, viscosity, manufacturability, bioavailability, and immunogenicity.

Purpose of the Study:

• To address the key challenge of maximizing drug dosage in subcutaneous high-concentration antibody formulation development.
• To examine methods for increasing protein concentration and/or delivered volume in s.c. HCAF.

Main Methods:

• Review of methodologies for increasing protein concentration in antibody formulations.
• Analysis of strategies to increase the volume of s.c. administered drug products.
• Discussion of combined approaches to maximize dose delivery.

Main Results:

• Key hurdles in HCAF development include physical protein instability and limitations in solution volume.
• Strategies to increase protein concentration and delivery volume are crucial for maximizing s.c. dosage.

Conclusions:

• Overcoming protein instability and volume constraints is essential for successful s.c. HCAF development.
• Recommendations are provided to aid formulation scientists in developing s.c. HCAF for new mAb candidates.