Dear PV Professionals and PV Aspirants,
Today we will see some basic facts about PADER (Periodic Adverse Drug Experience Report).
What is PADER?
A PADER is a type of aggregate safety report required to be submitted by a sponsor or marketing authorization holder (MAH) to the US Food and Drug Administration (FDA) after obtaining marketing authorization approval.
PADER serves the purpose of collating, updating, evaluating, and providing a summary of post-approval information of a product along with its benefit-risk (B/R) profile evaluation. In PADER, a detailed analysis is not required as per PBRER/PSUR format.
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| PADER (Periodic Adverse Drug Experience Report) |
The main purpose of a PADER is to update and evaluate a medicine’s global data and provide information about drug safety. It provides a brief summary of changing post-approval information of a drug along with the benefit-risk profile evaluation. This evaluation provides insights, whether further changes are required for a medicine’s labeling or if additional investigations are required.
Aim of a PADER
- Report if any new information is obtained from the source medicine
- Evaluate information to find any exposure related to the medicine
- Accumulate the status of the medicine’s approval across various countries and regions
Frequency of PADER
PADERs are required to be submitted quarterly for the first 3 years after drug approval in the USA, and annually thereafter.
Waiver not to submit PADER
An MAH can take waiver from FDA and update the NDA listing and submit PBRER/PSUR instead of PADER in ICH regions.
Table of Content for a PADER
- A Narrative summary and Analysis of Information in the report
- A Medwatch form 3500A, for each adverse drug experience not reported as 15-day expedited report
- Action taken since the last report
- Periodic reporting except 15-day alert report
- Follow up information to adverse drug experiences submitted in a periodic report
Key points while drafting PADER
- Ensure all the ICSR are already submitted during the review period (15 day reports), and their submission dates are entered in safety database.
- If any ICSR not submitted then MAH need to submit it ASAP and initiate CAPA as per internal process.
- The cases/ICSR that are going to be submitted as part of PADER are closed in safety database to generate their XML’s.
- The ICSR that needs description should be 15 day expedited cases along with their clinical significance.
- The Narrative should be brief, with emphasis on data only about serious and unlisted event, hence avoid copy paste of narratives.
- The Company comments explaining MAH causality of case should be retained.
- Explain 15 day expedited and other cases in brief and corelate their significance in terms of impact on benefit-risk profile of product.
- Attaching the recent USPI and describing a very briefly what were the changes in USPI made during review period.
- Adding any postmarking studies, regulatory actions and any new safety measures implemented in respective sections.
Important differences between PADER and PBRER
| PADER | PBRER |
|---|---|
| It consists of individual case narratives for cases with fatal outcome and/events of special interest | It consists of detailed analysis on the benefit-risk evaluation of the given medicinal product |
| It is prepared per US 21 CFR 314.80 and is submitted to US FDA | It is prepared per ICH E2C R2 and European Medicines Agency Module VII guidelines and is submitted to the European Union and rest of the world |
| It consists of around 5 sections and is relatively less complex document | It consists of 20 sections and is a more complex document |
| It includes case presentation of serious unlisted events and regulatory updates | It mainly includes sections on regulatory updates, cumulative and interval exposure, interventional and noninterventional clinical trials, overview of signals, and benefit-risk assessment |
| A separate PADER is to be submitted with each NDA approval (for different indications and/or formulations of an investigational medicinal product) though sometimes MAH can prepare one PADER for different NDAs for different strengths of a formulation with appropriate justification | Usually, one PBRER is prepared for an investigational product with different formulations, dosage forms, or indications. In exceptional cases with provision of appropriate justification, for example, entirely different indications, submission of separate PBRERs might be acceptable |
| The frequency of submission is quarterly for first 3 years followed by annually | For newly approved products, PBRERs are submitted 6 months for first 2 years followed by annually (with exception of ad hoc requests) |
| Quarterly and annual PADERs are submitted within 30 and 60 calendar days of DLP, respectively | Annual or multiyear PBRERs are submitted within 70 or 90 calendar days of DLP, respectively |