Formulation Development Course - Protein Drug Development

September 29, 2011

Speaker Roster and Topics

Overview and Challenges in Biologics Drug Development

Zahra Shahrokh, Ph.D., Senior Vice President, Aura Biosciences

Quality by Design

Nick Warne, Ph.D., Senior Director, Formulations, Pfizer

Getting from Discovery to Phase 1

Bret Shirley, Ph.D., Senior Director, Pharmaceutical & Process Development, Stryker Biotech

Biologics Quality Issues in Subcutaneous Delivery

Henryk Mach, Ph.D., Senior Investigator, Merck Research Laboratories

Panel Discussion

Topics covered: Product development and life cycle management; Drug delivery systems; Regulatory pathways; In-licensing:perspectives of licensees and licensors; and Biosimilars

Nick Warne, Ph.D., Senior Director, Formulations, Pfizer

Bret Shirley, Ph.D., Senior Director, Pharmaceutical & Process Development, Stryker Biotech

Henryk Mach, Ph.D., Senior Investigator, Merck Research Laboratories

Moderator: Zahra Shahrokh, Ph.D., Senior Vice President, Aura Biosciences

Course Description

This short course is the third in a series we started last year, and is intended to provide a foundation for people who are involved in early drug development.

Protein therapeutics present significant challenges to the development of stable, commercially viable pharmaceutical products. Proteins are highly complex, and each molecule presents unique challenges that must be appropriately understood and addressed during the formulation development process. Protein Drug Development is designed to impart to scientists the tools and knowledge necessary to systematically approach the development of therapeutic protein products. 

The course will detail protein product development requirements within the context of each phase of the clinical development process, with the ultimate goal of a robust, stable, user-friendly commercial product. An overview of the entire product development lifecycle will be considered from a technical perspective.  The Quality by Design initiative will be discussed, with a case study on how it impacts both strategic and tactical planning in drug product design.  In early development, knowledge of protein structure, analytical methodologies and a mechanistic understanding of degradation pathways are leveraged to inform the regulatory and clinical hurdles of late development.   Examination of the development pathway will be complimented by strategic assessment of product quality and safety issues associated with aggregation.  Case studies will be used to illustrate important aspects of product development to allow scientists to gain firsthand knowledge of solutions to real-world challenges in the development of protein pharmaceutical formulations.

Attendees will include scientists (B.S.-Ph.D.) from Boston-area biopharmaceutical companies.  These scientists are eager to learn practical applications so that they are better equipped to perform their job. 

One-on-one sessions with speakers are available on a first come, first served basis.  Attendees will receive booklets of the relevant course information. 

Session Overviews and Speaker Bios

Session 1. Overview and Challenges in Biologics Drug Development

Overview: Efficiently advancing products through the development pipeline requires an integrated approach that provides foresight and predictability while utilizing resources smartly.  Whether the business model is “fast-to-clinical POC” or “fast-to-approval”, gaining such predictability requires process technology capabilities and a business planning that integrates process development (PD) with clinical, preclinical, and regulatory aspects of product development. 

This presentation will discuss PD Life Cycle planning as a disciplined approach to process development to facilitate learning across programs and minimize rework.  PD Life Cycle takes an integrated approach among the 4 disciplines of process development to answer critical questions early in the development cycle, ensuring timely and appropriate adjustments to the overall program plan and better use of resources. Efficiency is further gained by developing and applying process platforms with small scale models that are predictive of manufacturing scale performance.  Such platforms have been established for antibody-based products and are evolving for enzyme replacement therapies, but are lacking for most non-antibody products.  Nonetheless, key questions to ask at a given stage of development remain similar. This presentation will give case examples to highlight such key questions while comparing the development of antibody versus non-antibody based products.

With two decades career in CMC development of biologics, Zahra Shahrokh, Ph.D., is currently the Senior Vice President of Development at Aurabiosciences, overseeing CMC development, nonclinical development, and regulatory aspects of nanoparticle delivery systems using viral capsid proteins.  Prior to that, she was Senior Director of Pharmaceutical and Analytical Development at Shire Human Genetic Therapies since 2002, where she built the organizational capability and drove technical excellence in product development.  Since 2009, she was also appointedas Head of CMC Operations and later was responsible for Process Development Operations, where she built project management systems, team training programs, and business processes for integrated product development planning.  Dr. Shahrokh was at Genentech’s department of Pharmaceutical R&D and prior to that at Scios-Nova, where she held technical and leadership roles in the Pharmaceutical development of biologicsand small molecules.  Dr. Shahrokh has a track record in successful regulatory submissions, leading to approval of 5 biologics and progressing clinical development of several diverse class of therapeutics.  She holds a PhD in Biophysics from University of California, Berkeley, and BA in Chemistry and in Physics from University of Pennsylvania, Philadelphia. 

Session 2. Quality by Design

Overview: Recent guidance from the regulatory agencies as well as discussions with various industry groups have resulted in a concerted effort to define and implement elements of a Quality-by-Design paradigm (QbD) to process and product development.  QbD represents a systematic approach to development that begins with predefined objectives that establish the target product for the patient, and emphasizes product and process understanding and control based on good science as well as sound quality risk management.

