Welcome to the CMC Strategy Forum

We are pleased to welcome you to the CMC Strategy Forum. The purpose of the CMC Strategy Forum is to provide a venue for biotechnology/biological product discussion. The meetings focus on relevant CMC issues throughout the lifecycle of a product and thereby foster collaborative technical and regulatory interactions. The Forum strives to share information with the regulatory agencies to assist them in merging good scientific and regulatory practices. Outcomes of the Forum meetings are published in an appropriate peer-reviewed journal.

Each meeting will focus on a CMC related issue such as product characterization, comparability, specifications, etc. The format of each meeting will consist of case studies and presentations by Industry and/or FDA experts to introduce the topic and the key issues of concern. Breakout sessions will then be conducted to allow for additional discussion on the technical and regulatory details of the topics. It is envisioned that the final outcome of the workshop discussions will be the development of a document to be submitted to the appropriate Regulatory Agency designees for their consideration in developing and/or clarifying good regulatory practice guidelines for biotechnology derived products.

The success of the CMC Strategy Forum will depend on your active participation in discussing and raising issues pertaining to development of biologics. We encourage you to participate wholeheartedly in the workshops that have been designed to stimulate exchange of ideas and information.

We would like to thank the speakers who are giving generously of their time and resources, and to you, for your attendance. We acknowledge the generosity of our program partners: AbbVie, Inc., Amgen Inc., Biogen, Bristol-Myers Squibb Company, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, a Member of the Roche Group, Janssen R&D, LLC, MedImmune, A member of the AstraZeneca Group, Merck & Co., Inc., National Institute of Standards and Technology (NIST) and Pfizer, Inc. We are grateful for the expert management from CASSS and the audio-visual expertise of Michael Johnstone from MJ Audio-Visual Productions. Their experience and guidance in the preparation of this Forum has been invaluable.

ACKNOWLEDGEMENTS

CMC STRATEGY FORUM NORTH AMERICA PROGRAM COMMITTEE

Siddharth Advant, Celgene Corporation Yves Aubin, Health Canada John Bishop, CBER, FDA Barry Cherney, Amgen Inc. JR Dobbins, Eli Lilly and Company Julia Edwards, Biogen Sarah Kennett, CDER, FDA Joseph Kutza, MedImmune, A member of the AstraZeneca Group Kimberly May, Merck & Co., Inc. Anthony Mire-Sluis, AstraZeneca Stefanie Pluschkell, Pfizer, Inc. Nadine Ritter, Global Biotech Experts, LLC Dieter Schmalzing, Genentech, a Member of the Roche Group Timothy Schofield, GlaxoSmithKline Zahra Shahrokh, STC Biologics and ZDev Consulting Jeffrey Staecker, BioPhia Consulting, Inc. Andrew Weiskopf, Biogen Marcel Zocher, Bristol-Myers Squibb Company

CMC STRATEGY FORUM GLOBAL STEERING COMMITTEE

Siddharth Advant, Celgene Corporation, USA Daniela Cerqueira, ANVISA-Brasilian National Health Surveillance Agency, Brasil Yasuhiro Kishioka, PMDA-Pharmaceutical and Medical Devices Agency, Japan Steven Kozlowski, CDER, FDA, USA Junichi Koga, Daiichi Sankyo Co., Ltd., Japan Rohin Mhatre, Biogen, USA Ingrid Markovic, CBER, FDA, USA Anthony Mire-Sluis, AstraZeneca, USA Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland (Chair) Ilona Reischl, AGES-Austrian Federal Office for Safety in Health Care, Austria Anthony Ridgway, Health Canada, Canada Nadine Ritter, Global Biotech Experts, LLC, USA Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland Mark Schenerman, MedImmune, A member of the AstraZeneca Group, USA Karin Sewerin, BioTech Development AB, Sweden

The Organizing Committee gratefully acknowledges the pharmaceutical and biotechnology industry for their generous support of the CMC Strategy Forum North America series:

