Cambridge Healthtech Institute’s Eleventh Annual

Lyophilization and Emerging Drying Technologies

Formulation and Process Optimization, Models, QbD, Delivery and Devices

January 9-10, 2018

 

The popular Eleventh Annual Lyophilization and Emerging Drying Technologies conference covers latest trends and challenges in lyophilization and emerging drying technologies. This conference will feature in-depth case studies, new and unpublished data and discussions on developing scientifically sound freeze dried formulation, process optimization for biologics and vaccines. It will also present cutting edge research and case studies on freeze/thaw and formulation challenges, drying in cartridges, storage stability, QbD and PAT approaches and strategies for scale-up from R&D scale to full production level, and selection of container closure systems. We are seeking cutting edge research findings and unpublished data to be featured at this forum.

We invite you to present a poster and attend to join with colleagues in this discussion of the key challenges and solutions in lyophilization and other drying technologies.

Final Agenda

In Memory of Michael "Mike" Pikal

 Dr. Michael Pikal, Emeritus Professor and former Department Head of Pharmaceutical Sciences at University of Connecticut, passed away on Monday, Feb. 26, 2018. He was a leader in the field of freeze-drying technology. He had been part of Lyophilization and Emerging Drying Technologies conference as a scientific advisor and eminent speaker since its inception. We will all miss him. We extend our sincere condolences to his family, friends, and the scientific community. 

– Cambridge Healthtech Institute (CHI)

TUESDAY, JANUARY 9

1:00 pm Registration

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing
Prediction of Stability in Freeze Dried Products: New Tools and Strategies

2:00 Chairperson’s Opening Remarks

Elizabeth M. Topp, Ph.D., Dane O. Kildsig Chair and Department Head, Department of Industrial and Physical Pharmacy, Perdue University

KEYNOTE PRESENTATION

2:05 Hydrogen Deuterium Exchange in Lyophilized Solids: Correlation with Protein Stability

Elizabeth M. Topp, Ph.D., Dane O. Kildsig Chair and Department Head, Department of Industrial and Physical Pharmacy, Purdue University

Solid-state hydrogen deuterium exchange with mass spectrometric analysis (ssHDX-MS) provides high resolution structural information for proteins in lyophilized solids. Recent studies with a lyophilized monoclonal antibody (mAb) show that deuterium incorporation is highly correlated with chemical and physical stability on storage, and will be presented here.

2:45 Prediction of Protein Stability in Lyophilized Formulations: Miscibility, Mobility, and Microenvironmental pH

Eric J. Munson, Ph.D., Patrick DeLuca Endowed Professor, Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky

The stabilization of proteins in lyophilized matrices requires that the protein and cryoprotectant, such as sucrose or trehalose, be in intimate contact with each other and have reduced mobility in the matrix, and that the buffer maintains the optimized solid-state ionization (i.e., pH equivalent). We have been using solid-state NMR spectroscopy to show that the stability of the protein, especially against aggregation, requires that the protein and cryoprotectant remain intimately mixed and relatively immobile.

3:15 Roles for Antifreeze Polypeptides in Optimizing Lyophilization Formulations and Protecting Stability of Proteins

Xin Wen, PhD, Professor, Department of Chemistry and Biochemistry, California State University, Los Angeles

In this talk, we will discuss the potential use of antifreeze polypeptides (AFPs) in optimizing lyophilized formulations and protecting stability proteins. Naturally produced by many cold-adapted organisms including fish, insects, and plants, AFPs are known for their ability to inhibit ice growth and recrystallization efficiently. We have demonstrated that AFPs can also control the crystallization of carbohydrates and nucleosides and protect proteins under extreme temperatures.

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 Predicting Stability of Freeze Dried Proteins Using Materials Dynamics

Marcus T. Cicerone, Ph.D., Biomaterials Group, National Institute of Standards and Technology

I will describe efforts in our lab towards understanding the fundamental connection between picosecond timescale, molecular length scale motions and protein degradation processes in lyophilized formulations. I will also discuss our efforts in developing benchtop methods to rapidly predict protein stability using this fundamental understanding.

