CMC Strategy Forum / WCBP 2024

Health care providers and patients are frequently required to manipulate biological drugs prior and during administration. This might include procedures such as dilution of the drug into admixtures for infusion, limited storage, transportation to the hospital or exposure to new contact materials, such as intravenous bags.

The instructions for use are provided by the drug manufacturer and are based on studies to support in-use stability and compatibility with administration components, simulating drug handling and hold times throughout the defined in-use period. The studies are challenging, because there is a wide range of in-use conditions and administration components used globally. In addition, only limited guidance is available from regulators on expected in-use stability data.

In four workshops we will present and discuss industry approaches to assess in-use stability and compatibility for classic biological products as well as emerging trends. Each workshop is scheduled for 90 minutes, and includes 2 presentations followed by a discussion with the presenters and additional panel members.

Platform technologies are used extensively across the biopharmaceutical industry to develop drugs efficiently and effectively.  The application of prior knowledge and platforms from established products lays a strong foundation to guide development and advance new medicines to the patients. From cell line development, upstream and downstream operations, formulation development, devices, and analytical methodologies, platforms have proven that they work and are a powerful tool.  However, there are no universal standards on how to create, justify and maintain platforms. The inclusion of platform information and the level of detail in the dossier is key for regulatory agencies to evaluate the applicability of the platform using a risk-based assessment.  Moreover, the rationale and justification on how prior knowledge and platform data are suitable for the intended product is essential in a review.  This session will look at the application of platform approaches and technologies and how they can be applied to programs to support development and registration. Insight into how prior knowledge for a platform is fully leverage across products and supporting rationale will be presented in case studies.  The objective from the session should help developers and health authorities better align on expectations and paths to use platforms for clinical development through commercialization.

Session Speakers:

Platform Technologies Designation Program: Highlights of Statutory Language

Phillip Kurs, CBER, FDA

Leveraging Prior Knowledge for Practical Application of Platform Analytical Procedures in Late-Stage Development of Monoclonal Antibodies

Hetalben Patel, Pfizer, Inc.

Platform Approaches in Analytics for rAAV based Gene Therapies 

Van Hoang, Spark Therapeutics, Inc.

Planning Platform Analytical Approaches for Cell Therapy

Emily English, Cartesian Therapeutics, Inc.

Session Speakers:

How to Design and Perform In-Use Stability and Compatibility Studies?

Markus Blümel, Novartis Pharma AG

In-Use Stability Study Design: A Regulatory Perspective

Paula Russell, Health Canada 

Additional Panelist:

Ankit Patel, Denali Therapeutics 

Isabella de Jong, Genentech, a Member of the Roche Group

Panelists:

Emily English, Cartesian Therapeutics, Inc.

Phillip Kurs, CBER, FDA

Van Hoang, Spark Therapeutics, Inc. 

Hetalben Patel, Pfizer, Inc., 

Da Ren, BioTherapeutics Solutions, Inc.

Session Speakers:

In-Use Studies Microbial Challenge Studies: Cross-Industry Efforts to Harmonize Strategies in Collaboration with Health Authorities

J. Paul Kirwan, Amgen Inc. 

Pharmaceutical Industry Perspective on Closed System Transfer Devices (CSTDs): Balancing Overfill, Evaluating, Communicating

Christian Lehermayr, Novartis Pharma AG

Additional Panelists:

Virginia Carroll, CDER, FDA

Nicholas Clark, Amgen Inc.

John Metcalfe, CDER, FDA

Session Speakers:

Incorporation of Platform Based Approaches and Prior Knowledge Leveraging Into the Recently Revised ICH Q5A (R2) Guideline

Kathryn King, CDER, FDA

Power of Platform to Accelerate Therapies Beyond a Pandemic 

Ronan Kelly, Eli Lilly and Company 

Leveraging Platforms to Accelerate ADC Formulation and Drug Product Development

Karen Rutherford, Pfizer Inc.

Continuous Platform Improvement to Propel Drug Substance Development,

Heather Nunn, Amgen Inc. 

Session Speakers:

Patient and User-Centric Considerations on In-use Study Design

Sarah Weiser, Pfizer, Inc

Leveraging AI to Meet Patient Needs: Improving Product Quality in Biotechnology

Prashanth Chodagiri, Amgen Inc.

Additonal Panelist:

Sarah Donegan, AstraZeneca 

Panelists:

Carl Frye & Ronan Kelly, Eli Lilly and Company

Kathryn King, CDER, FDA

Heather Nunn, Amgen Inc.

Karen Rutherford, Pfizer Inc.

Dean Smith, Health Canada

Session Speakers:

In-Use Compatibility Testing of Cell and Gene Therapies (CGT)

Philip Grossen, F. Hoffmann-La Roche Ltd.

Abbygail Foster, Genentech, a Member of the Roche Group

Challenges of In-Use of Low – Dose High Potent Product- Case Studies and Potential Mitigations

Basma Ibrahim, AbbVie Inc.

Additional Panelists:

Andrew Chang, Novo Nordisk Inc.

