FINAL PROGRAM. Midwest Discussion Group. Co-chairs: John (J.R.) Dobbins, Eli Lilly and Company Michelle Frazier, AbbVie, Inc.

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1 FINAL PROGRAM Midwest Discussion Group Co-chairs: John (J.R.) Dobbins, Eli Lilly and Company Michelle Frazier, AbbVie, Inc. University Center of Lake County Grayslake, IL October 29,

2 Table of Contents Conference Program Partners.. 3 Acknowledgements.4 General Information 5 Scientific Program Summary..6 Program and Speaker Abstracts..7 Roundtable Discussion Point Sheets...8 Note Paper..14 2

3 The Organizing Committee gratefully acknowledges the Conference Program Partners for their generous support of this inaugural Midwest Discussion Group Program Partners AbbVie, Inc. Cook Pharmica, LLC Covance, Inc. Pfizer, Inc. 3

4 Acknowledgements Special Thanks to all the Program Committee Members who helped develop this Midwest Discussion Group Program Committee Leslie Bloom, Pfizer, Inc. James Carroll, Pfizer, Inc. John (J.R.) Dobbins, Eli Lilly and Company John Dougherty, Eli Lilly and Company Michelle Frazier, AbbVie, Inc. Ashley Gucinski, CDER, FDA Kathy Lee, Eli Lilly and Company Ed Moore, University of Illinois Ned Mozier, Pfizer, Inc. Leslie Redfern, AbbVie, Inc., Vic Vinci, Cook Pharmica Veda Walcott, Cook Pharmica Roundtable Facilitators Maje Babatola, Therapeutic Proteins International Phoebe Baldus, Pfizer, Inc. Joseph Berry, Eli Lilly and Company Brian Dipaolo, AbbVie, Inc. Will Hatcher, Cook Pharmica Amisha Kizhakkedathu, Pfizer, Inc. Thomas Lerch, Pfizer, Inc. Michelle Lytle, Eli Lilly and Company Wen Luo, Eli Lilly and Company Donna Santucci, AbbVie, Inc. Qin Sheng, Eli Lilly and Company Shiqian Zhu, Covance, Inc. CASSS Staff Stephanie L. Flores, CAE, Executive Director Anna Lingel, Registration Manager 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 at 8:00 a.m. to 3:00 p.m. We will accept walk-in registrations. Registration is located in the Multi-Purpose Room (Rooms 142, 143, and 144). Roundtable Session There are 6 roundtable topics for you to determine which table topic you would like to be involved in the discussion. The 6 table topics are: Table Topic 1: Table Topic 2: Table Topic 3: Table Topic 4: Table Topic 5: Table Topic 6: Don t Get In a Bind over Specifications Setting Appropriate Specifications Leveraging Platform Information Appropriately S-T-A-B-I-L-I-T-Y - You Ain t Got No Alibi: Stability Strategies for Phase I and Beyond Structural Characterization Global Filing Challenges To Infinity and Beyond Analytical Method Development Tables are set with 10 seats to a table. 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 discussion even if they could not participate. The discussion notes will be shared with all attendees during the summary period of the program. Wi-Fi Access The entire University Center has Wi-Fi availability. 5

6 Scientific Program Summary THURSDAY, OCTOBER 29, :00 15:00 Registration in the Multi-Purpose Room Foyer 08:00 09:00 Registration and Continental Breakfast in the Multi-Purpose Room (Rooms 142, 143, and 144) 09:00 09:30 CASSS Welcome and Introductory Comments Edwin Moore, University of Illinois 09:30 10:15 Building A Quality Dossier Howard Anderson, CDER, FDA 10:15 11:00 Let s Start at the Very Beginning, a Very Good Place to Start! Building and Maintaining a Quality CMC Dossier Michelle Frazier, AbbVie, Inc. 11:00 11:15 AM Break in Multi-Purpose Room 11:15 12:00 Panel Discussion Facilitated by: John (J.R.) Dobbins, Eli Lilly and Company and Michelle Frazier, AbbVie, Inc. Panel Members: Michael Boyne, BioTech Logic Eva Essig, Hospira, Veda Walcott, Cook Pharmica, LLC 12:00 13:00 Lunch in the Multi-Purpose Room 13:00 13:45 Roundtable Discussions in the Multi-Purpose Room. Refer to Page 8 for topics. 13:45 14:15 PM Break and Roundtable Summaries Created in the Multi-Purpose Room 14:15 15:00 Summary of Roundtable Discussions by Table Facilitators 15:00 15:15 Closing Remarks James Carroll, Pfizer, Inc. and Kathy Lee, Eli Lilly and Company 6

