preliminary program wcbp 2016...chi-ting huang, cth analytical consulting peter johnson, 3m drug...

PRELIMINARY PROGRAM

WCBP 2016

20th Symposium on the Interface of

Regulatory and Analytical Sciences for

Biotechnology Health Products

Symposium Co-Chairs:

Michael Kennedy, CBER

Juhong Liu, CDER

Brian K. Nunnally, Biogen

The Mayflower Hotel

Washington, DC

January 26-28, 2016

Table of Contents

The Organizing Committee gratefully acknowledges the Symposium Program

Partners for their generous support of WCBP 2016

Sustaining Diamond Program Partner

F. Hoffmann-La Roche, Ltd.

Sustaining Platinum Program Partner

AbbVie, Inc.

Biogen

MedImmune, a member of the AstraZeneca Group

Sustaining Gold Program Partner

Novo Nordisk A/S

Sustaining Silver Program Partner

Pfizer, Inc.

Gold Program Partners

Agilent Technologies

Amgen Inc.

Bill & Melinda Gates Foundation

Celgene Corporation

Silver Program Partners

Baxalta

BioMarin Pharmaceutical, Inc.

Bristol-Myers Squibb Company

Silver Program Partners - Continued

Catalent Pharma Solutions

Eli Lilly and Company

ProteinSimple

SCIEX

Waters Corporation

Bronze Program Partners

Bruker Daltonics, Inc.

Genzyme Corporation, a Sanofi Company

GlaxoSmithKline

Friend of CASSS Program Partners

Bayer Healthcare, LLC

Janssen Pharmaceutical, Research & Development, LLC

Seattle Genetics, Inc.

Exhibitor Partners

AAPS

ABC Laboratories, Inc.

Agilent Technologies

Avid Bioservices, Inc.

BioPhia Consulting, inc.

Bio-Rad Laboratories, Inc.

BioReliance Corporation

Bruker Daltronics, Inc.

Caprion

Catalent Pharma Solutions

Covance, Inc.

Eurofins Lancaster Labs

Hunter Lab

Genedata

Genovis AB

KBI Biopharma Inc.

NanoImaging Services

New England Biolabs, Inc

PPD

Protein Metrics, Inc.

ProteinSimple

ProZyme, Inc.

SCIEX

SGS Life Science Services

Thermo Fisher Scientific

Waters Corporation

Wyatt Technology Corporation

Media Partners The Scientific Organizing Committee gratefully acknowledges the following

media for their promotional consideration of WCBP 2016

American Laboratory

American Pharmaceutical Review

Bio Process International

BioProcessing Journal

Bio Tech International

Genetic Engineering and Biotechnology News

IPQ Publications

LCGC North America

Pharmaceutical Outsourcing

RSC Advances

The Analytical Scientist

The Medicine Maker

The Pathologist

SeparationsNOW.com

Technology Networks Limited

Acknowledgements Symposium Co-Chairs Workshop Committee Co-Chairs

Michael Kennedy, CBER, FDA Anissa Cheung, OVRR, FDA

Juhong Liu, FDA Michele Dougherty, CDER, FDA

Brian K. Nunnally, Biogen Joe Kutza, MedImmune, a member of the

AstraZeneca Group

Shawn Novick, Seattle Genetics, Inc.

Steering Committee

John Dougherty, Eli Lilly and Company Christopher Joneckis, CBER, FDA

Kathy Francissen, Genentech, a Member of the Edwin Moore, University of Illinois

Roche Group Ilona Reischl, BASG/AGES

John Frenz, Alnylam Pharmaceuticals, Inc. Marjorie Shapiro, CDER, FDA

Robert Sitrin, PATH

Emeritus Members of the Steering Committee

Robert Cunico, Pacific Bio Labs

William Hancock, The Barnett Institute, Northeastern University Michael Kunitani, Marin Analytical Consulting

Thomas Layloff, Supply Chain Management System

WCBP 2016 Program Committee

Sid Advant, Kemwell Biopharma

Vince Anicetti, Coherus Biosciences

Mehrshid Alai-Safar, Baxalta, Inc.

Kris Antonsen, BioMarin Pharmaceutical, Inc.

Laura Bass, Bristol-Myers Squibb

Cheryl Blasie, Bristol-Myers Squibb

Marcus Blȕmel, Novartis Pharma AG

Andrew Chang, Novo Nordisk, Inc.

Xiao-Ping Dai, Celgene Corporation

Bharat Dixit, Genocea Biosciences, Inc.

John (JR) Dobbins, Eli Lilly and Company

Roman Drews, LFB-USA

Julia Edwards, Biogen Idec

William Egan, GlaxoSmithKline

Elizabeth Fowler, CMC Consulting Services

Michelle Frazier, AbbVie, Inc.

Rajesh K. Gupta, Biologics Quality &

Regulatory Consultants, LLC

Reed Harris, Genentech, a Member of the

Roche Group

John Hennessey, NovaDigm Therapeutics, Inc.

Ping Hu, Janssen Pharmaceutical R & D, Inc.

Stephen Hadley, Bill & Melinda Gates

Foundation

David Lee, AbbVie, Inc.

Karen Lee, Sanofi Global Biotherapeutics

Kathy Lee, Eli Lilly and Company

William Matousek, Regeneron Pharmaceuticals,

Inc.

Jamie Moore, Genentech, a Member of the Roche

Group

Shawn Novick, Seattle Genetics, Inc.

Joann M. Parker, Pfizer, Inc.

Stefanie Pluschkell, Pfizer, Inc.

Lesley Redfern, Abbvie Inc.

Roberto Rodriguez, Bristol-Myers Squibb

Mark Schenerman, MedImmune, a member of the

AstraZeneca Group

Sally Seaver, Seaver Associates, LLC

Emily Shacter, Think FDA

Zahra Shahrokh, STC Biologics, Inc.

Joseph Siemiatkoski, BioProcess Technology

Consultants, Inc

Brian Silvey, Baxalta, Inc.

Dan Some, Wyatt Technology Corporation

Arne Staby, Novo Nordisk A/S

Lisa Stephenson, MedImmune, a member of the

AstraZeneca Group

Chi-Ting Huang, CTH Analytical Consulting

Peter Johnson, 3M Drug Delivery Systems

Maura Kibbey, United States Pharmacopeial

Convention (USP)

Carol Krantz, ProNAi Therapeutics, Inc.

Bob Kuhn, Amgen Inc.

Annie Sturgess, Bristol-Myers Squibb

Garry Takle, Merck, Sharp and Dohme

Michael Washabaugh, MedImmune, a member of

the AstraZeneca Group

Ziping Wei, Novavax, Inc.

Yuan Xu, Merck Research Labs

Heidi Zhang, Genentech, a Member of the Roche

Group

CASSS WCBP 2016 Student Travel Grants

CASSS is pleased to provide a limited number of student travel grants for PhD students and post-

docs who present applicable posters at the 20th Symposium on the Interface of Regulatory and

Analytical Sciences for Biotechnology Health Products (WCBP 2016). PhD students or post-

doctoral fellows conducting research at academia throughout the world are eligible.

Requirements are:

Present a poster on a WCBP 2015 topic

Proof of studentship/post-doc status

Recommendation from the supervisor/advisor

An abstract submission

A CV for the candidate

This year’s winners include:

Development of a Customizable Microwell Array for Controlled Study of Heterogeneous

Cell Populations

Natasha Arora and Marianna Sofman

Massachusetts Institute of Technology (MIT), Boston, MA USA

Insulin: A Case Study for the Global Supply of a Protein Pharmaceutical

Raeann Dalton

The Barnett Institute, Northeastern University, Boston, MA USA

Rapid 3D Extrusion of Synthetic Tumor Vascular Microenvironments

Joshua M. Grolman

University of Illinois at Urbana-Champaign

Procainamide Labelling as Part of a Flexible Glycoprofiling System for Monitoring of Gal-

α1-3Gal Related Glycosylation Critical Quality Attributes (GCQAs) of Monoclonal

Antibody (mAb) Therapeutics Throughout the Product Life Cycle.

Radoslaw Kozak

Demasking of Endotoxin in a Drug Product

Johannes Reich

University of Regensburg, Regensburg, Germany

Biopharmaceutical Stability Studies on Therapeutic Proteins with off-line Tandem Mass

Spectrometry and Real Time Raman Techniques

Di Wu

The Barnett Institute, Northeastern University, Boston, MA USA

WCBP 2016 Scientific Program Summary

TUESDAY, JANUARY 26, 2016

07:00 – 17:00 Registration in the Senate Room

07:00 – 08:00 Continental Breakfast in the East/State Rooms

Sponsored by ProteinSimple

08:00 – 08:15 CASSS Welcome and Introductory Comments

08:15 – 08:35 5th Annual William S. Hancock Award Announcement in the Grand

Ballroom

Sponsored by CASSS and Presented by Wassim Nashabeh, F.

