Understanding PADER: Periodic Adverse Drug Experience Report

What is PADER?
The Periodic Adverse Drug Experience Report (PADER/PAER) is an essential regulatory requirement for pharmaceutical companies operating in the United States. This aggregate safety report must be submitted by the Marketing Authorization Holder (MAH) to the U.S. Food and Drug Administration (FDA). PADER includes Individual Case Safety Reports (ICSR) along with their analysis, as stipulated under FDA guidance sections 314.80(c) and 600.80(c)(2).

Key Features of PADER:
  • Aggregate Safety Reports: Combines and reviews safety data over a specified reporting period.
  • ICSR Submission: Ensures that all Individual Case Safety Reports are accounted for.
  • Regulatory Compliance: Helps meet FDA’s post-marketing surveillance requirements.

Why is PADER Needed?
  • PADER is crucial for post-marketing safety surveillance. It serves several important purposes:
  • Safety Evaluation: PADER provides an updated summary of the product's safety profile.
  • Benefit-Risk Analysis: It evaluates the product's benefit-risk profile over time.
  • Labeling Changes: The report includes details of any labeling changes made during the review period but avoids in-depth analysis typically associated with Periodic Benefit-Risk Evaluation Reports (PBRER) or Periodic Safety Update Reports (PSUR).

Note: While PADER mentions labeling changes already performed, the detailed analysis that leads to such changes is managed separately.

When is PADER Needed?
  • The submission timeline for PADER depends on the duration since FDA approval.
  • First Three Years Post-Approval: Reports must be submitted quarterly.
  • Deadline: Within 30 days after the end of each quarter.
  • Beyond Three Years Post-Approval: Reports must be submitted annually.
  • Deadline: Within 60 days after the anniversary of the product’s approval date.


Waivers for PADER Submission
In certain scenarios, the MAH can request a waiver from the FDA to submit PBRER/PSUR in place of PADER, particularly in ICH regions. This requires updating the New Drug Application (NDA) listing.

Key Points for Drafting PADER
Creating a compliant and effective PADER involves attention to detail and adherence to regulatory guidelines. Below are the critical steps:

1. ICSR Submission Review
  • Ensure all 15-day expedited ICSRs have been submitted during the reporting period.
  • Verify that the submission dates are recorded in the safety database.
  • If any ICSRs were not submitted, prioritize submission and initiate Corrective and Preventive Actions (CAPA).

2. Finalizing Cases for PADER
  • Confirm all ICSRs included in the PADER are closed in the safety database to generate XML files for submission.

3. ICSR Narratives
  • Include descriptions of 15-day expedited ICSRs with emphasis on serious and unlisted events.
  • Keep narratives concise and focused on clinical significance.
  • Avoid verbatim narrative copies; instead, provide brief company comments explaining causality assessments.

4. Clinical Case Analysis
  • Provide a brief explanation of both 15-day expedited and other ICSRs.
  • Correlate their significance to the product’s benefit-risk profile.

5. USPI Updates and Safety Measures
  • Attach the latest U.S. Prescribing Information (USPI).
  • Summarize any changes made during the review period.
  • Include details about post-marketing studies, regulatory actions, or newly implemented safety measures.

Conclusion
PADER is a pivotal component of FDA’s post-marketing drug safety framework, ensuring transparency and accountability in adverse event reporting. By adhering to the outlined timelines and reporting requirements, MAHs not only maintain regulatory compliance but also contribute to the safety and efficacy evaluation of their products.

For pharmaceutical companies, mastering the nuances of PADER submission is essential for maintaining trust with regulators and protecting patient safety. By following the best practices for drafting PADER, companies can efficiently manage their post-marketing safety obligations.

Optimizing PADER Submission for Compliance and Efficiency
Understanding PADER timelines, ensuring accurate ICSR reporting, and summarizing updates effectively are critical for seamless FDA compliance. Pharmaceutical companies must invest in robust pharmacovigilance systems to streamline the PADER process.













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