Northeast Regional Forum

Transcription

1 Northeast Regional Forum Accelerated CMC Development Wyndham Boston Beacon Hill 5 Blossom Street Boston, MA Monday, October 8, 2018 Forum Co-chairs: Francis Poulin, Sanofi Bernice Yeung, Shire Pharmaceuticals

2 The program committee gratefully acknowledges the following program partners and exhibitors for their generous support of the CASSS Northeast Regional Forum Strategic Platinum Program Partner Biogen Strategic Gold Program Partner Pfizer Strategic Silver Program Partner AbbVie, Inc. Program Partner Sanofi Exhibitors Charles River Laboratories Waters Corporation 2

3 Acknowledgements Special thanks to the organizing committee who helped develop this program! Program Committee: Bem Atsma, Biogen Hirak Bhartiya, Shire Pharmaceuticals Petra Cavallaro, Eli Lilly and Company Wesley Church, AbbVie, Inc. David Cirelli, Pfizer, Inc. Steve Cohen, SAC Analytical Consultants Bharat Dixit, Finch Therapeutics Joseph Glajch, JLG AP Consulting LLC. Chi-Ting Huang, CTH Analytical Consulting Yan Jiang, Sanofi Todd Mabe, Merck & Co., Inc. Francis Poulin, Sanofi Czeslaw Radziejewski, AbbVie, Inc. Zahra Shahrokh, ZDev Consulting and STC Biologics Joseph Siemiatkoski, J Siemiatkoski Consulting Andrew Weiskopf, Biogen April Xu, Pfizer, Inc. Bernice Yeung, Shire Pharmaceuticals CASSS Staff: Noelle Atkins, Administrative Coordinator Karen A. Bertani, CMP, Director, Global Engagement and Knowledge Sharing Stephanie L. Flores, CAE, Executive Director Julie Fowle, Program Planning and Event Specialist Anna Lingel, CMP, Exhibitor Relations and Technology Specialist Renee Olson, Senior Program Manager Catherine Stewart, Finance Manager Audiovisual Support: Mike Johnston, MJ Film/Video Production 3

4 Scientific Program Summary Monday, October 8, :00 09:00 Registration and Breakfast in the Ballroom Foyer 08:15 08:45 Sunrise Session: Accelerated CMC Development Primer in Beacon ABC Joseph Glajch, JLG AP Consulting LLC, and Bharat Dixit, Finch Therapeutics 09:00 09:10 CASSS Welcome and Introductory Comments in Beacon ABC Steven Cohen, SAC Analytical Consultants 09:10 09:20 Welcome to the Northeast Regional Forum in Beacon ABC Bernice Yeung, Shire Pharmaceuticals 09:20 09:50 Efficient Analytical Development Strategies to Support Accelerated CMC Development Marc Verhagen, Sanofi 09:50 10:20 Efficient Process Validation Strategies for Accelerated Programs Kartik Subramanian, AbbVie, Inc. 10:20 10:50 Leveraging mab Platform to Control Product Quality Chris Kwiatkowski, Biogen 10:50 11:15 Networking Break in Commonwealth AB 11:15 12:15 Panel Discussion in Beacon ABC Panel Members: Chris Kwiatkowski, Biogen Jaclyn Moxham, Pfizer, Inc. Kartik Subramanian, AbbVie, Inc. Marc Verhagen, Sanofi 12:15 13:15 Networking Lunch in Commonwealth AB 12:15 13:15 Career Development Roundtable in Beacon ABC 13:15 14:30 Roundtable Discussion Session I in Beacon ABC 14:30 14:45 Networking Break in Commonwealth AB 4

5 Monday, October 8, 2018, continued 14:45 15:30 Roundtable Discussion Session II in Beacon ABC 15:30 15:40 Closing Remarks in Beacon ABC Francis Poulin, Sanofi 15:40 16:45 Networking Reception in Capitol AB 5

6 Accelerated CMC Development Program Abstract This Forum will focus on technical and regulatory approaches to accelerate CMC development. To support development of new therapeutics addressing unmet medical needs, several health authorities have implemented expedited regulatory pathways. These programs focus on increasing communication between industry and health authorities to reduce review timelines and deliver transformative therapies to patients more rapidly. Shorter clinical trials result in condensed CMC timelines and increase pressures to deliver a commercializable process early in development. As a result, various CMC development strategies may have to be implemented to meet the needs of the product and indication. Roundtable discussions as well as speaker presentations will focus on a range of topics including: developability assessment, rapid process development, accelerated control strategies, setting specifications on small number of batches, authoring submissions with limited development and manufacturing experience, analytical assay development and bridging to enable commercial facilities earlier in development. Learning Objectives: The learning objectives of this forum will be comprised of: Regulators perspective on accelerated programs. Process validation approaches including process design, qualification and continuous verification. Historical manufacturing experience. Platform knowledge (process and analytical development), and application of PAT. Post-registration approval challenges. Early development of potency assay(s). 6

7 Speaker Abstracts Accelerated CMC Development Primer Joseph Glajch, JLG AP Consulting LLC, and Bharat Dixit, Finch Therapeutics Accelerated CMC development is typically required to support and bring new therapeutics to market in the area of unmet medical needs. This training session will provide an overview of CMC development from early stage to approval with a special emphasis on accelerated CMC development approach. Expedited regulatory pathways offered by various regulatory agencies that supports frequent communication between industry and regulators will also be summarized NOTES: 7