Hoffmann-La Roche, Ltd.

08:35 – 08:45 WCBP Welcome and Introductory Comments

Brian K. Nunnally, Biogen

08:45 – 09:00 Tribute to Past Chairs of WCBP

09:00 – 09:45 Keynote Speaker – Gerd Binnig, Definiens AG

09:50 – 10:50

Opening Regulatory Panel with the FDA

Panel Discussion in the Grand Ballroom

Session Chair: Brian K. Nunnally, Biogen

Moderator: Stefanie Pluschkell, Pfizer, Inc.

Panel Members:

Ashley Boam, Acting Director, CDER/OPQ/OPPQ, FDA, USA

David Deloski, CDER, FDA USA

Christopher Joneckis, Associate Director, CBER,, FDA, USA

Steven Kozlowski, Director, CDER, FDA, USA

10:50 – 11:15 AM Break – Visit the Exhibits in the East/State Rooms and the Posters in

the Promenade Room

TUESDAY, JANUARY 26, 2016 - Continued

One Global Specification

Plenary Session in the Grand Ballroom

Session Chairs: Neha Frantz, Biogen and Annie Sturgess, Bristol-Myers Scribb

11:15 – 11:40 Right Sizing Release and Stability Testing, Agency Responses and

Future Directions

Barry Cherney, Amgen Inc., Washington, DC USA

11:40 – 12:05 Chasing the Holy Grail: Global Streamlined Approach to

Specifications… or Let There Be Light!

Diane Wilkinson, Biogen, Ltd,, Berkshire, United Kingdom

12:05 – 12:30 PMDA Perspective on Specifications for Biotechnological Products

Yasuhiro Kishioka, Pharmaceuticals and Medical Devices Agency

(PMDA), Japan

12:30 – 12:45 Panel Discussion - Questions and Answers

12:45 – 14:15 Lunch Break - Participants on their own

13:00 – 14:00 Technical Seminars

Deploying LC/MS Technologies Beyond the Realm of Biotherapeutic Characterization

Sponsored by Waters Corporation Chinese Room

NOTE: Lunch is provided for first 100 attendees

N-Glycan Analysis: From High-Throughput Screening to In-Depth Characterization

Sponsored by ProZyme, Inc District Room


Sponsored by Catalent Pharma Services Palm Court Room


TUESDAY, JANUARY 26, 2016 - Continued

Pay Now or Pay Later: Diverse Process Development Pathways that Ultimately Support

Commercialization


Session Chairs: Xiao-Ping Dai, Celgene and Jamie Moore, Genentech, a Member of the

Roche Group

14:15 – 14:40 A Regulatory Perspective on Product Development

Laurie Graham, CDER, FDA, Silver Spring, MD USA

14:40 – 15:05 Evaluation of Production from Cell Pools as an Enabling Technology

for Rapid Advancement of Biologics

Trent Munro, Amgen, Inc., Thousand Oaks, CA USA

15:05 – 15:30 Balancing Speed Versus Risk—When to Make Investment Choices in

Development Projects.

John Joly, Genentech, a Member of the Roche Group, South San

Francisco, CA USA


15:45 – 16:00 Transition Time and PM break for Roundtable Session

16:00 – 16:45 Roundtable Session:

Select Your Table Topic in One of Four Rooms

Chinese Room

District Room

Exhibitor Hall (East/State Rooms)

Palm Court Room

Please refer to table topics listing in the back of this program book.

Table seats are on a First Come, First Serve Basis

16:45 – 17:00 Transition Time

17:00 – 18:15 Workshop Session 1

Regulatory and Compendial - Combination Products

Rakhi Dalal, CDER, FDA, Donna French, Genentech, a Member of the Roche Group,

Steve Hertz, CDER, FDA, Ed Patton, CBER, FDA, Michael Soberg Christensen, Novo

Nordisk AG, John Weiner, OCP, FDA

Pay Now or Pay Later: Prioritizing CMC Development Activities in Early Development

Christopher Downey, CDER, FDA, Catherine Eakin, Seattle Genetics, Inc., Michelle Frazier,

AbbVie, Inc., Sara Gagneten, CBER, FDA

Regulators’ Perspectives on Trends in the Regulation of Biopharmaceutical Products in

Europe and Asia

Co-chairs: Kathy Francissen, Genentech, a Member of the Roche Group, Anthony Ridgway,

Health Canada, – Presentations By: Peter Richardson, European Medicines Agency (EMA),

United Kingdom, Daisaku Sato, Pharmaceuticals and Medical Deveices Agency (PMDA),

Japan, and Anis Talib, Malaysian Health Authority

Emerging Trends for Higher Order Structure Characterization in Biopharmaceutical

Development

Frances Namuswe, CDER, FDA, Anders Dybdal Nielsen, Novo Nordisk, Andrey Sarafanov,

CBER, FDA, William Weiss, Eli Lilly and Company

18:15 – 19:15 Poster Session I in the Cabinet Room

19:15 – 19:30 Transportation will be provided at 19:15

19:30 – 22:30 Welcome Reception at the National Archives Museum

WEDNESDAY, JANUARY 27, 2016



08:30 – 08:40 Announcements by Brian K. Nunnally, Biogen

Implications of Product-Specific Monographs for Biotherapeutic Products

Parallel Session in the Grand Ballroom

Session Chairs: John Dougherty, Eli Lilly and Company and Tina Morris, USP

08:40 – 09:05 The Role of European Pharmacopoeia Monographs in Setting Quality

Standards for Biotherapeutic Products

Emmanuelle Charton, EDQM, Council of Europe, Strasbourg, France

09:05 – 09:30 Implications of Product-Specific Monographs for Biotherapeutic

Products

Anthony Mire-Sluis, Amgen, Inc., Thousand Oaks, CA USA

09:30 – 09:55 The Role of Product-Specific Monographs in Biosimilar Product

Development

Xiaoyu Chen, Hospira, a Pfizer Company, Lake Forest, IL USA


Analytical Control Strategy of Vaccine Products

Parallel Session in the District Ballroom

Session Chairs: Arifa Khan, CBER, FDA and Ziping Wei, Novavax

08:40 – 09:05 Analytic Control Strategies of Vaccine Products During Product

Development

Freyja Williams, CBER, FDA, Silver Spring, MD USA

09:05 – 09:30 GARDASIL®9 Control Strategy Evolution During Late-Stage

Development and Beyond

Jennifer L. Dashnau, Merck & Co, Inc., West Point, PA USA

09:30 – 09:55 Definition of Analytical Control Strategy for Robust Vaccine

Development

Christina Campa, GlaxoSmithKline Vaccines, Siena, Italy


WEDNESDAY, JANUARY 27, 2016 - Continued

10:10 – 11:00 AM Break – Sponsored by Pall ForteBio, LLC

Visit the Exhibits in the East/State Rooms and the Posters in the Cabinet

Room, or attend one of the Technical Seminars


Advances in Analytical Characterization of Biotherapeutics: Powerful Data Processing

Software Leveraging High-Resolution Accurate Mass data and High-Throughput, High-

Resolution N-glycan Analysis using Multi Capillary Electrophoresis

Sponsored by Thermo Fisher Scientific Chinese Room

At-line and off: The Light Scattering Toolkit for Essential Biophysical Characterization

Sponsored by Wyatt Technology Corporation Palm Court Room


Product Quality Attributes, Risk Assessment and Control Strategies

Amin Khan, GlaxoSmithKline, Robin Levis, CBER, FDA, Pat McGeehan, MedImmune, A

member of the AstraZeneca Group, Leslie Rivera-Rosado, CDER, FDA, Joseph Siemiatkoski, BioProcess Technology Consultants, Inc

How to Succeed with Breakthrough

Kimberly May, Merck and Company, Mikhail Ovanesov, CBER, FDA, Emily Shacter, Think

FDA, Joanna Zhou, CDER, FDA

Global Regulators Focus Americas

Gerald DiDonato, Bristol-Myers Squibb, Thomas Schreitmueller, F. Hoffmann-La Roche, Ltd.

