Cambridge Healthtech Institute’s 6th Annual

Overcoming Formulation Challenges for Biopharmaceuticals Development

Hot topics, Platform Technologies, Case Studies and Highlights from Industry

August 13-14, 2018

The popular sixth annual Overcoming Formulation Challenges for Biopharmaceuticals Development conference will cover latest trends and challenges in formulations development of novel biologic formats, process optimization, manufacturing, and device and packaging considerations for existing and emerging protein therapeutics. We are seeking case studies, especially unpublished and innovative work on co-formulation, formulation of novel biologics, effective scale up strategies, excipient induced instability, process challenges, fill finish challenges, and predictive tool for rapid formulation and stability screening.

Final Agenda

Monday, August 13

8:00 am Short Course Registration Open (Grand Ballroom Foyer) and Morning Coffee (Break Foyer)

9:00 - 11:30 Recommended Short Course*

SC3A: Application of New Analytical Tools in Protein Formulation Development and Subvisible Particle Characterization

Instructor: Danny K. Chou, PharmD, PhD, President and Founder, Compassion BioSolution; Former Senior Research Scientist, Biologics Development, Gilead Sciences

* Separate registration required.

11:30 Main Conference Registration Open (Grand Ballroom Foyer)

Back Bay C

1:00 pm Chairperson’s Opening Remarks

Nicholas Warne, PhD, Senior Director, Pharmaceutical R&D, BioTherapeutics Pharmaceutical Sciences, Pfizer, Inc.


1:10 Delivering Flexible Dosage Forms for Innovative Modalities and an Evolving Development Plan

Nicholas Warne, PhD, Senior Director, Pharmaceutical R&D, BioTherapeutics Pharmaceutical Sciences, Pfizer, Inc.

The development of biopharmaceutical processes and products is predicated on assumptions of dose range, time to customize the dosage form and market preferences. While seeking efficient approaches to screening compounds to assess developability, the increased complexity of biologics requires innovative approaches to formulation and dosage form development. The balance of platform processes to create capacity to provide innovative formulation solutions to novel modalities will be the focus of this presentation.

1:45 Challenges in Downstream Processing and Analytics of a Large Diversity of Molecules/Formats in the Discovery Setting

John E. Harlan, PhD, Principal Research Scientist, Global Protein Sciences, AbbVie

Downstream processing in support of Biologics Drug Discovery provides challenges that are distinct from those encountered in Development. Here we will discuss the approach we have taken to develop platform processes that can address the large diversity of molecules we encounter in the Discovery setting in the shortened timelines needed to facilitate the Discovery process, including the fit for purpose analytical approach we take, and automated processes we have developed.

2:15 A Holistic Approach to Formulation Development: From Cell Line to Drug Product Development

Sonal Saluja, PhD, Scientist II, Technical Development, Biogen

An end-to-end approach is needed for formulation development. Process impurities and heterogenous drug substance generated from upstream/downstream processes can negatively impact drug stability. This might not always be resolved by optimizing the formulation. Hence, a holistic development approach involving balancing yield, productivity, quality attributes and drug product stability is needed to guarantee success. This talk will highlight this concept using case studies.

2:45 Refreshment Break (Foyer)

3:15 Formulation Challenges in the Increasingly Complex Patent Landscape

Jan Jezek, PhD, CSO, Research & Development, Arecor, Ltd.

With growing competition in the market and more complex regulatory requirements, the demands for formulation of therapeutic proteins are increasing. In addition, the formulation patent landscape is becoming more complicated which further contributes to the challenge. This talk will describe several examples of successful formulation-related blocking patents as well as strategies for developing successful products in the increasingly complex patent landscape.

Back Bay C

3:45 Development of Parenteral Multidose Product – The Challenge of Preservatives

Helen Sjögren, PhD, Principal Scientist, Global Pharmaceutical R&D, Ferring Pharmaceuticals

It is a regulatory requirement to prove the efficacy of the preservation system in a multidose product. The preservation efficacy is not only depending on the concentration of the preservative, but also on other components in the formulation. It has previously been shown that interaction between peptides and preservatives reduces the preservation efficacy. This has also been proven to be the case for various excipients as surfactants, buffers and stabilisers. The effect varies with both excipient and preservative used.

