Cambridge Healthtech Institute’s Tenth Annual Optimizing Biologics Formulation Development is an essential international gathering of analytical and formulation scientists from leading industry companies, offering an exchange of
scientific developments and emerging technologies in an environment that encourages discussion with colleagues. For 2018, the conference focuses on a set of best practices for resolving key formulation development challenges. Each talk in the program
will be presented by a different industry or academic group to ensure the widest possible range of perspectives.
This important annual congress kicks off the weeklong PepTalk Formulation & Stability pipeline, which also includes separate meetings on Lyophilization and Drying Technologies and Protein Aggregation. By attending, you may also
participate in the full set of eight PepTalk pipelines, including three-meeting sets on analytics and impurities, process technologies, protein engineering, antibody therapeutics and more.
SUNDAY, JANUARY 7
4:00 - 6:00 pm Pre-Conference Registration
MONDAY, JANUARY 8
7:00 am Registration and Morning Coffee
9:00 Welcome by Conference Organizer
Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute
9:05 Chairperson’s Opening Remarks
Tarik Khan, Ph.D., Group Leader, Late-Stage Pharmaceutical and Processing Development, F. Hoffmann-La Roche Ltd., Switzerland
9:10 An End to End Approach to Formulation Development: Considerations from Cell Line to Drug Product Process Development
Kapil Gupta, Ph.D., Associate Director, Protein Pharmaceutical Development, Biogen
Development of high concentration stable formulations requires an end to end approach. Product heterogeneity and process impurities generated from upstream process can impact drug product stability and might not be solved by formulation optimization.
An integrated development approach is needed by balancing bioreactor productivity, yield, quality attributes and drug product stability to ensure success. This talk will highlight this concept using some recent case studies.
9:50 Present and Future Trends in Biotherapeutic Device-Mediated Delivery Technologies
Didier Pertuy, Vice President, Global Drug Device Integrated Development & Device Strategy,
Biotherapeutic device-mediated delivery is dominated by self-injectable devices like prefilled syringes, pens and auto-injectors. Next incremental step should be Large Volume Devices driven by dosing frequency reduction and low device-ability profile
of new formats. In parallel, emerging mHealth-enabling technology is bringing new opportunities for smarter devices and integrated care solutions. Even though longer-term evolution stays difficult to predict some potential trends could be considered.
10:20 Networking Coffee Break
10:45 The Challenges and Considerations of Protein and Peptide Coformulations
Rebecca Davis-Harrison, Ph.D., Research Scientist, BioTechnology
Discovery Research, Eli Lilly and Company
The coformulation of two therapeutic peptides and/or proteins into a single dose is an emerging area of biological therapeutics and brings additional complexity to the already complex field of protein formulations. Preserving the physiochemical integrity
of each molecule often requires that formulation conditions needed for one be applied simultaneously to the other. Analytical methods must also be able to detect changes in either molecule in this more complex environment.
11:15 Challenges in mAb Combination Drug Products: A CMC Overview
Jiali Du, Ph.D., Scientist, Formulation Sciences, MedImmune
The use of two mAbs in combination to improve treatment outcomes, and increase patient convenience and compliance is receiving increased scientific interest. This talk will provide a CMC outlook on challenges when formulating mAb combinations. Case
studies of challenges during in-use stability, development of formulation and presentations, analytical characterization, and fill/finish processes will be discussed.
11:45 Case Study: Clinical In-Use Stability Evaluation: Co-Administration of Two Antibody Therapeutics
Zhen Wu, Ph.D., Senior Scientist, AbbVie
Concomitant IV administration of drugs, if clinically feasible, is a convenient approach for the patients and may offer competitive advantage. In this presentation, co-administration of two antibody therapeutics will be presented as an example. Both
drugs were diluted in an IV bag and an in-use study was performed to evaluate dose solution stability. The approach taken to adapt the analytical methods and overcome the analytical challenges will be discussed.
12:15 pm See Stability in Hi-Def with Hunky
Greg Manley, Ph.D., Senior Applications Specialist, Unchained Labs
Developing biologics requires identifying ideal constructs and assessing a wide range of formulation space to ensure stability and minimize aggregation. Assessing ΔG is a powerful approach for the quantitative assessment of conformational stability
and aggregation. Unchained Labs automates the tedious and manual task of determining ΔG, allowing for quantitative stability and aggregation assessment throughout biologic development. We'll discuss how automated chemical denaturation can
be used with more traditional approaches to assess stability.
12:45 Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
Arun Alphonse Ignatius, Ph.D., Principal Scientist, Pfizer
2:05 Formulation Development for AAV-Based Gene Therapy Products
Arun Alphonse Ignatius, Ph.D., Principal Scientist, Pfizer
Over the past few years, adeno-associated viruses (AAV) have evolved significantly with few products moving into late stage clinical development, and many others in early trials showing significant promise in the clinic. However, there are significant
challenges that remain primarily due to the rapid transition into industry. This presentation will use case studies to showcase some of the challenges and considerations in the formulation development for AAVs.
2:35 Biophysical Characterization of mRNA Loaded Lipid Nanoparticles Formulations
Flaviu Gruia, Ph.D., Principal Scientist, Drug Product Analytical Development, Moderna
Developing a delivery vehicle capable of transporting the mRNA cargo to its intended target is a key challenge that should be addressed during development of mRNA-based products. Lipid nanoparticles represent a class of non-viral delivery systems
that show potential in this space. The presentation will review some analytical development aspects, with specific examples of techniques that are valuable for biophysical characterization of nanoparticle formulations. Selected case studies will
3:05 Transition to BuzZ Sessions
3:15 BuzZ Sessions with Refreshments
Join your peers and colleagues for interactive roundtable discussions.
