Changes to the Periodic Safety Update Report (PSUR) July 2012

Richard Watson, Senior Director Medical Writing, Quality Assurance

As a result of changes to the PSUR guidelines in July 2012, the way we write all PSURs will be affected.  These changes put more emphasis on risk-benefit, and introduce measures that should help streamline the writing of safety documents.

The good pharmacovigilance practice (GVP) guidelines came into effect in July 2012.  The guidelines bring together a set of measures drawn up to facilitate the performance of Pharmacovigilance (PV) in the European Union (EU).  The GVP guidelines are divided into 16 modules, each covering a major process in PV.  Module VII discusses changes to the format and content of the PSUR. 

What is the purpose of this new legislation?

A key aim of the PV legislation is to change the emphasis of the PSUR from a detailed presentation of individual case reports, to an evaluation of the risk benefit balance of a product.  The major changes to the content of the PSUR are:

  • Risk-benefit analyses:
    •  Risk evaluation: signals (new, ongoing or closed), evaluation of risks and new information, and effectiveness of risk minimisation activities.
    • Benefit evaluation: important baseline efficacy/effectiveness, evaluation of efficacy/effectiveness and new information.
    • Integrated risk-benefit analysis.
  • The detailed adverse drug reaction (ADR) line listings will be replaced by more concise cumulative summary tabulation of serious adverse events from clinical trials and cumulative and interval summary tabulations of ADRs.
  • There is no longer a requirement for detailed analyses of cases for special populations (e.g. pregnant/lactating women; organ-impaired patients; paediatric/elderly patients) unless being assessed as a potential risk.

 What improvements have been made?

The PSUR now has a modular format, which is intended to maximise efficiencies between different document types, since the same modules can be used in different documents. 

  • PSUR vs. Development Safety Update Report: These documents share a number of common sections – synchronisation of submission schedules for these documents should facilitate the use of common text.
  • PSUR vs. Risk Management Plan (RMP): It is envisaged that certain PSUR and RMP sections will be used interchangeably across reports.

Are there new timelines for submission?

PSURs with a submission date from Jan 2013 onwards should be in the new format.  To accommodate the additional effort required to produce a PSUR in the new format, the submission timelines (post data lock point) have been amended.

  • PSURs covering intervals of up to 1 year – within 70 calendar days.
  • PSUR covering intervals longer than 1 year and ad hoc PSURs - within 90 calendar days.

What other changes have been made?

Finally, there is no longer a routine requirement for PSURs for generic, well established, homeopathic and herbal products; however, PSURs may be required for such products if a risk is identified or if there is a lack of information.  The European Medicines Agency (EMA) will generate a list of EU reference dates and frequency of submission, including products and substances for which PSURs are required.  This list will be displayed on the EMA web-portal and is expected to be updated monthly.  Each marketing authorisation holder has the responsibility to check the web-portal for any updates.

Relevant Reference Documents
  1. Directive 2010/84/EU (adopted – effective July 2012)
  2. Regulation 1235/2010 (adopted – effective July 2012)
  3. Guideline on Good Pharmacovigilance Practices (GVP) Module VII – Periodic Safety Update Report (EMA/816292/2011) (draft – effective July 2012)
  4. ICH guideline E2C(R2) Periodic Benefit-Risk Evaluation Report (PBRER) – Step 3 (EMA/CHMP/ICH/544553/1998) (draft – effective Q4 2012)

About Medical Writing at ICON:
ICON provides an established medical writing service that has the experience, organisation and global resource capacity to support the full spectrum of medical writing projects during the development and post approval phases.  As specialists in the provision of safety documents, ICON medical writers have the expertise to ensure a successful transition to all requirements of the developing regulatory environment.


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