January 18-22, 2016 | Town and Country Resort Hotel | SAN DIEGO, CA 
January 18-22, 2016 | Town and Country Resort Hotel | SAN DIEGO, CA 

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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 This conference features in-depth case studies, new and unpublished data and discussions on developing scientifically sound formulation, process optimization for biologics and vaccines.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. We are seeking cutting-edge research findings and unpublished data to be featured at this forum.

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

Final Agenda

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TUESDAY, JANUARY 19

1:00 pm Conference Registration


QUALITY BY DESIGN (QbD) AND PAT IN FREEZE DRYING

2:00 Chairperson’s Opening Remarks


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.

4:15 Sponsored Presentation (Opportunity Available)

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.


5:30-5:45 Short Course Registration

5:45-8:45 Dinner Short Courses


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WEDNESDAY, JANUARY 20

8:00 am Conference Registration and Morning Coffee


ADVANCES IN LYOPHILIZATION AND ALTERNATE DRYING TECHNOLOGIES

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 Microheterogeneity in Frozen and Desiccated Formulations

Alptekin Aksan, Ph.D., Associate Professor, Mechanical Engineering, University of Minnesota

To minimize damage to biologicals during freezing, drying and storage protectants are added to the formulation or biospecimen. Physical separation of the biological from the cryo-/lyoprotectant usually occurs. Furthermore, these phenomena may cause spatial variations in distributions of the different phases and excipients. The spatial variations in local phase and composition in frozen or desiccated medium is called microheterogeneity. This talk focuses on the detection and minimization of microheterogeneity in frozen and desiccated systems.

9:35 Sponsored Presentation (Opportunity Available)

10:05 Coffee Break with a Poster Pavilion

PepTalk is proud to support and recognize the protein scientists of tomorrow during the Poster Pavilion. This time has been set aside to view the Student Fellowship posters and interact with presenters one on one. This opportunity gives job seekers the chance to share their expertise with future/potential employers or develop contacts to further their research.

10:50 Co-Presentation: Advances in Alternative Drying Technologies to Lyophilization for Biotherapeutics Applications

Satoshi Ohtake, Ph.D., Senior Principal Scientist, Pharmaceutical R&D, BioTherapeutics Pharmaceutical Sciences, Pfizer, Inc.

Bakul Bhatnagar, Ph.D., Scientist, 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 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.

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

A common method for temperature monitoring is the usage of thermocouples, which are placed in some product containers of a batch. A major drawback of thermocouples is their contact with the product, the difficult handling to assure their optimal and reproducible positioning in the vial center close to the bottom and their limitation in usage in aseptic manufacturing. The aim of this study was to evaluate heat flux measurements using LyoPAT™ as a new, non-invasive monitoring technique during freeze drying. The heat flux sensor is mounted on the shelf and analyzes the heat transfer from shelf to product.

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own


OPTIMIZATION OF FREEZE-DRIED FORMULATIONS: CONTROLLED NUCLEATION, NEW TOOLS AND ELEGANCE ISSUES

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

Joseph E. Curtis, Ph.D., Research Chemist, Condensed Matter Science Group, 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 Estimation of Shelf Life Stability Based on Fast Dynamics of Lyophilized Protein Formulations

Ken K. Qian, Ph.D., Research Chemist and NIST-MedImmune Fellow, Biomaterials Group, National Institute of Standards and Technology

Disaccharides (trehalose and sucrose) are commonly used to preserve therapeutic proteins in lyophilized formulations; however, there is currently no systematic approach to predict product shelf stability. We have shown firm evidence that protein stability in sugar glasses is directly linked to the high-frequency, fast dynamics of the sugar matrices, occurring on a nanosecond timescale. Here, we present a new fluorescence technique to probe the fast dynamics of lyophilized formulations.

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.


5:45 BuzZ Session B

Join your peers and colleagues for interactive roundtable discussions


6:30-7:30 Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Conference


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