Webinar Abstract

Formulation development often focuses on developing a solution formulation because it is considered the quickest to proceed to clinical trials. However, formulation development for solutions and lyophilized solids initially follow the same path. This study examines an antibody drug conjugate (ADC) prepared at 10 mg/mL to determine if it could be formulated as a solution or as a lyophilized solid. A statistical design of experiments was utilized to decrease the number of formulations needed for the study and to conserve materials. A 2-week, accelerated stability study was conducted to examine the effect of the buffer type, buffer concentration, and pH on the stability of the formulation. The data were used to identify the best formulation candidates to examine using a lyophilization feasibility study that also examined the effect of the carbohydrate concentration on the stability of the lyophilized solid. A heat flux sensor can be utilized at development-scale to construct a design space for primary drying. The design space utilizes the critical product temperature for the formulation and is suitable for supporting lyophilization of the product at full-scale.

Highlights

• Statistical design of experiments for an ADC
• Examination of experimental data to facilitate a formulation decision
• Creation of a primary drying design space using data from a heat flux sensor

Dr. Gregory Sacha is a global senior scientist for Simtra Biopharma Solutions and has been a member of the company for 20 years. Dr. Sacha has over 26 years of experience in the pharmaceutical industry with expertise in injectable drug product development. Greg serves as the technical expert for Simtra and leads formulation and process development at their sites in Bloomington, IN, and in Halle, North Westfalen, Germany. He and his team are especially well-versed in lyophilization process development where they follow a design space approach to primary drying cycle development. Greg supports manufacturing operations through his expertise in lyophilization and also through isolation and identification of particles. Greg directed a short course titled Sterile Products: Formulation, Manufacture and Quality Assurance and developed a lyophilization workshop. He and the development teams at Simtra are active members of LyoHUB where they lead the development of best practice papers on lyophilization operations.

Spencer Holmes is an Applications Engineer at Millrock Technology, where he works with the engineering team to continually develop and improve new tools for both analyzing the thermal dynamics of freeze-drying and optimizing lyophilization protocols. Spencer’s main area of focus is the MicroFD and LyoPAT, and he also instructs lyophilizer operators in how to use these technologies to analyze and optimize their lyophilization cycles. Spencer graduated from Northeastern University in 2017 with a BS in Chemical Engineering.