4:30 Formulation Challenges for Low and High Concentration Proteins
Shiang Gwee, Scientist, Drug Product Sciences, MacroGenics, Inc.
DART® molecules are bi-specific antibody-based proteins developed for immuno-oncology indications. These molecules are manufactured using conventional antibody platforms, and demonstrate
comparable product quality and stability to conventional antibodies. Increased potency and lower dose requirement of certain bi-specific molecules present challenges for intravenous administration in early stage development. Case studies will
be presented of approaches for IV administration of low/high concentration protein formulations that highlight these challenges.
5:00 Pulse Proteolysis: A Novel High-Throughput Tool for Formulation Screening
Lavanya Iyer, Ph.D., Research Investigator, Bristol-Myers Squibb
Biologics formulation selection is typically based on shelf-life stability data obtained over months. In this work, a novel analytical method called Pulse Proteolysis was used to rank-order formulations, based on resistance to proteolysis. The results
demonstrate that formulations could be rank-ordered based on T-zero stability, as measured by pulse proteolysis. The high correlation with storage stability indicates that pulse proteolysis could prove to be a useful tool for formulation screening.
5:30 Characterization and Control of Interfacial Antibody Adsorption and Aggregation
Ian Shieh, Ph.D., Scientist, Genentech
Exposure to interfaces can accelerate aggregation of antibody therapeutics during manufacture, transportation, and administration. Controlling interfacial antibody adsorption is critical to limiting aggregation. A panel of mAbs was characterized
by multiple surface-sensitive techniques to predict their risk of interfacially mediated aggregation. We also measured and visualized antibody coadsorption with surfactant at the air-water interface to understand the protective mechanisms
of the surfactants included in antibody formulations.
00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing
7:15 Close of Day
TUESDAY, JANUARY 9
8:00 am Registration and Morning Coffee
8:30 Chairperson’s Remarks
Rebecca Davis-Harrison, Ph.D., Research Scientist, BioTechnology Discovery Research, Eli Lilly and Company
8:35 Non-Ideal Colligative Properties in High Concentration Mab Solutions and Impact to Biopharmaceutical Manufacturing
William Callahan, Senior Scientist, Amgen
Osmolality measurement is routinely used to monitor physical properties of protein formulations. In this work, osmolality of high concentration protein solutions was found to either drift to higher than expected values or to be immeasurable
due to a failure to freeze in the freezing point depression (FPD) osmometer. This presentation highlights the problem inherent in determining osmolality of high concentration protein solutions and that caution must be taken in interpreting
9:05 Challenges and Solutions in Polysorbate Degradation
Steven LaBrenz, Ph.D., Scientific Director, Cell and Developability Sciences,
PDMS, Janssen R&D
Polysorbate degradation events in biopharmaceuticals are becoming more understood, moving beyond the original autooxidation work of Donbrow. Understanding degradation processes, relating that knowledge to actual conditions of use and controlling
degradation events involving polysorbate are essential to developing a stable protein formulation. When controlling for external effectors that lead to issues in a protein formulation, degradation events involving polysorbate can be controlled.
9:35 Molecular Knowledge and Experience as the Driving Forces Behind Successful Protein Formulation Development
Katherine Bowers, Ph.D., Principal Scientist, Group Leader, Analytical and Formulation Development, FUJIFILM Diosynth Biotechnologies
9:50 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Poloxamer 188 as an Alternative Surfactant
Tarik Khan, Ph.D., Group Leader, Late-Stage Pharmaceutical and Processing Development, F.
Hoffmann-La Roche Ltd., Switzerland
Polysorbates have long been the workhorse surfactant for stabilizing biologics. However, due to their susceptibility to degradation there is a clear desire to identify alternative surfactants. Poloxamer 188 (P188) is one such stable surfactant
that has been successfully utilized in the formulation of biologics. This talk will highlight real formulation/stability data as well as mechanistic characterization of how P188 stabilizes biologics by interfacial activity and solution behavior.
11:30 Prospects for the Identification and Application of Excipient Mixtures and Novel Excipients
Miko Schleinitz, PhD Student, Biochemical and Chemical Engineering, Technical
University, Dortmund, Germany
Classically, novel excipients and excipient mixtures are identified based on heuristic approaches often neglecting synergetic effects and hindering transferability of the results to novel formulations. It is thus desired, to develop a physically-sound
method to identify excipient mixtures and novel excipients based on modeling/predicting the intermolecular interactions in solution. This allows for considering the mutual influence of multi-excipient systems and to determine the optimal excipient
mixture circumventing cost-intensive screening methods.
12:00 pm Formulation of Hard-to-Stabilize Biopharmaceuticals
Phil Morton, Ph.D., Science Director, Bioprocess Characterisation, Albumedix
Modern biopharmaceuticals are changing. Increasingly, the industry is shifting towards more complex biological molecules intensifying formulation challenges requiring more advanced excipients. Human albumin is well known to stabilize proteins
through a variety of roles, therefore recombinant human albumin is a promising stabilizer for hard-to-formulate biopharmaceuticals. We present data on the use of Albumedix® Recombumin® as a stabilizing agent across several different stress tests showing its versatility as an advanced excipient.
12:30 Close of Optimizing Biologics Formulation Development Conference