Q&A: Periodic Safety Update Report (PSUR)

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Once a veterinary product has received approval from the Commission (the “Commission Decision”) all further procedures connected with the product will fall under “Post-Authorisation Procedures”.

This guidance provides an overview for a number of procedures that occur frequently and addresses a number of questions which Marketing Authorisation Holders (MAHs) may have.

More information on this post-authorisation procedural advice Q&A.

As of 1 January 2017 it is mandatory for applicants to use the eSubmission Gateway / Web Client for all veterinary procedural submissions to the Agency. For more information, including links to guidance on registration with the system, see:

Additional information

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1. What is a Periodic Safety Update Report (PSUR)? Rev. July 2015

A PSUR is a safety update report, at defined time points after authorisation, of the worldwide safety experience of a veterinary medicinal product sent to all Member States and to the Agency. At these time points the marketing authorisation holder (MAH) is expected to provide succinct summary information together with a critical scientific evaluation of the benefit-risk balance of the veterinary medicinal product in the light of new or changing post-authorisation safety information. This evaluation should ascertain whether further investigations need to be carried out and whether changes should be made to the marketing authorisation, and/or to the product information.

A single PSUR is submitted for one product authorised to one MAH, which includes information on all indications, dosage forms and presentation, with a single data lock point (DLP) common for all aspects of product use. The content and format of PSURs should be in accordance with Volume 9B of The rules Governing Medicinal Products in the European Union - Guidelines on Pharmacovigilance for Medicinal Products for Veterinary Use, Part I, Section 6 – Guidelines for marketing authorisation holders.

References

2. What is the difference between the International Birth Date (IBD) and the European Birth Date (EBD) of my veterinary medicinal product?

The birth date of a veterinary medicinal product is used as the basis for defining the time points for submission of the PSURs after authorisation.

The European birth date (EBD) is defined as the date of the first marketing authorisation granted by a decision of the European Commission for a veterinary medicinal product to the MAH in the EU.

The international birth date (IBD) is defined as the date of the first marketing authorisation for a veterinary medicinal product granted to the MAH in any country in the world.

In the case the veterinary medicinal product is first authorised in EU, the EBD equals the IBD.

Reference

3. What is a Data Lock Point (DLP) and how shall I calculate the first data lock point?

The data lock point (DLP) is defined as the cut-off date for data to be included in a PSUR. It may be set according to the European birth date (EBD) or international birth date (IBD) of the medicinal product.

After obtaining the marketing authorisation for a medicinal product, the MAH is requested to inform the Agency of their choice of birth date (EBD or IBD) and of the chosen first data lock point (1st DLP).

DLP according to EBD

If the DLP is set according to the EBD, the 1st DLP should be exactly 6 months after the Commission Decision date or, alternatively, on the last day of the same month.

Example: If the Commission Decision date for granting the marketing authorisation is 6 May 2007; the first DLP can be either 6 November 2007 or 30 November 2007.

DLP according to IBD

If the DLP is set according to the IBD, the 1st DLP should be IBD or IBD + 6 months, so that the 1st DLP is within the 6 months following the EBD or, alternatively, on the last day of the same month.

Example: The IBD is 13 May 2006 and EBD (i.e. Commission Decision date) is 23 January 2007. The 1st DLP could then be either 13 May or 13 November or, alternatively, on the last day of the same months. In this case, the 1st DLP should be 13 May 2007, or, alternatively, on 31 May 2007, as it is within the 6 months following the date of the Commission Decision.

Reference

4. When should the PSURs be submitted? Rev. July 2015

Each PSUR should be submitted within 60 days after the DLP. It is strongly recommended that, before submitting the PSUR, the MAH makes sure that all reports from the line listings have been submitted electronically (without duplicate reporting) as described in Volume 9B Part III: Guidelines for Marketing Authorisation Holders, Competent Authorities and the Agency on Electronic Exchange of Pharmacovigilance Information in the EU.

  • 6-monthly intervals until and including the date for initial placing of the product on the market in the Community
  • 6-monthly intervals for the first full 2 years after placing the product on the market in the Community
  • annually for the subsequent 2 years
  • thereafter at 3-year intervals

If a product is not yet placed on the market, and if no adverse event reports have been received during the reporting period after exposure to the product anywhere in the world, a MAH may prepare and submit an abridged PSUR in the recommended format.

A PSUR may be submitted together with the renewal application in case both these submissions are due at the same time.

Non-submission of a PSUR is considered as a non-compliance issue of the MAH in terms of their pharmacovigilance obligations and may lead to regulatory action.

References

5. How is the PSUR cycle for my veterinary medicinal product calculated? Rev. July 2015

Once the 1st DLP has been established, the cycle of submission of subsequent PSURs can be determined according to the table below. Regardless of whether the EBD or the IBD is used, the PSUR should always be submitted within 60 days after the DLP.

The MAH is obliged to inform the Agency of the date of initial placing of the product on the market of the European Union. See also ‘Must a product be marketed after the authorisation has been granted (Sunset Clause)?’

Before initial placing on the market, 6 monthly PSURs are submitted.

Initial placing of the product on the European Union market triggers the start of the PSUR cycle of four 6 monthly reports followed by two yearly reports and thereafter three-yearly reports, unless other requirements have been laid down.

