Cambridge Healthtech Institute’s 6th Annual

Rapid Methods to Assess Quality & Stability of Biologics

Improving Prediction and Screening

August 13-14, 2018

Increasing regulatory expectations and aggressive development timelines call for rapid methodologies to predict, assess and assure the quality and stability of biologics throughout the shelf life. The sixth annual Rapid Methods to Assess Quality & Stability of Biologics conference will bring together experts in analytical and formulation development to discuss regulatory expectations, prediction, measurement and manipulation for protein stability and instabilities in early and late-stage development. We are seeking case studies, unpublished and innovative work on methods employed in real time and accelerated stability studies for proteins, cell and gene therapy products, high-throughput analytics, multi attribute methods, HOS, use of DOE and QbD and immunogenicity.

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

Nick_WarneNicholas 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_HarlanJohn 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)

Back Bay D

3:15 Biophysical Characterization of Lipid Nanoparticles for RNA Delivery

Mark_BraderMark Brader, PhD, Research Fellow, Drug Product Analytical Development, Moderna Therapeutics, Inc.

Unlocking the potential of RNA therapeutics requires a sophisticated delivery system. Lipid nanoparticles can protect the RNA cargo from degradation in the bloodstream and facilitate cellular uptake. However, their physical and structural complexities present a special set of challenges for pharmaceutical analysis and control. This presentation will provide an overview of applicable biophysical approaches with an emphasis on colloidal properties and product development considerations.

3:45 Rapid Amino Acid Analysis (AAA) Methods for Protein Concentration in Novel Drug Delivery Platforms

Scott H. Chamberlain, Senior Research Associate, Protein Analytical Chemistry, Genentech

Protein concentration measurements by UV spectroscopy and other dye assay methods may be ineffective when biotherapeutics are conjugated to hydrogels, scaffolds or encapsulated in drug delivery devices. AAA can provide accurate quantification following assessment of the drug delivery platform prior to hydrolysis and analysis. Accelerated AAA analysis methods can allow for high-throughput and rapid determination of protein concentration. Several case studies will be discussed highlighting accelerated AA analysis.

Protein Dynamic Solutions  4:15 High-Throughput Critical Quality Attribute Testing for Enhancing Speed to Market & Minimizing Risk

Belinda_PastranaBelinda Pastrana, PhD, CEO, Protein Dynamic Solutions

A walkaway, high throughput, array based platform will be presented that provides simultaneous assessment of eight CQA parameters, sample visualization and mechanistic determination of changes in therapeutic proteins. Up to 200 samples/day are assessed for developability and comparability across a range of formulations and stressors for improved pipeline success.

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.

Impact of Statistics on Subvisible Particle Quantification

Moderator: Marina Gühlke, PhD, Analytical Scientist, Coriolis Pharma

  • How statistically relevant are particle concentrations obtained from low volume, microliter-sized samples?
  • Do particle number limits of USP<787>/<788>/<789> include measurement uncertainties?
  • Does pooling of low volume drug products solve our statistical issue or does pooling introduce more uncertainty?

How Do We Address Analytical Challenges With Novel Formats And Drug Delivery Platforms?

Moderator: Scott H. Chamberlain, Senior Research Associate, Protein Analytical Chemistry, Genentech

  • What are the early development challenges encountered?
  • How do we develop rapid platform methods?
  • How do we reconcile results from multiple assays of novel formats which often use indirect methods of measuring attributes?

