PEGS EuropeSummit Impurities Stream

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

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Unpublished Data Icon: Unpublished Data | Case Study Icon: Case Study

 

 

Thursday, 5 November

12:30 Registration

13:00 Dessert Break in the Exhibit Hall with Poster Viewing

 

FORMULATION APPROACHES TO MINIMISE
CHEMICAL DEGRADATION

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 SchoneichChristian 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

Case Study Icon
Wolfe Janet
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.) 

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Friday, 6 November

07:30 Morning Coffee

 

FORMULATION CONSIDERATIONS
FOR EXISTING AND EMERGING BIOMOLECULES

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

Narang AjitAjit 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.

Case Study Icon  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

Kueltzo LisaLisa 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 HeyThomas 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.

Case Study Icon12:00 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

 

ADVANCED AND HIGH-THROUGHPUT TECHNIQUES FOR FORMULATION DEVELOPMENT

14:00 Chairperson’s Remarks

Lisa A. Kueltzo, Ph.D., Staff Scientist, Formulation Development, Vaccine Production Program Laboratory, National Institutes of Health

Unpublished Data Icon
Erik Sedlak
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.

Case Study Icon
Gesche Graf
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 FreireErnesto 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 Icon: Unpublished Data | Case Study Icon: Case Study

Day 1 | Day 2 | Speaker Biographies | Download Brochure