Analytical Control Strategy for Vaccine Products

Steven Rubin, CBER, FDA, Garry Tackle, Merck, Sharp and Dohme, Michael Washabaugh,

MedImmune, A member of the AstraZeneca Group, Freyja Williams, CBER, FDA

12:15 – 14:00 Lunch Break – Participants on their own

https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=8&cad=rja&uact=8&ved=0CDMQFjAHahUKEwjFwO-NzJ3IAhXGMogKHcmvDRk&url=http%3A%2F%2Fus.gsk.com%2Fen-us%2Fcareers%2F&usg=AFQjCNGqOOzYXMMYwvll4NfAPVBkxgSwLQ&sig2=HP8QMaHjmo83xHITknTVww

WEDNESDAY, JANUARY 27, 2016 - Continued


Higher Order mAb Aggregate Analysis Using New Innovative Size Exclusion

Chromatography (SEC) Technology and

Simplifying 2D-LC, 2D-LC/MS Automated Workflows

Fast and Efficient Multi-Dimension LC & LC/MS Method Development

Sponsored by Agilent Technologies Chinese Room


Advancing the Intact mAb and mAb Subunit Mass Spectrometry Profiling Workflows

with Improved Fragmentation Strategies on Ultrahigh Resolution QTOF Sponsored by Bruker Daltonics, Inc. District Room


Breakthrough Applications to Expand and Speed Biopharmaceutical Characterization Sponsored by SCIEX Palm Court Room


Facing the Challenges of Drug Product and Device Development & Manufacturing


Session Chairs: Shan Jiang, Seattle Genetics and Margaret Speed Ricci, Amgen Inc.

14:00 – 14:25 An Integrated, Science and Risk based Approach to the Development

and Control of Biotechnology Drug Product

Anthony Mire-Sluis, Amgen Inc., Thousand Oaks, CA USA

14:25 – 14:50

Donna French, Genentech, a Member of the Roche Group, South San

Francisco, CA USA

14:50 – 15:15 Aseptic Processing of Biological Products: Current Regulatory Issues

Patricia Hughes, CDER, FDA, Silver Spring, MD USA


15:30 – 15:45 PM Break and Transition Time

15:45 – 16:30 Round Table Session II: Select Your Table Topic in One of Three

Rooms

Chinese Room

District Room

Exhibitor Hall (East/State Room)

Palm Court Room

Please refer to table topics listing in the back of this program book.

Table seats are on a First Come, First Serve Basis


16:45 – 17:45 Poster Session II in the Cabinet Room

17:45 – 19:15 Exhibit Reception in the East/State Rooms

THURSDAY, JANUARY 28, 2016



08:30 – 08:45 Announcements by Brian K. Nunnally, Biogen

Biosimilars Parallel Session in the Grand Ballroom

Session Chairs: Martin Schiestl, Sandoz and Marjorie Shapiro, CDER FDA

08:45 – 09:10 Recent Trends in the Evaluation of Analytical Biosimilarity

Thomas Stangler, Sandoz GmbH, Kundl, Austria

09:10 – 09:35

Maria-Teresa Gutierrez-Lugo, CDER, FDA, Silver Spring, MD USA

09:35 – 10:00 Similarity Assessment of Biosimilars. The Past, Present and Future

State James Anderson, Momenta Pharmaceuticals, Inc. Cambridge, MA USA


Comparability for Blood Products – How Did We Get Here and Where Are We Going?

Parallel Session in the District Ballroom

Session Chairs: Andrew Chang, Novo Nordisk and Timothy Lee, CBER, FDA

08:45 – 09:10 Twenty Years of Comparability, Where Are We Now?

Nancy Kirschbaum, CBER, FDA, Silver Spring, MD USA

09:10 – 09:35 The Development of Novel Modified Recombinant Blood Factors with

Extended Half-lives in vivo: A CMC Perspective

Stephen Raso, Biogen, Cambridge, MA USA

09:35 – 10:00 How to Mitigate Issues with Potency Assignment Assays for Clotting

Factor Products - Recent Examples from Baxalta

Peter Turecek, Baxalta GmbH, Vienna, Austria USA


10:15 – 11:15 AM Break – Visit the Exhibits in the East/State Rooms and Posters in

the Cabinet Room

THURSDAY, JANUARY 28, 2016 - Continued


Using Micro Flow Imaging as a Stability Indicating Method

Sponsored by Eurofins Lancaster Laboratories Chinese Room

Structural and Functional Biosimilarity – Concepts and Technical Considerations

Sponsored by SGS Life Science Service Palm Court Room



Stability: Strategy and Expectations for Biotech/Biological Products

Bazarragchaa Damdinsuren, CDER, FDA, Annick Gervais, UCB, Philip Krause, CBER, FDA,

Patsy Lewis, Seattle Genetics, Donnie Pullman, Biogen

Steps Towards Developing a CASSS Global Health Initiative

Workshop presented through a collaboration between MIT/CBI and CASSS

John Frenz, Alnylam Pharmaceuticals, Stacy Springs and James Leung, Center for Biomedical Innovation, Massachusetts Institute of Technology, William Hancock, The Barnett

Institute, Northeastern University

Advanced Process Control Opportunities for Biologics

Jay Higgins, Amgen, Inc., Richard Ledwidge, CDER, FDA, Hailun Ma, CBER, FDA,

Arne Staby, Novo Nordisk

Facing the Challenge of Drug Product Manufacturing, Validation, and Comparability

Strategies

Hung-Wei Chih, Genentech, a Member of the Roche Group, Emily Dubis, Biogen, Chikako

Torigoe, CDER, FDA, Nicole Trudel, CBER, FDA

12:30 – 13:45 Hosted Lunch Break in the East/State Rooms

THURSDAY, JANUARY 28, 2016 - Continued


Endotoxin Testing: Not Always as Easy as it Seems

Michael DeFelippis, Eli Lilly and Company, Patricia Hughes, CDER, FDA, Jenny Kenney,

CBER, FDA, Maura Kibbey, USP, Edwin Moore, University of Illinois

“Hot Topic” Workshop

Kathy Lee, Eli Lilly and Company, Nadine Ritter, Global Biotech Experts

New and Emerging Analytical Technologies that have been driven by the

Characterization of Biosimilars

Chi-Ting Huang, CTH Analytical Consulting, Peter Johnson, 3M Drug Delivery, Eva Marszal,

CBER, FDA, Rachel Novak, CDER, FDA

Comparability Studies in Blood derived Products and Their Recombinant Analogs

Mahmood Farshid, OBRR/CBER, FDA, Reed Harris, Genentech, A Member of the Roche

Group, Alexey Khrenov, OBRR/CBER, FDA, Bryan Silvey, Baxalta, Inc.

15:00 – 15:30 PM Break in the Promenade Foyer

15:30 – 15:55 Achieving Product Attribute Control by Implementation of

Predefined Product Quality Targets and Process Analytical

Technologies Rohini Deshpande, Amgen, Inc., Thousand Oaks, CA USA

15:55 – 16:20 Avoiding Facility Obsolescence: Immortal Facilities for Increasing

Drug Diversity

Parrish Galliher, Xcellerex Inc. GE Healthcare Life Sciences,

Marlborough, MA USA

16:20 – 16:45 Oxygen Uptake as a Virtual Cell Culture Probe

Steven Rose, MedImmune, A member of the AstraZeneca Group,

Gaithersburg, MD USA


17:00 – 17:15 Closing Comments and Invitation to WCBP 2017

Joseph Kutza, MedImmune, A member of the AstraZeneca Group,

Next Big Thing in Biologics Processing and Controls


Session Chairs: Richard Rogers, JUST Biotherapeutics, and Richard Scott Rosenthal,

MedImmune, A member of the AstraZeneca Group

Keynote Speaker

Gerd Binnig, Definiens AG, München, Germany

Born in Frankfurt, Germany, Dr. Binnig studied at the J.W. Goethe University in Frankfurt, where

he received his doctorate degree in 1978. He then immediately joined IBM's Zurich Research

Laboratory and stayed with IBM till 2002. During this time Dr. Binnig invented and developed

the Scanning Tunneling Microscope, STM, together with his colleague Dr. Heinrich Rohrer. He

went on to invent the Atomic Force Microscope, AFM, which he developed together with Calvin

Quate and Christoph Gerber during a sabbatical at IBM Almaden Research Center (1985/86) and

a guest professorship at Stanford University (1985-88). Additionally, he opened and headed a

small IBM research group from 1987 to 1995 within the University of Munich, from which he

received an honorary professorship.

Through both techniques, STM and AFM, atoms on the surface of matter are imaged and

manipulated so that features of single atoms, such as electronic states (STM) and interaction forces

(AFM), can be measured. The potential of investigating and manipulating matter on the atomic

scale started the new discipline of nanotechnology. In addition to receiving numerous awards and

honors, Dr. Binnig was awarded the Nobel Prize in Physics together with his colleague Dr.

Heinrich Rohrer for the invention of the STM.

In 1995, Dr. Binnig together with the journalist Dieter Herold founded a small research group,

which was the precursor of Definiens. In 2000 he founded the company Definiens by bringing in

investors. With his team at Definiens he developed the Cognition Network Technology, CNT, to

automatically understand complex data. This technique was initially applied to image analysis

which uniquely enabled Definiens software to analyze large numbers of images automatically, just

like the human eye and brain are capable of doing. Later, CNT was extended to the automated

analysis of data tables derived from the analysis and rich quantification of tissue images, enabling

the novel field of Tissue Phenomics.

