Cambridge Healthtech Institute’s Inaugural

Formulation, Stability & Aggregation

Improving and Accelerating Protein Production Processes

New Dates - 22-23 July 2020

 

This inaugural conference brings together leading industry experts to advance formulation, stability and aggregation studies in the production of traditional and novel biotherapeutics. Exploring the latest methods, technologies and solutions being employed to overcome your most pressing challenges. We invite you to join us to share best practices with like-minded peers.

Final Agenda

 

Wednesday, 22 july

OPTIMISING FORMULATION DEVELOPMENT

10:40 Chairperson’s Remarks

Shahid Uddin, Director, Drug Product, Formulation & Stability, Immunocore

10:45 New Approaches to Profiling the Solution Behaviour of Therapeutic Proteins

McCoy_MarkMark McCoy, PhD, Principal Scientist, Screening, Target and Compound Profiling, Merck & Co

Protein self-interactions are an intrinsic behaviour that can adversely affect the developability of therapeutic proteins. Our recent work on NMR-based interaction & behaviour assessments permits the simultaneous detection of weak protein-protein and protein-excipient interactions. We discuss applications to protein formulation optimisation, de-risking mAb co-formulations, candidate developability assessments as well as residue-level structural details that can guide protein design.

11:05 3D Printed Delivery Systems for Drugs and Biologics

Lamprou_DimitriosDimitrios Lamprou, PhD, Reader in Pharmaceutical Engineering, Queen’s University Belfast

Progress in drug design has led to the development of new peptides, proteins, and drug molecules. However, the limited ability to selectively deliver these molecules at well-defined dosing regimens remains a significant challenge. These challenges can be bypassed by using novel technologies such as 3D Printing/Bioprinting. Various designs with high drug payloads that formulated by 3D printing and characterised using advanced characterisation techniques (e.g., μCT, ToF-SIMS) will be discussed.

11:25 Demystifying Label-Free Techniques and Applications for High-Quality Data in a Fraction of the TimeForteBio

José CatitaJosé Catita, PhD, Paralab

Cell line development includes the screening of thousands of clones. The aim is to find the few that are stable, grow as expected, and produce high yields of the bioproduct. Speed up antibody discovery and development by moving higher quality candidates downstream. How? Carry out expression level analysis label-free in crude samples. Combine it with early-stage glycan characterization both in a high-throughput mode.

11:45 Antibody Formulation Using Bacterial Spore Derived Excipients 

Batalha_IrisÍris Luz Batalha, PhD, Research Associate, University of Cambridge

Dipicolinic acid (DPA) is a small organic molecule that comprises 10-15% of the dry weight of spores and is involved in spore stability and resistance to wet heat. The application of DPA as a pharmaceutical excipient is somewhat hampered by its low aqueous solubility. Through counterion screening studies, we discovered two novel salts of DPA, ethanolamine-DPA and diethanolamine-DPA, which showed improved solubility and significantly reduced the viscosity of high concentration mAb formulations.

 

12:00 Lunch Break - Come and View our Virtual Exhibit Hall

PLENARY SESSION:
NEXT-GENERATION PROCESSES AND PRODUCTS

12:25 Chairperson’s Remarks

To be Confirmed

12:30 Continuous Processing for Vaccine Manufacturing: Challenges and Opportunities

Yang-PingYangYan-Ping Yang, PhD, Head of Bioprocess Research & Development, North America, Sanofi Pasteur

Over the last decade, there have been significant investments in continuous manufacturing in the pharmaceutical industry, as it holds great promise to lead the reduction of process steps, smaller footprint, higher product quality, and better pharmaceuticals for patients. While it’s still in its early stage, the vaccine industry has embraced this concept and is ready to explore the full advantages associated with this approach. This presentation explores the challenges and opportunities to make continuous vaccine manufacturing a reality.