4:15 SELECTED POSTER PRESENTATION: Raman Spectroscopy to Detect Protein Structural Changes in the Solid State

Fontana_LaurenLauren Fontana, PhD Candidate, Department of Pharmaceutical Sciences, University of Connecticut

A simple analysis of the lyophilized protein solid immediately after processing (requiring no reconstitution) that predicts stability would be ideal. FTIR is used to monitor secondary structural changes, but with limited prediction ability. Raman spectroscopy has been investigated to characterize solid state secondary and tertiary protein structure. Principal component analysis of Raman spectra can detect some of the more subtle structural changes that are not apparent using traditional data analysis.

4:30 Breakout Discussions

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.

Product Differentiation Through Innovative Formulation

Moderator: Jan Jezek, PhD, CSO, Research & Development, Arecor, Ltd.

  • How to deal with an increasingly complex formulation patent landscape
  • Need for product differentiation in the increasingly competitive biologics market
  • Enabling successful products through innovative formulation

How to Incorporate Excipient Quality and Specification Limits in Formulation Robustness Studies

Moderator: Helen Sjögren, PhD, Principal Scientist, Global Pharmaceutical R&D, Ferring Pharmaceuticals

  • Surfactants, how to control quality, levels and stability in drug product – regulatory requirements
  • Strategies for in-use stability, focus on infusion products with preparation steps before administration

Screening Methods That Are Most Indicative of Final Formulation Parameter and Most Useful in Formulation Development and Selection

Moderator: John E. Harlan, PhD, Principal Research Scientist, Global Protein Sciences, AbbVie

  • What screening method(s) are the most predictive of formulation stability?
  • Are there new methods/instruments that have the potential to be a “step change” in the way formulation screening is conducted?
  • How do you probe high concentration behavior with limited sample available for screening?

Understanding the Role and Effect of Buffers in Biopharmaceutical Formulation Development

Moderator: Shreya Kulkarni, PhD Candidate, Pharmaceutical Sciences, University of Connecticut

  • Importance of buffers in formulation design and stability.
  • Do buffer ions play a role other than buffering? (eg. by interacting with ionized residues on the protein)
  • Is it possible to completely strip ions during buffer exchange? (Donnan equilibrium)
  • What is the effect of buffers on drug product stability?

5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing (Grand Ballroom)

7:00 End of Day

Tuesday, August 14

7:30 am Registration Open and Morning Coffee (Grand Ballroom Foyer)

Back Bay C

7:55 Chairperson’s Remarks

Andrea Hawe, PhD, CSO, Coriolis Pharma Research GmbH

8:00 Analytical Strategy for Polysorbate Degradation in Biopharmaceutical Products

Andrea_HaweAndrea Hawe, PhD, CSO, Coriolis Pharma Research GmbH

Setting up an appropriate analytical strategy to characterize polysorbate and degradation products thereof, is crucial for the development of polysorbate-containing drug products. The talk will focus on analytical methods for soluble PS species, e.g., LC-CAD, LC-MS, as well as polysorbate-related particles, and discuss the phase-appropriate application of the different methods. Case studies on polysorbate degradation relevant for biopharmaceutical formulations will be presented to show the application of the different methods.

8:30 A Case Study utilizing EDTA as a Stabilizing Excipient for Monoclonal Antibody Oxidation and Polysorbate 80 Degradation

Melissa_YarbroughMelissa Yarbrough, MS, Scientist, Pharmaceutical Research and Development, Pfizer, Inc.

