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FDA Provides New Guidance on Submitting Safety Update Reporting

Posted 05 April 2013 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) today released a new draft guidance on how to provide regulators with periodic safety reports using a format developed by the International Conference on Harmonization known as the ICH E2C(R2) periodic benefit-risk evaluation reports (PBRERs).


The format has been under development for several years, and was finalized in November 2012, when ICH, a pharmaceutical regulatory harmonization group, received approval from all three core regulatory authorities-the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and Japan's Ministry of Health, Labour and Welfare-to approve the revised E2C PBRER guideline.

The guideline aims to "ensure that the periodic safety update reports for marketed drugs … cover: safety evaluation, evaluation of all relevant available information accessible to marketing authorization holders."

The Draft Guidance

FDA's draft guidance is intended to help sponsors and manufacturers interpret the ICH guideline, explaining "the conditions under which applicants can use an alternative reporting format"-that is, PBRER-"in place of the US periodic adverse drug experience report (PADER), US periodic adverse experience report (PAER) or ICH e2C Periodic Safety Update Report (PSUR)."

Companies are currently required to submit to FDA periodic reports using the approved PADER/PAER format for products approved under a New Drug Application (NDA) or a biologics licensing application (BLA), as well as any generic products such as those approved under an abbreviated new drug application (ANDA).

Those reports are to be submitted to regulators every three months for the first three years after a product is first introduced on the market, and annually thereafter. The regulations (21 CFR 314.80(c)(2) and 600.80(c)(2)) are intended to make sure that FDA is made aware of any emerging safety problems, such as those not detected during the course of clinical testing or those issues that are more serious than originally thought.

ICH's PBRER standard was first introduced in 1996, and has since been modified twice (2003 and 2012).

The latest revision "replaces the PSUR with the PBRER for postmarket periodic safety reporting, and describes the recommended format, content, and timing of PBRER submissions," FDA explained.

"Like its predecessor, the PSUR, the harmonized PBRER is intended to promote a consistent approach to periodic postmarket safety reporting among the ICH regions and to enhance efficiency by reducing the number of reports generated for submission to the regulatory authorities," FDA continued. "FDA has initiated the process to adopt the ICH E2C(R2) step 4 guideline as final FDA guidance. We anticipate that some applicants will wish to begin using the PBRER format in the United States before the necessary administrative procedures are completed."


Under the new rules, any applicant may request a waiver from FDA to use the PBRER format instead of the PSUR/PAER format so long as they submit copies of all non-expedited individual case safety reports received during the last PSUR reporting interval and a narrative identifying any changes made to the approved labeling.

The reporting frequencies are "generally" the same, FDA said, and it is not in the practice of waiving or otherwise changing those frequencies. However, some may be permitted "on the condition that the applicant submit a PSUR Addendum Report as needed to fulfill the reporting requirements."

Applicants who have no changes to make to the data lock point of reporting frequency in a PSUR can submit a PBRER without delay and without submitting a waiver request. If the reporting frequency is altered, a PSUR addendum report, PADER or PAER may be necessary.

Similar changes also require PADERs, addendum reports or PAERS, FDA explained.

Applicants without a PSUR waiver should seek one under 314.90(a) or 600.90(a), which will allow them to submit a PBRER instead of a PADER/PAER.

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