12:55 Gene Therapy Manufacturing and Technical Development

Blumenthal_DianeDiane Blumenthal, PhD., Head, Technical Development, Spark Therapeutics

In the past few years, several cell and gene therapy products have gained regulatory approval in the US and EU with many more in the pipeline. Manufacturers of cell and gene therapy products must tackle technological challenges under the pressure of short timelines resulting from streamlined clinical development. This presentation will focus on the key technical development challenges facing the industry as product development programs move the into the later stages of process development and scale-up, process performance qualification and ultimately commercialization.

13:20 Q&A, Session Wrap-up, Host intro to special virtual features

13:35 Break Time to View our Virtual Exhibit Hall

13:55 Chairperson’s Remarks

Mark McCoy, PhD, Principal Scientist, Screening, Target and Compound Profiling, Merck & Co

14:00 KEYNOTE PRESENTATION: Comparative Evaluation of Chelating Agents to Prevent Polysorbate and API Degradation in Biologic Formulations

Bensaid_FethiFethi Bensaid, PhD, Section Head, Formulation & Process Development, Sanofi Aventis

EDTA and other chelators are used in several products, few of which are biologics. Their needs, pros and cons as excipients are however still poorly understood. In this case study a head-to-head comparison of EDTA with other chelating agents is presented, including recommendations for their correct use in the formulation of protein-based therapeutics.

14:20 Biopharmaceutical Product Differentiation Through Innovative Formulation

Jezek_JanJan Jezek, Chief Scientific Officer, Arecor

With growing competition in the market and patient-centric product strategies, the demands for product differentiation are increasing. Innovative formulation together with appropriate device strategy is key in achieving such differentiation. This talk will demonstrate on several case studies how novel formulation principles can be used to develop products with superior stability with clear benefits for the patient, as well as leading to new patent applications extending the product exclusivity.

14:40 Fast, Low Volume Subvisible Particle Analysis with HORIZONHalo-Labs

Mercado_GabrielGabriel Mercado, Senior Marketing Applications Scientist, Marketing, Halo Labs

Halo Labs knows particles. The HORIZON, our flagship product, detects, counts and characterizes subvisible particles. A simple, plate-based approach enables low-volume (25 µL), high-throughput (96 samples) particle imaging and analysis at any stage of the biologics workflow from developability assessment through formulation and quality control.

15:00 Q&A, Session Wrap-up

15:15 Virtual Happy Hour in our Virtual Exhibit Hall


Thursday, 23 july

PROTEIN AGGREGATION

9:00 Chairperson’s Remarks

Paul Matejtschuk, PhD, Section Head Standardisation Science, NIBSC (National Institute for Biological Standards & Control)

9:05 Aggregation of Biologics in Liquid and Freeze-Dried State – Formulation and Processing

Matejtschuk_PaulPaul Matejtschuk, PhD, Section Head Standardisation Science, NIBSC (National Institute for Biological Standards & Control)

Biologics are labile molecules and are prone to aggregation. I will review our experience with model biologics, comparing the impacts of formulation and process on aggregate levels. Freeze drying can mitigate aggregation by delivering a stable format for long term storage and optimisation in terms of excipients used and freeze-drying cycle design will be presented. The value of Design of Experiments and high-throughput screening in optimising formulation will be described.

9:25 Towards an Improved Understanding of Aggregation: Interactions Between Partially Folded Proteins Formed Under Chemically Denaturing Conditions

Curtis_RobinRobin Curtis, PhD, Senior Lecturer, Chemical Engineering and Analytical Science, Manchester University 

A key stumbling block towards predicting and controlling aggregation is isolating properties of partially folded or unfolded intermediates in the pathways.  Here, we present a few examples, covering monoclonal antibodies and antibody fragments, where we have measured the association behaviour of unfolded intermediates using chemically denaturing conditions.  The results provide insight into key structural properties controlling aggregation propensity and how excipients alter different steps in the aggregation pathways.