STRATEGIC DIAMOND PROGRAM PARTNERS F. Hoffmann-La Roche Ltd. Genentech, a Member of the Roche Group STRATEGIC PLATINUM PROGRAM PARTNERS AbbVie, Inc. Biogen MedImmune, A member of the AstraZeneca Group STRATEGIC GOLD PROGRAM PARTNERS Eli Lilly and Company Pfizer, Inc. STRATEGIC SILVER PROGRAM PARTNER Merck & Co., Inc. PROGRAM PARTNERS Amgen Inc. Bristol-Myers Squibb Company Janssen R&D, LLC National Institute of Standards and Technology (NIST) The Scientific Organizing Committee gratefully acknowledges the following media for their promotional consideration of CMC Strategy Forum North America January 2017:

LEADING MEDIA PARTNERS BioProcess International International Pharmaceutical Quality MEDIA PARTNERS American Laboratory / LabCompare American Pharmaceutical Review Analyst / Analytical Methods BioProcessing Journal ChemComm / ChemSocRev / Chemical Science Genetic Engineering & Biotechnology News G.I.T. Laboratory Journal Green Chemistry / Integrative Biology LC / GC MedChemComm / Molecular BioSystems Pharmaceutical Outsourcing Royal Society of Chemistry separationsNOW.com Technology Networks The Analytical Scientist / The Pathologist

Forum Abstract

Methods on the Move: Addressing Method Transfer Challenges for the Biopharmaceutical Industry

FORUM CO-CHAIRS: Kathy Lee, Eli Lilly and Company, USA Jeffrey Staecker, BioPhia Consulting, Inc., USA

SCIENTIFIC ORGANIZING COMMITTEE: Sarah Demmon, Eli Lilly and Company, USA Mark DiMartino, Amgen Inc., USA Hugo Hamel, Health Canada, Canada Ned Mozier, Pfizer, Inc., USA Julia O’Neill, Tunnell Consulting, Inc., USA Ramesh Potla, CDER, FDA, USA Timothy Schofield, GlaxoSmithKline, USA

Business and regulatory drivers have led to increased activity of analytical and biological method transfers, in the biopharmaceutical industry. Method transfer may occur between labs at the same company site, between sites of a company, or between companies. This increased activity in method transfers is occurring in the absence of clear regulator expectations and comes at a time of increasing scrutiny from both regulators and industry in defining what is needed for successful transfers. Questions range from whether a formal transfer is required for moving QC operations to a new building at the same site to technical requirements and submission strategy for transfer of complex analytical methods between companies. During this forum regulators and industry experts will discuss issues and successes they are observing with method transfers, approaches and regulatory strategies for submitting transfers to regulatory agencies.

CMC Strategy Forum Program Summary

Methods on the Move: Addressing Method Transfer Challenges for the Biopharmaceutical Industry

Monday, January 23, 2017

07:30 – 17:00 Registration in the Senate Room

07:30 – 08:30 Breakfast in the Palm Court Ballroom, Lobby Level

08:30 – 08:45 CASSS Welcome and Introductory Comments in the Grand Ballroom Nadine Ritter, Global Biotech Experts, LLC

CMC Strategy Forum Welcome and Introductory Comments in the Grand Ballroom Kathy Lee, Eli Lilly and Company Jeffrey Staecker, BioPhia Consulting, Inc.

Regulatory Compliance Workshop Session One in the Grand Ballroom Session Chairs: Sarah Demmon, Eli Lilly and Company, Julia O’Neill, Tunnell Consulting, Inc. and Timothy Schofield, GlaxoSmithKline

08:45 – 09:10 Regulatory Perspectives on Analytical Method Transfer for Biopharmaceutical Products Ramesh Potla, CDER, FDA, Silver Spring, MD USA

09:10 – 09:35 Regulatory Expectations for Method Transfers: Health Canada’s Perspective Hugo Hamel, Health Canada, Ottawa, ON Canada

09:35 – 10:00 TBD Alfred Del Grosso, CBER, FDA, Silver Spring, MD USA

10:00 – 10:25 TBD Dawn Sailer, Eli Lilly and Company, Indianapolis, IN USA

10:30 – 11:00 Networking Break in the Palm Court Ballroom

11:00 – 12:15 PANEL DISCUSSION – Questions and Answers Alfred Del Grosso, CBER, FDA, USA Hugo Hamel, Health Canada, Canada Ramesh Potla, CDER, FDA, USA Dawn Sailer, Eli Lilly and Company, USA TBD TBD

12:15 – 13:45 Networking Lunch in the Palm Court Ballroom Monday, January 23 continued…

Key Ingredients Needed for Successful Method Transfers: Cases Included Workshop Session Two in the Palm Court Ballroom Session Chairs: Mark DiMartino, Amgen Inc., Hugo Hamel, Health Canada and Ned Mozier, Pfizer, Inc.

