Why FDA’s Advancing RWE Program Matters for Quality Teams

What the RWE Program Is

The Advancing Real-World Evidence (RWE) Program is an optional, sponsor-initiated pathway run by the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER), with Oncology Center of Excellence (OCE) participation for oncology applications, under Prescription Drug User Fee Act (PDUFA VII), in effect for fiscal years 2023–2027. It implements one of FDA’s commitments under the 21st Century Cures Act §3022, which directed FDA to build a formal program for evaluating RWE in regulatory decision-making. This section of the Act defines real world evidence as data regarding the usage, or the potential benefits or risks, of a drug derived from sources other than randomized clinical trials.

In this pilot program, selected sponsors meet with FDA staff before protocol development or study initiation to discuss whether their proposed use of real-world data (RWD) and RWE can support a new intended labeling claim, typically a new indication, population, or dosing change for an already-approved product, or satisfy a post-approval study requirement. Eligibility requires an active IND or pre-IND number and a pivotal RWE study proposal; methods-development or replication studies do not qualify.

The program’s stated goals are to

1. Identify approaches for generating RWE that meet regulatory requirements for effectiveness labeling
2. Develop FDA processes for consistent decision-making
3. Promote awareness, as accepted study designs may be shared publicly in guidance or workshops

How It Aligns with Industry

The FDA’s evidentiary standards are recalibrating around analytical sophistication rather than data volume, and RWE is one of a number of pieces in this shift. Other changes include the single pivotal trial standard, the plausible-mechanism framework for ultra-rare diseases, Bayesian methodology guidance, and new approach methodologies (organoids, organs-on-chips, in silico models). The Advancing RWE Program is the structured front door through which sponsors can get FDA buy-in on a specific RWE design before committing protocol resources.

For the broader industry, this aligns with the trends that regulators increasingly expect well-governed, interoperable data from collection through submission. RWE is being supplemented with electronic health records, registries, and claims data that require provable provenance, and this data governance has effectively become a compliance attribute in modern pharma. Global harmonization (FDA, EMA via DARWIN EU, PMDA) is also shrinking the gap between what each agency will accept in their submissions.

Data relevancy (is this data appropriate for the regulatory question?) and data reliability (is it good enough to support a regulatory decision?) are also considered by regulatory reviewers and can be demonstrated not only by the dataset in question, but also quality system evidence.

How It Aligns with eQMS Platforms

The 2023 final guidance on RWD/RWE explicitly ties acceptability back to data standards, IND-equivalent oversight, and traceable analytic transparency, all of which are eQMS-resident controls.

Data integrity as a submission attribute. FDA’s recent data integrity warning letters to contract labs show the same control gaps that would disqualify submissions from utilizing RWE: deficiencies in audit trail review and raw data review, lack of system-level access controls, and insufficient Quality Unit oversight. An eQMS like ACE addresses these by embedding the reviews and controls into workflows rather than relying on manual execution, with 21 CFR Part 11–compliant audit trails and e-signatures for recordkeeping.

Documented provenance and analytic transparency. Reviewers look for clear documentation of provenance and analytic decisions. A document management system like ACE Docs stores the protocols, SOPs, data management plans, and amendments under version control with role-based access and audit trails.

Source-system interoperability. RWE needs sponsors to pull data from EHRs, claims data, registries, digital health technologies, and more, of which most are not natively integrated. ACE supports integration with other systems like ERPs and LIMS, and ACE Analytics centralizes quality-related data with analyses and dashboards, which helps a sponsor present a single source of truth built into their eQMS.

Inspection-readiness for RWE-driven approvals. Approvals carrying RWE are likely targets for follow-up inspection. ACE Inspection makes the same eQMS records available to a sponsor’s internal team and to inspectors without bespoke export work. This can help teams stay inspection-ready and reduce the need for manual document retrieval during inspections. Additional tools like inspector portals and scribe notes with translations also support teams during both scheduled and unplanned inspections.

Net Take

The Advancing RWE Program is a way for the FDA to evaluate RWEs as a primary evidentiary pathway, as well as the incorporation of quality of the data infrastructure as part of the evidence being reviewed in a submission. An eQMS connect the dots between regulatory modernization and key QMS controls to show the program reviewers that the data behind a submission is traceable, attributable, and defensible from source to decision.

The pharmaceutical and biotech landscapes often change and evolve with new technology, and the Advancing RWE Program is but a part of these evolutions. At PSC Software, we are lockstep with our partners to provide support in their operations, providing and building new solutions as the industry advances. If you are looking for a partner to help you succeed, contact us today for a demo to see what we can do to help.