9:45 Sponsored Presentation (Opportunity Available)

10:05 Q&A, Session Wrap-up

10:20 Break Time to View our Virtual Exhibit Hall

ADVANCES IN STABILITY AND DEGRADATION TESTING

10:45 Chairperson’s Remarks

Paul Matejtschuk, PhD, Section Head Standardisation Science, NIBSC (National Institute for Biological Standards & Control)

10:50 How to Define a Stability Strategy for Adenoviral Vectored Vaccines

Binai_NadineNadine Binai, PhD, Scientist Product Characterization, Janssen Vaccines

Adenoviral vectors used in vaccine development are challenging study objects due to their complex composition of viral proteins as well as viral and transgene DNA. Determining routes of degradation is part of the stability strategy. Stability studies performed based on ICH guidelines in development are indented to define the shelf life. By additionally applying characterization methods to aged or stressed samples the route of degradation can be studied in more detail.

11:10 Advances in Stability and Degradation Testing to Demonstrate Physicochemical Similarity of Originator and Biosimilar Products

Arvinte_TudorTudor Arvinte, PhD, CEO, Therapeomic; Professor of Biopharmaceutics, University of Geneva

The talk will document the importance of using different orthogonal analytical methods to assess the similarity of originator products and biosimilar drug candidates. Case statues will include development projects and products such as bevacizumab and pegfilgrastim.

11:30 Sponsored Presentation (Opportunity Available)

11:50 Q&A, Session Wrap-up

12:05 Lunch Break - Come and View our Virtual Exhibit Hall

12:30 Chairperson’s Remarks

Zahir Akhunzada, PhD, Research Scientist, Drug Product Science Development, Bristol-Myers Squibb

12:35 Stability Challenges and Control of Product for Oxidation Sensitive mAb

Bach_Kristensen_DanDan Bach Kristensen, PhD, Principal Scientist, Symphogen

Batch variation can be a major problem for drug product stability and early knowledge of critical quality attributes (CQAs) and degradation mechanism can be essential to reduce/avoid challenges related to Chemistry, Manufacturing and Controls (CMC) processes at a later stage. In the current case study, it is highlighted how oxidation can affect product stability, and thus product quality for a complex product containing six different monoclonal antibodies.

ANALYSIS OF IMPURITIES, SUB-VISIBLE AND VISIBLE PARTICLES

12:55 Challenges in Analyzing High Concentration Proteins: Aggregates Characterisation of SVPs with MFI/FlowCam

Zahir Akhunzada, PhD, Research Scientist, Drug Product Science Development, Bristol-Myers Squibb

Analysis of protein biopharmaceuticals with high concentrations pose a number of challenges. Dipole-dipole interactions due to molecular crowding in high concentration biologics lead to self-association with increase in viscosity and changes in fluid dynamics. The presence of sub-visible particles (SVPs) is a major challenge in the development of therapeutic protein formulations. Distinction between proteinaceous and non-proteinaceous SVPs is vital in monitoring the formulation stability. The current compendial method based on light obscuration (LO) has limitations in analyzing translucent particles, and therefore demands the need for an unambiguous method to characterize SVPs. This presentation will discuss how to characterize and distinguish, both potentially proteinaceous and non-proteinaceous SVPs in protein formulations by using Microflow Imaging (MFI) in conjunction with the MIA (MFI Image Analysis) (Bio-techne USA), FlowCam and Lumetics software (Lumetics LINK, Canada).

PROTEIN AGGREGATION

13:15 Chemical and Physical Protein Attributes that Influence the Self-Assembly of Proteins

McManus_JenniferJennifer McManus, PhD, Associate Professor, School of Physics, University of Bristol  

The self-assembly and aggregation of proteins during production and storage can produce assemblies with sizes ranging from nanometres to micrometres. I will discuss how the physio-chemical characteristics of a protein can influence formulation stability and will discuss the challenges associated with development and analysis of high concentration formulations.

13:35 Q&A, Session Wrap-up

13:50 Break Time to View our Virtual Exhibit Hall

14:05 Breakout Discussion Groups

Table: Emerging Technologies for Biopharmaceutical Manufacturing

Moderator: Dimitrios Lamprou, PhD, Reader in Pharmaceutical Engineering, Queen’s University Belfast

  • Examining additive manufacturing
  • Benefits of electrospinning
  • Microfluidics as a tool for drug delivery
  • Delivering drugs with Microelectromechanical Systems (MEMS) 

15:05 Close of Summit


BPDE Brochure RC