FINAL PROGRAM. CASSS Bay Area Discussion Group. Co-chairs: Judy Chou, Medivation, Inc. Lance Wong, Strand Bio

Transcription

1 FINAL PROGRAM CASSS Bay Area Discussion Group Co-chairs: Judy Chou, Medivation, Inc. Lance Wong, Strand Bio South San Francisco Conference Center Thursday, October 13,

2 Table of Contents Conference Program Partners.. 3 Acknowledgements.4 General Information 5 Scientific Program Summary..7 Program and Speaker Abstracts..8 Career Development Luncheon Roundtable..11 Roundtable Discussion Point Sheets..12 Note Paper..21 2

3 The Organizing Committee gratefully acknowledges the Conference Program Partners for their generous support of this Bay Area Discussion Group Program Program Partners Agilent Technologies Covance Inc. Genentech, a Member of the Roche Group ProteinSimple 3

4 Acknowledgements Special thanks to all the Program Committee Members who helped develop this Bay Area Discussion Group Program Committee Kris Antonsen, BioMarin Pharmaceutical Inc. Dawn Benson, Coherus BioSciences Min Chen, Ultragenyx Pharmaceutical Judy Chou, Medivation, Inc. Kathleen Francissen, Genentech, a Member of the Roche Group Malou Gemeniano, Boehringer Ingelheim Vinaya Kapoor, Johnson & Johnson David Passmore, Bristol-Myers Squibb Company Aran Paulus, Thermo Fisher Scientific Joanne Severs, Bayer Lance Wong, Strand Bio Christopher Yu, Genentech, a Member of the Roche Group Eike Zimmermann, Boehringer Ingelheim Roundtable Facilitators Greg Cantin, Five Prime Therapeutics Sianna Castillo, BioMarin Pharmaceutical Inc. Jenny Chen, Nektar Therapeutics Raghu Chitta, Bayer Lisa Erickson, Medivation, Inc. Guifeng Jiang, Boehringer Ingelheim Weijun Li, Bayer Ying Liu, Johnson & Johnson Sarah Maifeld, Genentech, a Member of the Roche Group Robert McCombie, Genentech, a Member of the Roche Group Steve Rabin, Janssen Research & Development, Johnson & Johnson Karin Regnstrom, Boehringer Ingelheim Shelley Suggett, Bayer Trevor Swartz, Genentech, a Member of the Roche Group Kieu Tran, BioMarin Pharmaceutical Inc. Min Young, Ultragenyx Pharmaceutical Shiqian Zhu, Covance Inc. Audio Visual Michael Johnstone, MJ Audio-Visual Productions CASSS Staff Stephanie L. Flores, CAE, Executive Director Anna Lingel, Meeting Coordinator Linda Mansouria, CMP, CMM, Conference Manager 4

5 General Information Name Badges Please wear your name badge throughout the day. Registration The registration desk will be open from 8:00 a.m. to 3:45 p.m. We will accept walk-in registrations. Roundtable Session There are 7 roundtable topics for you to choose from. The goal is for these to be active discussion, not presentations or lecture. The table topics are listed below. Note that Topics 1 and 2 will be repeated at Tables 8 and 9. Table Topic 1: Table Topic 2: Table Topic 3: Table Topic 4: Table Topic 5: Table Topic 6: Table Topic 7: Table Topic 8: Table Topic 9: Transferring Processes and Analytical Methods to CMOs/CROs Phase Appropriate Comparability Assessments Powering Bioassays for Transfer Comparability Bridging Analytical Methods Statistical Based Approach for Analytical Method Transfer Tech Transfer Considerations for Breakthrough Therapy Designation Transfer Considerations for Inspections (Post Approval Commitments) Transferring Processes and Analytical Methods to CMOs/CROs (Repeated Topic) Phase Appropriate Comparability Assessments (Repeated Topic) Tables are set with 12 seats each. Table topics are on a first come, first serve basis. These roundtables will include two facilitators, whose role is to help assist the discussion and ensure a lively exchange, and a scribe, whose role is to make general, anonymous notes about the discussion so others can have a chance to view the main discussion points even if they could not participate. The discussion notes will be shared with all attendees during the session summary at the end of the program and also posted on the CASSS website after the program concludes. 5