Tissue Phenomics – Discovering Spatial Cell Patterns to Predict Drug Response in

Immunotherapy

Gerd Binnig, Definiens AG, München, Germany

Immunotherapy is an exciting and fast emerging field in oncology enabling highly effective

treatments of cancer patients. Selecting patients, however, for a specific cancer therapy is not

trivial. For several reasons this is in particular true for immune mediated therapy as the number of

different treatments will increase drastically in the near future. This is mainly due to the large

amount of potential combination therapies in this field and it has to be decided which of those

treatments is best for a specific patient at what stage of his disease. Tissue Phenomics represents a

novel technique to discover relevant patterns in tissue slides that predict clinical outcome. For

immunotherapy the characterization of the tumor with its defense mechanisms as well as the state

and the configuration of the immune cells are most important. Especially the interaction of both

can be evaluated most precisely through tissue Phenomics. First results for predicting drug

response are shown for anti-PDL1 NSCLC therapy and anti-PDL1/CTLA4 combination therapy.

NOTES:

Plenary Session Abstracts

2016 WCBP Opening Regulatory Panel with FDA Session Chair: Brian K. Nunnally, Biogen, Research Triangle Park, NC

Moderator: Stephanie Pluschkell, Pfizer, Inc., Groton, CT

Panel Members:

Ashley Boam OPQ/OPPQ, FDA, USA

David Deloski, CDER, FDA USA

Christopher Joneckis, CBER, FDA, USA

Steven Kozlowski, CDER, FDA, USA

This year’s opening regulatory panelists represent leading members of FDA who have been invited

to have an open conversation at WCBP 2016 to discuss key developments and focus areas for the

FDA that can have substantial impact on the regulatory development pathways of biologics from

the very early stages of clinical evaluation through license application and market entry. Topics

will include (1) the reorganization that has established the Office of Pharmaceutical Quality (OPQ)

and its go-forward imperatives; (2) recent experiences and new perspectives on the acceleration of

patient access to highly innovative breakthrough biotherapeutic medicines and vaccines, and any

potential hurdles in this effort; and (3) insights and key learnings from the progression of the

biosimilar development pathway in the US to date.

Regarding the first theme, the Office of Pharmaceutical Quality (OPQ) was officially launched in

January 2015, after having first been announced by longtime Center for Drug Evaluation and

Research (CDER) director Janet Woodcock in September 2012. "Quality is the underpinning of

everything we do, and it is imperative that we have a drug quality program as robust as those

programs we presently have for drug efficacy and drug safety," said Woodcock in a 2012 memo

to FDA staff. The conversation with the panelists will include details on the organizational changes

and how they have impacted or are intended to impact both pre- and post-approval quality

oversight, the speed of reviews and decision making, and the industry’s implementation of

innovative, superior manufacturing technologies along the entire lifecycle of a product. In addition,

the ability of the new OPQ to manage the reality of increasingly complex global supply chains for

the manufacture of medicines and vaccines and the sourcing of raw materials will also be

discussed.

On the topic of accelerated development pathways, the dialogue will include an update on FDA’s

recent experience with its programs that are intended to expedite patients’ access to critical

medicines, including therapies designated as “breakthrough”. The focus will center on the

challenges of expedited clinical development on the sponsors’ CMC organizations and any

recommendations that FDA can make on how to prioritize and streamline the elements of

regulatory CMC requirements either before or after market entry (may also include specifics for

combination products, devices). Furthermore, a discussion of a variety of issues that can hinder

innovation and speed of development will also take place, including any obstacles to science- and

risk-driven decisions on manufacturing process and quality testing strategies (e.g. the role of

product-specific monographs for biotherapeutics).

For the discussion on biosimilars, we look forward to FDA’s insights into their growing experience

interacting with sponsors of biosimilar development programs, pre-approval expectations to

demonstrate biosimilarity, and the evolution of FDA’s biosimilar guidelines. The FDA’s

perspective on their requirements for biosimilar market entry relative to other geographical regions

such as the EU or Canada, biosimilar naming (e.g. relative to WHO proposals) and product labeling

will also be covered.

NOTES:

Chasing the Holy Grail: A Global Approach to Specifications:

Session Chairs: Neha Frantz, Biogen and Annie Sturgess, Bristol-Myers Squibb

Specifications ranges for biotherapeutics have traditionally been defended based on process

capability and statistical analysis of manufacturing experience. As the industry implements the

principles of quality by design (QbD) both in bioprocess and assay development as well as and

“fit-for-purpose” control strategies, we find ourselves at odds between increased product and

process understanding and antiquated arguments for defending the tests and acceptance criteria

that define the specifications that support commercial registration and life-cycle management of

products globally.

Building on the WCBP themes since 2013 with the mindset of global regulatory convergence, and

driven by the increasing complexity of the biotherapeutics commercialized world-wide, this

plenary session will explore through case studies the industry’s desire to move to a scientifically-

sound, patient-centered and risk-based approach to developing and defending specifications, with

the goal of ensuring and maintaining the integrity of global supply.

NOTES:

Right Sizing Release and Stability Testing, Agency Responses and Future Directions

Barry Cherney, Amgen Inc., Washington, DC USA

Amgen has performed a holistic review of our integrated control strategy utilizing QbD principles

including scientific understanding and risk based assessments to create a streamlined, focused

testing program for our products that eliminates non-value added testing while maintaining or

enhancing our ability to ensure product quality with a high degree of confidence. While the initial

implementation of this program was described during WCBP 2015, we have now expanded the

program to include multiple products and regulatory jurisdictions. This presentation will provide

an update on our progress, using real life examples and will describe the feedback we have received

from the various regulatory authorities and the challenges we face in fully implementing our

strategy. In addition to the right size testing initiative, Amgen is leveraging advances in mass

spectrometry that are capable of replacing many of the methods currently used in establishing

specifications. The utility of this method and the regulatory implications and challenges will be

discussed along the role a robust pharmaceutical quality system can play in defining a science and

risked based control strategy that allows manufactures increased flexibility to make appropriate

decisions.

NOTES:

Chasing the Holy Grail: Global Streamlined Approach to Specifications… or Let There Be

Light!

Diane Wilkinson, Biogen, Ltd., Berkshire, United Kingdom

A key component of Pharmaceutical Product Quality controls are the specifications developed

based on science and agreed prior to and during review and approval with worldwide Regulatory

Agencies. Traditionally these are based on data from batches tested prior to application, in clinical

efficacy and safety assessment, with statistical analysis applied. Over the last few years the

Industry has implemented aspects of the principles of quality by design (QbD) in bioprocess and

in assay development and developed “fit-for-purpose” control strategies, as part of Quality

Management systems. So we therefore find ourselves in a situation where we need to take a fresh

approach to defining and agreeing specifications for development, commercialization and life-

cycle management of products and continue to strive for globalization of the approaches.

In this presentation we explore the current activities taking place in Europe and globally to move

forward with fresh approaches, via identification of regulatory pathways to expedite CMC

development and in new guidance development. The concepts of PRIME and Adaptive Pathways

and their place in defining agreement to specifications will be reviewed.

From a guidance perspective, while acknowledging that the concepts in ICH Q8, Q9, Q10 and Q11

provide opportunities for a more science- and risk-based approach for assessing changes across

product lifecycle, including to specifications, there are still opportunities to improve and expand

how specifications can be developed and controlled. We will therefore also look at the potential

impact of developing new guidance e.g. ICH Q12, where a framework to facilitate the management

of post-approval CMC changes in a more predictable and efficient manner across the product

lifecycle is being developed. This will include exploring approaches for improved post-approval

‘operational flexibility’, through alignment on the necessary information and level of detail in the

dossier and its impact on change management and regulatory reporting, for established conditions.

Concepts of improved utilization of post-approval change management plans and comparability

protocols will also be discussed. It is hoped from progression of this guidance, that the benefits of

global development and changes to global specifications will be improved on its adoption, whilst

still ensuring patient safety, efficacy and quality. We will look at the role played by Industry in

this, in partnering with Trade Associations, and Regulatory Agencies and bodies, to achieve our

goal, of scientifically-sound, patient-centered and risk-based approaches to develop and defend

specifications and move closer to our holy grail of global specifications.

NOTES:

PMDA Perspective on Specifications for Biotechnological Products

Yasuhiro Kishioka, Pharmaceuticals and Medical Devices Agency (PMDA), Japan

Since insulin was since the first recombinant insulin was approved in 1985, more than 100

biotechnological products have been approved in Japan. Based on this experience, this presentation

will give PMDA perspective on specifications for biotechnological products.

NOTES:

Pay Now or Pay Later: Diverse Process Development Pathways that Ultimately Support

Commercialization

Session Chairs: Jamie Moore, Genentech, a Member of the Roche Group, and Xiao-Ping

Dai, Celgene

This plenary session will highlight two distinct aspects of CMC development: CMC activities

completed proactively in early development that can expedite late stage development; accelerated

early phase CMC development to support fast to FIH and proof of concept.