7 Program Abstract Building a Quality Dossier from Phase 1 and Beyond Development of a Quality Dossier containing the appropriate level of Chemistry, Manufacturing and Control information is an integral element of global regulatory submissions to support clinical development programs. First and foremost, regulations and guidance must be considered as the dossier is being prepared. Additionally, the phase of development, molecule complexity, and available molecule knowledge are key elements to consider when developing the dossier content. This meeting will provide an interactive forum for individuals from academia, industry and the FDA to come together to discuss the challenges and best practices for preparing a phase appropriate Quality Dossier. Key discussion topics will include, establishing specifications, analytical method development, structural characterization, stability approaches, and leveraging platform information when preparing dossiers to support global clinical programs. The meeting format is designed to provide attendees the opportunity to hear current perspectives from the FDA and Industry and to network through participation in facilitated small group discussions. Building A Quality Dossier Howard Anderson, CDER, FDA Speaker Abstracts This presentation will provide a FDA product reviewer s perspective on building a quality dossier from the pind meeting through filling BLA supplements to change the commercial manufacturing process. Focused quality regulatory submissions make FDA sponsor meeting more productive, facilitate application review, and best utilize FDA resources for application decisions. In contrast a deficient submission may delay the product development program. The goal for all stake holders is to facilitate the rapid clinical development and approval of high quality biopharmaceuticals for patients. Case studies will be provided for FDA therapeutic monoclonal antibodies and proteins regulated by the Office of Biotechnology Products at CDER. The case studies will illustrate lessons learned and best practices for providing adequate information to the FDA at the various stages of product development. The examples involve analytical method development, product characterization, justifying specifications, and stability commitments. Let s Start at the Very Beginning, a Very Good Place to Start! Building and Maintaining a Quality CMC Dossier Michelle Frazier, AbbVie Inc. High quality submissions are essential for the success of any development program from pre-first in human (FIH) through post-licensure, whether they are meeting packages or Module 3 quality sections in support of a clinical trial application or a marketing application. In contrast, submissions that are not focused and do not contain the appropriate level of detail or data can have a negative outcome for a given clinical program. This presentation will outline Industry best practices and lessons learned in building quality regulatory submissions throughout the product lifecycle. 7

8 Roundtable Discussion Points TABLE 1 TOPIC: FACILITATORS: SCRIBE: Don t Get in a Bind over Specifications Setting Appropriate Specifications Phoebe Baldus, Pfizer, Inc. Will Hatcher, Cook Pharmica Lesley Redfern, AbbVie, Inc. SCOPE: Setting realistic specifications for analytical analyses is an exercise that almost every company conducts routinely. However, the strategies and practices could be diverse. We will discuss strategies for setting specifications and what to consider when setting specifications BULLET POINTS FOR DISCUSSION: 1. Are quantitative specifications required or is report results sufficient? a. When is Report Results acceptable for early-phase products? What analyses (appearance, ID, assay, impurities/degradation products, counterion potency, etc.)? b. Should Report Results be used alone or should a Target be listed as well? c. DS versus DP? Does this matter? 2. What is the focus for setting specifications for early-phase products? Patient safety, efficacy, etc? a. Typically, early-phase products focus on patient safety first and foremost. Is this the correct approach? What else should be focused on for early-phase products? b. What other attributes with regards to specifications should be focused on as the product moves throughout its lifecycle? 3. Control strategy for setting specifications a. Where does information come from for final drug product specifications? (IP testing, FP testing, stability testing, etc.)? b. Is monitoring IP testing results helpful in setting of specifications? c. How does this process evolve from early-phase to late-phase products? 8

9 TABLE 2 TOPIC: FACILITATORS: SCRIBE: Leveraging Platform Information Appropriately Maje Babatola, Therapeutic Proteins International Wen Luo, Eli Lilly and Company J.R. Dobbins, Eli Lilly and Company SCOPE: The pharmaceutical industry has accumulated a large body of platform knowledge in process development. Many organizations have been successfully leveraging their technology platforms to streamline process development activities. However, companies continue to face challenges on how to leverage platform information in the dossier to support successful global submissions. This round table discussion will focus on these issues through open discussion of current strategies. BULLET POINTS FOR DISCUSSION: 1) What are the considerations for establishing a platform data set? a. What is the definition of platform data set? b. Do they vary based on the phase of development (IND vs BLA?) c. How much data and / or how many molecules are needed to be considered a platform? How is the platform process verified? d. What are the considerations to account for the target molecule profile? e. What is the eligibility of next-in-class-molecule to leverage platform process? 2) What are examples of successful of incorporation of platform information into the dossier (e.g. Viral Clearance)? 3) How is platform information incorporated into the CMC Dossier? a. What has worked well? b. What are the challenges? c. How is platform information maintained when additional information is obtained for the platform 4) Is the use of platform information in a dossier globally accepted? What are the challenges globally? 9