6 Career Development Luncheon Roundtable Successful career progression requires planning. This is particularly the case in the Biopharmaceutical industry where career advancement typically occurs over long time frames. Young scientists may not have a complete understanding of how to plan for a typical career progression, while experienced scientists may be seeking knowledge of how to achieve a midcareer transition. If you are seeking information about career development in Biotech/Biopharma, then please join the CASSS Career Development roundtable session which will be held during lunch. This table topic will be facilitated by Malou Gemeniano, Boehringer Ingelheim, and David Passmore, Bristol-Myers Squibb Company. Refer to Page 11 for additional information. 6

7 Scientific Program Summary 08:00 15:45 Registration Thursday, October 13, :00 09:00 Continental Breakfast in Salons G-J 09:00 09:30 CASSS Welcome and Introductory Comments in Salon F Kathleen Francissen, Genentech, a Member of the Roche Group 09:30 10:15 FDA Recommendations for Comparability Studies to Support Manufacturing Changes Joslyn Brunelle, CDER, FDA 10:15 11:00 Biopharmaceutical Method Transfer as Part of the Quality System Camille Dycke, Genentech, a Member of the Roche Group 11:00 11:30 AM Break in Salon F 11:30 12:15 Panel Discussion Moderated by: Lance Wong, Strand Bio Panel Members: Joslyn Brunelle, CDER, FDA Judy Chou, Medivation, Inc. Camille Dycke, Genentech, a Member of the Roche Group Sara Wright, Boehringer Ingelheim 12:15 13:15 Networking Lunch in Salons G-J 13:15 14:00 Roundtable Discussions in Salon F 14:00 14:30 PM Break and Creation of Roundtable Summaries in Salon F 14:30 15:30 Summary of Roundtable Discussions by Table Facilitators in Salon F 15:30 15:45 Closing Remarks by Lance Wong, Strand Bio 7

8 Successful Strategies for Tech Transfer Program Abstract Transfer of manufacturing processes is critical part of drug development to accommodate transition to commercial process, scale changes and site changes. These may occur within an organization or to contract manufacturing facilities. Issues such as scale, equipment, facility infrastructure, and analytical methods transfer should be considered in order to ensure consistency of product quality attributes. The phase of development drives the amount of data needed to support successful transfer of a manufacturing process using a risk-based approach. Generally, early phase transfers require less data. However, by phase 3 and post-licensure/approval the expectations are that a more thorough evaluation will be performed and rigorous analytical comparability data will be evaluated. Depending on the changes required to transfer the process and the evaluation of the analytical comparability data, additional clinical studies may be required to support the manufacturing site transfer. Analytical methods are often transferred during drug development and post-licensure/approval. Again the methods may be transferred to laboratories within company (e.g. analytical development labs to QC for clinical material batch release testing), or to contract analytical labs. The US FDA expects method transfer to occur under a transfer protocol that details the parameters evaluated with predetermined acceptance criteria. Considerations for successful transfer include sufficient number product lots tested at both the originating laboratory and the new laboratory as well as a statistically sound evaluation of the data generated at both labs. This workshop will provide insight into the transfer of a manufacturing process and the transfer of analytical methods to alternative sites that commonly occur during drug development. 8

9 Speaker Abstracts FDA Recommendations for Comparability Studies to Support Manufacturing Changes Joslyn Brunelle, CDER, FDA Manufacturers of biotechnology products frequently make changes to manufacturing processes of products both during development and after approval. Common manufacturing changes include: scale up, site changes, changes in equipment, new cell line/master cell bank, and/or formulation changes. Pre-change and Post-change products should be assessed for comparability, which involves an analysis of relevant physicochemical and biological characterization data to assess whether there are any significant differences in the quality attributes of the product. For many biotechnology products, quality attributes include potency and both product-related and processrelated impurities. Analytical comparability exercises typically include some combination of release testing, extended characterization methods, and stability studies (real time and stressed conditions). However, the amount of information varies depending on your stage of development (Phase 1, Phase 3, or post-approval). If comparability cannot be demonstrated, then non-clinical or clinical studies may be needed to assess whether any differences would negatively impact the safety or efficacy of the product. The basic principles of ICH Q5E (Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Process) will be outlined. Examples of comparability studies at different stages of clinical development will be provided. Biopharmaceutical Method Transfer: How to Marry Quality & Compliance with Productivity & Speed Camille Dycke, Genentech, a Member of the Roche Group Approaches to non-compendial biopharmaceutical analytical method transfer usually focus on a point-in-time comparison between two data sets generated by the Donor site and the Receiving site. Despite general guidance documents available, sample types, size of the data set, statistical design for the comparison, and transfer acceptance criteria are left to the authors of the method transfer protocol to define and defend. Challenges are often faced, such as differences observed in method performance during the point-in-time transfer and the long term use of the method during release testing, or such as which site to consider as the donor site when the method is already executed at multiple sites... Complying with Health Authority requirements and expectations, and ensuring quality of the transfer design is core to the analytical transfer strategy. However, considerations for productivity, such as maximizing the resource utilization and minimizing the size of the data set to be generated, as well as considerations for speed, in order to avoid the analytical method transfers being the bottle neck of the overall process transfer, are continuously pushing biopharmaceutical companies 9

