SOP for Preparation and submission of Periodic Adverse Drug Event Reports (PADERs)

Purpose

Purpose of this SOP is to lay down a process for collection of required data, Preparation and Submission of Periodic Adverse Drug Experience Reports incompliance with the Regulatory requirements for Marketing Authorization Holder products to the Regulatory Agency.

As per Legislative regulations of 21CFR314.80, it is responsibility of ANDA Holder.

Scope

MAH have legal obligation to maintain the records of all suspected Adverse reactions to their products to the competent Authority (FDA) and maintain a proper pharmacovigilance system to ensure about an appropriate action towards the drug to reduce the Adverse reports occurrence.

This procedure applies to all personnel of ANDA Holder, Service providers and affiliates of ANDA Holder.

Responsibility

PADER Personnel: Responsible for Collection and collation of data from all sources of information and prepare PADER form as pr the template and sop.

Procedure

Timeline:

The Applicant must report PADER for all their NDA (New Drug Applications), ANDA (Abbreviated New Drug Applications), BLA (Biologic License Applications).

• At quarterly intervals for 3 years from the date of approval of the application. Must submit each quarterly report within 30 calendar days of the close of the quarter
• At annual intervals later-on. Must submit each annual report within 60 calendar days of the anniversary date of approval of the application.
• Upon written notice, FDA may extend or reestablish the requirement that an applicant submit quarterly reports or require that the applicant submit reports under this section at different times than those stated. For example, the agency may reestablish a quarterly reporting requirement following the approval of a major supplement.
• Follow-up information to adverse drug experiences submitted in a periodic report may be submitted in the next periodic report.

PADER Structure:

• A narrative summary and analysis of the information in the report.
• An analysis of the 15-day Alert reports submitted during the reporting interval (all 15-day Alert reports being appropriately referenced by the applicant's patient identification code, adverse reaction term(s), and date of submission to FDA).
• A history of actions taken since the last report because of adverse drug experiences (for example, labeling changes or studies initiated).
• An index consisting of a line listing of the applicant's patient identification code, and adverse reaction term(s) for all ICSRs which are not reported under paragraph Serious unexpected category i.e. ICSRs of only domestic spontaneous, serious expected and nonserious adverse drug experiences. All such ICSRs must be submitted to FDA (either individually or in one or more batches). ICSRs must only be submitted to FDA once.

Detailed structure:

A. Narrative summary: 

A narrative summary and analysis of the information submitted during the reporting period must include.

• The number of non-15-day initial adverse experience reports and the number of non-15-day follow up reports contained in this periodic report and the time period covered by the periodic report.
• A line listing of the 15-day reports submitted during the reporting period. This line listing should include the manufacturer report number, adverse experience term(s), and the date the 15-day report was sent/submitted to the FDA.
• A summary tabulation by body system (e.g., cardiovascular, central nervous system, endocrine, renal) of all adverse experience terms and counts of occurrences submitted during the reporting period. The information should be taken from

1. 15-day reports submitted to the FDA;
2. non-15-day reports submitted in the periodic report (domestic spontaneous cases which includes serious listed cases, non-serious listed cases and non-serious unlisted cases).
3. reports forwarded to the applicant by the FDA; and
4. any nonserious, expected adverse experiences not submitted to the FDA but maintained on file by the applicant.

For the adverse experience term product interaction, the interacting products should be identified in the tabulation.

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• A summary listing of the adverse experience reports in which the drug or biological product was listed as one of the suspect products, but the report was filed to another NDA, ANDA, or BLA held by the applicant.
• A narrative discussion of the clinical significance of the

1. 15-day reports submitted during the reporting period,
2. Any increased reporting frequency of serious, expected adverse experiences when, in the judgment of the applicant, it is believed the data reflect a clinically meaningful change in adverse experience occurrence.
3. Assessment of clinical significance by type of adverse experience, body system, and overall product safety relating the new information received during this reporting period to what was already known about the product.
4. should also state what further actions, if any, the applicant plans to undertake based on the information gained during the reporting period and include the time period for completing the actions (i.e., when the applicant plans to start and finish the action and submit the information to the Agency).

• The narrative discussion should indicate, based on the information gained during the reporting period, whether the applicant believes either that

1. No change in the product’s current approved labeling is warranted or
2. There are safety-related issues that need to be addressed in the approved product labeling. If changes in the approved product labeling are under consideration by the FDA, the applicant should state in the narrative the date and number of the supplemental application submitted to address the labeling changes.

B. Narrative discussion of actions taken: 

A narrative discussion of actions taken must be provided, including any labeling changes and studies initiated since the last periodic report. This section should include:

• A copy of current U.S. product labeling.
• A list of any labeling changes made during the reporting period.
• A list of studies initiated.
• A summary of important foreign regulatory actions (e.g., new warnings, limitations in the indications and use of the product).
• Any communication of new safety information (e.g., a Dear Doctor letter)

C. An index line listing of FDA Form 3500As or VAERS forms or E2B Forms or SRP Acknowledgement forms must be provided.

The line listing for each FDA Form 3500A or VAERS form or SRP Acknowledgement forms submitted should include:

1. Manufacturer report number
2. Adverse experience term(s)
3. Page number of FDA Form 3500A or VAERS form or SRP Acknowledgement forms as located in the periodic report. Identification of interacting products for any product interaction listed as an adverse experience.

• FDA Form 3500As or VAERS forms or SRP Acknowledgement forms must be provided for Domestic Spontaneous cases only

1. Serious and expected
2. Nonserious and unexpected
3. Nonserious and expected

• Adverse experiences due to a failure to produce the expected pharmacologic action (i.e., lack of effect) should be included in this section.

D. Waivers taken if any regarding for non-submission of domestic spontaneous nonserious listed cases.

Note: An FDA Form 3500A or VAERS form or SRP Acknowledgement forms for a serious, unexpected adverse experience should not be included in a periodic report because this adverse experience should have been previously submitted to the FDA as a 15-day report.

Note: If no adverse experiences were identified for the human drug or biological product for the time period involved and no regulatory actions concerning safety were taken anywhere in the world where the product is marketed, the periodic report should simply state this and be submitted to the FDA along with a copy of the current U.S. labeling.

Procedure and Responsibilities:

• ANDA Holder: Need to inform other sources (Domestic spontaneous reports) of information to Service provider within 2 business days.
• Service Provider: Collect all safety reports from ICSR team and prepare PADER Report Form (Form 1) as per above explanation and submit the quarterly and annual reports to ANDA Holder within 20 and 50 business days (internal timeline) respectively from the DLP.
• ANDA Holder: Finally, ANDA Holder will submit the PADERs to Regulatory Agency.

Abbreviation

NDA (New Drug Applications)

ANDA (Abbreviated New Drug Applications),

BLA (Biologic License Applications).

ANDA-Abbreviated new drug application.

SRP- Safety Reporting Portal.

Annexure

Form 1: PADER Form

References

US-FDA Guidelines 21 CFR 314.80

Revision History

Nil

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