New Methods for Prediction of Protein Aggregation During Storage for Lyophilized Products Based on Initial Release Data

Moderator: Lauren Fontana, Graduate Student, Pharmaceutical Sciences, University of Connecticut

  • Measurement techniques: Solid state amide hydrogen/deuterium exchange with mass spectrometric analysis (ssHDX-MS), solid-state nuclear magnetic resonance spectroscopy (ssNMR), Neutron back scattering and others
  • Prediction of formulation stability rank order prior to "accelerated" or real-time assays: Accuracy, limitations
  • Pros & cons of various techniques: Ease of use, sample limitations, assay time, sample size

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 D

7:55 Chairperson’s Remarks

Jay(Zhi) Guo, PhD, Senior Scientist, Biologics, AbbVie

8:00 Analytical Strategies for Development of Biopharmaceuticals: One Size Fits All

Zahra_ShahrokhZahra Shahrokh, PhD, CMC Consultant and Chief Development Officer, STC Biologics

The principles for development of biopharmaceuticals apply to different classes of molecules, yet each molecule is guaranteed to pose its own unique challenges. This talk focuses on best practices in pharmaceutical development, with a focus on analytical tools that could minimize future surprises. Case examples of excipient degradation and potential mitigation strategies will be discussed.

8:30 Developing a Screening Platform for Novel Biotherapeutics

Jay_GuoJay(Zhi) Guo, PhD, Senior Scientist, Biologics, AbbVie

Novel bi-functional biologics with a variety of formats to choose from (scFv, Fab, mAb, etc.) and fused to different payloads (cytokines, growth factors, a different scFv, etc.) is of immense interest for targeted delivery and improved efficacy. Payloads can be fused at different positions and spacer lengths and it is now apparent that payloads dominate production and stability of biologics, thus confounding drug-like properties (DLPs). To better understand structure-function relationship and rapidly advance candidates with good DLPs, we will discuss our throughput screening process.

9:00 Accelerating Potency Assays to Support Early Stage Product Quality and Formulation Decisions

Nathan P. Oien, PhD, Senior Scientist, Analytical Development Department, KBI Biopharma, Inc.

Potency assays are often unused during early stage biopharmaceutical development for various reasons including assay development timelines, high variability, and assay execution timelines. However, potency assays using a fully optimized assay could provide powerful data to help guide product quality and formulation decisions. Technologies and processes that exist to help increase throughput and decrease variability will be highlighted.

9:30 SELECTED POSTER PRESENTATION: Freeze-Drying of Highly Concentrated Proteins: Effect of Formulation and Processing on Phase Composition, Porous Structure and Reconstitution Time

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

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

10:30 Chemical Stability Screening in Early Stage Antibody Discovery

Tingwan_SunTingwan Sun, PhD, Senior Scientist, Protein Analytics, Adimab LLC

Isomerization and deamidation of therapeutic leads can often delay development timelines and provide challenge and risks for downstream process. Sequence-based prediction to scan for NG and DG can often lead to false positive results. Here we report the chemical liability analysis of ~140 clinical stage antibodies, under forced degradation conditions.

11:00 Towards an Improved Predictor for Shelf Stability: Using Denaturants to Measure Interactions between Partially Folded Proteins

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

A key obstacle to predicting aggregation is difficulties in isolating the partially folded states believed to be key intermediates in the aggregation pathways. We have measured protein-protein interactions under chemically denaturing conditions as a surrogate parameter to reflect the colloidal stability for partially folded proteins under native conditions. We show the measurements provide an indicator for aggregation propensity and provide a complementary technique for assessing storage stability.

11:30 PANEL DISCUSSION: Assessing the Comparability and Stability of New Biologics and Novel Formulations

  • Examples for cell and gene therapy products
  • Guidance and expectations
  • Tools and techniques


Rajiv Nayar, PhD, President, HTD Biosystems, Inc.


Jay(Zhi) Guo, PhD, Senior Scientist, Biologics, AbbVie

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

Mark Brader, PhD, Research Fellow, Drug Product Analytical Development, Moderna Therapeutics, Inc.