It will consist of case studies examining successful technical development approaches such as

implementation of molecular/developability assessment, developing comprehensive host cell

protein (HCP) assays, sequence variant analysis, establishing clonality; as well as strategies to

speed development and delivery for FIH.

NOTES:

A Regulatory Perspective on Product Development

Laurie Graham, CDER, FDA, Silver Spring, MD USA

The use of 21st century pharmaceutical principles, such as those described in the International

Conference on Harmonization (ICH) Guidelines Q8-Q11, is expected to result in increased

product and process understanding leading to enhanced, risk based control strategies. During early

product development, the use of these principles can strengthen and provide flexibility to the CMC

development strategy. For example, as described in ICH Q9, an effective quality risk management

approach is expected to not only provide a proactive means to identify and control potential quality

issues, but also to facilitate better and more informed development decisions. Ms. Graham will

give a regulatory perspective, with case studies, on how early CMC efforts, in the context of 21st

century principles, can impact different stages of the product lifecycle.

NOTES:

Evaluation of Production from Cell Pools as an Enabling Technology for Rapid

Advancement of Biologics

Trent Munro, Amgen, Inc., Thousand Oaks, CA USA

With an increasing number of candidate molecules under development, probing the biology as

quickly as possible is critical for rapidly delivering next generation therapies to patients with unmet

medical need. During advancement of a biologic to the clinic, cell cloning and subsequent process

development activities are on the critical path and directly impact the time for clinical introduction

of a biotherapeutic. Program acceleration is possible if cell pools can be leveraged for early

material generation and process development activities. To successfully use cell pools during

development, it is important for cell-pool derived product quality attributes to be comparable to

those derived from clones. To better understand the relationship between pool and clone derived

product quality attributes, we compared data across recent programs. Cell pool and clone derived

material was purified and tested for a number of product quality attributes including expression

stability, post-translation modifications, and higher order species. Overall, our results indicate

feasibility of matching product quality attributes between cell pools and subsequently derived

clones. These findings support the strategic use of cell pools to accelerate the advancement of

biologics to the clinic.

NOTES:

Balancing Speed Versus Risk—When to Make Investment Choices in Development Projects.

John Joly, Genentech, a Member of the Roche Group, South San Francisco, CA USA

In the world of biopharmaceutical development speed to market is critical for bringing innovative

medicines to patients with significant unmet medical needs. Whether its breakthrough

designations or priority reviews, the ability to move swiftly through development is prized by

patients and companies alike. When positive data emerges from early trials, timelines are

scrutinized and the frequent mantra of “can you go faster?” is heard from many corners. With an

ever constant focus on development timelines, project teams are often confronted with balancing

speed versus risk. In this talk I’ll present several vignettes of when to take risks and when to

further invest time and resources into late stage research and development projects. The choices

are important ones as only a fraction of the development pipeline will make it to commercial launch

and in order to efficiently produce successful products, one must decide thoughtfully when to

invest and when it’s prudent to defer investment to a later stage. I’ll discuss how a rich

development history with monoclonal antibodies provides platform knowledge that informs a

development organization of the risks involved with such choices.

NOTES:


Session Chairs: John Dougherty, Eli Lilly and Company and Tina Morris, USP

Product-specific monographs for biologics have been used in the major pharmacopoeias of the

world since the early 20th century. As biologics manufacturing, development and quality control

have changed over time, especially with the introduction of recombinant biotherapeutics into the

market, development challenges and expectations for compendial standards have also evolved.

Most recently, the global discussion about quality expectations for biosimilars has added another

dimension in considering the role of product-specific compendial standards. This session will bring

together different viewpoints on the value, role, and challenges in the development, applicability

and use of compendial monographs for modern biotherapeutic medicines. In addition, the session

will endeavor to establish a conceptual framework for productive dialogue around the use of

standards in enabling access to quality biotherapeutic medicines for patients worldwide.

NOTES:

The Role of European Pharmacopoeia Monographs in Setting Quality Standards for

Biotherapeutic Products

Emmanuelle Charton, EDQM, Council of Europe, Strasbourg, France

The European Pharmacopoeia (Ph. Eur.) sets up quality standards for medicinal products and their

constituents that are legally binding in Europe and accepted in countries from all over the world.

It has always been committed to adapting to a fast developing environment, keeping pace with the

advancement of scientific technologies and taking care of regulatory needs. These achievements

apply also to biotherapeutic products, a class of products to which the Ph. Eur. has devoted the

highest attention over decades. With the appearance of new generation biotherapeutics, new

challenges have to be solved. The presentation will show, with the support of specific case studies,

how the Ph. Eur. has overcome the difficulties linked to these products and which challenges

remain ahead.

NOTES:


Anthony Mire-Sluis, Amgen, Inc., Thousand Oaks, CA USA

Traditional small molecule product specific pharmacopoeia monographs serve several purposes,

such as ensuring a consistent approach to quality for innovator and generic products, assessing the

quality of drug products in commerce, providing specifications that new manufacturers can target,

monitoring for counterfeit and substandard products as well as monitoring the quality of imported

drug products. However, there are challenges with creating product monographs for biotechnology

products since they are inherently complex proteins that generally contain multiple product

variants. The criticality of such variants differs – some impacting safety or efficacy whilst others

do not. However, specification tests and their associated limits for some attributes are often set to

assure consistency of production and may have no impact on safety and efficacy directly. In

addition, specifications often change during the product lifetime, and thus are only a snapshot in

time. Setting a single set of limits is not necessarily relevant for example, for terminal

heterogeneity of a monoclonal antibody product, where variants have been shown to have no

quality, safety or efficacy impact and can be very process and even site specific. The same applies

for the glycosylation patterns for biotechnology products where some glycosylation structures are

impactful while others are not. Therefore, applying attribute limits of the innovator to biosimilars

may not be meaningful since a biosimilar can have analytical differences that have no clinical

impact. Other issues apply to the testing and limits for host cell proteins where company/process

specific test reagents and standards restrict the ability to compare between products. Alternative

approaches to help assure the quality of biotechnology products have been developed in the form

of class specific method chapters such as USP for assays for monoclonal antibodies as well

as chapters that cover best practices for glycosylation and host cell protein testing amongst others.

NOTES:

The Role of Product-Specific Monographs in Biosimilar Product Development

Xiaoyu Chen, Hospira, a Pfizer Company, Lake Forest, IL USA

The compendial standards defined in pharmacopoeia product-specific monographs include

reference materials, testing methodologies and acceptance criteria. These standards are used to

establish a common set of requirements for product identity, strength, quality, and purity testing,

and are of great value in the development of small molecule generic products. Biosimilar products,

however, are regulated based on the totality of the data from comparative analytical, non-clinical,

and clinical studies for the reference product and proposed biosimilar product. The goal of a

biosimilar development program is to demonstrate a high degree of analytical similarity between

the proposed biosimilar product and the reference product for attributes defined as Critical Quality

Attributes (CQAs). Due to the complexity of protein structures and functions and the

manufacturing processes used for the production of therapeutic protein products, individual

manufacturers also often adopt different control strategies based on their own product and process

knowledge to ensure control of the relevant CQAs. Standardized compendial methods may be

insufficient to address all possible product-related and process-related impurities for recombinant

therapeutic proteins produced using different processes and having different formulations. In

addition, extensive additional characterization above and beyond standard release and stability

testing using internally developed or compendial methods is required for demonstration of

biosimilarity. Therefore, the monograph physicochemical and biological tests and associated

pharmacopoeia reference standards have different roles in the development of biosimilar products

relative to their roles in the development of generic medicines. In this presentation, the utility and

challenges of applying product-specific monographs will be discussed in the context of biosimilar

product development.

NOTES:

Analytical Control Strategy of Vaccine Products

Session Chairs: Arifa Khan, CBER, FDA and Ziping Wei, Novavax

This plenary session will discuss how the analytical control strategy evolves over the course of

vaccine product development. Stage-appropriate and risk-based analytical control strategy needs

to be developed to meet the product development needs. At the early stages of vaccine product

development, analytical control strategy is based on limited product understanding and process

knowledge. As the product moves to late stage development, product understanding and process

knowledge accumulate and it is expected that an enhanced analytical control strategy is established

to ensure product quality. As an example, product development for a Phase 1 clinical program,

where the major concern is patient safety and less product knowledge is gained, would likely have

a very different analytical control strategy in comparison to one being performed for a Phase 3

pivotal study, where safety and efficacy are relevant factors and more product knowledge has been

accumulated. The wide range of vaccine products (which include recombinant proteins, live-

attenuated viruses, inactivated viruses, polysaccharides, and polysaccharide-protein conjugates)

present unique aspects and challenges for establishing analytical control strategy. Depending on

the complexity of vaccine type, it may be challenging to characterize or measure quality attribute

changes, and define complexity of process and product attributes. This plenary session will give

examples for how to set control strategy when there is limited product and process knowledge and

how it evolves as vaccine products move to late stage development.

