2015 Archived Content
Cambridge Healthtech Institute’s Inaugural
Protein Formulation and Stability
Advanced Formulation Strategies to Minimise Degradation and Establish Long-Term Stability
5-6 November 2015
Maintaining drug product stability is the ultimate goal in formulation development, and thus determining and minimizing physical and chemical degradation, controlling viscosity, and reducing E&L and contamination risks are of paramount importance.
CHI’s Inaugural Protein Formulation & Stability conference will invite scientists to showcase advances in high throughput methods for formulation screening, discuss approaches to minimize degradation and explore
the challenges in formulation development for novel biotherapeutics.
Final Agenda
Day 1 | Day 2 | Speaker Biographies | Download Brochure
: Unpublished Data | 
: Case Study
Thursday, 5 November
12:30 Registration
13:00 Dessert Break in the Exhibit Hall with Poster Viewing
13:30 Chairperson’s Opening Remarks
Shahid Uddin, Ph.D., Director, Formulation, MedImmune
KEYNOTE PRESENTATION
13:35 Light-Induced Degradation and Aggregation of Antibodies and Antibody Drug-Conjugates
Christian Schoneich, Ph.D., Takeru Higuchi Distinguished Professor and Chair, Department
of Pharmaceutical Chemistry, University of Kansas
Antibody-drug conjugates (ADCs) provide a promising approach to deliver large payloads of toxic drugs. However, chemical and physical stability problems of ADCs may arise from the exposure of ADCs to light, as several ADCs contain drug conjugates,
which may act as photosensitizer and drug conjugation may change the general sensitivity towards light. This talk will focus on product formation and mechanisms of light-induced degradation of antibodies and model ADCs.
14:20 Practical Considerations in Screening Excipients for Protein Drugs
Andrea Ji, Ph.D., Senior Scientist, Genentech, Inc.
The presentation will address the critical factors to be considered in protein formulation development such as oxidation, deamidation and excipient degradation as well as mitigation strategies.
14:50 Meet the UNit and the HUNK
Daniel Lund, Ph.D., Product Manager, Unchained Labs
The UNit lets you look at more protein stability parameters than any other tool out there. Up your knowledge base on every formulation, find the right candidates exponentially faster and use way less sample. Do it all on the first and only multiplex stability
system for biologics. The HUNK lets you identify the most stable formulations and proteins. You'll be able to predict the future — whether your protein aggregates from the native or denatured state — which is exactly what will happen to
it during storage.
15:20 Refreshment Break in the Exhibit Hall with Poster Viewing
16:05
Rational ADC Formulation Design as a Tool to Prevent Chemical and Physical Instabilities
Janet L. Wolfe, Ph.D., President, Wolfe Laboratories, Inc.
Understanding of the multiple degradation pathways that an ADC can undergo will enable rational ADC formulation design. Such an approach requires an array of biophysical and analytical characterization techniques, and yields a de-risked development path
that minimizes the timeline to clinical testing. A case study will be presented of formulation approaches that mitigate aggregation and chemical degradation pathways.
16:35 Selected Poster Presentation I:
Stabilization of Proteins Encapsulated in Injectable Polypseudorotaxane Hydrogels
Keiichi Motoyama, Ph.D., Associate Professor, Physical Pharmaceutics, Kumamoto University
Protein aggregation of biopharmaceutical drugs is caused by various chemical or physiological stresses during manufacturing, shipping, and storage. Therefore, stabilization of therapeutic proteins is an important issue. We have established a novel protein
stabilization method with polypseudorotaxane hydrogels (PPRXs) composed of biocompatible cyclodextrins and polyethylene glycol. PPRXs can encapsulate proteins or peptides in their structure, and are applicable to subcutaneous administration due to
its thixotropic nature whereas they form illiquid hydrogels. In the present study, human IgG included in PPRXs was highly stabilized toward physicochemical stresses like shaking and heating in comparison with human IgG solution. Such a stabilization
effect has been confirmed with several kinds of therapeutic proteins and peptides, and also with highly concentrated human IgG. The subcutaneous administration of antibody encapsulated in PPRXs showed almost the same pharmacokinetics compared with
the antibody solution. In addition, safety of PPRXs as drug excipients for subcutaneous application was investigated using rat, showing no toxicity by histopathology and seological values. Based on these results, we will offer a new insight
into protein and peptide stabilization with injectable PPRXs.