Peter Fung, PhD, Senior Manager, Product Marketing, NanoTemper Technologies

Scott H. Chamberlain, Senior Research Associate, Protein Analytical Chemistry, Genentech

Zahra Shahrokh, PhD, CSO, STC Biologics

12:00 pm Dig Deeper into Protein Quality and Stability

Lisa Adamiak, PhD, Applications Scientist, Marketing, Unchained Labs

Underlying all biologics development is finding the best protein candidates along with optimal formulation conditions to minimize aggregation while preserving stability. Whether you’re trying to understand more about your molecules earlier or later in your process, Unchained Labs can simplify your work. We’ll discuss how you can use a combination of applications like thermal melting and aggregation, sizing and polydispersity, and chemical denaturation to thoroughly characterize more biologics with less sample and faster than before.

12:30 Luncheon Presentation: A Quick Protein Quality Check that Will Improve Biotherapeutic Candidate Purification and Characterization Workflows

Peter_FungPeter Fung, PhD, Senior Manager, Product Marketing, NanoTemper Technologies

Starting with material of questionable quality for protein purification and characterization leads to irreproducible or ambiguous results. Transitioning between upstream and downstream workflows can be a challenge for bioprocessing researchers, particularly when the quality of the sample material is not known. We present a new platform that swiftly identifies sample quality and relative functionality in minutes complementing and guiding bioprocessing workflows—making go/no go decisions easy and quick—saving time, effort and producing more consistent results.

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

Back Bay D

1:55 Chairperson’s Remarks

Rajiv Nayar, PhD, President, HTD Biosystems, Inc.

2:00 Protein Engineering Methods to Increase the in vivo Potency and Half-Life of Therapeutic Proteins

Krishna M.G. Mallela, PhD, Associate Professor of Biophysical Chemistry, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus

In this talk, we will discuss the protein engineering methods to increase the in vivo potency and half-life of therapeutic proteins. We will share some unpublished results where we were able to extend the in vivo potency of a pharmaceutical protein by 12-fold, and significantly increase its half-life.

2:30 NEW: Increasing Pharmaceutical Discovery and Development through a Rapid One Platform Approach: Getting More with Less without Losing Quality

Rajiv Nayar, PhD, President, HTD Biosystems, Inc.

One of the major challenges facing drug developers is how to evaluate the “developability” of their biomolecules with respect to formulation and stability issues with very limited amounts of precious drug substance. An effective approach to rapidly identify an appropriate formulation in the minimum number of trials and getting the maximum amount of information using a multivariate response-surface DoE platform and high throughput analytics with principles of QbD is presented.

3:00 How to Utilize Design of Experiments (DoE) Principles for the Development of High Throughput, Robust Methods for the Assessment of Product Quality

Jeremy_SpringallJeremy Springall PhD, Scientist I, Analytical Sciences, MedImmune, A member of the AstraZeneca Group

Being able to generate accurate and precise analytical data to provide information on product quality in a timely manner is a great challenge facing analytical groups. By adopting a Design of Experiments (DoE) approach, we can overcome many hurdles facing the implementation and adoption of these high-throughput methods with the data generated being of comparable quality to that from longer lot release methods.


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

  4:15 Sampling Statistics for Subvisible Particle Analysis of Drug Products

Marina_GühlkeMarina Gühlke, PhD, Analytical Scientist, Coriolis Pharma

Subvisible particles analysis is required by the authorities for biopharmaceutical drug product development. Available sample volumes of biologics are often limited, and USP<787> allows light obscuration measurements at sample volumes of ~ 1 ml, in contrast to the traditional USP<788> (25 ml). However, careful consideration of analyzed sample volumes is necessary to obtain statistically relevant results, in particular for samples with low particle counts.

4:45 Mechanism for the Screening of Patchy Anisotropic Interactions in Protein Solutions Using Hydrophobic Excipients

Prasad_SarangapaniPrasad Sarangapani, PhD, Staff Scientist, Protein Biochemistry, Regeneron Pharmaceuticals

In this presentation, we will discuss and share results on mechanism for the screening of patchy anisotropic interactions in protein solutions using hydrophobic excipients.

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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