FDA’s Knowledge-aided Assessment and Structured Application (KASA) and related Product Quality/CMC (PQ/CMC) initiatives have been laying some important conceptual and information technology (IT) groundwork for the ICH effort now underway to revise its M4Q guideline on the quality component of the Common Technical Document (CTD).
The mutual goals of the FDA and ICH initiatives are to help improve CMC registration and lifecycle management efficiency, leverage innovative digital cloud-based IT, and facilitate patient access.
FDA’s efforts to modernize the way quality information is submitted, processed, and managed during application review – and how these efforts relate to the ICH initiative to make review process improvements at the international level through the MQ4 revision – were in focus in a session on the third day of the FDA/Product Quality Research Institute (PQRI) conference, held virtually in early December 2021.
The session also included a review of a recently launched consortium, Accumulus Synergy, set up to support the FDA and international regulatory efforts to develop a more cloud-based, structured CMC data ecosystem.
The five parts of the story follow the presentation order at the December 2021 FDA/PQRI session:
● PART I: The Advancing Knowledge-aided Assessment Component of KASA
CDER Office of Pharmaceutical Quality (OPQ) Office of Lifecycle Drug Products (OLDP) Director Susan Rosencrance led off the session with an overview of the development and progress of the KASA initiative. Addressed are: ● internal and external challenges to assessing quality ● knowledge-aided assessment, and ● a structured application in the future KASA system.
● PART II: Bringing Biological Products into the KASA System
OPQ Office of Biotechnology Products (OBP) Director Steven Kozlowski then focused on some of the unique challenges and opportunities in implementing KASA for biologics. He discussed: ● a module being developed on the drug substance for fed-batch monoclonal antibodies ● the basic algorithm for building a series of these structured data modules, and ● the plans for these modules to encompass various types of biologic processes and products and be integrated into the KASA system.
● PART III: The Progress of FDA’s PQ/CMC Initiative
OPQ OLDP Deputy Director Geoffrey Wu followed Kozlowski with an update on the PQ/CMC initiative and how it fits into the structured application (“SA”) component of KASA. Wu chairs OPQ’s PQ/CMC Workgroup. He commented on: ● the scope and objectives of the PQ/CMC initiative ● Phases 1 and 2 of the initiative and the progress being made in drug product data standards for Module 3 of the CTD and the move into drug substances, and ● the benefits for FDA and industry.
● PART IV: The Goals of Accumulus Synergy in CMC Data IT and Regulatory Communication
Following Wu’s discussion of FDA’s PQ/CMC initiative, Amgen Global Regulatory Affairs CMC Executive Director Michael Abernathy presented on the complementary efforts underway by the industry collaboration, Accumulus Synergy. He explained Accumulus’ overall aim of providing a cloud-based ecosystem to facilitate sponsor/health authority structured data exchange and submission, review, and post-approval change management, and the two “use cases” it is developing to pursue the goal: ● “Submission Review and Collaboration” (SRC), and ● “Data Exchange” – a project Abernathy is leading, aimed at making data more structured and usable. Included are insights, offered by Roche Global Regulatory Policy Associate Director Rodrigo Palacios at the ISPE Annual Meeting in November 2021 on the contribution the Accumulus consortium is seeking to make in deploying cloud-based IT to improve and harmonize the CMC review process.
● PART V: The Drivers for Revising ICH M4Q and Evolving the CMC Regulatory Process
OPQ Office of New Drug Products Director Lawrence Yu concluded the series of presentations at the FDA/PQRI session with a review of how the KASA effort ties into the revision of ICH M4Q. Yu is rapporteur for the newly formed Expert Working Group (EWG) handling the guideline revision. Yu’s talk encompassed: ● moving to a cloud-based quality regulatory submission and assessment ● the ICH M4Q revision process, including perceived issues with the current version, and the revision’s objective, impact, progress, and work plan, and ● the data standards and review platform upgrades needed along with M4Q(R2). A Q&A followed Yu’s presentation, which was moderated by Amgen Regulatory Affairs Director Nina Cauchon and included the five presenters. The questions dealt with: ● industry engagement with KASA ● the timing of FDA guidance on PQ/CMC ● device and combination product integration with KASA and PQ/CMC ● detecting data integrity problems ● integration with the DMF ● handling differences in health authority requirements ● ICH and EMA collaboration on KASA, and ● implementing KASA.
December 2021 KASA and PQ/CMC Discussions Built on Previous FDA/PQRI Conference
The discussions of KASA and PQ/CMC at the December 2021 FDA/PQRI conference built on those at the FDA/PQRI conference held in April 2019. [See IPQ August 11, 2019 for an in-depth review of the 2019 conference discussions.]
At the earlier conference, OPQ leaders also explored the challenges and limitations in the current review process and the burdens it places on both regulators and industry, and how KASA and PQ/CMC are driving toward a process that is more standardized, transparent, streamlined, IT rich and knowledge management friendly.
Insights were also provided at the earlier conference on how the initiatives were focusing on creating more transparency around what and how information needs to be communicated in order to reduce subjectivity and inefficiencies during review and allow the information to be used in a more powerful way in understanding and managing the risks across products, processes, and facilities.
The other sessions of the recent FDA/PQRI conference, which will be referenced in upcoming IPQ stories, covered:
● on day one, patient-centric dissolution, international harmonization, and biopharmaceutics for complex drug products and nano-drug delivery
● on day two, accelerating development through fast tracking of critical treatments, antibody platforms, and quality standards for emerging modalities, and the use of modeling and simulations to enable rapid decision making, and
● on day three, along with the KASA/M4Q session, remote site evaluations and advanced manufacturing concepts beyond continuous manufacturing. The latter session offered presentations on agile manufacturing, pre-fabricated solutions for new facilities, decentralized pharmaceutical manufacturing, and FDA’s efforts to support advanced manufacturing.
[Click HERE for recordings of the full FDA/PQRI conference and relevant resources.]
[Click HERE for the complete story, which will include the five parts as they are made available. Nonsubscribers can get information on individual IPQ subscriptions and organization-wide licenses by contacting Jonathan Trethowan (Jonathan@ipq.org).]