CBER Labeling Changes Related to Safety Findings that Used Real-World Evidence – FDA and Sponsor Conducted Studies
FDA Use of Real-World Evidence in Regulatory Decision Making
510(k) - 510(k) premarket notification
ACE - Angiotensin-converting enzyme
AEMS – Adverse Event Monitoring System
ARB - Angiotensin receptor blocker
BLA - Biologics License Application
CBER - Center for Biologics Evaluation and Research
CDER - Center for Drug Evaluation and Research
CDRH - Center for Devices and Radiological Health
CMS - Center for Medicare and Medicaid Services
DSC - Drug Safety Communication
EHR- Electronic health records
EMR - Electronic medical records
ESA - Erythropoietin stimulating agent
GBCA - Gadolinium-based contrast agent
GLP-1 RA - Glucagon-like peptide-1 receptor agonists
HCTZ - Hydrochlorothiazide
HDE - Humanitarian device exemption
IAA - Inter-Agency Agreement
IDE - Investigational Device Exemption
MACE - Major adverse cardiac event
NDA - New Drug Application
OSE - Office of Surveillance and Epidemiology
OUS - Outside the U.S.
PLLR - Pregnancy and Lactation Labeling Rule
PMA - Premarket approval application
PPI - Proton pump inhibitor
REMS - Risk Evaluation and Mitigation Strategy
RWD - Real-World Data
RWE - Real-World Evidence
SEE – Substantial Evidence of Effectiveness
U.S. - United States
VHA - Veterans Health Administration
VTE - Venous thromboembolism
| Study Responsibility | Product Name & Number | Sponsor/Applicant | Data Source(s) | Data Source Description(s) | Study Design(s) | Summary of RWE use and/or Regulatory Action | Type / Date of Regulatory Action(s) and/or Other Action(s) | Related Document(s) or Communication(s) |
|---|---|---|---|---|---|---|---|---|
| Sponsor/Applicant | FluBlok (Influenza Vaccine) BLA 125285 | Sanofi Pasteur, Inc | Registry | Observational data owned by Sponsor/applicant | Descriptive | Post-licensure observational, retrospective safety surveillance study of 14,981 pregnant individuals. It found no increased risk of birth defects or miscarriages from Flublok Quadrivalent, leading to updated prescribing information. | Labeling Update: 7/1/2025 | Flublok |
| FDA | Comirnaty, Spikevax, MNEXSPIKE (mRNA COVID-19 vaccines) BLA 125742 BLA 125752 BLA 125835 | Pfizer-BioNTech and Moderna Tx, Inc | Administrative Healthcare Claims | CBER BEST | Cohort | Two FDA-funded postmarket retrospective cohort studies using medical claims and the MACiV (Myocarditis After COVID-19 Vaccination) study contributed to updates to the prescribing information for COVID-19 vaccines to include new safety information about the risks of myocarditis and pericarditis following vaccination. | Labeling Update: 6/25/2025 | FDA Approves Required Updated Warning in Labeling of mRNA COVID-19 Vaccines Regarding Myocarditis and Pericarditis Following Vaccination |
| FDA | Abrysvo and Arexvy(RSV vaccines) BLA 125769 & BLA 125768 BLA 125775 | Pfizer Inc. and GlaxoSmithKline Biologicals | Multiple | CBER BEST medical and pharmacy claims | Self-Controlled | An FDA funded postmarketing study using a self-controlled case series analysis in the CBER Best System contributed to safety labeling changes to the Prescribing Information for Respiratory Syncytial Virus (RSV) vaccines on a suggested increased risk of Guillain-Barré syndrome (GBS) during the 42 days following vaccination. | Labeling Update: 01/07/2025 | FDA Requires Guillain-Barré Syndrome (GBS) Warning in the Prescribing Information for RSV Vaccines Abrysvo and Arexvy |
| Sponsor/Applicant | Hydroxyethyl starch (HES) products (various products) Multiple BLAs | Various | Multiple | Multiple | Multiple | Postmarketing observational studies (non-FDA funded), combined with evidence from a RCT and a meta-analysis led to labeling changes. | 7/7/2021 | Labeling Changes on mortality, kidney injury, and excess bleeding with hydroxyethyl starch products |
| FDA | SHINGRIX (Herpes Zoster Vaccine) BLA 125614 | GlaxoSmithKline Biologicals | Multiple | CBER BEST medical and pharmacy claims | Multiple | An FDA funded postmarket cohort study with self-controlled case series analyses using medical claims contributed to safety labeling changes to the Prescribing Information for Shingrix to include a new warning about the risk for Guillain-Barré Syndrome (GBS) following administration. | 3/24/2021 | FDA Requires a Warning about Guillain-Barré Syndrome (GBS) be Included in the Prescribing Information for Shingrix |
| FDA | Fluzone, TIV (Influenza Vaccine) BLA 103914 | Sanofi Pasteur | Administrative Healthcare Claims | Mini-Sentinel PRISM | Self-Controlled | During the 2010-2011 influenza season, an increased number of reports of febrile seizures following vaccination with Fluzone were received into the Vaccine Adverse Event Reporting System (VAERS). A Sentinel assessment using a self-controlled risk interval design found no statistically significant association with febrile seizures and provided reassurance of safety. | 5/16/2014 | FDA Postlicensure Rapid Immunization Safety Monitoring (PRISM) Study Demonstrates No Statistically Significant Association between Trivalent Inactivated Influenza Vaccine and Febrile Seizures in Children during the 2010-2011 Influenza Season | Sentinel Initiative |
| FDA | RotaTeq (Rotavirus Vaccine )<br>BLA 125122 | Merck Sharp & Dohme Corp | Administrative Healthcare Claims | Mini-Sentinel PRISM- commercial claims data | Cohort | An FDA funded post market cohort study in the Mini-Sentinel PRISM initiative led to revisions to the Prescribing Information and Patient Information for RotaTeq as a result of the new safety data. New information was added to the label Highlights, the existing intussusception subsection of Section 5 (Warnings and Precautions), Section 6 (Post-Marketing Experience), and Section 17 (Patient Counseling Information). | 6/13/2013 | FDA Releases Final Study Results of a Mini-Sentinel Postlicensure Observational Study of Rotavirus Vaccines and Intussusception |
| FDA | Human immune globulin products (various products, Immune Globulins)<br>Multiple BLAs | Various sponsors | Multiple | Medicare medical and pharmacy claims data, and AEMS data | Cohort | An FDA funded postmarket retrospective cohort study using medical claims as well as adverse event reports contributed to the decision to add information on thrombosis to the boxed warning in the labels of all intravenous human immune globulin products and to add a boxed warning to the labels of all subcutaneous and intramuscular human immune globulin products. | 11/14/2013 | FDA Safety Communication: New boxed warning for thrombosis related to human immune globulin products |
| Sponsor/Applicant | Rotarix (Rotavirus Vaccine) BLA 125265 | GlaxoSmithKline Biologicals | Medical Records | Inpatient medical records from hospitals/medical facilities in Mexico | Self-Controlled | A postmarket safety study (hospital-based active surveillance study) using self-controlled case series analysis was conducted by the sponsor in Mexico. The study examined intussusception following Rotarix administration. Study findings led to safety labeling changes stating that cases of intussusception were observed in temporal association within 31 days following the first dose of ROTARIX, with a clustering of cases in the first 7 days. | 9/17/2010 | September 17, 2010 Approval Letter - Rotarix |