13:45 – 14:10 Case Studies and the Validation and Transfer of Analytical Methods for mAbs and Vaccines to Enable Commercial Launch Jason Starkey, Pfizer, Inc., Chesterfield, MO USA

14:10 – 14:35 Practical Points in Method Tech Transfers: Three Scenarios Nadine Ritter, Global Biotech Experts LLC, Germantown, MD USA

14:35 – 15:00 Risk-based Approach to Method Transfer Jeffrey Staecker, BioPhia Consulting, Inc., Lake Forest, IL USA

15:00 – 15:25 A Balancing Act: Streamlining Method Transfer without Compromising Compliance or Science Julie Frost, Amgen Inc., West Greenwich, RI USA

15:30 – 16:00 Networking Break in the Palm Court Ballroom

16:00 – 17:15 PANEL DISCUSSION – Questions and Answers Julie Frost, Amgen Inc., USA Nadine Ritter, Global Biotech Experts LLC, USA Jeffrey Staecker, BioPhia Consulting Inc., USA Jason Starkey, Pfizer, Inc., USA TBD TBD

17:15 – 17:45 Recap of Program Summary Slide Presentation Nadine Ritter, Global Biotech Experts, LLC

17:45 – 18:00 Invitation to CMC Strategy Forum July 2017

18:00 – 19:15 Networking Reception in the Palm Court Ballroom

Regulatory Compliance

Session Chairs: Sarah Demmon, Eli Lilly and Company, Julia O’Neill, Tunnell Consulting, Inc. and Timothy Schofield, GlaxoSmithKline

Analytical method transfer constitutes an integrated step in the method life cycle. In today’s rapid paced developments, new thinking in regulatory strategy is needed to reduce time through approval and transfer, while providing robust evidence of reliable method performance. This session will focus on perspectives from regulators and submitters on evolving approaches to method transfer. Regulatory expectations for different transfer scenarios will be discussed and practical experiences with biotech and vaccines method transfers and common problems encountered will be shared.

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Presenter’s Abstracts

Regulatory Perspectives on Analytical Method Transfer for Biopharmaceutical Products

Ramesh Potla

CDER, FDA, Silver Spring, MD USA

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Regulatory Expectations for Method Transfers: Health Canada’s Perspective

Hugo Hamel

Health Canada, Ottawa, ON Canada

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TBD

Alfred Del-Grosso

CBER, FDA, Silver Spring, MD USA

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TBD

Dawn Sailer

Eli Lilly and Company, Indianapolis, IN USA

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Regulatory Compliance Workshop Session One

Panel Discussion – Questions and Answers Alfred Del Grosso, CBER, FDA, USA Hugo Hamel, Health Canada, Canada Ramesh Potla, CDER, FDA, USA Dawn Sailer, Eli Lilly and Company, USA TBD TBD

The following questions will guide the panel discussion:

 What type of regulatory filing is required for the transfer of a method for the following scenarios:

o Same building, different room o Different building, same license number (DEL) o Different building, different license number o If the same equipment and same staff are relocated to the new location o Any differences for US FDA or European Official Medicines Laboratories (OMCLs)

 What are the regulatory requirements in term of method transfer?  What are the verification approaches for transfer of a compendial method?  What are the validation parameters required to support the transfer of an ID test, protein concentration, HPLC methods, cell-based bioassay, ELISA, IEF, etc.?  What is the best design of a method transfer? Should multiple batches be used, or should samples be fabricated (perhaps from a reference standard) to cover the range of the method. What’s the basis for the number of runs performed in the Sending and Receiving laboratories?

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Key Ingredients Needed for Successful Method Transfers: Cases Included

Session Chairs: Hugo Hamel, Health Canada, Mark DiMartino, Amgen Inc. and Ned Mozier, Pfizer, Inc.