In the discussion, we seek to describe how the elements of a sound QbD strategy help to define robust, reproducible freeze-thaw processes that are well controlled and have a lower risk profile.  We will begin by focusing on defining a QbD program as it is applied to a freeze-thaw process.  We will then discuss various considerations regarding the processes one could utilize including equipment and scale and how these processes relate to a QbD approach.  Finally, we will present several case studies which will demonstrate how these principles can be implemented.

Dr. Nick Warne, Ph.D., is the Senior Director of the Pharmaceutics R&D   Group at Pfizer BioTherapeutics Pharm Sciences in Andover, Massachusetts. Nick has been at Pfizer, formerly Wyeth BioPharma and Genetics Institute, for 21 years and has focused on protein stabilization, formulation development and drug product process development.   Nick holds numerous protein formulation patents and, with his group, has made over 100 presentations at nationa l meetings and in journals. 

Session 3. Getting from Discovery to Phase 1

Overview: For discovery-stage products, one of the first significant milestones is the initiation of a Phase I clinical trial.   While significant challenges exist to enter the clinic for any potential therapeutic, the temptation is often to proceed as rapidly as possible without appropriately taking into account the risks that this strategy introduces to further development.   This strategy often translates into entering clinical trials with a rudimentary production process or formulation, which may necessitate expensive and time consuming bridging strategies to introduce subsequent process changes into the clinic.

This talk will focus on the development of production processes, analytical methods and formulations for therapeutic proteins that are appropriate for early stage clinical trials, while also being sufficiently robust and scaleable to provide for further development without an undue impact on clinical timelines.  Risk mitigation strategies, costs and timelines for major areas of process and formulation development will be discussed within the context of developing a rapid, yet comprehensive, development strategy for therapeutic proteins. 

Bret Shirley, Ph.D., is currently the Senior Director of Pharmaceutical & Process Development at Stryker Regenerative Medicine (Hopkinton, MA) where he has responsibility for the development of cell culture and purification processes, analytical methods, formulations and drug delivery systems. Prior to his current position, he held positions at Altus Pharmaceuticals, Syntonix Pharmaceuticals, the Chiron Corporation and Boehringer Ingelheim Pharmaceuticals. Dr. Shirley has over 20 years of experience in the development of manufacturing processes and formulations for therapeutic proteins. He received a doctorate in Protein Biochemistry from Texas A&M University.

Session 4. Biologics Quality Issues in Subcutaneous Delivery

Overview: As the share of therapeutic proteins that are delivered subcutaneously continue increasing, new analytical challenges arise that are specific for this route of delivery, that include characterization of self-interaction as well as post-injection phenomena. A number of new approaches will be presented that allow efficient and precise measurement of critical parameters relevant to safety and efficacy.

The techniques include use of atomic force microscopy to visualize proteinacious subvisible particles, determination of the concentration of monoclonal antibodies by the analysis of second derivative UV spectra, flow cytometry for the determination of subvisible particle counts, high-throughput acidic variant analysis and fluorescence spectroscopy to study phase separation phenomena as well as photo-degradation kinetics, an adaptation of a high-pressure liquid chromatography (HPLC) system for the measurement of solution viscosity and a variable-speed streamlined analytical ultracentrifugation method. An ex-vivo model for understanding the factors that affect bioavailability after subcutaneous injections, including buffer charge effects, and a sensor-based method for the assessment of serum compatibility will also be described. Most of these approaches allow not only a more precise insight into the nature of the formulated proteins, but also offer increased throughput while minimizing sample requirements.

Dr. Henryk Mach, Ph.D., is a member of Vaccine Drug Product and New Technology Development group at Merck Research Laboratories, focusing on biophysical analysis of biological macromolecules. He is an author of over 40 professional papers and book chapters that reflect his research interests in the area of near-UV derivative spectroscopy, virus assembly phenomena, and computational methods. Before joining vaccine development area at Merck in 1990, he was a research associate in Prof. Middaugh’s laboratory at the University of Wyoming. Dr. Mach received a M.S. degree in Biotechnology from Agricultural University and Ph.D. in biophysics from Jagiellonian University, both in Krakow, Poland.

Time

Registration and breakfast is from 8:00-8:45am – we ask that you please arrive by 8:00am and highly encourage speakers to stay the duration of the day to network with attendees. The course will start promptly at 8:45am. Complimentary breakfast and lunch will be provided, along with facility tours during morning and afternoon breaks.  The event will conclude with a networking cocktail reception.

Location and Parking

Wolfe Laboratories Facility

134 Coolidge Avenue

Watertown, MA 02472

Free parking is located in the back of Wolfe Laboratories' facility. The parking lot can be accessed to the left of the building – the gate will be open. Once parked, please walk to the front of the building. We are located on the second floor.

Registration

Registration fees are $85. The course will be limited to 30 attendees to ensure that we have a small and intimate group to facilitate learning and provide attendees with ample opportunities for one-on-one interaction with the course instructors. 

Who Should Attend?

This course is designed for Pharmaceutical Industry personnel involved in the design and development of formulations for therapeutic proteins.  

• Pharmaceutical Chemists
• Protein Chemists
• Bioanalytical Chemists
• Biochemists
• Regulatory Affairs
• Project Management
• Manufacturing
• Quality Control

Contact

Wolfe Laboratories 
events@wolfelabs.com 
617-923-7600 

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