16:50 Selected Poster Presentation II:
The Downstream Procedure from E.coli Influences Stability, Functionality and
in vivo Biodistribution of CD44-Targeted Protein Nanoparticles
Mireia Pesarrondona, MSc., Nanobiotechnology Group, Institute of Biotechnology and Biomedicine of Autonomous University of Barcelona
Protein based nanoparticles
are gaining interest in nanomedicine but protein
stability and therefore activity might be sensitive to production conditions
and purification strategies applied. How structure and biological performance
of self-assembling CD44-targeted protein-only nanoparticles is affected by the
downstream procedure is presented as a comparative analysis between particles
purified from soluble cell fraction and protein versions obtained by in vitro
extraction from inclusion bodies applying non-denaturant agents
17:05 End of Day
17:00 – 17:30 Dinner Short Course Registration*
SC8: The Challenge of Protein Aggregation and Formation of Sub Visible Particles in the Development of Biopharmaceuticals
SC9: Advanced Techniques for Characterisation of Protein Aggregates, Particulates and Contaminants
(*Separate registration required.)
Day 1 | Day 2 | Speaker Biographies | Download Brochure
Friday, 6 November
07:30 Morning Coffee
08:30 Chairperson’s Remarks
Ajit Narang, Ph.D., Principal Scientist, Drug Product Science and Technology, Bristol-Myers Squibb
08:35 Technical Development Considerations in the Design of Parenteral Protein Solutions
Ajit Narang, Ph.D., Principal Scientist, Drug Product Science and Technology, Bristol-Myers Squibb
Emerging data suggests that aggregation instability of a ready-to-use protein solution drug product may be linked to the shear forces experienced by the protein during downstream purification. Sustained conformational changes due to shear during processing
may contribute to long-range hydrophobic protein-protein interactions in protein solutions. These interactions manifest in changes in the physicochemical properties of proteins including viscosity and hydrodynamic diameter, in addition to protein
aggregation during accelerated stability testing.
09:05 Understanding Your Molecule Using Design of Experiment Modeling
Jonathan Armer, Scientist I, Formulation Sciences, MedImmune Ltd.
Different strategies exist for examining specific attributes of a molecule. This data can be used to make judgements on formulation choices by weighing each of the key stability indicating attributes. Identifying the correct formulation parameters, against
often conflicting data, can be challenging. The use of Design of Experiment software to analyze and model these data will be discussed. Ways to leverage these models to make long term stability predictions will also be explored.
09:35 PROBLEM SOLVING ROUNDTABLE DISCUSSIONS
Table 25: Approaches to and Prediction of Long Term Stability
Moderator: Ernesto Freire, Ph.D., Professor, Biology and Biophysics, Johns
Hopkins University
Table 26: Characterization of ADC Degradation Pathways
Moderator: Janet L. Wolfe, Ph.D., President,, Wolfe Laboratories, Inc.
Table 27: High Concentration Protein Formulations – What Are The Limitations of Our Current Analytical Methods?
Moderator: Thomas Hey, Ph.D., Director, Biochemistry, Innovation Center
Complex Formulations, Fresenius Kabi Deutschland GmbH
Table 28: Early/Pre-formulation Strategies to Assess Developability of a New Molecule
Shahid Uddin, Ph.D., Director, Formulation, MedImmune
10:35 Coffee Break with Poster Viewing
11:00 Comparison of Isothermal and Thermal Ramping Approaches to Vaccine Formulation
Lisa A. Kueltzo, Ph.D., Staff Scientist, Formulation Development, Vaccine Production Program Laboratory, National Institutes
of Health
The use of isothermal methods, such as kD and ICD measurements, has gained renewed interest. This talk will examine the comparative value of accelerated temperature methods with alternate isothermal methods, specifically in the development of low concentration
vaccine formulations. The benefits and disadvantages of the thermal ramping methods such as DSC and DSF techniques will be reviewed, and the relative predictive ability for real-time stability will be examined.