10 TABLE 3 TOPIC: FACILITATORS: SCRIBE: S-T-A-B-I-L-I-T-Y - You Ain t Got No Alibi: Stability Strategies for Phase I and Beyond Donna Santucci, AbbVie, Inc. Michelle Lytle, Eli Lilly and Company Michelle Frazier, AbbVie, Inc. SCOPE: This table will discuss stability strategies applied to Phase I through the Marketing Application for Biologics. Table members will provide areas of challenge and success for clinical trials and marketing applications with a global perspective in mind. Participants will consider the use of unique strategies as well as stability modeling and extrapolation to support shelf-life. BULLET POINTS FOR DISCUSSION: 1. What regulatory challenges have you faced for stability with respect to agency questions globally? 2. What unique or different stability strategies have you used for Phase I and how did those progress to Phase II, III and the marketing application? 3. How do you manage in-use stability studies to support clinical use as well as to support the marketing application? 4. Have you used modelling to support product shelf life in lieu of full stability data? How successful have you been gaining regulatory approval? What types of challenges have you faced? 5. What is your strategy for placing material on stability with respect to the manufacturing site? If not from the commercial site, what is your strategy for bridging? 6. What unique strategies have you used for primary stability? 10

11 TABLE 4 TOPIC: FACILITATORS: SCRIBE: Structural Characterization Tom Lerch, Pfizer, Inc. Shiqian Zhu, Covance, Inc. James Carroll, Pfizer, Inc. SCOPE: This table will discuss characterization strategies for early phase development candidates. Table members will provide examples of best practices as well as experiences with regulators. BULLET POINTS FOR DISCUSSION: 1. Risk-based approach for determining the level of structural characterization needed to support early phase candidates how much is enough and how much is too much? 2. What to include in a Ph1 IND and where in the CTD? 3. What guidance information is available from regulatory bodies? 4. Which samples are used for characterization? 5. Which analytical techniques are used for structural characterization? 6. What level of method assessment is needed for structural characterization analytical methods? 11

12 TABLE 5 TOPIC: FACILITATORS: SCRIBE: Global Filing Challenges Joe Berry, Eli Lilly and Company Brian DiPaolo, AbbVie, Inc. Kathy Lee, Eli Lilly and Company SCOPE: This table will discuss the CMC challenges associated with regulatory submissions for global clinical studies. Table members will provide examples of best practices as well as experiences with regulators. BULLET POINTS FOR DISCUSSION: 1. Can the same CMC content / level of detail be used in all geographies? a. One size fits all dossier versus Country-specific dossiers 2. Managing content (e.g., keeping track of what is filed where) 3. Strategies for responding to questions a. Making & tracking commitments 4. Managing changes across geographies (e.g., manufacturing process, specifications, ) 5. Handling divergence across geographies (e.g., specifications, expiry dating, ) 6. How much and what source (i.e. development or CT lot) of Drug Product stability data is required to establish at least 12 months of initial shelf-life in various countries? Which specific countries pose the most risk? 7. Strategy for viral safety reporting requirements across geographies. 12

13 TABLE 6 TOPIC: FACILITATORS: SCRIBE: To Infinity and Beyond Analytical Method Development Amisha Kizhakkedathu, Pfizer, Inc. Qin Sheng, Eli Lilly and Company Ed Moore, University of Illinois SCOPE: Analytical method development can be a balancing act during the early stages of a product s development. Companies continue to struggle with defining the ideal timing and scope for method development, qualification, and validation, as well as deciding what data is appropriate to include in a submission. This table will focus on these issues through open discussion of current strategies. BULLET POINTS FOR DISCUSSION: 1. Too much testing early on vs. too little lot data what is just right for a Phase 1 submission? 2. When does a characterization method become routine testing? 3. Qualification vs. validation what s appropriate for early stage development? 4. Setting appropriate system suitability criteria at different phases balancing failures and investigations against the risk of data variability 5. Challenges associated with high throughput screening (for example, microfluid technology) 6. Critical quality attributes do common method sets drive criticality assessments or do quality attributes determine the need for methods? 13

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