10 to innovate in their method transfer designs. Co-validation executed simultaneously by the various testing laboratories, re-validation at the receiving sites, performance verification studies, are alternative method transfer strategies that are worth evaluating in terms of quality, cost, risk and lead time in order to define the most appropriate transfer strategy. This talk will present pros and cons, challenges and successes with these various analytical transfer approaches. 10

11 Career Development Luncheon Roundtable Two tables will be set aside during the networking lunch to discuss career development. The volunteer facilitators for these tables are: Malou Gemeniano, Boehringer Ingelheim and David Passmore, Bristol-Myers Squibb Company. There will be a total of 20 seats available for this career development discussion - 10 seats per table. Seating will be on a FIRST COME, FIRST SERVE basis. The discussion points are listed below. TOPIC: FACILITATORS: Career Development Transferable Skills Malou Gemeniano, Boehringeh-Ingelheim David Passmore, Bristol-Myers Squibb Company SCOPE: We will be discussing career development within the Biotech and Pharma Industries. We will explore myths regarding the numbers of years one has to acquire to attain a desired position of different area or discipline in the industry. And we will discuss transferable skills, management experience and strategic skills sets. DISCUSSION POINTS: 1) Is important to have a degree in the field that you are pursuing? a. For example, if the goal is to be a Director of Analytic, does one need degree in chemistry, Biology. Does one require a PhD? b. Is this the case for all careers? For example, does this hold true for Regulatory affairs or project management? 2) How does one move from technical jobs to Regulatory affairs, project management, Quality assurance, and vice versa etc.? a. What are transferable skills in the industry? b. How can start thinking more cross-functionally? c. How can you think more strategically? 3) Is it better to have a more diverse background or focus on one field for many years to be successful? a. How can one gain more experience in one discipline yet still stay in their current position? 11

12 Roundtable Discussion Points TABLE 1 TOPIC: FACILITATORS: SCRIBE: Transferring Processes and Analytical Methods to CMO s/cro s Guifeng Jiang, Boehringer Ingelheim Steve Rabin, Janssen Research & Development, Johnson & Johnson Eike Zimmermann, Boehringer Ingelhheim SCOPE: Open discussion on Transfer Process and Analytical Method Transfer Process from the CMO s/cro s perspective. Participants are encouraged to provide insights on the bullet points according their area of expertise and experience. BULLET POINTS FOR DISCUSSION: 1) What are the regulatory guidances/expectations on process and method transfer? FDA 2) How do the strategies vary based on the phase of development (IND vs BLA) 3) What are the responsibilities of the transferring and receiving laboratories? 4) What are the criteria and approach you have used for risk based testing? 5) What are the considerations for selection of acceptance criteria? 6) What are the most likely failures during method transfer? What are the challenges? 7) How are deviations documented with regards to acceptance criteria handled? 12

13 TABLE 2 TOPIC: FACILITATOR: SCRIBE: Phase Appropriate Comparability Assessments Rob McCombie, Genentech, a Member of the Roche Group Joanne Severs, Bayer SCOPE: This table will discuss phase-appropriate analytical comparability requirements and strategies that are used during development and technology transfers. The discussion will focus on challenges and successful examples used throughout development, commercialization and post-licensure with a global perspective in mind. BULLET POINTS FOR DISCUSSION: 1) How does a comparability strategy differ for a manufacturing process change versus the transfer of an existing process to different manufacturing site? 2) What type of analytical comparability protocol/plan is used for early versus late clinical development? a. Are pre-defined acceptance criteria included? What if results indicate that materials are not comparable? b. Formal versus informal protocol used? c. Number of batches needed? d. Use of Release, In-process, Extended Characterization and Stability data within the Comparability protocol and acceptance criteria e. For post market changes how to determine requirements for comparability following changes with only moderate potential to impact product quality. 3) How is comparability handled when you have limited data sets and/or limited number of batches? 4) How is comparability impacted by the changes in analytical methods through development? 5) How have analytical comparability plans been communicated to Health Authorities? a. Included as part of a Health Authority meeting? b. Submitted prior or after initiating? c. Are interim reports shared with Health Authorities? 13