5:00 New Tools for Prediction of Stability of Freeze Dried Products - A Cold Perspective

Miguel Ângelo Rodrigues, Ph.D., Researcher and Invited Professor, Chemical Engineering, Instituto Superior Técnico, University of Lisbon

Reactions that can compromise stability and quality of the freeze dried products happen within the ice structure. However, it’s difficult to correlate parameters with results, because of the complexity and intricate relation between thermodynamic and kinetic variables leading to cryoconcentration, cold-denaturation, precipitation or aggregation. Experimental and modeling approaches were developed to understand and anticipate some of these mechanisms, which can assist the development of more rational formulations and optimized freeze drying procedures.

5:30 Close of Day

5:30 - 5:45 Short Course Registration

5:45 - 8:45 Dinner Short Courses*

* Separate registration required

WEDNESDAY, JANUARY 10

8:00 am Registration and Morning Coffee

Models and Tools for Process Design, Scale Up and Technology Transfer

8:30 Chairperson’s Remarks

Xiaofeng Lu, Ph.D., Principal Research Scientist, Pharmaceutical Development, AbbVie, Inc.

8:35 Optimizing the Vial Heat Transfer Coefficient for Pharmaceutical Freeze Drying: A Case Study Illustrating a New Press-Blow Technique for the Manufacturing of Molded Vials

Tim Wenzel, Scientist, Ph.D. Candidate, University of Erlangen GILYOS GmbH on behalf of Henning Gieseler, Ph.D., CSO, Pharmaceutical Development, GILYOS GmbH

The vial heat transfer coefficient (Kv) serves as a key parameter to assess the total heat flow to a vial during primary drying. The present case study discusses the heat transfer characteristics of a vial manufactured by a blow-blow and new press-blow process, and subsequently discusses the impact of such a design and manufacturing features on Kv. The results clearly suggest a significant impact of the manufacturing technique on Kv.

9:05 Freeze Drying of a Low Tg’ and High Fill Protein Drug Product: The Critical Role of Freezing on Primary Drying Process Performance and Final Product Quality Attributes

Xiaofeng Lu, Ph.D., Principal Research Scientist, Pharmaceutical Development, AbbVie, Inc.

Development of an efficient and robust freeze drying cycle was challenging for low Tg’ and high fill protein drug product. A regular freezing protocol resulted in a long primary drying process and undesired product appearance. In this presentation, the critical role of freezing conditions on primary drying process performance and product quality attributes will be demonstrated. An effective freezing protocol will be recommended to achieve an efficient primary drying process and desired product quality attributes.

9:35 Emerging Drying Techniques for Manufacturing of Pharmaceutical Biologics

Qi (Tony) Zhou, Ph.D., Assistant Professor, Industrial and Physical Pharmacy, Purdue University

Traditional lyophilization is a batch and time-consuming process with low energy consumption efficiency. There are increasing interests to develop emerging drying techniques that have higher processing efficiency and lower costs while maintain product quality. A few drying techniques have been attempted such as spray drying and spray freeze drying. This talk will discuss the advantages and disadvantages of these emerging drying techniques for the application of biologics.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 Use of Model in Process Design and Scale-Up: A Case Study Using Lab, Pilot and GMP Equipment

Alina Alexeenko, Ph.D., Professor, School of Aeronautics and Astronautics, Purdue University

In this presentation, we will discuss use of model in process design and scale up. We will present a case study of freeze-drying cycle variations for lyophilizers of different scale and cleanroom environment using a typical protein formulation.

11:20 Lyophilization Development of a High Concentration Antibody Formulation: Technology Transfer from Lab to Pilot Plant

Akhilesh Bhambhani, Ph.D., Principal Scientist & Group Leader, New Technologies-Vaccine Drug Product Development, Merck & Co., Inc.

Recommendations for a successful scale-up of a high concentration mAb will be shared with emphasis on a) formulation characterization, b) product and process design space, c) significance of engineering runs and d) robust manufacturing process.

