Understanding PADER: A Key Pharmacovigilance Requirement for the US Market

Pharmacovigilance is a global responsibility, and regulatory requirements may differ significantly depending on the region. One such region-specific requirement is the Periodic Adverse Drug Experience Report (PADER), a post-marketing safety report mandated by the U.S. Food and Drug Administration (FDA). While many in the pharmaceutical industry may already be familiar with the Periodic Safety Update Report (PSUR), which we previously covered on our website, understanding how PADER differs from PSUR is critical for maintaining compliance and ensuring patient safety across different markets.

What is a PADER?

A PADER is a post-marketing safety report submitted to the FDA by holders of approved new drug applications (NDAs) or abbreviated new drug applications (ANDAs). It serves as a cumulative and interval summary of adverse drug experiences associated with a marketed product. PADERs are required for drugs approved for marketing in the U.S. and must include both domestic and foreign safety data.

The report typically contains information on:

• Individual case safety reports (ICSRs)
• Summary tabulations of adverse events
• Regulatory actions and labeling changes
• Safety-related findings from clinical studies or literature

PADERs follow a structured format as per 21 CFR 314.80(c)(2) and must be submitted at defined intervals based on the date of U.S. market approval.

In addition to NDAs and ANDAs, Biologics License Applications (BLAs) are also subject to periodic safety reporting obligations in the form of a PADER, submitted to the FDA under 21 CFR Part 600.80. This regulation outlines post-marketing reporting requirements for licensed biological products and aligns in structure with those required for NDAs (21 CFR 314.80).

Why is PADER Important?

The PADER plays a crucial role in evaluating a drug's safety profile once it is available to patients in the real world. It helps the FDA monitor:

• Emerging safety signals
• Unexpected adverse events
• Trends that may warrant changes in labeling or risk management

By systematically compiling post-marketing safety data, the PADER contributes to the early detection of risks, ultimately safeguarding public health.

Which Products Require PADER and How Often Are They Submitted?

PADERs are required for:

• New Drug Applications (NDAs)
• Abbreviated New Drug Applications (ANDAs)
• Biologics License Applications (BLAs)

The frequency of PADER submission depends on the time since U.S. market approval:

• Quarterly for the first 3 years following U.S. approval (i.e., every 3 months)
• Annually thereafter

These requirements apply unless the FDA grants a waiver or modifies the schedule in agreement with the sponsor.

Report Content and Case Inclusion Rules

Each PADER includes both 15-day "Alert Reports" and non-15-day periodic safety data:

• 15-day reports refer to serious and unexpected adverse events submitted on an expedited basis.
• Non-15-day reports encompass periodic ICSRs not qualifying for expedited reporting, but still required for inclusion in cumulative summary analyses.

Regarding the inclusion of safety data, FDA guidance specifies:

• Domestic ICSRs: All adverse events reported in the U.S. must be included.
• Foreign ICSRs: Only serious and unexpected foreign reports are required, consistent with the 21 CFR 314.80 and 600.80 definitions.
• Published literature: Relevant case reports or aggregate findings from scientific literature must be included, particularly if they describe serious and unexpected events.
• Clinical study data: Any safety-related findings from post-marketing studies, observational research, or formal safety surveillance must be summarized and assessed.

PADER vs. PSUR: Purpose and Key Differences

While PADER and PSUR (Periodic Safety Update Report, as required by the EMA and other non-U.S. regulators) are pharmacovigilance documents intended to monitor post-marketing safety, their scope and regulatory intent differ.

Understanding these differences is essential for global pharmacovigilance teams to align reporting strategies with regulatory expectations.

Let Experts Support Your PADER Compliance

Ensuring timely, accurate, and high-quality PADER submissions requires deep expertise in U.S. pharmacovigilance regulations, data analysis, and regulatory writing. ProPharma's global team of pharmacovigilance and medical writing experts supports pharmaceutical and biotech companies in meeting their FDA post-marketing requirements.

From compiling and analyzing safety data to preparing submission-ready reports, our team works as an extension of yours, helping ensure compliance, maintain product integrity, and protect patient safety. Whether you're a small biotech launching your first product or a global pharma managing a broad portfolio, ProPharma has the experience and infrastructure to support your PADER obligations.

Blog Author

Igor Krupic

Pharmacovigilance Safety Scientist, Benefit Risk