CMC Strategy Forum North America/WCBP 2025

Forum Co-Chairs: Fiona Cornel, Health Canada, JR Dobbins, Eli Lilly and Company, Doug Richardson, Merck & Company, Inc., Shawn Novick, BioPhia Consulting

Quality standards is a term which encompasses management of quality from prior to manufacturing through patient dosing. Quality standards are applied in facility design, process design, product release, storage, and dosing. Quality standards are essential to develop and execute appropriate manufacturing process and product control strategies, that ultimately ensure that biopharmaceuticals remain safe, effective, and of consistent quality. A patient-centric quality standard (PCQS) has previously been defined as a set of patient-relevant attributes and their associated acceptance ranges to which a drug product should conform within the expected patient exposure range (see A. Mire-Sluis et al., J. Pharm. Sci. 2024, Vol 113, 837-855).

New tools and enhanced understanding of biopharmaceuticals, including prior knowledge, allow Sponsors to identify and better understand the safety and efficacy profiles for many critical quality attributes (CQAs). This understanding provides an opportunity to set requirements and ranges for manufacturing and release that are patient-centric rather than mainly reflecting manufacturing experience. Therefore, achieving patient-centricity is understanding patient-relevance, which is defined as the level of impact that a quality attribute could have on safety and efficacy within the potential exposure range.

By using a patient-centric approach to setting quality standards, batches of drug product (DP) will not be rejected due to an explainable shift in a quality attribute, if the shift is within the range determined to be safe and effective for the patient. Additionally, this can increase the flexibility of sponsors to explore newer or novel technologies during product life-cycle management.

This forum will explore the tools available to understand and set patient-centric quality standards including control strategies which ensure safety, efficacy, and product availability for the patient. Advancements, challenges and case studies in the development and application of patient-centric quality standards will be presented. Regulatory considerations and how to apply them in a fashion which is consistent with regulatory guidance to ensure a robust, safe and efficacious patient experience will also be explored.

The session will explore approaches towards developing enhanced product understanding that supports the establishment patient centric quality standards and control strategies.

Speakers will present recent advances on nonclinical tools that inform criticality of quality attributes (CQAs), such as use of biotransformation data for biotherapeutics and in vivo/ in vitro models for vaccines. In addition, the application of a structured CQA assessment will be discussed, to provide insights on risk assessment strategies to ensure appropriate knowledge of product safety and efficacy, and consequent establishment of effective control strategies. The session will conclude with sharing the regulatory perspective on these approaches.

Session Speakers:

What is Meant by Patient-Centric Quality Standards

Phil Krause, Independent Consultant

Patient-Centric Control Strategy Development: Principles, Tool, and mAb Examples

Claudia Gributs, Eli Lilly and Company

Leveraging Biotransformation Data to Refine Bioprocesses and Derisk PQAs

Maribel Beaumont, Merck & Company, Inc.

Defining CQAs Impacting Vaccine Efficacy: The Role of in Vitro and in Vivo Models

Barbara Capecchi, GlaxoSmithKline

Enhanced Approaches to Setting Specifications – A Regulatory Perspective

Jayda Siggers, Health Canada

Forum Co-Chairs: Natalie Ciaccio, Vir Technology and Marc Verhagen, Sanofi

The generation of technical data to support the development and manufacture of pharmaceutical products and associated regulatory submissions is fundamental to the pharmaceutical industry. The recent boom in artificial intelligence (AI) systems and large language models (LLM) has resulted in increased interest in the capability of these systems to support industry activities. By embracing technological advancement, the biopharmaceutical industry can make significant strides in reducing submission timelines and accelerating the delivery of therapeutics. This session will include discussion on current practices with examples of how structured data, digitalization, AI, and generative AI (GenAI) are being leveraged to support pharmaceutical development, manufacturing, and standardized regulatory authoring/submission with dynamic review. The focus will be on opportunities to improve efficiency or accelerate development timelines. Discussion will include considerations for emerging technologies and forward-looking approaches for analytical data modeling.