NOTES:

Analytic Control Strategies of Vaccine Products During Product Development

Freyja Williams, CBER, FDA, Silver Spring, MD USA

As products progress through clinical development, chemistry, manufacturing and control

information must be submitted to the regulatory agency appropriate to the clinical phase of the

product development. The requirements for specific control testing for each clinical phase cannot

be predefined but will depend on several factors, including the overall support for safety of the

product. The regulations applicable to investigative new drugs, and considerations when applying

them to specific applications will be discussed.

NOTES:

GARDASIL®9 Control Strategy Evolution During Late-Stage Development and Beyond

Jennifer L. Dashnau, Merck & Co, Inc., West Point, PA USA

GARDASIL®9 (HPV 9-valent Vaccine, Recombinant), is a nonavalent, recombinant vaccine

against human papillomavirus – the main cause of cervical, vulvar, vaginal, and anal cancers. This

second-generation vaccine combines the existing four types found in GARDASIL® (HPV Types

6, 11, 16, 18), with five additional types (HPV Types 31, 33, 45, 52, 58). HPV vaccines are based

on virus-like particles (VLP), which are complex structures consisting of approximately 72 L1

(major capsid protein) pentamers (capsomeres) arranged in an icosahedral formation. Although

their structure is complex, VLPs are amenable to characterization through a wide range of

analytical techniques and robust control strategies may be developed. GARDASIL®9 provides an

opportunity to understand the evolution of analytical control strategy for a well-characterized,

recombinant vaccine product from late-stage development to launch. Development of the

additional types was based largely on the first-generation process, thus allowing for leverage of

existing process and product understanding to inform development of the control strategy – from

selection of critical quality attributes to justification of specifications. However, challenges

encountered during late-stage development required modifications be made to some steps of the

process. For the attributes associated with these steps, more limited data were available, thus

requiring a different approach for setting control strategy. Finally, as the product enters the launch

phase, the control strategy continues to be enhanced as increased understanding of process and

product performance is gained during continued process verification. The presentation will give

examples for how to set control strategy in these situations.

NOTES:

Definition of Analytical Control Strategy for Robust Vaccine Development

Christina Campa, GlaxoSmithKline Vaccines, Siena, Italy

The establishment of a strong Analytical Control Strategy is instrumental to achieve consistent

manufacturing of safe and efficacious products. For this reason, it is critical to build analytical

knowledge since early development, leading to a systematic increase of product and process

understanding during life cycle. This presentation will focus on some key elements allowing the

realization of such challenging objective:

Definition of requirements of analytical methods (Analytical Target Profile, ATP), applicable to lot release/ stability testing, characterization/

comparability testing and process monitoring

Systematic reliability evaluation of methods for the scope, including considerations on reference standard use and suitability

Continued refinement of analytical approaches for ATP fulfillment during product life cycle, ensuring application of up-to-date analytical

technologies

Implementation of Quality by Design in method development (e.g., identification & ranges of critical variables impacting analytical result),

with assessment of implications on method qualification/ validation, as

applicable.

Case study examples will be provided on vaccine development, demonstrating how the

implementation of the above- mentioned concepts can be successfully achieved in this field.

NOTES:

Facing the Challenges of Drug Product and Device Development & Manufacturing

Session Chairs: Margaret Speed Ricci, Amgen Inc. and Shan Jiang, Seattle Genetics

This plenary session will cover the perspectives of both regulators and industry on challenges in

drug product and device development and manufacturing for therapeutic biologics. The criticality

of integrated drug product design considerations across formulation, drug product process,

container, and device will be discussed. Learnings from the development and commercialization

of adaptive manufacturing systems and new container and device technologies will be reviewed.

Establishing comprehensive control strategy and drug product comparability for aseptic

manufacturing of biologic products will be demonstrated with industry examples. Case studies will

be shared that illustrate technical considerations in container closure integrity, extractables and

leachables testing, process validation as well as new regulatory expectations for manufacturing of

parenteral products.

NOTES:

An Integrated, Science and Risk based Approach to the Development and Control of

Biotechnology Drug Product

Anthony Mire-Sluis, Amgen Inc., Thousand Oaks, CA USA

The development of commercial drug product has to start at the earliest phases of development in

considering the target product profile (TPP). The TPP should define the intended use of the

product and consider the dosage form and container and/or device associated with it. One cannot

ignore the fact that the drug product is derived from drug substance, which is derived from the

protein produced by a selected production cell clone. Therefore, the TPP should be considered

when selecting the protein sequence during molecule assessments, since this selection will have a

huge impact on the nature of the final drug product. Often a first in human drug product will be

in a different formulation and container than the final commercial product (e.g. frozen in a vial)

and thus commercial formulation plays a crucial role in defining the final drug product and its

stability. Therefore, end to end studies to show the ability of product to remain stable at room

temperature after storage at the recommended storage temperature and/or cycling studies can

provide the necessary data to support not only excursions during transport, but allow for patients

to keep product at room temperature for a time before use. The process of formulation and filling

cannot be ignored either as it can have impact on the quality attributes of the product. For example,

how the material is pumped through delivery needles (peristaltic versus time/filler pressure) can

impact subvisible particle load. How drug product is stored during formulation and filling can

impact bubble formation during filling. Lastly, drug product doesn’t magically appear in the hands

of a doctor or patient – it has to have a cold chain to get it from the company warehouse to delivery

to the patient in a way that retains all the desired quality attributes. Control of transport and storage

at the final destination also plays its part in providing quality drug product to patients. Taken

together, these concepts create the basis for an integrated control strategy for drug product that can

utilize risk based approaches for implementation.

NOTES:

Donna French, Genentech, a Member of the Roche Group, South San Francisco, CA USA

NOTES:

Aseptic Processing of Biological Products: Current Regulatory Issues

Patricia Hughes, CDER, FDA, Silver Spring, MD USA

An overview of the quality assessment by microbiology product quality reviewers at the

FDA/CDER of the drug product section of a Biological License Application (BLA) will be

presented. Examples of recurring application deficiencies and resolutions for BLA approval will

be presented. The presentation will also discuss the relationship between inspectional findings

during pre-approval inspection with the application quality assessments for BLA approval.

NOTES:

sEvolving Biosimilar Regulatory Science – Case Studies

Session Chairs: Martin Schiestl, Sandoz, and Marjorie Shapiro, CDER, FDA

The regulation of biosimilars is founded on the scientific principles of comparability, which were

established - with the publications of the FDA Guidance “Demonstration of Comparability of

Human Biological Products, Including Therapeutic Biotechnology-derived Products” in April

1996, followed by the ICH Q5E concept paper established in 2002 and the final adoption of ICH

Q5EComparability of Biotechnological/Biological Products Subject to Changes in Their

Manufacturing Process in 2004/2005. Prior to this, a biological product was often defined by its

manufacturing process. Without the acceptance of the concept of “comparability”, along with

advances in analytical methods, there would be no biosimilars today.

The comparability concept has also been used for the approval of follow-on-versions of biological

products regulated in the US for historic reasons as drugs using the 505(b)(2) pathway. One

example is a Somatropin approved by FDA in 2006 based on comparative quality, non-clinical

and clinical data. In the same year the same product was also approved as the first biosimilar

product in the EU using basically the same data package.

In the EU, EMA issued the first biosimilar guideline already in 2004 and the first products were

approved in the following years. In the US, the legal basis was created by the Biologics Price

Competition and Innovation act in 2009. Since then, the regulatory science evolved quickly and

continues to move forward, for example, new concepts with regard to quality evaluation taking

into account the clinical relevance of quality attributes, tailored confirmatory clinical studies, and

the scientific requirements for extrapolation have been developed allowing the science-based and

efficient development of safe and effective biosimilars. The revised and newly established

biosimilar guidances in US and EU reflect the current state-of-the-art in regulatory science, while

remaining open for further innovation in the field. This is important for the next step in the

evolution: the move from biosimilars to interchangeable biologics.

This session will illustrate this evolution in regulatory science with case studies of approved

biosimilar products or those currently in development. Speakers from FDA and Sponsors

developing biosimilar products will share their experience and provide an outlook to the future.

NOTES:

Recent Trends in the Evaluation of Analytical Biosimilarity

Thomas Stangler, Sandoz Biopharmaceuticals, GmbH, Tirol, Austria

The scientific principles of comparability are the foundation for the development of a biosimilar.