14 TABLE 3 TOPIC: FACILITATORS: SCRIBE: Powering Bioassays for Transfer Comparability Karin Regnstrom, Boehringer Ingelheim Sarah Maifeld, Genentech, a Member of the Roche Group Fengrong Zuo, Medivation, Inc. SCOPE: This table will discuss the strategies applied to execution, trouble-shooting, compliance, and tech transfer for bioassays. Table members will provide areas of challenge and success for bioassays in relation to pharmacokinetics, dose-responsiveness, techniques and new approaches while keeping a global perspective in mind. BULLET POINTS FOR DISCUSSION: 1) What strategies should be taken to ensure a smooth and successful tech transfer? 2) What are the key parameters that should be evaluated for effective training and troubleshooting during the tech transfer? 3) How can the originating and receiving laboratories set up ground rules and escalating process for timely and transparent communication? 4) Discuss the future of laboratory practices/techniques that will become the standard for bioassay development. What techniques/practices are currently being phased out? 14

15 TABLE 4 TOPIC: FACILITATORS: SCRIBE: Bridging Analytical Methods Jenny Chen, Nektar Therapeutics Raghu Chitta, Bayer Yan Chen, Genentech, a Member of the Roche Group SCOPE: Changes in analytical methodology over the development of a molecule are a normal occurrence. Companies must bridge between the different methods used to support the clinical development of the molecule to assure the critical quality attributes. However, companies continue to face challenges on how to successfully bridge the analytical methods used throughout development. This round table discussion will focus on these issues through open discussion of current strategies. BULLET POINTS FOR DISCUSSION: 1) What is the impact of changing methods? (pre and post approval) a. Regulatory impact b. Receiving lab site impact (do they have the instruments, training, etc) c. Cost associated with the change 2) What drives an analytical method bridging study? (pre and post approval) a. Change in analytical instrumentation b. Change in rare/critical reagents c. Optimized or new chromatography (columns, gradients, etc) 3) What sample types are required to be tested for bridging studies? (pre and post approval) a. Clinical/commercial lots b. GLP tox lot(s) c. Clinical/commercial stability samples d. Historical reference standards e. Force degraded samples 4) How is the bridging study designed? (pre and post approval) a. Head-to-head comparison? b. Statistical based comparison? c. Does the protocol include pre-defined acceptance criteria? 5) The bridging study results should be presented in (pre and post approval) a. Comparability protocol b. Briefing documents c. IND/IMPD updates d. BLA filing 15

16 TABLE 5 TOPIC: FACILITATORS: SCRIBE: Statistical Based Approach for Analytical Method Transfer Weijun Li, Bayer Greg Cantin, Five Prime Therapeutics David Passmore, Bristol-Myers Squibb Company SCOPE: Per the FDA Guidance for Industry document titled Analytical Procedures and Methods Validations for Drugs and Biologics, analytical method transfer is typically managed under a transfer protocol that details the parameters to be evaluated in addition to the predetermined acceptance criteria that will be applied to the results. However, no guidance is provided on how to compute the predetermined acceptance criteria. USP general chapter <1224> on Transfer of Analytical Procedures does mention that acceptance criteria should be based on method performance and historical data from stability and release results and also that statistical principles based on the difference between mean values, established ranges, and an estimate of the variability of the method should be used. This table will examine aspects that might be considered in generating acceptance criteria for a statistically based approach to method transfer. BULLET POINTS FOR DISCUSSION: 1) When are the use of statistics recommended/required for analytical method transfer? a. At what stage (discovery, Phase I/II/III, commercial) is a statistical approach recommended/required for method transfer? b. What type of transfer can utilize a statistical approach (comparative, covalidation, or other approach)? 2) What are the typical statistical approaches used? a. Classical Statistics (% mean difference and % CV?) b. TOST analysis c. Multi-Variate Analysis? 3) What are the pros/cons of the different statistical approaches? 4) What validation characteristics are normally included in the transfer for statistical comparison? a. Intermediate Precision b. Quantitation Limit (QL) c. Accuracy d. System suitability e. Etc. 16