11:30 Protein Conjugates with Hydroxyethylstarch - High Solubility and Low Viscosity
Thomas Hey, Ph.D., Director, Biochemistry, Innovation Center Complex Formulations, Fresenius Kabi Deutschland GmbH
HESylation® - the attachment of the biodegradable and poorly immunogenic polymer hydroxyethyl starch (HES) to therapeutic proteins - results in an increased efficacy by stabilization of the protein and prevention of renal excretion. The resulting
conjugates show high solubility, but low viscosity compared to the PEGylated protein, allowing s.c. administration also of highly concentrated solutions.
12:00 Toward Stable Formulations of Peptides: Lessons Learned
Anna-Karin Lundback, Ph.D., Formulation Scientist, MedImmune Ltd.
Peptides are becoming an increasing popular
drug target and therefor there is a demand to better understand how to successfully
formulate peptides to preserve stability and efficacy over time. The physical and chemical degradation
pathway of peptides can be very complex and require extensive studies to be
able to predict stable formulations. In this talk I aim to elucidate some of the learnings that have been made
during the course of developing a stable formulation of a peptide.
12:30 Enjoy Lunch on Your Own
13:30 Session Break
14:00 Chairperson’s Remarks
Lisa A. Kueltzo, Ph.D., Staff Scientist, Formulation Development, Vaccine Production Program Laboratory, National Institutes of Health
14:05
Advanced Analysis of Kinetic Stabilities of IgGs Modified by Mutations and Solvent Additives
Erik Sedlak, Ph.D., Associate Professor, Centre for Interdisciplinary Biosciences and Department of Biochemistry, P.J. Šafárik University in Košice
The complex thermal transitions of IgGs and their irreversibility pose a challenge to the proper determination of parameters describing their thermodynamic and kinetic stability. We present a mathematical model to study the thermal denaturation of
antibodies consisting of three (one reversible and two irreversible) consecutive transitions. The parameters obtained allowed us to examine the effects of mutations and solvent additives on the stabilities of individual domains within the full-length
IgG.
14:35
Protein Stabilisation and Formulation Using Semifluorinated Alkanes
Gesche Graf, Ph.D., Analytical Development Manager, Novaliq GmbH
Semifluorinated Alkanes (SFAs) serve as a well-tolerated alternative drug delivery medium to water. The SFA platform technology allows formulating APIs as solution or dispersion which are otherwise unstable or poorly water soluble. Formulating peptides
and proteins with the help of SFAs combines both, the stabilising effect of the SFAs on peptides and proteins as well as their superior physico-chemical properties for the use in fields such as ophthalmology.
15:05 Recent Advances in the Prediction of Long Term Stability of Biologics Using ICD
Ernesto Freire, Ph.D., Professor, Biology and Biophysics, Johns Hopkins University
New developments have demonstrated that ICD (Isothermal Chemical Denaturation) is capable of identifying the predominant mode of aggregation of biologics; quantifying the fraction of the protein that is denatured or aggregated and also quantifying
the total fraction of the protein that is aggregated. These can be achieved as soon as the protein solution is prepared. The predictive capability of ICD and its application to formulation optimization will be discussed.
15:35 Development of a High-Throughput Screening Platform to Study the Adsorption of Antigens onto Aluminum-Containing Adjuvants
Vanessa Jully, Ph.D. Student, Vaccine Discovery and Development, GlaxoSmithKline Vaccines
We have developed a robust, rapid, and reproducible high-throughput screening (HTS) platform to study the adsorption capacity of aluminium-containing vaccines. The adsorption isotherms on aluminum hydroxide and aluminum phosphate of two model proteins,
and two vaccine antigens were evaluated using a liquid handling system, which permitted rapid sample preparation in a small volume without nonspecific adsorption. This platform should accelerate data acquisition during the development of a new
vaccine.
16:05 End of Conference
: Unpublished Data | : Case Study
Day 1 | Day 2 | Speaker Biographies | Download Brochure