Polysorbates are frequently utilized in biotherapeutic formulations. Interest in assessing their stability, in particular the impact of their degradation products, on the stability of therapeutic proteins have been steadily growing in the past decade. A case study of a monoclonal antibody formulation that demonstrated a simultaneous loss of polysorbate and an increase in methionine oxidation will be presented. Further investigation demonstrated that the inclusion of EDTA decreased methionine oxidation and prevented surfactant degradation.

9:00 Oxidative Degradation of Polysorbate: Novel Mechanisms and Effects of Formulation Buffers

Christian_SchoneichIndira Prajapati, PhD Candidate, Schoeneich Lab, Department of Pharmaceutical Chemistry, The University of Kansas ON BEHALF OF

Christian Schoneich, PhD, Distinguished Professor and Chair, Pharmaceutical Chemistry, University of Kansas

Protein formulations frequently contain polysorbate as surfactant. The oxidative degradation of polysorbate leads to multiple products including free fatty acids and various polyoxyethylene esters. We report here on a new pathway to free fatty acid generation, as well as reactions of formulation buffers (e.g., histidine and acetate), which both inhibit and promote polysorbate oxidation.

Metabolon Logo 9:30 Using Metabolomics to Understand Genetically Determined and Environmental Cell Culture Needs

Brian_KepplerBrian Keppler, PhD, Associate Director, Project Management, Metabolon

We will describe how metabolomics can be applied across the bioprocess lifecycle from process development to process monitoring can yield biological insight to facilitate the development, implementation, and execution of robust and reproducible bioprocesses. In addition,we will discuss the role of biochemistry in immunometabolism and in development optimization of immunotherapies.

9:45 Coffee Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

10:30 Just below the Surface: New Excipient Alternatives to Polysorbate Surfactants

Philip_WuthrichPhilip Wuthrich, Senior Scientist, Research, Research & Development, ReForm Biologics

Commonly used polysorbate surfactants are prone to chemical degradation, compromising formulation storage stability. Polysorbates also create processing issues, because the micelles they form are similar in size to antibodies. Here we present data for a new alternative excipient that can match polysorbate performance at comparable addition levels without the chemical instability and processing limitations associated with polysorbates.

Back Bay C

11:00 Spray Drying of Biopharmaceuticals for Mitigation of Cold Chain Requirements – A Comprehensive Monoclonal Antibody Case Study

Sonia_BediSonia Bedi, PhD, Investigator, Biopharm Product Sciences, Biopharm R&D, GSK

The present work showcases a comprehensive approach to spray drying a monoclonal antibody with the objective of mitigating cold chain and driving the technology of spray drying biologics one step closer to being successfully industrialized. The ability to powder fill individual unit doses with high precision was also investigated. The topic is very pertinent to the current biopharmaceutical industry i.e. solid state stabilization of proteins. 


11:30 Mass Spectrometry for Equipment and Process Monitoring during Freeze Drying

Jason_StewartJason Stewart, BS, Senior Associate Scientist, Pharmaceutical Research and Development, Pfizer, Inc.

Mass spectrometry has emerged as a key technology for the detection of trace levels of silicone oil in freeze drying chamber. With the capability of measuring low molecular mass gasses such as water and nitrogen, mass spectrometry positions itself to be a powerful tool for not just equipment monitoring but the entire drying process.

12:00 NEW: SELECTED POSTER PRESENTATION:Improvement in Thermal Stability of Antibodies and ADCs with Rationally Chosen Formulations

Junia Dushime, Senior Research Associate, Biotherapeutics, Magenta Therapeutics

In this case study, an antibody presented with undesirable thermal instability as both an unmodified antibody and when conjugated to produce an ADC. A high throughput formulation screening was executed to study the impact of numerous buffers over a pH range. A clear improvement in thermal stability was observed when both the antibody and ADC were subjected to thermal stress in non-phosphate buffers. Thermal stability was confirmed by visual examination and relevant analytical assays such as turbidity, SEC, HIC, DSF, and CE-IEF. Here, we will describe our early formulation approach and development of appropriate analytical methods and present our results.

