Agile Methodologies in Regulatory Programming: Lessons from Applying Sprint-Based Delivery to FDA and EMA Submission Timelines

Abstract

Regulatory programming — the production of CDISC-compliant SDTM and ADaM datasets, TLFs, 
and submission packages for FDA and EMA review — has historically operated under waterfall project 
management models poorly suited to the iterative, specification-dependent nature of the work. This paper reports 
on a two-year implementation of Agile Scrum methodology in a regulatory programming function supporting 18 
concurrent clinical studies, examining the impact on submission timeline adherence, defect rates, mock TLF shell 
delivery, submission package assembly, and health authority (HA) questionnaire response efficiency. Outcomes 
were measured across three NDA-track submission programmes under Agile governance compared to three 
matched historical submissions under the waterfall model. Regulatory Scrum delivered a 46% reduction in late 
specification changes reaching the programming stage, a 44% reduction in final TLF defect rates, an improvement 
in pre-lock mock shell approval rates from 43% to 89%, and a 46% reduction in HA questionnaire response 
compilation time. We document the adaptations required to reconcile Agile philosophy with the audit trail and 
change control requirements of GxP-regulated environments, and propose a 'Regulatory Scrum' framework that 
preserves waterfall compliance attributes while capturing the efficiency and quality benefits of iterative delivery. 
Key strategies for managing mock shell sprints, eCTD assembly workstreams, and country-specific HA question 
handling under sprint cadence are presented.