Since the first approval of a biosimilar in the European Union in 2006, analytical technologies,

development concepts and regulatory sciences have continued to evolve. More and more powerful

analytical methods, applied to increasing numbers of reference product batches over many years,

result in larger and larger data sets as basis for the evaluation of analytical biosimilarity. This

wealth of data offers opportunities and challenges.

This talk will present recent experiences in Sandoz’ biosimilar development projects and

regulatory interactions with respect to the evaluation of biosimilarity, especially with respect to

the application of statistical approaches. Benefits and limitations of statistical approaches will be

discussed, in addition to how the statistical results fit into the overall evaluation of biosimilarity.

NOTES:

Maria-Teresa Gutierrez-Lugo, CDER, FDA, Silver Spring, MD USA

NOTES:

Similarity Assessment of Biosimilars. The Past, Present and Future State

James Anderson, Momenta Pharmaceuticals, Inc., Cambridge, MA USA

This talk will provide historical reference for concepts currently being applied for biosimilars

followed by an industry perspective on current regulatory guidance for the evaluation of

physiochemical and biological characterization data (analytical similarity). Challenges associated

with these assessments – especially early in a development program – will be highlighted.

A look to the future for establishing analytical similarity will also be presented, specifically the

application of the “science of comparison” including the incorporation of advanced analytics with

biological models.

NOTES:

Comparability for Blood Products – How Did We Get Here and Where Are We Going?

Plenary Co-chairs: Andrew Chang, Novo Nordisk, Inc. and Timothy Lee, CBER, FDA

This plenary session will address comparability issues related to plasma-derived and recombinant

blood coagulation factor products. Our speakers will describe how the comparability approach has

been applied, evolved and leveraged, against a historical backdrop of advancements of

recombinant technology in product manufacture, improvements in analytical capability and

changes in regulatory policies. We will set the stage by reviewing the comparability paradigm as

it is applied throughout the past 20 years since its inception. We will then look at case studies

illustrating some of the challenges related to specific classes of coagulation factor products, some

of which are unique to coagulation factors, and others which are relevant to biological products in

general. In the examples, we hope to cover the following topics:

• How differences in quality attributes in pre- and post-change materials were reconciled either

during product development or post-approval

• How interactions between the manufacturer and regulator helped resolve comparability-related

issues

• What are the considerations in the selection of analytical methods for the comparability exercise?

Are new analytical methods always considered?

• What are the characteristics that the manufacturer considers to be unique to blood products, and

those that are shared amongst other biopharmaceuticals, and how that affected the design of the

comparability exercises? For example, impurities in plasma-derived products could have their own

biological activities that can either be beneficial or deleterious.

Twenty Years of Comparability, Where Are We Now?

Nancy Kirschbaum, CBER, FDA, Silver Spring, MD USA

Twenty years ago, FDA published its first guidance document on comparability. Initially, the

comparability paradigm focused on supporting specified manufacturing changes within a single

manufacturer by generating relevant analytical, non-clinical and/or clinical PK/PD data, as

necessary, in a one-time exercise designed to obviate the need to repeat clinical efficacy trials.

Changes to plasma derivative manufacturing processes were often supported by complementing

analytical data with non-clinical and/or clinical data in the face of residual uncertainty, despite

advances in analytical capabilities and manufacturing science. Since then, industry and regulators

have partnered to implement the life-cycle approach to biopharmaceutical development and there

is now a legal pathway for applying the comparability paradigm to demonstrating biosimiliarity

across manufacturers. Moreover, there have been unprecedented advances in analytical science

and its application to development of cutting-edge in vitro functional tests. This talk will examine

improvements in analytical capability in the context of changes in regulatory policies to highlight

the benefits of implementing a risk-based, life-cycle approach to comparability, including

strategies for leveraging in vitro functional tests that reflect all critical biological functions.

NOTES:

The Development of Novel Modified Recombinant Blood Factors with Extended Half-lives

in vivo: A CMC Perspective

Stephen Raso, Biogen, Cambridge, MA USA

This talk will address not only Biogen’s approach to establishing comparability of biologics

throughout product development and commercialization, but some of the challenges unique to the

development and characterization of recombinant blood factor Fc-fusion proteins. Some of these

additional considerations include the assessment of new functionalities of the modified proteins,

comparison to existing treatments and alignment with international blood factor standards.

NOTES:

How to Mitigate Issues with Potency Assignment Assays for Clotting Factor Products -

Recent Examples from Baxalta

Peter Turecek, Baxalta GmbH, Vienna, Austria

There are different reasons for measuring clotting factor activities: diagnosis and assessment of

severity of the clotting factor defect, assessment of the hemostatic status of patients´ post infusion

samples, determination of recovery, trough levels and pharmacokinetics of concentrates, and

potency designation by the pharmaceutical manufacturer. These reasons could be subject to

conflict as the requirements for the assays used for these different purposes might be different.

Moreover, analytical issues have been reported with modified coagulation factor VIII (FVIII) and

also factor IX (FIX). There are also geographic differences in the use of certain assays and also

legal test requirements may differ for one and the same clotting factor.

In a recent workshop on “Characterization of new clotting factor concentrates (FVIII, FIX) with

respect to potency assays used for labelling and testing of post infusion samples” the following

key points were identified (Dodt J, et al. Haemophilia 2015):

Thorough characterization of new rFVIII and rFIX products, according to International Society of Thrombosis and Hemostasis (ISTH) recommendations, in a variety of potency

assays against the WHO IS (concentrate and plasma) is important.

For some modified rFVIII products and for all new rFIX products, one-stage clotting assay methods result in different potency assignments depending on the APTT reagent used.

For FVIII it was also said that clinicians wish to have one assay that could be used to assign

potency for product labelling and which correlates with FVIII levels measured by the clinical

laboratory. A particular concern is that using different assays could lead to discrepant high product

plasma values measured post-infusion and result in underdosing of patients.

The potency labeling strategies of two recently approved Baxalta treatments for hemophilia will

be presented in light of current requirements and demands from patients and physicians.

NOTES:

Back to the Future: The Next Big Thing in Biologics Processing and Controls

Plenary Co-chairs: Richard Rogers, JUST Biotherapeutics, and Richard Scott

Rosenthal, MedImmune, A member of the AstraZeneca Group

The tools, technologies and hardware that enabled the establishment of the biotechnology industry

continue to evolve and change, and as a result the current state of the industry looks very different

than it did in its infancy. Much of this evolution occurs as a result of incremental improvements,

which over time results in greater efficiency, capacity, robustness, utility, etc. Fundamental

paradigm shifts occur far less frequently, but can result in true step changes in terms of how the

industry operates. This session seeks to highlight disruptive technologies and processing trends

with the potential to bring about transformative change to the current state of the industry with

respect to bioprocessing and product attribute controls.

NOTES:

Achieving Product Attribute Control by Implementation of Predefined Product Quality

Targets and Process Analytical Technologies

Rohini Deshpande, Amgen Inc., Thousand Oaks, CA USA

Quality by Design (QbD) is a systematic approach to development of pharmaceuticals that begins

with pre-defined objectives, and emphasizes product and process understanding and attribute

control, based on scientific understanding and quality risk management. This requires an

understanding of how product, materials, methods, and process variables influence final product

quality. An integrated product development paradigm starts with a well-defined TPP and QTPP

to implement attribute control strategies that allow for better real time control of process and

product. Such an approach, if successfully implemented will permit testing on the manufacturing

floor while at the same time move the testing paradigm of biologics towards RTRT. In this

presentation, we will share our progress in application of a QTPP and process analytical

technologies for achieving attribute control and designing quality into the product.

NOTES:

Avoiding Facility Obsolescence: Immortal Facilities for Increasing Drug Diversity

Parrish Galliher, Xcellerex Inc. Marlborough, MA USA

As worldwide annual sales of biologics increase toward the 200 bn USD mark, so has the diversity

of treatment modalities and drug pipelines increased. Pipeline diversity has grown from

recombinant hormones and cytokines to monoclonal antibodies (MAb), MAb-toxin conjugates,

Mab antibody fragments, multivalent MAbs, cell-based and rDNA vaccines, precision cell and

gene therapies, therapeutic enzymes, biobetters, biosimilars, biofuels and more. Over the decades,

many manufacturing facilities have been unable to accommodate this increasing diversity and have

become underutilized, mothballed or obsolete. The presentation will discuss the challenges of

increasingly diverse pipelines and process flow architectures and how innovations in

manufacturing facility design and operations can maximize facility utilization and help avoid

facility obsolescence.

NOTES:

Oxygen Uptake as a Virtual Cell Culture Probe

Steven Rose, MedImmune, a member of the AstraZeneca Group, Gaithersburg, MD USA

During the scale-up and tech transfer of cell culture processes, we routinely evaluate whether the

bioreactors are capable of supporting the required cell culture oxygen demands. We have

developed a first principle oxygen transfer model to define how best to run the bioreactor to meet

the oxygen demand. The model enables us to successfully specify larger scale bioreactor operating

conditions without needing to perform an engineering run. We have found that we can also

leverage this engineering model as a virtual probe to monitor and control the cell culture process.