11:50 Process Monitoring by Mass Spectrometry during Freeze Drying

Jason Stewart, BS, Senior Associate Scientist, Pharmaceutical Research and Development, Pfizer, Inc.

Mass spectrometry has emerged as a key technology for the detection of trace levels of silicone oil in freeze drying chamber. With the capability of measuring low molecular mass gasses such as water and nitrogen, mass spectrometry positions itself to be a powerful tool for monitoring the entire drying process.

12:20 Lyophilisation of High Concentration Protein Formulations: Excipient Selection and Challenges

Valeria Gervasi, PhD Candidate, School of Pharmacy, Synthesis & Solid State Pharmaceutical Centre,University College Cork

The design of lyophilisation process for high concentration protein formulations can be challenging due to the necessity of employing products with high total solute concentration, resulting in high cake resistance. Excipient selection and modelling approaches, as well as the identification of critical parameters for the optimization of the lyophilisation process, can aid the efficient manufacture of a stable product with prolonged shelf-life.

12:35 Enjoy Lunch on Your Own

Advances in Ice Nucleation, Visual Inspection and Reconstitution Challenges

2:00 Chairperson’s Remarks

Theodore W. Randolph, Ph.D., Kenneth and Genevieve Gillespie Professor, Department of Chemical and Biological Engineering, University of Colorado, Boulder

2:05 Secondary Ice Nucleation as the True Driver for Product Heterogeneity When Controlling Ice Nucleation in Pharmaceutical Freeze Drying

Tim Wenzel, Scientist, Ph.D. Candidate, University of Erlangen GILYOS GmbH

The common ground for controlled ice nucleation technologies in freeze drying is that they can only control primary nucleation. However, formation of the ice network throughout the product solution determines the overall drying performance and product quality. To obtain optimum homogeneity, secondary nucleation and ice crystal growth must be controlled post primary nucleation. Impact factors and appropriate process set-up for two pressure-dependent nucleation technologies will be discussed.

2:35 Methods to Reduce the Reconstitution Time of High Concentration Lyophilized Protein Therapeutics

Jacob Luoma, Engineer II, Pharmaceutical Processing and Technology Development, Genentech

There is increasing interest in producing high concentration lyophilized protein therapeutics. Since reconstitution time increases as protein concentration increases, the product may become inconvenient to use in the clinic if reconstitution time is not addressed. This talk will review methods that Genentech has evaluated for reducing reconstitution time.

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 SELECTED POSTER PRESENTATION: CFD Simulation and Verification for Local Pressure over Vials During Lyophilization at Laboratory Scale

Tatsuhiro Kodama, Ph.D. Visiting Scholar, Birck Nanotechnology Center, Purdue University

4:30 Characterization of Universal Stabilized Stem Flu Vaccine Candidates

Sashikanth Banappagari, Ph.D., Scientist II, Formulation Development, Vaccine Production Program/VRC/NIAID/NIH

The Vaccine Research Center at the NIH has developed a series of pandemic flu vaccine candidate centered around self-assembling Ferritin-Hemagglutinin nanoparticle (HAF), intended to elicit responses across multiple influenza strains. This study describes a multi-valent biophysical characterization using CD, DSC, FTIR, Fluorescence and 2D UV. The data generated describes the basal physico-chemical properties, providing a basis for optimal formulation design and also to monitor vaccine quality during development and manufacturing.

5:00 Considerations for Assessment of Particles in Biologics Originating from Packaging and Standardization Initiatives

Diane Paskiet, MS, Director of Scientific Affairs, Scientific Affairs and Technical Services, West Pharmaceutical Services

It is critical to understand the types and sources of particulates in biologic products and how their presence may affect product quality and patient safety. The linkage between particles, biologic formulation and packaging development involves understanding contributions from all sources. This presentation will provide insight into measurements of particles originating from packaging components, comparison of data from various technologies and USP standardization initiatives.

5:30 - 6:45 Networking Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Lyophilization and Emerging Drying Technologies Conference