FDA official pushes for cloud-based regulatory assessments
A top US Food and Drug Administration (FDA) official touted the benefits of cloud-based regulatory submissions in ensuring consistent product reviews and explained how the agency is moving towards this platform through ongoing internal and international harmonization initiatives at a 30 November symposium on drug master files (DMFs) and structured data submissions.Lawrence Yu, director of the Office of New Drug Products (ONDP) in the Pharmaceutical Quality (OPQ) at the Center for Drug Evaluation and Research, and other agency officials discussed efforts to modernize the regulatory submission process. Yu is also the rapporteur of the International Council of Harmonisation’s (ICH) M4Q(R2) expert working group tasked with modernizing quality information that is submitted in the common technical document (CTD).
Yu said that much progress has been made in modernizing regulatory submissions since he first arrived at FDA, but much work lies ahead. “When I joined FDA 23 years ago, new drug applications were submitted in truckloads with paper documents,” he said. “To be the first generic applicant to file, applicants had to physically stand in lines at the door of FDA office building.”
This started to change with development of the CTD and the later adoption of the electronic CTD (eCTD) as the platform for regulatory submissions.
Yu said that “there is no question [the eCTD] is a significant improvement over the paper submissions … but in today’s digital age, this regulatory submission is outdated. First, the submission is a static snapshot in time versus individual documents … and is open to error. Second, it is cumbersome to extract and access PDF content, therefore the lengthy unstructured text narratives and the lack of efficient information exchange and knowledge management makes our system not only not efficient but not effective.”
Industry also complains that reviews are inconsistent as one assessor would not know what others have concluded for the same product or for similar products. Such consistency and uniformity could be achieved through a cloud-based regulatory platform.
“A cloud-based system would allow data to be readily exchanged between companies and regulators, and companies will inform the FDA that a product dossier is ready for assessment, and then FDA could access and analyze the data from the cloud environments. The use of a cloud-based system for regulatory assessment would enable a dynamic and more fluid exchange of information between industry and regulators.”
Yu said FDA is planning to launch elements of a cloud-like system in its Knowledge-aided Assessment and Structured Application (KASA) initiative, which will have “Google similar” search functions and artificial intelligence capabilities. He added that this effort, combined with work to produce ICH M4Q(R2) and the structured data approach in FDA’s Pharmaceutical Quality/Chemistry Manufacturing Controls (PQ/CMC) project “will provide the foundation for the future cloud-based submission and assessments.”
Complementary work of PQ/CMC and KASA
The work of PQ/CMC and KASA is complementary: KASA is geared towards reviewers and works to change how submissions are evaluated by the FDA, while the PQ/CMC initiative is geared for industry and involves a structured data approach in submitting data to regulators.
The KASA program was announced in 2019 as part of FDA’s work to improve and modernize the quality assessment of drug applications. FDA said last year that it is taking a “step-wise” approach to implementing its KASA drug review program. (RELATED: FDA Explains Plans for New Quality Assessment System, Regulatory Focus 16 September 2019; FDA taking incremental approach to launching KASA reviews, Regulatory Focus 5 November 2021).
Larisa Wu, ONDP’s associate director for science and communications, told the meeting that KASA has helped FDA manage information in its review workload. Annually, OPQ reviews about 3,000 investigational new drug applications (INDs), 240 new drug applications (NDAs) and biologics license applications (BLAs), 900 abbreviated new drug applications (ANDAs), and 10,000 supplements.
Wu explained that the PQ/CMC initiative aims to standardize the information in the quality section of the CTD without having reviewers input information manually. This work is divided into multiple phases. Phase 1 work was completed at the end of 2020 and covered the drug product, the drug substance and quality specifications. In this phase FDA standardized about 33% of the Module 3 data. Phase 2 data standards are under development and will cover drug product manufacturing, drug substance manufacturing; the phase was initiated in January 2021.
Sponsors can help expedite reviews in the quality area by using structured data (SD) fields in submitting information on chemical structure to FDA, said Wu. Currently, this information is submitted to the eCTD in PDF format. Wu said that “submission in the PDF format requires end users at the FDA to manually redraw each structure, which is tedious, prone to errors, and is an inefficient use of resources.”
On another front, the M4Q(R2) revision aims to revise the CTD quality sections by setting electronic data standards to support structured applications, according to the ICH concept paper published in November 2021.
The ICH expert working group plans to have a Step 2 document out by 2023, and to reach Step 4 document adoption in 2025
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