We have shown that with a virtual oxygen uptake rate probe, we can manage the carbon dioxide

accumulation and predict titer and cell culture growth performance. This provides greater insight

into the biology and results in consistent control for enhanced process performance. This

presentation will share the model results and its predictive ability across bench, pilot and

manufacturing scales.

NOTES:

NEW WCBP 2016 WORKSHOP DESCRIPTIONS

Expanding the Potential

Different Workshop topics need to be approached in different ways in order for their full potential

to be reached. WCBP 2016 will feature three different Workshop formats to enhance discussion

of key topics of interest.

1. The Standard Format

This is the Workshop you usually think of as being associated with WCBP. Industry and

Regulatory Agency co-chairs focus on generating discussion over the entire period of the

session. As with all Workshop Formats, audience participation is critical to success.

2. The Speed-Dating Format

This isn’t your grandmother’s Workshop! We’ve kicked it up a notch by essentially

facilitating 4 simultaneous round table sessions on four related Workshop issues. Every

attendee has the opportunity to add their thoughts to each topic in a smaller setting. The

facilitators then work hard (and fast) to summarize all the points and report out to the

Workshop attendees - all in real time.

3. The “Plenshop” Format

Sometimes, a presentation of background material before discussion begins is a good thing.

The Plenshop Format allows for that. In these sessions, one or more short presentations

will be followed by intensive discussion. It’s not a plenary session, it’s not a workshop -

it’s a Plenshop!

Additionally, we will have a Workshop in the Standard Format which will have the topic chosen

by WCBP 2016 attendees while at the meeting! We realized that sometimes we may miss an

important breaking topic because of how far in advance we work to ensure a high-quality

conference. The Hot Topic Workshop allows attendees to suggest and vote for a topic of their

choice and we will provide skilled facilitators, whatever the topic! The vote for a “hot topic” will

be through the Mobile APP. Please make sure to download the APP so that you can cast your

vote!

Discussion at Workshops, Round Table Sessions, and during formal and informal networking

times is critical to the success of our meeting, with the introduction of the new Workshop Formats,

we hope that you will get even more from WCBP 2016.

Workshop Descriptions

Workshop Session 1

Tuesday, January 26, 2016

17:00 – 18:15

Regulatory and Compendial - Combination Products

Rakhi Dalal, CDER, FDA, Donna French, Genentech, a Member of the Roche Group,

Steve Hertz, CDER, FDA, Ed Patton, CBER, FDA, Michael Soberg Christensen, Novo Nordisk

AG, John Weiner, OCP, FDA

In the Chinese Room – Standard Workshop

In January 2015, the FDA issued draft guidance on CGMP requirements for combination products

in support of the regulation (21 CRF Part 4). These regulations are intended to promote the public

health by clarifying which CGMP requirements apply when drugs, devices, and biological

products are combined to create combination products. Combination products are those that consist

of two or more different types of products, such as a drug/device combo like a pre-filled syringe.

There many different many different types of combination products and this session can address

the application of 21 CFR Part 4 to different type of products. This is a challenge for manufacturers

of combination products as industry has to the responsibility to comply with these regulations and

enforcement of 21 CRF Part 4 compliance is expected. Clarity of expectations regarding CGMP

requirements for combination products are crucial for establishing a robust and compliant quality

system and ensuring a consistent implementation of 21 CFR Part 4.

This session will address some of the important questions and issues for combination products in

relation to quality system, experiences/expectations in relation to inspection of combination

products as well as experiences from the review process. The following specific question will be

addressed:

a. How to establish an appropriate quality system for manufacturing of combination products?

b. How will the interaction between FDA review and inspection teams change future inspections of combination products?

c. How should design controls and purchasing controls be implemented for various types of combination product technologies (e.g., drugs co-packed with class 1 or class 2 devices)

d. How do companies meet the requirements for marketed products that were not developed under design controls?

NOTES:

Pay Now or Pay Later: Prioritizing CMC Development Activities in Early Development

Christopher Downey, CDER, FDA, Catherine Eakin, Seattle Genetics, Michelle Frazier, AbbVie,

Inc., Sara Gagneten, CBER, FDA,

In the District Room – Standard Workshop

With the advent of programs that can rapidly accelerate the normal product development lifecycle,

such as Breakthrough Therapy Designation, Industry is re-thinking product development strategies

to achieve shortened timelines. This session will consider the CMC activities that can expedite

both early and late stage development. Strategies discussed will include the use of platform

processes and methods, frontloading of characterization studies early in development, and new

approaches such as the use of pooled clones to enable more rapid entry into first in human

studies. The risks and benefits of these strategies will be evaluated in the context of technical

challenges and overall impact to development timelines.

NOTES:

Regulators’ Perspectives on Trends in the Regulation of Biopharmaceutical Products in

Europe and Asia

Session Chairs: Kathleen Francissen, Genentech, a Member of the Roche Group and Anthony

Ridgeway, Health Canada

Regulators: Peter Richardson, European Medical Association (EMA) and Daisaku Sato, PMDA

and Anis Talib, Ministry of Health Malaysia (MHM)

In the Grand Ballroom – Plenshop

In this session, regulators that represent EMA, PMDA, and MHM will present the highest priorities

of their agencies and discuss current trends in accelerated development strategies, (such as

Adaptive Pathways and Sakigake), biosimilars development, and regulatory convergence and

harmonization (particularly the involvement of their agency).

Among activities that support regulatory system strengthening, the Asia Pacific Economic

Cooperation (APEC) Regulatory Harmonization Steering Committee (RHSC) has a mandate to

work towards achieving regulatory convergence by 2020 among the 21 APEC economies. Japan

was identified as the new chair of RHSC, and will co-chair RHSC meetings with US FDA. In

terms of training and capacity building, APEC Training Centers of Excellence (CoE) for

Regulatory Science, which are partnerships of academia, regulators, and industry (at various stages

of implementation) identified the following priority work areas: (1) Biotherapeutics; (2) Multi-

regional clinical trials (MRCT), including Good Clinical Practices (GCP); (3) Pharmacovigilance;

(4) Good review practices (GRP), including good submission practices; and (5) supply chain

integrity. The potential opportunities and challenges of achieving regulatory convergence in the

APEC region and in other regions will be discussed.

NOTES:

Perspectives on Trends in the Regulation of Biopharmaceutical Products in Europe and

Asia (Japan)

Daisaku Sato, Pharmaceuticals and Medical Devices Agency (PMDA), Tokyo, Japan

The Japanese regulation has improved its review performance over the last decade. Bio-

pharmaceuticals were also the major parts of this expedited program.

PMDA continues further shortening its review period by 2018. MHLW and PMDA started the

“Sakigake” (forerunner) review assignment system on a pilot basis in May 2015. It is so called

break through therapy designation for novel products that are willing to be launched in the

Japanese market first. More than 50 products/indications were subject to the screening process

and finally 6 products/indications were assigned to be under Sakigake in October 2015.

The new legislations for regenerative medicine (cellular and tissue-based products) came into

effect on 25 November 2014. It introduced early access scheme (conditional and time-limited

approval) for regenerative medical product to expedite patient access to promising therapies. The

two products were newly approved under the regenerative medical product category of new

legislation in September 2015.

The biosimilar regulations have experienced growing number of consultations during clinical

trials and two new product approvals in 2015, which are linked with global product

developments. It may arise the global challenges of selection of comparator reference products

and statistical evaluation for multi-regional clinical and non-clinical studies. We will present the

current challenges of biologics CMC review, such as responses to ICH-Q12 guideline to

accommodate post-approval change in terms of the international harmonization. We will step

further global collaboration among regulators and biotech industries.

In Japan, MHLW and PMDA put forward the international cooperation with regulatory

authorities and set up the international strategic plan in June 2015. It will enable PMDA to

contribute to the world public health, and to maximize the common benefit through regulatory

innovation. PMDA has been actively participating in the international harmonization and

convergence fora including APEC, and promotes bilateral supports to Asian regulators for

capacity building.

NOTES:

EU Developments in Early Access Programs and International Cooperation

Peter Richardson, European Medicines Agency (EMA), London, United Kingdom

In recent years, the EMA and the European Network have been focused on ways to maximise the

benefit of existing regulatory pathways to facilitate early access to medicines. The EMA has

offered Adaptive Pathways as an opportunity for industry to benefit from increased regulatory

interaction by way of a pilot program for medicines with high unmet need. In addition, these

products should be developed by an iterative process (initially: restricted population or evolving

surrogate endpoints) and utilising real world data.

In 2015, the EMA has announced a further t

preliminary program wcbp 2016...chi-ting huang, cth analytical consulting peter johnson, 3m drug...

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