USP Continues to Refine Its Strategies for Keeping Pace with and Supporting the Rapidly Advancing Biotechnology in the MAb, Vaccine and CGT Arenas

USP is continuing to evolve and refine its strategies for providing standards that can keep pace with and support the rapid advances in biotechnology taking place across the monoclonal antibody (mAb), vaccine, and the cell and gene therapy (CGT) landscape.

The four-part story that follows explores what USP has been able to achieve and where it is looking to expand its contribution – in collaboration with industry, government and academic stakeholders – through a “solutions-based” approach that focuses on the development of standards addressing assay and process performance. [A listing is provided below of IPQ’s extensive coverage over the past few years of the evolving USP strategy for biologics standard-setting and the initiatives reflecting that strategy.]

Along with its conventional communication channels – such as participation at public conferences, Pharmacopeial Forum (PF) stimuli articles, and topic-specific workshops – in 2020, USP began holding forums with biologics stakeholders to assess the needs of the rapidly advancing biotech product field and where USP should prioritize its efforts. The forums include an overview and update on USP’s overall biologics program, as well as homing in on a specific front-burner topic.

Th story reviews the discussions that took place at the third forum held in late October 2022, which focused on the challenges and standards needs in developing CAR T cell therapies and their potency testing, in particular. Also reviewed are updates by USP experts at other recent meetings on USP efforts in the multiattribute method (MAM) and host cell protein (HCP) arenas, and more broadly across the mAb, vaccine, and CGT spectrum.

PART I: USP Bio Stakeholder Forum Opening Remarks and Mass Spec Standards for Proteins

The IPQ coverage begins with the opening session of the 2022 Biologics Stakeholder Forum at which USP’s Maura Kibbey and forum chair Ed Chess explained the agenda of the forum and the results of the previous two: ● on MAM, and ● analytical and digital tools to advance biomanufacturing and product quality, respectively.

The story then moves forward a few months to a “technical seminar” held at the 2023 CASSS WCBP annual meeting, at which USP’s Diane McCarthy and Niomi Peckham explored in more detail the standards and tools being developed to support mass spec-based characterization of proteins.

PART II: USP’s CGT Initiatives

The second part continues with the insights provided at the stakeholder forum by USP’s Ben Clarke on the standards work USP has been doing in the CGT arena. Clarke reviewed the chapters on cell cryopreservation and on the risk-based approach for handling and assessing CGT ancillary materials. Also reviewed by Clarke was the significance for CGT processing of the three new chapters on microbial control that were released for comment in the PF during 2022.

PART III: FDA and Industry Experience with CAR T Potency Testing

Following the discussion during the opening session on USP’s expanding role and current initiatives in the biotech product arena, the 2022 Biologics Stakeholder Forum homed in on the challenges of developing fit-for-purpose potency assays for CAR T cell products.

CBER CMC Reviewer Andrew Timmons shared insights from FDA’s increasing interactions with CAR T product developers. Part III conveys the insights Timmons provided on FDA’s gene therapy guidance – in particular, its 2022 draft guidance on CAR T product considerations – and on the challenges of potency assay development and strategies for addressing them.

Also reviewed are the presentations that followed by Kite and Janssen on the CAR T potency testing, and the panel discussion that concluded the morning session, which included the morning speakers. Issues addressed included: ● potency testing at the lentiviral vector/gene editing substance level, and ● the boundaries and timing of process and method qualification and validation. Timmons added more clarification on CBER’s expectations in the afternoon roundtable discussion that brought speakers and attendees together to discuss how USP can help address the lentivirus and CAR T product standards needs.

PART IV: Update on USP Strategies and Initiatives in the MAb, Vaccine, and CGT Arena

In focus in the last part of the story is an update on the USP strategies and collaborative initiatives in the mAb, vaccine, and CGT arenas provided by USP’s global biologics leader Fouad Atouf at the March 2023 University of Georgia/FDA International GMP Conference.

For mAbs, the focus is on developing best practices, methods, and physical reference standards to support CQA measurements. The collaborative efforts for vaccines are focused on the quality of critical raw materials, impurities, and tests to help with new modalities and platforms and increase global access. Addressing CGTs, Atouf explored the standards challenges stemming from the diversity and uniqueness of the products, and reviewed the documentary and physical standards USP is pursuing, with industry prompting, in the AAV-based gene therapy, CAR T cell therapy, and mRNA-based therapy arenas. The story ends with a reflection by Atouf on standards setting in a rapidly advancing field.


Here is a listing of IPQ’s coverage of the dialogue that has been taking place on: ● the evolving standards and guidance needs in the biotech arena, and the pharmacopeial role and initiatives in helping fill them, and ● the impact from the pandemic on these efforts and relevant learnings. 