Different aspects of the use of AI or LLMs during CMC development will be discussed including:

• Use of AI in drug discovery/developability – modeling of protein structure and properties based on sequence

• Bioprocess/ cell culture optimization using predictive analysis

• Stability modeling using AI and/or machine learning

• Leveraging commercial manufacturing data/modeling to optimize process conditions

• Automated generation of regulatory documents using LLM

Session Speakers:

The Challenge and Criticality of Data Contextualization to Support Effective AI/ML/Modeling in Bioprocess Development – an Industrial Case Study

Christian Airiau, Sanofi

Development of Realistic and Safe AI/ML Applications for Biotherapeutic Characterization and Process Development
Jeremy Shaver, Pfizer, Inc.

A “One-Click” Submission with AI and Digital Authoring

Kabir Ahluwalia, Amgen Inc.

Practical and Regulatory Considerations for Machine Learning Models Applied to Process Development and Control

Ben Stevens, GlaxoSmithKline

Additional Panelist: Douglas Roepke, Eli Lilly and Company

Additional Panelist: Paula Russell, Health Canada

This session presents cases studies and practical experiences from industry on implementing the advanced concepts of patient-centric quality standards. This includes challenges observed and examples from protein therapeutics as well as cell & gene therapies. The perspective and experience from regulators will be shared. The presentations will be followed by a plenary discussion to improve mutual understanding and establish good practices to ensure a robust, safe and efficacious patient experience.

Session Speakers:

A High Threshold of Aggregate Numbers Is Needed to Induce Immunogenic Response in Vitro, in Vivo, and in the Clinic

Kimya Nourbakhsh, Amgen Inc.

Strategies for Defining Specifications in Autologous Cell Therapy Products

Daisy Nie, Novartis Pharmaceuticals Corporation

Case Studies for Patient-Centric Specification Setting for a Therapeutic Protein and IQ Readout on Endotoxin Acceptance Criteria

Katrina Kearns, Pfizer, Inc.

Allowable Excess Volume and Gross Content Requirements and Challenges For Injectable Drug Products in Vials

Ehab Moussa, AbbVie Inc.

Additional Panelist:

Fiona Cornel, Health Canada

Session Speakers:

Empowering 5.0 BioSolutions Through Realtime PAT and Computational Controls

Edita Botonjic-Sehic, ReciBioPharm AB.

Predictive Stability Modeling of mRNA Vaccines

Gang Wang, Moderna, Inc.

AI-Accelerated Stability for Biologics

Seyma Bayrak, Amgen Inc.

Regulatory Expectations for Data Models to Support a Marketing Application

Jayda Siggers, Health Canada

Keynote Speaker: Sonia Vallabh, Ph.D., Broad Institute

Monitoring and control of endotoxin are critical aspects of an overall microbial control strategy necessary to ensure drug product quality and patient safety. It has been over a decade since Low Endotoxin Recovery (LER) came into prominence as a major challenge in biologics manufacturing, due to the common use of formulation excipients such as polysorbate, phosphates, etc. that have been shown to interfere with the compendial endotoxin detection methods. Since then, industry and regulators have made gains in understanding LER and developing standardized approaches for evaluating and overcoming it. However, there still is much progress to be made. Developing alternative methods that address LER is sometimes a labor intensive task and may result in complicated methods that lack robustness or are difficult to implement, in some occasions leaving Sponsors with the Rabbit Pyrogen Test as the “only option” for endotoxin detection. This is further complicated as some health authorities and industry take steps towards removing animal testing. The purpose of this session is to provide an overview of endotoxin methods and microbial controls to mitigate LER and discuss evolving regulatory expectations, challenges, and potential solutions. 

Session Speakers: 

Overcoming Low Endotoxin Recovery from Theory to Practice 

Jessica Hankins, Bristol-Myers Squibb Company

Defining the Microbial Control Strategy for Low Endotoxin Recovery Impacted Biologics

Lindsey Silva, Genentech, a Member of the Roche Group 

Additional Panelists:

Jay Bolden, Eli Lilly and Company

Claudia Müller, Swissmedic

Jody Peraino, Pfizer, Inc.

Potency analytical control strategies are critical to support biopharmaceutical drug and vaccine development throughout the product lifecycle. For biopharmaceutical drugs, it is generally expected that a quantitative potency assay be included in the control strategy and that the assay adequately reflects the physiological Mechanism of Action (MOA). Most often these assays are developed using cell lines that mimic MOA-relevant, physiological responses. However, the development, validation, and transfer of cell-based potency assays can be challenging due to multiple factors inherent to working with living systems/live cells. Therefore, non cell-based alternatives are of great interest to the more complex cell-based potency assays to ensure the consistent generation of accurate results for drug substance/drug product release and stability specifications.

