Cambridge Healthtech Institute’s 9th Annual
Lyophilization and Emerging Drying Technologies
Formulation Development, QbD, Process Optimization and
Delivery and Devices Challenges
January 19-20, 2016
The popular Lyophilization and Emerging Drying Technologies conference covers latest trends and challenges in lyophilization, spray drying, foam drying and emerging drying technologies. This conference features in-depth case studies,
new and unpublished data and discussions on developing scientifically sound formulation, process optimization for biologics and vaccines. It also presents cutting-edge research and case studies on freeze/thaw and formulation challenges, drying
in cartridges, storage stability, Quality by Design approaches and strategies for scale-up from Research & Development scale to full production level, and selection of container closure systems.
Final Agenda
TUESDAY, JANUARY 19
1:00 pm Conference Registration
2:00 Chairperson’s Opening Remarks
Serguei Tchessalov, Ph.D., Associate Research Fellow, Biotherapeutics Pharmaceutical Research & Development, Pfizer, Inc.
KEYNOTE PRESENTATION
2:05 Freeze Dryer Operational Qualification to Allow Science Based Scale-Up and Quality by Design
Michael Pikal, Ph.D., Distinguished Endowed Chair in Pharmaceutical Technology & Professor of Pharmaceutics,
University of Connecticut
Traditionally, freeze dryer qualification has involved studies of shelf temperature variation under no load conditions and testing whether or not the condenser can “hold” the intended mass of ice. However, this testing does not allow
meaningful science based scale-up and therefore is insufficient for supporting “Quality by Design”. The use of science-based operational qualification protocols in facilitating scale-up and definition of “Design Space”
will be discussed.
2:45 Quantifying Pressure Variation and Convection Effects in Lyophilization
Alina A. Alexeenko, Ph.D., Associate Professor, School of Aeronautics and Astronautics, Purdue University
Control of the chamber pressure is critical for maintaining a desired product temperature and sublimation rate during primary drying. Typically chamber pressure is measured at a fixed location, normally through a port at the top of the freeze dryer,
and controlled by introducing non-condensable gas. We examine the pressure variation within chamber, the resulting flow patterns and effects on drying rate and uniformity.
3:15 Refreshment Break in the Exhibit Hall with Poster Awards
4:00 New Breakthroughs in Understanding Freeze Drying Heat Transfer for Better Protocol Transfer
T.N. Thompson, President, Millrock Technology, Inc.
One variable that affects freeze drying times is batch size. As the number of vials is reduced the drying time decreases, therefore a critical mass of vials has been required for protocol development. In this presentation, we will discuss a new
methodology using as few as 19 vials to simulate the heat transfer dynamics of much larger freeze dryers. The technique shows promising results which will allow development of transferrable protocols to laboratory and production freeze dryers.
4:30 Variation in Heat Flow to Vials within a Batch is a Complex Function of Shelf Temperature and Chamber Pressure in a Laboratory Freeze-Dryer
Robin Bogner, Ph.D., Associate Professor, Pharmaceutical Sciences, School of Pharmacy, University of Connecticut
Heat flows from the temperature-controlled shelves and other non- controlled surfaces to the vial for sublimation of ice from the product during primary drying. While the batch average heat flow is relatively independent of shelf temperature,
the position-dependent heat flow is highly dependent on shelf temperature. The variation in “soak time” added to the calculated primary drying time will be discussed relative to design space development.
5:00 Effect of Pressure upon Secondary Drying Rate
Jim Searles, Ph.D., Technical Fellow, Global Manufacturing Science and Technology, Hospira
The scientific literature suggests that pressure has little or no impact upon the final moisture content or the holding time needed to achieve it. However the past work was over a relatively narrow pressure range. This presentation will
include new data, over a wider pressure range, that does indeed show an effect of chamber pressure.
WEDNESDAY, JANUARY 20
8:00 am Conference Registration and Morning Coffee
8:30 Chairperson’s Remarks
Robin Bogner, Ph.D., Associate Professor, Pharmaceutical Sciences, School of Pharmacy, University of Connecticut
⊲ Featured Presentation
8:35 Freezing and Drying of Protein: What We Know, What We Think We Know, and What We Don’t Know
Evgenyi Shalaev, Ph.D., Research Investigator, Pharmaceutical Development, Allergan Inc.
Many therapeutic proteins are stored as either frozen solutions (common for protein drug substance) or freeze-dried powders, to achieve an acceptable shelf life. However, freeze/storage/thaw and freeze-drying/storage/reconstitution
can (and does) result in protein destabilization. Such destabilization, as is currently believed, could be associated with ice formation. The presentation provides a critical overview of the existing data and formulates specific
questions to be addressed in future studies.
9:05 Poster Presentation: Predicting Vial-to-Vial Variation in Maximum Temperature and Drying Time Within a Lyophilized Product Batch During Primary Drying
Pooja Sane, Ph.D. Candidate, Department of Pharmaceutical Sciences, University of Connecticut.
Our long-term objective is to develop a mathematical model for determining a priori variation in product quality of lyophilized products. The aim of this report was to measure variation in key process parameters for a model formulation;
then using a probability analysis, combined with a first principles model of primary drying determine the distribution of drying times within a batch at realistic operating conditions. The agreement of the predicted drying
times with experimental results were used to assess the model.