The recent increase in approval of biologics, and their growing market share, has increased the number of analytical method transfers needed to support production. These assays are very numerous and highly complex, including bioassays, so reliable work processes are critical for business success. Increasingly, the health authorities are showing interest in order that the testing capabilities are robust and product quality is not compromised when processes and QC methods are moved from research to commercial or between commercial facilities. The speakers and panelists in this forum have extensive experience and tips for avoiding the pitfalls and traps that can beset corporations transferring QC test methods. The forum will address topics such as planning and timing for transfers, how to select samples and reference materials, setting transfer acceptance criteria, and the benefits of parallel testing and co-validation. Unique challenges will be discussed, including country-specific requirements (instrumentation, availability of reagents) and cultural issues where receiving and transferring labs have some variance in incentives as well as much common ground.

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Presenter’s Abstracts

Case Studies and the Validation and Transfer of Analytical Methods for mAbs and Vaccines to Enable Commercial Launch

Jason Starkey

Pfizer, Inc., Chesterfield, MO USA

The transfer of analytical methods across a global manufacturing and support network is a routine exercise as compounds progress in clinical development. Despite the routine nature of this activity, a significant amount of planning, preparation, and attention to details are necessary ingredients for success. This discussion will review some common technical and operational learnings and tools implemented at Pfizer during the transfer of analytical methods from clinical development laboratories into commercial launch sites. Approaches in setting acceptance criteria for the transfer exercise and how this is woven into method validation is also discussed. Key considerations for sample identification and preparation, transfer design, and the pre-transfer activities are reviewed.

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Practical Points in Method Tech Transfers: Three Scenarios

Nadine Ritter

Global Biotech Experts LLC, Germantown, MD USA

Transferring analytical methods from one laboratory to another involves one of three possible scenarios: (1) the identical procedure using an identical SOP, (2) the same methodology using a modified SOP, (3) the same assay principle using a highly adapted SOP. The experimental design and amount of data needed to assure successful tech transfer varies depending upon the operational situation encountered, the intended use(s) of the method, and the state of qualification or validation of the procedure. This talk will provide practical examples of assessing, planning, conducting and evaluating method tech transfer studies under each of these situations.

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Risk-based Approach to Method Transfer

Jeffrey Staecker

BioPhia Consulting, Inc., Lake Forest, IL USA

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A Balancing Act: Streamlining Method Transfer without Compromising Compliance or Science

Julie Frost

Amgen Inc., West Greenwich, RI USA

Many biotech companies are faced with increased method transfer activity and scrutiny. There is significant benefit to streamlining the method transfer process but this can create risk to product safety as well as to regulatory reputation and supporting the ultimate launch plans globally. This presentation discusses some options and challenges to manage the complex work of moving methods from site to site. Real word examples highlight the formidable task of setting meaningful acceptance criteria as the industry faces new scenarios for multi-site transfers. Specific pain-points will be shared along with best practices to develop a robust method transfer program at 21st century companies.

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Key Ingredients Needed for Successful Method Transfers: Cases Included Workshop Session Two

Panel Discussion – Questions and Answers Julie Frost, Amgen Inc., USA Nadine Ritter, Global Biotech Experts LLC, USA Jeffrey Staecker, BioPhia Consulting Inc., USA Jason Starkey, Pfizer, Inc., USA TBD TBD

The following questions will guide the panel discussion:

 What are the triggers to start planning for transfers and how long will it take?  How should I choose the samples to use in the transfer exercise? DP vs DS, how many lots, degraded, reference standards?  How much supply of custom critical assay reagents (e.g. for bioassay or impurity methods) should the transferring R&D lab provide to the commercial QC lab?  Is co-validation possible or is it better to separate the method validation and transfer exercise?  What special processes / precautions are needed for transfers of cell based bioassays?  What is the practical reality of following regulatory guidance for transfers? Are they adequate?  What unique challenges occur when transferring to CROs, especially those with reluctance to follow exactly the transferring lab procedures (sample handling, pipetting, etc.)?  How to derive the specific acceptance criteria prior to the transfer exercise? How to use existing data / specification targets to set the transfer criteria without being too strict or too lenient?

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