Cambridge Healthtech Institute’s Ninth Annual
Optimizing Biologics Formulation Development
Formulation Strategies in an Era of Accelerated Timelines, New Product Formats and Novel Delivery Systems
January 9-10, 2017 | Hilton San Diego Bayfront | San Diego, CA

Each year, the PepTalk Optimizing Biologics Formulation Development meeting brings together an international audience of analytical and formulation scientists from leading industry companies to hear solutions to the most significant challenges in their field. For 2017, the conference focuses on the science and strategies of formulation development in an era of compressed timelines, novel molecular and product formats and products based on novel device and packaging systems.

MONDAY, JANUARY 9

7:30 am Conference Registration and Morning Coffee

9:00 Welcome by Conference Organizer

Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute

9:05 Chairperson’s Opening Remarks

Murali Bilikallahalli, Ph.D., Senior Director, Ultragenyx

Keynote Presentation

9:10 Formulation Development in the Rapidly Evolving Biotechnology Environment

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

Formulation development of biologics is evolving rapidly. While teams seek efficient approaches to screening compounds to assess developability, the increased complexity of biologics is demanding innovative approaches to formulation and dosage form development. It is critical to make ‘simple things simple’ and streamline efforts on monoclonal antibodies amenable to platform approaches. This efficiency creates capacity for challenging multi-antigenic vaccines, enzymes, and novel modalities such as gene and cell based therapies.

EARLY STAGE MOLECULAR ASSESSMENT

9:50 Techniques and Strategies for Evaluating Developability of Novel Modalities

Francis Kinderman, Ph.D., Senior Scientist, Drug Product and Formulation Technologies, Amgen

Novel therapeutic modalities present new challenges for drug development. New techniques and additional characterization are required for such products due to unique product quality attributes and poor platform fits. Early characterization of attributes and exploration of formulation space are crucial to improve the understanding of newly engineered molecules and to screen for candidates with the best potential to fulfill the intended target product profile.

10:20 Coffee Break

FORMULATION IMPACTS OF PRODUCT AND DOSAGE FORM DESIGN

10:45 Patient Centricity and System Integration as New Drivers of Biologic Drug Product Design Strategy

Didier Pertuy, Vice President, Global Drug Device Integrated Development, Sanofi

Health ecosystem evolution and the rise of chronic treatments are shifting customer decision power from physicians to patients and payers. In parallel, the technology demand for self-administrated injectable Drug Device Combinations, which are complex integrated systems, is increasing significantly with emerging penetration of the digital ecosystem into the drug delivery world. These trends make patient-centricity and system integration two key drivers of Biologic Drug Product design.

11:15 Early Device and Container Closure System Evaluation

Adam McCullough, Principal Engineer, Advanced Device Technologies, Amgen

Early identification of risks enables focused evaluation of ‘devicibility’ and ‘show-stoppers’ early in the assessment process. Factors such as user needs, drug product compatibility, container closure integrity, particulate risks, development status, and fit to manufacturing network are important to consider before committing significant resources to new biologics delivery platforms. Some underlying principles around design space consideration and case studies will be included in this presentation.

11:45 Overcoming the Challenges in Developing Multi-Dose Formulations of Aggregation-Prone Peptides

Jingtao Zhang, Ph.D., Principal Scientist, Pharmaceutical Sciences, Merck Research Laboratories

Preservatives needed in multi-dose peptide formulations can greatly increase stability risks and can frequently cause compatibility concerns. This talk will discuss these challenges, present state-of-the-art understandings in peptide formulation, and highlight several strategies in overcoming the challenges. The unique aspect of formulation development experiences in the talk could be highly applicable to other biologicals that may require preservatives or stabilizers.

12:15 pm Meet GRUNT: Ditch Dialysis and Amicon for Good

Greg Manley, Ph.D., Senior Applicantions Scientist, Unchained Labs

Traditional approaches for buffer exchange include dialysis and centrifugal UF/DF devices which are manual and extremely labor intensive. Unchained Labs' GRUNT is the first fully automated buffer preparation and buffer exchange system offering a unique automated UF/DF buffer exchange of a single protein into 12 different system-made buffers with only one hour of hands-on time. It will even concentrate your protein and add excipients at the end. Dialysis no more, Grunt is here.

12:45 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

FORMULATION DEVELOPMENT FOR NOVEL MODALITIES

2:00 Chairperson’s Remarks

Krishnan Sampath, Ph.D., Senior Director, Drug Product Sciences, MacroGenics, Inc.

2:05 Pushing Formulation Development into Discovery through Antibody Design and High-Throughput Screening

Bruce Kerwin, Ph.D., Vice President, Drug Product Design, Just Biotherapeutics

The stability of the protein is considered in the context of drug development as a whole from inception of the biopharmaceutical to understanding the needs of the patient and commercialization which then defines strategies for stabilization, concentration and delivery. This talk will focus on an integrated approach to drug product design encompassing in silico tools, high throughput screening and development of predictive tools that can integrate with the commercialization process.

2:35 Formulation Development for Dual Affinity Antibody-Based Molecules

Krishnan Sampath, Ph.D., Senior Director, Drug Product Sciences, MacroGenics, Inc.

Dual-Affinity Re-Targeting (DART) are antibody-based molecules designed to simultaneously bind to two or more targets. These versatile molecules have the potential for improved safety profile through enhanced selectivity and recruitment of specialized effector cells. Some of these DARTs pose formulation and process challenges related to self-association properties of the molecules. The presentation will discuss the formulation and process development strategy using this novel class of molecules as a case study.