9:20 Poster Presentation: Continuous Intensified Lyophilisation
Andrew Tait, MEng, Postgraduate Research Engineer, Biopharmaceutical Bioprocess Technology Centre, Newcastle University
Intensification of the current lyophilisation process to increase the heat and mass transfer capabilities has been achieved by reducing the volume scale from millilitre filled vials to nanolitre monodispersed droplets. The increased
surface area to volume ratio resulted in rapid freezing and drying. The batch process will be made continuous by integrating the atomisation of the feed solution, freezing, and drying stages. Greater process control can assure
improved product uniformity through enhanced characterisation and modelling.
9:35 Sponsored Presentation (Opportunity Available)
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Advances in Alternative Drying Technologies to Lyophilization for Biotherapeutics Applications
Satoshi Ohtake, Ph.D., Senior Director, Pharmaceutical R&D, BioTherapeutics Pharmaceutical
Sciences, Pfizer, Inc.
Lyophilization is the gold standard for processing of biologics to enhance stability. Spray drying and spray freeze-drying technologies have been evaluated in comparison to vial lyophilization for process efficiency and physical
properties of the solid dosage form produced. Initial feasibility results suggest benefits and promise for their use and implementation in the biotechnology industry.
11:20 New Life of Spray Freeze-Drying- Application to Dehydration of Protein Solutions
Serguei Tchessalov, Ph.D., Associate Research Fellow, Biotherapeutics Pharmaceutical
Research & Development, Pfizer, Inc.
Spray-freeze drying of biological materials is well documented in the literature. Until recently, however, no commercial application of this method has been demonstrated. Advances in high-throughput spray nozzle design in combination
with rotary drying could potentially support implementation of this method to large scale manufacturing. Examples of spray-freeze drying of protein solutions, including low collapse materials, will be provided, focusing on
improvement of product characteristics and process economics.
11:50 Co-Presentation: Integrated Heat Flux Measurements as a Non-Invasive Monitoring Technique for Freeze Drying
T.N. Thompson, President, Millrock Technology, Inc.
Ilona Konrad, Ph.D., Coriolis Pharma
We critically evaluated heat flux measurement (HFM) for its ability to non-invasively monitor freeze drying processes. It was shown that integrated HFM is a reliable new tool to record Tp during primary drying, to detect nucleation
events and to determine the end of primary drying. Besides studying robustness and linearity of different types of sensors at different shelf positions we were also able to investigate effects of formulation parameters on Kv.
12:20 pm Sponsored Presentation (Opportunity Available)
12:50 Session Break
1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
Michael Pikal, Ph.D., Distinguished Endowed Chair in Pharmaceutical Technology and Professor, Pharmaceutics, University of Connecticut
2:05 Investigating Structure and Dynamics of Proteins in Amorphous Phases Using Neutron Scattering
Maria Monica Castellanos, Ph.D., Research Associate, Institute of Bioscience and Biotechnology Research, NIST Center for Neutron Research, National Institute of Standards and Technology
Neutron scattering is an established technique to study structure and dynamics of materials in various phases. In this talk I will outline our work to study protein structure and dynamics at high concentration, frozen, and
in lyophilized phases. Through the use of contrast methods, small-angle neutron scattering has proven useful to determine the packing and sequestration of proteins in solid phases. Our work is complemented using molecular
simulation technology.
2:35 Atmospheric Spray-Freeze Drying (ASFD): A New Approach to Drying Pharmaceuticals
Thomas Robinson, M.D., Managing Director, Aerosol Therapeutics, LLC
Atmospheric Spray Freeze Drying (ASFD) is an innovative, “next generation” process with broad potential. The process yields a fine, uniform powder from a solution. Specifically, the patented ASFD process promises
an efficient, cost effective alternative to standard manufacturing. It should be ideal for heat sensitive products and, especially, the more expensive, easily degraded proteins. The more expensive and fragile the molecule,
the greater should be the economic benefit.
3:05 Case Study: Optimize Protein Stability by Formulation and Lyophilization Process Design
Charlie (Xiaolin) Tang, Ph.D., Director, Formulation Development, Regeneron Pharmaceuticals,
Inc.
Different formulations and lyophilization cycles are used for freeze drying a monoclonal antibody protein. Protein aggregation formation was observed after lyophilization. Experiments were performed to understand the stress
to protein during different stages of lyophilization process including stages of freezing, annealing, primary drying and secondary drying. The specific lyophilization stages were identified to have the most stresses to
cause protein aggregation formation. By optimization of the freeze drying cycle and protein formulation, the protein degradation was minimized.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:30 Application of Controlled Nucleation during Lyophilization to Improve Cake Appearance and Protein Stability
Bingquan (Stuart) Wang, Ph.D., Senior Scientist, Technical Development, Biogen
It has been well understood that controlled nucleation could result in a lower cake resistance due to the formation of larger ice crystal and thus a shorter primary drying cycle. This case study examined the performance of
controlled nucleation using several different proteins, and the quality attributes were compared side-by-side to those from the cycle without controlled nucleation. Improved product quality attributes including cake appearance,
recon time and stability will be presented.
5:00 Lyophilized Drug Product Cake Appearance: What is Acceptable?
Sajal M. Patel, Ph.D., Senior Scientist, Formulation Sciences, Biopharmaceutical Development,
MedImmune, Inc.
6:30-7:30 Reception in the Exhibit Hall with Poster Viewing
7:30 Close of Conference