Martin Nemec, Health Canada

Jennifer Swisher, CDER, FDA

Donald E. Ingber, Wyss Institute for Biologically Inspired Engineering, Harvard University 

The large number of failures observed in human clinical trials is a problem that must be overcome for the benefit of patients and the survival of the pharmaceutical industry. Failure of animal models to predict therapeutic responses in humans is a major part of the problem.  In this presentation, I will describe Organ-on-a-chip (Organ Chip) microfluidic devices lined with living human tissues that form tissue-tissue interfaces, reconstitute vascular perfusion and organotypic mechanical cues, integrate immune cells, contain living microbiome, and recapitulate organ-level physiology and pathophysiology with high fidelity. Work will be presented describing how single human Organ Chips and multi-organ human Body-on-Chips systems have been used to model complex diseases and rare genetic disorders, study host-microbiome interactions, quantitatively predict drug pharmacokinetic and pharmacodynamic parameters, recapitulate whole body inter-organ physiology, and reproduce human clinical responses to drugs, radiation, toxins, and infectious pathogens. We also have used human Organ Chips to gain new insight into mechanisms of host immunity to viral infections and to develop new therapeutics for potential pandemic respiratory viruses, including influenza and SARS-CoV-2. My message is that the possibility that human Organ Chips can be used in lieu of animal models for drug development and as living avatars for personalized medicine is coming ever closer to becoming a reality. In addition, I will briefly review new technologies being pursued at the Wyss Institute at Harvard that I lead, including artificial intelligence approaches for accelerated drug discovery, novel drug shuttles that cross the blood-brain barrier with high efficiency, and handheld multiplexed companion diagnostic devices for clinical trials and home healthcare.

Technological innovation and advancements have enabled novel designs for antibody-based products, vaccines, blood products, gene and cell therapy candidates. While mAB conjugates like ADCs and novel mAB constructs like bispecifics molecules have been maturing as approved therapies for unmet medical needs, additional molecules like mAb fragments, trispecifics, cocktails, bifunctional (e.g., mAb-cytokine fusion proteins), and non-IgG isotype molecules are in development. Novel approaches to vaccine design include the expression of antigen to elicit a protective immune response and development of universal vaccines for flu and SARS-CoV-2. Gene and cell therapies continue to evolve, including new designs for CAR-T cell constructs to decrease side effects, improve proliferation and cytotoxicity, and increase specificity of therapeutic targets.  The emerging allogenic/ Induced Pluripotent Stem Cells (IPSC) CAR-T cells will further the reach of CAR-T applications.  In addition, macrophage CAR which are in development may better target solid tumors. This springs the questions, do novel modalities warrant novel product quality controls because of product quality concerns? It is acknowledged that based on the modality, additional testing based on novel analytical techniques, control and characterization may be recommended and should be determined on an individual case basis. This should be informed by scientific knowledge and risk-based approach aligned with guidance documents. In this session we will discuss the industry’s current trend and application of innovative approaches for new modalities, with a focus on the success, challenges, and lessons learned during product development. 

Session Speakers:

Enhanced Quality Attribute Understanding Enabled Accelerated Development of a RSV Vaccine

John Davis, Pfizer, Inc.

Analytical Considerations in the Development of Engineered Therapeutic IgM Antibodies

Devinder Ubhi, IGM Biosciences, Inc.

Jaime Marach, IGM Biosciences, Inc.

6+ Years of Autologous CAR-T Therapy  

Mehrshid Alai-Safar, Kite, a Gilead Company

Session Speakers:

From High Order Aggregates to Peptide Maps: Comprehensive Protein Characterization Using Advanced UHPLC-HRAM MS Platforms

Andrew Mahan, Janssen Research & Development, LLC

This regulatory panel will bring together regulators from several global regions for an interactive discussion about evolving practices and initiatives. 

Current trends in agency-agency and agency-industry collaborations, including:  

- Discussions on the role of regional and international harmonization and regulatory convergence initiatives, including ICH, WHO, and regional initiatives  

- Sharing experiences from collaborative reviews, e.g., ICMRA pilots, Project Orbis/Access Consortium and other collaborative and reliance pathways 

Accelerating the pace of acceptance for innovative solutions, including:  

- Achieving the blue-sky vision “One dossier, one submission, one review, one inspection, one approval”, e.g., ICH M4Q revision, CMC dossier content alignment, ICH Q12 benefits, Accumulus 

- Addressing how rapid advances in pharmaceutical science, novel technology, new modalities analytics, data management, and regulatory concepts can be accepted globally. 

Session Speakers:

Update From WHO: Global Perspective on Regulatory Harmonization and Convergence to Support Reliance

Samvel Azatyan, WHO - World Health Organization

Additional Panelists:

Nelio Aquino, ANVISA

Yasuhiro Kishioka, PMDA - Pharmaceuticals and Medical Devices Agency 

Steve Kozlowski, CDER, FDA

Ingrid  Markovic, CBER, FDA

Nino Mihokovic, EMA - European Medicines Agency