3:05 Linking Molecule Specific Characteristics to Process Development: The Power of “Getting to Know” the Molecule

Katherine Bowers, Ph.D., Principal Scientist/Group Leader, Analytical and Formulation Development, FUJIFILM Diosynth Biotechnologies

This presentation will provide some examples of how “getting to know” the characteristics of protein molecules along the process development trajectory (using biophysical techniques such as light scattering, chemical and heat denaturation, spectroscopy, etc.) played a crucial role in developing robust processes and overcoming challenges associated with inherently complex molecules.

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Development of Coformulated Protein Biologics

Murali Bilikallahalli, Ph.D., Senior Director, Ultragenyx

Having a two or more therapeutic proteins in a single drug product has several advantages for oncology and infectious diseases therapeutics area. Advantages may include patient compliance, cost reductions, market capture and differentiation. This talk will highlight the challenges  involved in developing such combination drug products.   

4:30 Development of Formulations Containing Monoclonal Antibodies and Recombinant Hyaluronidase (rHuPH20)

Claudia Mueller, Ph.D., Senior Scientist, Late-Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, F. Hoffmann-La Roche Ltd.

Subcutaneous application faces limitations regarding the drug volume to be administered. Potential strategies to enable delivery of the necessary doses are increase in drug concentration and/or temporary enlargement of the interstitial space at the injection site, e.g. by using rHuPH20. The presentation focuses on challenges for product development arising from combination of two proteins, rHuPH20 and a mAb, in order to maintain both stability and activity in a single formulation.

5:00 Formulation Development for Novel Antibody Drug Conjugates

Mike Fleming, Scientist, Analytical and Pharmaceutical Sciences, ImmunoGen, Inc.

Antibody-drug conjugate (ADC) formulation development can be particularly challenging, not only due to the complexity and heterogeneity of the product, but also due to potential changes in higher order structure of the monoclonal antibody (mAb) component that can occur during the conjugation process. Conjugation of hydrophobic compounds to mAbs also adds to these challenges. This presentation will address several case studies where these formulation challenges have been addressed.

6:20-7:30 Welcome Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

TUESDAY, JANUARY 10

8:00 am Conference Registration and Morning Coffee

INNOVATION

8:30 Chairperson’s Remarks

John Wang, Ph.D., FAAPS, Principal Scientist, Genentech

8:35 Characterization of Excipient Phase Behavior and its Impact on Product Quality

Vishal Nashine, Ph.D., Senior Research Investigator, Bristol-Myers Squibb

9:05 New Grade of Polysorbate to Overcome Particle Formation

John Wang, Ph.D., FAAPS, Principal Scientist, Genentech

It has been shown that residual enzymes, present in drug substance in minute quantity, are capable of degrading polysorbate 20 and 80 in drug products and subsequently generate subvisible and visible particles. A new grade of polysorbate 20 that is composed of >98% lauric ester was evaluated and found to generate no particle upon enzyme hydrolysis. We proposed to USP to include this material in polysorbate monograph.

9:35 Spray Dried Biologics: Formulation Considerations

Michael Burke, Senior Research Chemist, Bend Research

Spray drying is a method for the continuous collection of dry powder. The process is tunable and scalable, which allows for rapid small-scale formulation screening and cGMP manufacture. Key aspects include mild temperature exposures, rapid drying kinetics, and ability to vary particle size, bulk densities, and reconstitution quality. Functional excipients can be added and include high Tg sugars, polymers, amino acids, buffer salts and/or surfactants to enhance selected properties.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

FORMULATION CHALLENGES DURING CLINICAL DEVELOPMENT

11:00 Clinical Stage Evaluation of a Biologic Formulation Using Novel Robustness Diagrams

Radhakrishna Maroju, Ph.D., Senior Scientist, Drug Product Development and Operations, Teva Biopharmaceuticals

Formulation robustness is critical to ensure product quality and is required to be demonstrated in a marketing application. An effective QbD approach associated with a novel method of displaying robustness will be presented. Termed in context as ‘robustness diagrams,’ they allow comprehending the acceptable limits of all formulation variables simultaneously at one glance across multiple quality attributes. Such diagrams are handier and would potentially help accelerate the review process.

11:30 In-Use Stability Evaluations for Enabling Low Dose Intravenous Administration

Xiaofeng Lu, Ph.D., Principal Research Scientist, AbbVie Biotherapeutics, Inc.

In-use stability evaluations are performed to assess the effect of dose preparation, handling and administration on product quality attributes. In this presentation, technical and practical challenges encountered in enabling low dose intravenous administration for a bispecific protein will be discussed. A testing approach for robust in-use stability assessment will be recommended.

12:00 pm When Standard Formulation Strategies Fail - Recombinant Albumin for Stabilization of Hard-to-Formulate Biotherapeutics

Phil Morton, Ph.D., Science Director, Bioprocess Characterisation, Albumedix Ltd.

The expanding field of biotherapeutics gives promise for improvement of several treatment options. Many of the biopharmaceuticals found to be efficacious, however, continue to face ex vivo instability challenges that are not readily solved by standard excipients. Recombinant human albumin, however, can potentially alleviate these shortcomings. The mechanisms by which albumin helps stabilize biopharmaceuticals are multiple and dependent on the specific drug. Data are presented here that exemplify these different mechanisms.

12:30 Session Break

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Close of Conference