17 TABLE 6 TOPIC: FACILITATORS: SCRIBE: Tech Transfer Considerations for Breakthrough Therapy Designation Shelley Suggett, Bayer Trevor Swartz, Genentech, a Member of the Roche Group Vinaya Kapoor, Johnson & Johnson SCOPE: This table will discuss the implications of breakthrough therapy designation on technology transfer during drug development. Participants will discuss successful strategies or lessons learned in the face of accelerated timelines and increased regulatory interaction. BULLET POINTS FOR DISCUSSION: 1) What regulatory challenges have you faced for technology transfer with respect to agency questions? 2) How has breakthrough therapy designation impacted timelines for technology transfer? 3) Are there additional challenges that you have faced? 4) Given the limited amount of historical data that is inherent to breakthrough therapies, how have you adjusted or modified your approach to technology transfer? 17

18 TABLE 7 TOPIC: FACILITATORS: SCRIBE: Transfer Considerations for Inspections (Post Approval Commitments) Shiqian Zhu, Covance Inc. Sianna Castillo, BioMarin Pharmaceutical Inc. Malou Gemeniano, Boehringer Ingelheim SCOPE: Inspectional preparation activities need to be completed prior to and after a submission for a transfer of manufacturing activities. These activities require careful and detailed planning to assure compliance with regulation and with the application. The scope of this activity will be those items to support the content of the application and the anticipated FDA inspection. BULLET POINTS FOR DISCUSSION: This round table discussion will focus on these issues through open discussion of current strategies. ANALYTICAL METHOD TRANSFERS 1) What are the considerations prior to analytical method transfers as part of planning? 2) What are some of the timeline perspectives for implementing transferred methods at the labs (readiness)? Are they different based on type of method? 3) Are there any lessons learned from having completed analytical method transfers? MANUFACTURING SITE TRANSFERS 1) What are the considerations prior to manufacturing site transfers as part of planning? 2) What are some of the timeline perspectives for transferred process at the site (readiness)? Are they different based on complexity of the process? 3) Are there any lessons learned from having completed site transfers? CHANGE MANAGEMENT PLANS & RISK ASSESSMENTS 1) Where are risk assessments done as part of your change management process? 2) What is your approach for method and site transfers? 3) What functional area drives the program or responsibility? 18

19 TABLE 8 TOPIC: FACILITATORS: Transferring Processes and Analytical Methods to CMO s/cro s Ying Liu, Johnson & Johnson Kieu Tran, BioMarin Pharmaceutical Inc. SCRIBE: SCOPE: Open discussion on Transfer Process and Analytical Method Transfer Process from the CMO s/cro s perspective. Participants are encouraged to provide insights on the bullet points according their area of expertise and experience. BULLET POINTS FOR DISCUSSION: 1) What are the regulatory guidances/expectations on process and method transfer? FDA 2) How do the strategies vary based on the phase of development (IND vs BLA) 3) What are the responsibilities of the transferring and receiving laboratories? 4) What are the criteria and approach you have used for risk based testing? 5) What are the considerations for selection of acceptance criteria? 6) What are the most likely failures during method transfer? What are the challenges? 7) How are deviations documented with regards to acceptance criteria handled? 19

20 TABLE 9 TOPIC: FACILITATOR: SCRIBE: Phase Appropriate Comparability Assessments Min Young, Ultragenyx Pharmaceutical Lisa Erickson, Medivation, Inc. Jonathan Tsang, Bayer SCOPE: This table will discuss phase-appropriate analytical comparability requirements and strategies that are used during development and technology transfers. The discussion will focus on challenges and successful examples used throughout development, commercialization and post-licensure with a global perspective in mind. BULLET POINTS FOR DISCUSSION: 1) How does a comparability strategy differ for a manufacturing process change versus the transfer of an existing process to different manufacturing site? 2) What type of analytical comparability protocol/plan is used for early versus late clinical development? a. Are pre-defined acceptance criteria included? What if results indicate that materials are not comparable? b. Formal versus informal protocol used? c. Number of batches needed? d. Use of Release, In-process, Extended Characterization and Stability data within the Comparability protocol and acceptance criteria e. For post market changes how to determine requirements for comparability following changes with only moderate potential to impact product quality. 3) How is comparability handled when you have limited data sets and/or limited number of batches? 4) How is comparability impacted by the changes in analytical methods through development? 5) How have analytical comparability plans been communicated to Health Authorities? a. Included as part of a Health Authority meeting? b. Submitted prior or after initiating? c. Are interim reports shared with Health Authorities? 20

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