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.