Current day vaccine potency analytical control strategies typically do not involve cell-based assays, but generally rely on binding, chromatographic or physical chemical methods. However, many legacy vaccines still utilize in vivo potency assays; these assays are inherently more variable, require weeks to perform, and are more prone to invalid test results, necessitating repeat testing. The transition to in vitro alternatives has been challenging due to less robust characterization of vaccine products, compounding the establishment of in vitro alternatives, as well as regulatory acceptance of new methods. Fortunately, recent industry driven collaboration and novel regulatory approaches have accelerated the development of in vitro alternative assays and regulatory acceptance.

In this session, we plan to discuss the following topics:

- Successful and/or failed biopharmaceutical case studies regarding strategies used to support the phase-appropriate introduction of a new non-cell-based potency assay as a replacement to an existing cell-based potency assay in the lot release and stability program, 

- Successful and/or failed biopharmaceutical case studies regarding strategies used to support the phase-appropriate removal of an existing cell-based potency assay from the lot release and stability program while leveraging an existing non-cell-based potency assay. 

- Vaccine industry collaboration and regulatory innovation that has accelerated the transition from in vivo to in vitro potency and safety assays for legacy vaccines. 

Session Speakers:

Successful Implementation of Potency Control Strategy - Two Binding Assays Rather Than One Cell-based Assay

Catherine Shoemaker-Ramsey, Biogen

How Industry and Regulatory Innovation and Collaboration Can Promote the Transition From in Vivo to In Vitro Potency Testing for Human Legacy Vaccines 

Emmanuelle Coppens, Sanofi

Replacement of in Vivo Immunogenicity Assay With in Vitro Antigenicity ELISA for Pertactin Antigen in Acellular Pertussis Combination Vaccines

Belma Ljutic, Sanofi

Additional Panelists:

Elena Grabski, Paul-Ehrlich-Institut

Emily Shacter, ThinkFDA LLC

Jayda Siggers, Health Canada

Yasuhiro Kishioka, Pharmaceuticals and Medical Devices Agency (PMDA)

Session Speakers:

Jeff Patrick,  BioAgilytix Labs

Shiqian Zhu,  BioAgilytix Labs

In this session, regulatory leaders from the EMA, Health Canada, PMDA, Health Canada, and international health authorities including WHO will delve into the challenges hindering the path to regulatory reliance and approval of advanced technologies. By sharing their insights and experiences, they will illuminate potential solutions to overcome these obstacles and accelerate the journey towards a unified "One Submission/One inspection/One Assessment" approach. 

Join us as we explore the latest advancements in technology and reliance that are reshaping the regulatory landscape. Together, we can foster a collaborative environment that benefits all companies and countries. 

Ahead of and during the session, we invite attendees to share their most pressing challenges and transformative solutions. Your contributions will help shape a more productive and insightful discussion. 

Key Highlights: 

- Regulatory Reliance Progress: Are recent advancements in reliance tools and pilots being shared across all regions and companies? 

- Future of Biopharmaceutical Manufacturing: What does the future hold for biopharmaceutical manufacturing, and how can regulators support these changes? 

- Advanced Technologies: How are regulators incorporating advancements in technology to improve efficiency and speed to patient? 

- Global Convergence: What steps can be taken to promote greater convergence and collaboration among regulatory authorities? 

Session Panelists:

Rogério Gaspar, World Health Organization

Yasuhiro Kishioka, Pharmaceuticals and Medical Devices Agency (PMDA)

Anabela Marçal, European Medicines Agency (EMA)

Claudia Müller, Swissmedic

Sophie Sommerer, Health Canada

Innovations in therapeutic modalities are continually emerging as viable treatment options for a multitude of disease indications. These novel therapies can be complex biologics with multiple product components such as bioconjugates, volume limited therapies where the suit of established characterization and release testing cannot be performed due to low volumes as in the case of certain Cell and Gene therapies or molecules that are invisible by established analytical tools. Re-evaluation of established analytical technologies or reimagining the use of established analytical tool kits to provide novel characterization approaches can accelerate and enhance product understanding.  