12:30 Luncheon Presentation: Rip Through Formulation Prep with a Junior, a Lunatic and an Uncle

Joe Barco, PhD, Senior Director, Marketing, Unchained Labs

Identifying formulations for biologics is a painful process Automated buffer exchange coupled with volume control can streamline the buffer exchange process Lower volume analytic measurements provides a means to get to key formulations faster and more effectively Combining automated buffer exchange with low sample volume analytics increases throughput and reduces sample burdens for discovery.

1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

Back Bay C

1:55 Chairperson’s Remarks

Atul Saluja, PhD, Associate Director, Global Pharmaceutical Development Biologics, Sanofi

2:00 Considerations for Designing Robust Clinical In-Use Studies

Atul_SalujaAtul Saluja, PhD, Associate Director, Global Pharmaceutical Development Biologics, Sanofi

Clinical in-use stability studies are critical in assigning an in-use period and in defining necessary study components to enable administration of an active drug product in a safe and efficacious manner. Designing these studies is often challenging given the multitude of factors that need to be considered. This talk will focus on various clinical, CMC, regulatory, analytical, and logistical aspects that must be considered in order to design robust clinical in-use studies.

2:30 An Intercompany Perspective on Biopharmaceutical Drug Product Robustness Studies

James Kranz, PhD, Principal Scientist, Process Development Formulation, Shire

Drug Product (DP) robustness studies ensure a product meets quality standards when formulation and process parameters are within established ranges. The BioPhorum Development Group (BPDG) authored a commentary on DP robustness (S. Morar-Mitrica, et al., J.Pharm.Sci. (2018), 107: 529-542) focused on the current scope, design and execution of biopharmaceutical DP robustness studies. Common themes were identified with regard to the use of DP robustness studies, with integrated case studies.

3:00 Early Stage Physicochemical Characterization of Novel Format ADCs

Pamela Thompson, PhD, Senior Scientist II, ADC Preformulation, NBE Development, AbbVie

Bridging early drug discovery and downstream development of novel format ADCs offers a challenging task in identifying the optimal biophysical techniques to investigate their developmental risk and physicochemical stability. This presentation will focus on our ADC Preformulation approach which implements an efficient and robust screening funnel platform for ADC candidate selection.

RepliGen 3:30 Refreshment Break in the Exhibit Hall with 1st Session Poster Winner Announced (Grand Ballroom)

4:15 Preventing Photo-Induced Degradation of an ADC

Amit_GangarAmit Gangar, PhD, Scientist II, Analytical and Pharmaceutical Sciences, ImmunoGen, Inc.

Stabilizing antibody-drug conjugates (ADCs) during manufacturing and storage poses several challenges to the formulation development scientists. Formulation optimization is further complicated for a photosensitive ADC and requires additional excipient screening studies to ensure stability during manufacturing and drug administration. A case study focused on addressing the light induced instability of an ADC will be discussed in this presentation.

4:45 Effect of Light Source and UV Quotient on Monoclonal Antibodies Stability during Manufacturing and Storage

Haresh_MoreHaresh T. More, PhD, Research Investigator II, Parenteral Science and Technology, Bristol-Myers Squibb

Biologics molecules are known to be photosensitive, especially to UV light, and photo-induced degradation of proteins can occur at any point from drug substance and drug product manufacturing up to final delivery to patient. During this entire process, the biologics drug product is exposed to different types of lights that may include some degree of UV in the 200 - 400 nm range. In this study, we evaluated different light sources for their UV quotient and light fixture UV-filter capabilities. The effect of UV leakage on aggregation was explored under these lights.

5:15 End of Conference

6:00 - 8:30 Recommended Dinner Short Course*

SC6B: Protein Aggregation: Mechanism, Characterization and Consequences

Instructors: Thomas Laue, PhD, Professor Emeritus, Molecular, Cellular and Biomedical Sciences, University of New Hampshire

Matthew Brown, PhD, Applications Manager, Bioscience, Malvern PANalytical

* Separate registration required.

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