Postmarketing Reporting of Adverse Drug Experiences
The US regulation requiring applicants to report postmarketing adverse drug experiences to the FDA — serious and unexpected reports as expedited 15-day "Alert Reports", plus periodic safety reporting — feeding the FDA Adverse Event Reporting System (FAERS).
What this does not cover
stated in the document's own scope- Covers post-marketing adverse-experience reporting for approved drugs; safety reporting during an IND is the separate subject of 21 CFR 312.32.
- Applies to drugs under an NDA/ANDA; biologics licensed under the PHS Act report under the parallel 21 CFR 600.80.
- Governs adverse-experience reports, not the field-alert reports for product/manufacturing defects, which fall under 21 CFR 314.81.
Always verify against the current published text before relying on it for a submission or inspection.
Overview
21 CFR 314.80 is the US regulation that governs how the holder of an approved drug application reports adverse drug experiences once the product is on the market. It defines the terms it uses — adverse drug experience, serious, unexpected — and then sets two reporting streams: expedited 15-day "Alert Reports" for events that are both serious and unexpected, and periodic reports that summarise everything else at defined intervals. The reports feed the FDA Adverse Event Reporting System (FAERS), the post-marketing safety database FDA uses for signal detection.
Scope & applicability
Holders of approved NDAs/ANDAs for marketed drugs. Parallel biologics reporting sits under 21 CFR 600.80.
Legal basis & how it acquires force
Section 314.80 is a binding regulation in Title 21 of the Code of Federal Regulations, issued under the Federal Food, Drug, and Cosmetic Act. It applies to holders of an approved NDA; §314.98 extends the same post-marketing reporting duties to ANDA (generic) holders, and §600.80 mirrors them for licensed biologics. Because it is codified regulation rather than guidance, its timelines and definitions are legal obligations, not recommendations.
Document structure
| Part | Covers |
|---|---|
| Definitions | Adverse drug experience, serious adverse drug experience, unexpected adverse drug experience |
| Post-marketing 15-day Alert Reports | Expedited reporting of serious, unexpected experiences within 15 calendar days |
| Periodic adverse drug experience reports | Quarterly then annual periodic reporting for the remaining events |
| Scientific literature and other sources | Reports arising from the literature, studies, and foreign sources |
| Recordkeeping | Retention of adverse-experience records and the basis for not reporting |
Quick reference · Which report, and by when
How a marketed drug’s postmarketing adverse experiences reach the FDA.
| Report | Covers | Deadline |
|---|---|---|
| 15-day “Alert Report” | Adverse experiences that are both serious AND unexpected (foreign or domestic) | 15 calendar days from receipt |
| Periodic (PADER) | All other reports — non-serious, or expected | Quarterly for 3 years after approval, then annually |
The applicant must investigate all reports and submit follow-up within 15 calendar days; each quarterly report is due within 30 days of the close of the quarter. Reports feed the FDA Adverse Event Reporting System (FAERS).
Source: 21 CFR 314.80(c). Verify against the current text before relying on it for a submission.
Key requirements
- Submit serious, unexpected ADEs as 15-day expedited reports
- Submit periodic safety reports on the required schedule
- Conduct and document diligent case follow-up
Implementation tips
- Automate the 15-day clock from receipt date and reconcile submissions against the safety database monthly
Revision notes
Aligned over time with electronic ICSR submission to FAERS using the ICH E2B(R3) standard.
International alignment
The 15-day expedited standard is the US implementation of the serious-and-unexpected principle harmonised in ICH E2A/E2D, and reports are increasingly submitted electronically in the ICH E2B format through FAERS. The regulation sits alongside 21 CFR 314.81 (other post-marketing reports) and the REMS provisions, which together make up the post-approval safety-reporting obligations for drugs.
21 CFR 314.80: frequently asked questions
Quick answers to common questions about 21 CFR 314.80.
What is a 15-day Alert Report under 21 CFR 314.80?
It is an expedited post-marketing report an application holder must submit within 15 calendar days for any adverse drug experience that is both serious and unexpected, whatever the source. The 15-day clock runs from first receipt of the information.
What is the difference between 21 CFR 314.80 and 312.32?
§314.80 governs post-marketing adverse-experience reporting for approved drugs; §312.32 governs safety reporting during clinical investigation under an IND. Different lifecycle stage, different regulation.
Where do 314.80 reports go?
They feed the FDA Adverse Event Reporting System (FAERS), FDA’s post-marketing safety database, and are increasingly submitted electronically in the ICH E2B format.