In this session we will explore case-studies where established technologies are enhanced or leveraged in a novel manner to characterize complex therapeutic modalities. Additionally, we will explore the current state of the art analytical tools utilized for process analytical technologies and release testing. We will discuss which technologies are QC ready and which remain as characterization tools in the development labs. This session will highlight the evolving trend of reimagining established analytical technologies to tackle the characterization and product release challenges posed by the modern-day innovative therapies.  

Session Speaker:

A Novel, High-Throughput Imaged Capillary Isoelectric Focusing (iCIEF)-Western Method to Characterize Charge Heterogeneity of Monoclonal Antibody (mAb) Heavy and Light Chains 

Gangadhar Dhulipala, Regeneron Pharmaceuticals Inc.

Genetic Medicine Characterization via 2nd and 3rd Generation Sequencing Tools

Beth Ostrander, Pfizer, Inc.

Carly Daniels, Pfizer, Inc. 

Additional Panelists:

Methal Albarghouthi, AstraZeneca

Da Ren, BioTherapeutics Solutions

Nadine Ritter, Global Biotech Experts, LLC

Drug-device combination products such as prefilled syringes, autoinjectors, etc. can play an important role to ensure patient convenience, compliance, and enhance therapeutic impact of the drug. An integrated control strategy for combination products is critical to ensure that the products are designed, manufactured, and released with the desired product quality and robustness. Building an integrated control strategy starts with a thorough understanding of the materials, components, product design, and the associated processes; this understanding usually begins early during clinical development. The extent of the control strategy should be risk-based and assessed throughout the product lifecycle. This session will cover the following topics: (a) development and implementation of an integrated control strategy throughout clinical development, commercial marketing authorization, and post-approval life cycle management and (b) effective use of design controls framework, prior knowledge, and risk management process to implement an effective control strategy. In this session, the audience will have the opportunity to learn from real-world case studies as well as interact with industry-leading experts and key regulatory opinion leaders.  

Session Speakers:

Considerations for Developing an Autoinjector Control Strategy: A Case Study

Kristin Benokraitis, Biogen

Maintaining an Integrated Control Strategy Throughout Combination Product Lifecycle Changes

Amir Tabaian, Pfizer, Inc.

Additional Panelists:

Ben Stevens, GlaxoSmithKline

Chin-Wei Soo, Genentech, a Member of the Roche Group

Peptides, proteins and oligonucleotide are becoming essential medical treatments for many progressive, debilitating, or life-threatening diseases. However, the development of these potential therapies can be derailed by product immunogenicity as it can impact on safety and efficacy. Establishment of validated methods to measure anti-drug antibody responses during clinical trials is currently used to identify potential immunogenicity-related adverse outcomes and intervene early on. However, this approach is limited by incidence and study size particularly when there is low frequency of occurrence for many unwanted immunogenic outcomes.  As a result, understanding of product immunogenicity risk is often still incomplete late in development and during early commercialization.  Moreover, this also limits the information yielded by abbreviated regulatory paths for follow-on products such as complex generics and biosimilars.   To mitigate this risk, sponsors are increasingly utilizing analytical, in silico, and in vitro tools to compare and control product attributes such as propensity to aggregate, likelihood to undergo post-translational modifications, and presence of product and process related impurities that could act as adjuvants to reduce the failure risk in their product target selection.  Unfortunately, studies linking the result of these studies in the context of clinical results are rarely shared, even with the regulatory agencies, which is an important missed opportunity to connect critical quality attributes with clinical outcomes.  Thus, currently, our understanding of the levels of product and process related impurities that can impact on immunogenicity risk are frequently based on analytical and process capabilities rather than safety considerations, which can result in unnecessary burdens on development and lead to delay in getting potential therapies to patients.   This session will focus on emerging strategies to connect product quality attributes to immunogenicity risk, and how they could inform not only product selection and development but also the regulatory process for new products as well as for follow on products such as complex generic peptides, oligonucleotides and biosimilars. 

Session Speakers: 

Tiered, Data-driven Approach for Assessing the Safety of Product-Related Impurities in Support of Commercial Control Strategy Development

Robert Siegel, Eli Lilly and Company

Additional Panelists: 

Andrea Ferrante, Eli Lilly and Company

Mark Schenerman, CMC Biotech-MAS Consulting   

Jayda Siggers, Health Canada