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By Bakul Bhatnagar and Pankaj Paranjpe

Freeze-drying, or lyophilization, is the most widely utilized drying method for improving the stability of biopharmaceuticals. As our knowledge of freeze-drying science has improved, there have been increased and focused efforts to move from trial-and-error-based approaches to rational formulation design and process development for lyophilized biologics.

Lyophilization processing times can be long and are typically on the order of days, or even weeks in the case of poorly designed formulations and/or processes. In such scenarios, a combination of rational formulation and process strategies can be suitably employed to design efficient lyophilization processes. Over the years, researchers engaged in freeze-drying have faced unique challenges arising from the stochastic nature of the freezing process, heterogeneity in drying behavior, incomplete understanding of protein stability in the dried state, and long, variable reconstitution times of highly concentrated, lyophilized proteins.

shutterstock_194781299shutterstock_199242089An improvement in our understanding of the science of freeze-drying, coupled with the availability of newer technologies, has also led to the development of approaches to increase drying rates, decrease cycle duration, and enhance process efficiency. The introduction of controlled nucleation approaches during freezing has enabled the formation of larger ice crystals that facilitate faster ice sublimation, formation of larger pores in the cakes, and more homogeneous drying behavior. Efforts have also focused on the use of higher drying temperatures (either close to or above the collapse temperature) to increase the ice sublimation rates in high concentration protein formulations without compromising protein stability. Further, there have been advances in understanding the roles of mobility (global and local), protein structure, and surface effects (in addition to formulation and processing effects) on stability in the dried state. Systematic approaches have been developed to understand and mitigate long reconstitution times in the case of highly concentrated lyophilized proteins.

In recent years, the potential of other drying technologies (for example, spray drying, microwave drying, and foam drying) as alternatives to freeze-drying have been evaluated. In the upcoming 2015 AAPS National Biotechnology Conference short course, Recent Advances in Freeze-Drying of Biopharmaceuticals, we have identified several categories of newer advances that we hope the current practitioners and students of freeze-drying will find interesting and attractive. Join us for this short course on June 11 to learn about some of these key developments in the field of lyophilization in recent years. The emphasis of the course will be on recent advances with lectures centered on the following topics:

  1. Current/future challenges in lyophilization
  2. Use of controlled ice nucleation during freezing
  3. Application of aggressive drying processes and their impact on the stability of biologics
  4. Learning beyond the ABCs of scale-up and tech transfer
  5. Efforts to understand reconstitution behavior of highly concentrated, dried proteins
  6. Advances in PAT tools to monitor lyophilization processes

This course is recommended for colleagues currently engaged in freeze-drying within academia and industry. Join us to learn more!

Bakul Bhatnagar, Ph.D., works within BioTherapeutics Pharmaceutical Sciences at Pfizer where he is engaged in the formulation and process development of liquid and lyophilized biopharmaceuticals. He serves on the Steering Committee of the AAPS Sterile Products focus group.
Pankaj Paranjpe, Ph.D., is in the Biologics/Drug Product Development group at Celgene, where he is involved in pharmaceutical development and tech transfer to manufacturing sites for early to late stage molecules. He is the current chair of the AAPS Sterile Products focus group.