ICH Q3D Implementation Continues with Workshops, Research, and Guideline and Pharmacopeial Revisions

Part I: Role of PQRI/FDA Workshop in Q3D Implementation Dialogue
Part II: Regulatory Experience and Perspectives in Implementing Q3D
Part III: Pharmacopeial Harmonization with ICH Q3D
Part IV: Outcomes of PQRI Study on Variability in Elemental Impurity Analysis


mRNA-LNP Vaccines Spur Global Dialogue on Nanomaterial Standards and Regulatory Approaches

Part I: Pfizer/BioNTech Lipid Challenges with mRNA-LNP COVID Vaccine
Part II: FDA’s Novel Excipient Review Pilot Program and Nanomaterials Guidance
Part III: USP’s Draft Guideline and Other Efforts on mRNA Vaccine Quality
Part IV: The EDQM Nanomedicines Dialogue and WHO on Regulating mRNA Vaccine Quality
Part V: Potency Assays for mRNA-LNP Vaccines

Progress in Addressing Impurity Challenges in Focus at USP’s 2022 Peptide/Oligo Workshop

Part I: US and European Regulator Perspective on the CMC Challenges of Oligonucleotides
Part II: USP Standards Development Efforts for Peptides and Oligos
Part III: Peptide and Oligo Analytical, Manufacturing and Raw Material Considerations


USP and Ph. Eur. Initiatives in the Biologics Arena Continue to Bear Fruit; FDA Joins the Pharmacopeias in Upgrading Particulate Guidance

Part I: Update on USP’s Evolving Role and Current Initiatives In the Biologics Arena
Part II: European Pharmacopoeia and FDA Join USP in Focusing on Particulate Control

Biomanufacturer Raw Material Control on Regulatory Front Burner as Analytical Power and Formulation Challenges Intensify

Part I: Biotech Regulator Vantage Point on Raw Material Control
Part II: The Added Challenges of Materials Management for CGTs
Part III: Biomanufacturer Use and Control of Polysorbates

Manufacturing, Impurities, and Characterization Methods Are Key Regulatory Focal Points for Peptides and Oligonucleotides 

Part I: Recent CMC/Regulatory Challenges of Oligonucleotide Drugs
Part II: Comparability Challenges in Crossing Over to Generics
Part III: Comparing Peptide and Oligonucleotide CMC Issues
Part IV: Starting Material Specifications for Oligonucleotides


Pandemic Intensifies USP’s Focus on Supply Chain Vulnerabilities and Vaccine Development 

Pandemic Spurs Deepening of Pharmacopoeia/Regulator/Industry Communication Channels

Part I: EDQM Pandemic Actions Continue Apace in Fall 2020
Part II: Pharmacopeia, Regulator and Industry Expert Panel Explores Pandemic and Nitrosamine Communications
Part III: Second Panel Focuses on Pandemic Organizational Impacts and Key Learnings
Part IV: EDQM and Ph. Eur. Evolution Addressed by Leaders Keitel and Vielle

USP’s Global Efforts to Strengthen Standards and Accelerate Innovation for Biologics Include ICH Engagement

Synthesis and Analysis Advancements Are Unleashing the Potential of Peptides and Oligos, Spurring CMC Regulatory Dialogue

USP Convention Meets Virtually in May 2020 to Review Upcoming Priorities, with Both 200-Year Legacy and Current Pandemic in Focus 

Attention Heightens on Creating an Independent Regulatory Pathway for Introducing Novel Excipients 

Part I: FDA’S Novel Excipient Program Proposal and Stakeholder Comments
Part II: IPEC/IQ Thought Leaders on the Novel Excipient Drivers
Part III: Subcutaneous Biotherapeutics, Pediatrics, and Delayed Release
Part IV: USP Initiatives Supporting Novel Excipient Development
Part V: Assessing and Managing Excipient Risks


The Processing and Formulation Complexities of Therapeutic Biologics Compel Heightened Focus on Excipient Needs 

USP Views Early Broad Stakeholder Engagement as Essential in Developing Performance-Based Standards for Biologics 

Cell and Gene Therapy Initiatives Prominent on Biomanufacturing Agenda of U.S. National Institute of Standards and Technology 

Pharmacopoeia/Industry/Agency Global Dialogue on Compendial Compliance and Harmonization Continues, with Medicine Availability at Stake

Technology Roadmapping Leads NIIMBL Project Expansion Across Biopharmaceutical Manufacturing/Analytics/Workforce Landscape 


FDA’s BLA Review Sheds Light on Evolution of Biotherapeutic Product Analytical Methods and Their Regulation

NIST is at Intersection of Industry/Government/Academia Efforts to Support the “Ecosystem” Needed for Cell/Gene Therapy Advancement

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