Keeping the End in Mind: Reviewing U.S. FDA Inspections of Submissions including Real-World Data

Cheryl Grandinetti; Donna R Rivera; Lee Pai-Scherf; Anna Choe; Paul G Kluetz; Stefanie Kraus; Gabriel K Innes; Kassa Ayalew

doi:10.1007/s43441-025-00791-1

Keeping the End in Mind: Reviewing U.S. FDA Inspections of Submissions including Real-World Data

Ther Innov Regul Sci. 2025 Sep;59(5):956-962. doi: 10.1007/s43441-025-00791-1. Epub 2025 May 24.

Authors

Cheryl Grandinetti¹, Donna R Rivera², Lee Pai-Scherf³, Anna Choe⁴, Paul G Kluetz², Stefanie Kraus⁵, Gabriel K Innes⁶, Kassa Ayalew³

Affiliations

¹ Division of Clinical Compliance Evaluation, Office of Scientific Investigations (OSI), Office of Compliance, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD, USA. Cheryl.Grandinetti@fda.hhs.gov.
² Office of Oncologic Diseases, Center for Drug Evaluation and Research and Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD, 20993, USA.
³ Division of Clinical Compliance Evaluation, Office of Scientific Investigations (OSI), Office of Compliance, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD, USA.
⁴ Division of Rare Diseases and Medical Genetics, Office of Rare Diseases, Pediatrics, Urology, and Reproductive Medicine, Office of New Drugs, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD, USA.
⁵ Office of Regulatory Policy, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD, USA.
⁶ Office of Medical Policy, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD, USA.

Abstract

The increasing use of real-world data (RWD) to generate real-world evidence (RWE) presents unique opportunities and challenges for drug development and regulatory decision-making, particularly in the area of good clinical practice inspections. FDA typically focuses their application review-based inspections on pivotal studies that generate evidence submitted to support new drug and biological product applications. This focus applies regardless of the data sources used in those studies. In this article, we discuss the fundamental role of good clinical practice inspections in verifying the quality, integrity, and reliability of RWD used in regulatory submissions. Through case examples, we highlight specific challenges related to accessing RWD source records, assessing data quality, and evaluating processes for data curation, transformation, and analysis. Our experience underscores the importance of early engagement with regulatory agencies as well as the implementation of robust quality management practices throughout the study lifecycle. As RWD continues to shape the regulatory landscape, these case examples provide insights in navigating the complexities associated with submissions utilizing RWE for drug approval.

Keywords: Data quality and integrity; Drug approval submissions; Good clinical practice (GCP); Real-world data (RWD); Real-world evidence (RWE); Regulatory inspections.

Publication types

Review

MeSH terms

Drug Approval*
Humans
United States
United States Food and Drug Administration*