8 Efficient Analytical Development Strategies to Support Accelerated CMC Development Marc Verhagen, Sanofi The increase in our understanding of disease pathways continues to generate additional targets for the development of new therapeutic compounds. Unfortunately, the establishment of suitable translational models to evaluate these compounds remains challenging. As a result accelerated CMC development of new compounds continues to be important to reduce the time it takes to make safe and efficacious treatments available to patients. To enable rapid CMC development a variety of analytical methods need to be available to support process and formulation development activities as well as QC release testing of GMP supplies. An efficient approach for developing the necessary methods used at the different stages of the program relies on prospectively defining the method requirements using tools such as the Analytical target profile (ATP). Risk assessments can subsequently be leveraged as part of the method development process to obtain an understanding of the key analytical quality attributes which can influence method performance. This will ensure that the method development activities are consistently focused on the attributes most likely to affect the accuracy and precision of the method. Platform approaches have proven to be very effective during early stage development to minimize the time and effort required to apply an existing method to new compounds from the same platform class. The experiments required to confirm that the method remains suitable for the analysis of the new compound are based on the risk assessments previously established for the method. These experiments can be prospectively defined for a platform method using job aids or protocol templates to minimize the planning and documentation required during execution. In addition, knowledge of the critical quality attributes gained from compounds which fall within the platform class provides a rationale to establish a lean release and stability paradigm while ensuring an appropriate level of control at the different stages of the program. The presentation will provide an overview of the approaches which have been used successfully over the years to efficiently create robust analytical methods to support multiple programs. In addition, considerations for establishing efficient information flows to further reduce the CMC development time will be discussed. NOTES: 8

9 Efficient Process Validation Strategies for Accelerated Programs Kartik Subramanian, AbbVie, Inc. To enable program acceleration, novel approaches towards process validation activities are often needed. Case studies will be presented that reflect different scenarios for enabling process performance qualification (PPQ) runs. In one case, a tiered approach to process characterization was adopted where process characterization studies (PCS) were divided between some activities prior to PPQ and others after PPQ. In another case, PPQ runs were initiated after a rapid techtransfer with majority of PCS performed post-ppq. Key factors enabling both scenarios and lessons learned will be summarized. In addition, utility of novel experimental designs, mathematical modeling and knowledge management as additional drivers for speed will also be discussed. NOTES: 9

10 Leveraging mab Platform to Control Product Quality Chris Kwiatkowski, Biogen Biopharmaceutical therapeutic development timelines can be reduced by quickly generating material to initiate clinical trials and begin the process of drug development. One way Biogen has addressed these challenges is the generation of a high productivity host. The high productivity host enables the use of representative cell pools that produce sufficient material for toxicology studies faster than previous workflows which used an individual clone. In general, one caveat of using cell pools is the risk of generating material that may not be fully representative of the commercial process. As product quality may vary from clone to clone, a less productive clone may need to be selected in order to avoid repeating toxicology studies. Biogen has mitigated this risk through changes in the platform process in order to have more predictable product quality outputs across pools, clones, and products. Platform modifications to the host cell line, media composition, process parameters and unit operations have enabled a predictable quality profile for both clones and pools, thereby enabling a fast to tox strategy that is also consistent with generating a commercially desirable process. NOTES: 10

11 Career Development Luncheon Roundtable We will have two tables set aside during the lunch hour for attendees to discuss career development. The facilitators for this table topic are Chi-Ting Huang, Surface Oncology and Todd Mabe, Merck & Co., Inc. The seating will be available on a first come, first serve basis. SCOPE: We will be discussing career development within the biotechnology and pharmaceutical industry. We will explore myths regarding the experience one has to acquire to branch into a position in a different area or discipline in the industry. We will also discuss transferable skills, management experience, and strategic skill sets. Below are some of the example topics we may explore at this roundtable. The discussion will require active engagement from participants. DISCUSSION QUESTIONS: 1. Is it important to have a degree in the field that you are pursuing? a. For example, if the goal is to be a Director of Analytics, does one need a degree in chemistry, biology, other fields? b. What degree is required, B.Sc., M.Sc., Ph.D.? c. Is this the case for all careers in our industry? For example, does this hold true for regulatory affairs or project management? 2. How does one move from technical positions to management, regulatory affairs, project management, quality assurance, and vice versa? a. Is it better to start with a technical position before moving into regulatory affairs or project management and, if so, how much experience is required? b. What are transferable skills in our industry? c. How can you start thinking more cross-functionally? d. How can you think more strategically? e. How do you transition from individual contributor to manager? 3. Is it better to have a more diverse background or focus on one field for many years? a. How can one gain more experience in one discipline yet still stay in their current position? b. How can one gain more visibility in other disciplines through collaboration and cross-functional work? c. Is it important to change companies every few years to increase one s skills? NOTES: 11

12 Roundtable Discussion Topics The roundtable session will feature active discussions where colleagues can learn from each other, not presentations or lectures. There will be two sessions and all ten topics will be repeated at both sessions. The topics for the October meeting will be: Table 1: Control Strategies for Accelerated Projects Table 2: Early Development of Potency Assays in Research with CMC Mindset Table 3: Leveraging Prior Knowledge to Accelerate CMC Table 4: Strategies to Transition Research Programs into Development Quickly to Reduce Time to First in Human Table 5: Authoring Regulatory Submissions with Limited Development and Manufacturing Experience Table 6: Analytical Development and Bridging to Enable Commercial Facilities Earlier in Development Table 7: How to Conduct Expedient Tech Transfer to GMP Functions (Process and Analytical)? Table 8: Use of Developability Assessments to De-risk Fast Transitions to FIH Table 9: High Throughput Development: What Can be achieved and What are the Issues? Table 10: PAT On-line/In-line/At-line Testing NOTES: 12