Marketing statusPeriodPeriod covered
Before initial placing on the market6 months11. EBD/IBD date to EBD/IBD + 6 months (1st DLP)
2. From 1st DLP + 1 day + 6 months (2nd DLP)
3. Etc until placing on the market
After initial placing on the
market in the European Union
6 months

 

Last DLP + 1 day + 6 months

6 months
6 months
6 months
1 yearLast DLP + 1 day + 1 year
1 yearLast DLP + 1 day + 1 year
3 yearsLast DLP + 1 day + 3 years

1 6-monthly periodicity continues until placing on the market

Example: Product A was authorised on 23 January 2007 in the EU. The EBD is therefore 23 January 2007. The MAH has chosen the DLP to be on the last day of the month. This date is therefore 31 July 2007, 6 months after the EBD. The product is initially placed on the market on 3 February 2008.

Marketing statusPeriodPeriod covered (order of PSUR)
Before initial placing on the market6 months223 Jan 07 – 31 Jul 07 (1. PSUR)
1 Aug 07 – 31 Jan 08 (2. PSUR)
1 Feb 08 - 31 Jul 08 (3. PSUR)3
After initial placing on the
market of the European Union
6 months1 Aug 08 – 31 Jan 09 (4. PSUR)
6 months1 Feb 09 - 31 Jul 09 (5. PSUR)
6 months1 Aug 09 – 31 Jan 10 (6. PSUR)
6 months1 Feb 10 - 31 Jul 10 (7. PSUR)
1 year1 Aug 10 – 31 Jul 11 (8. PSUR)
1 year1 Aug 11 – 31 Jul 12 (9. PSUR)
3 years1 Aug 12 – 31 Jul 15 (10. PSUR)

2 Six-monthly periodicity continues until placing on the market.
3 Period during which the product is placed on the market. Product is placed on the EU market on 3 Feb 2008. Thereafter, the PSUR cycle described below commences, unless otherwise required.

References

6. Can I amend the PSUR submission cycle, in which circumstances?

There may be circumstances where an amendment to the normal submission cycle of PSURs is requested by the CVMP for a given veterinary medicinal product at the time of authorisation or during the post-authorisation period.

The CVMP may impose an amendment to the PSUR cycle resulting in an increased reporting frequency e.g. in situations when giving an opinion on:

  • A new indication
  • A new target species or a previously unapproved use in a subgroup of the target species
  • A new formulation
  • A new route of administration

The decision on whether to change the PSUR cycle would be made at the CVMP no later than the time of the opinion. The modification of the cycle of submission will be reflected in the CVMP assessment report.

References

7. Can the Data Lock Point (DLP), which was initially based on the EBD change during the PSUR cycle?

In order to allow synchronisation of all PSUR submissions to regulatory authorities worldwide, the MAH can request that the submission of PSURs is based on the IBD instead of the EBD (i.e. Commission Decision date). As this would lead to a shift in the DLP, the next PSUR would cover the period between the last EBD based DLP and the new IBD based DLP.

8. How shall I present my PSURs? Rev. July 2015

A single PSUR is submitted for one product authorised to one MAH, which includes information on all indications, dosage forms and regimens, with a single DLP common for all aspects of product use.

When relevant, data relating to a particular target species, indication, dosage form, or dosing regimen should be summarised and discussed separately within the body of the PSUR.

Content and format:

The content and format of PSURs should be in accordance with Volume 9B and MAHs should refer to these guidelines when compiling these reports. PSURs should also be in compliance with CVMP requests from previous PSURs and/or FUMs/SOs or conditions of the marketing authorisation, if any.

The following information is expected in each PSUR, unless an abridged PSUR is applicable:

  • Update on regulatory authority or MAH actions taken for safety reasons anywhere in the world
  • Exposure (sales volume and data on estimated number of animals treated) and incidence of adverse events
  • Data review of adverse events supported by tables summarising main findings and corresponding line listings (appended) and structured as follows:
  • Adverse events in target species, including events of suspected lack of expected efficacy and those occurring after off-label use in target species
  • Adverse events reported in humans
  • Other pharmacovigilance fields:
    • Adverse events after use in non-target species
    • Potential environmental problems arising from the use of the VMP
    • Investigations of the validity of the withdrawal period
    • Transmission of any infectious agent via a veterinary medicinal product
  • A narrative overview of non spontaneous reports e.g. post-authorisation safety studies, published adverse event reports, user experience studies
  • Other information on adverse events arising from prescription or medication errors
  • Overall safety evaluation (primarily organised by VeDDRA system organ class) including a scientific analysis of the data presented and critical evaluation of the benefit-risk balance of the product. This section should include the following (lack of significant new information should be mentioned for each):
    • information on any previous action taken by either regulatory authorities or the MAH as a result of safety issues
    • any new important information on the following:

i) evidence of previously unidentified toxicity or safety concerns

ii) increased frequency of known toxicity or expected undesirable effects

iii) drug interactions

iv) adverse events in animals associated with off-label use, including overdose and its treatment

v) human adverse reactions related to the use of the product

vi) lack of efficacy

vii)prescription errors/medication errors, including those associated with invented names or with the presentation of the VMPs, that have safety implications, if available

viii) information on investigation regarding the validity of withdrawal periods arising from the use of the VMP

iix)any environmental issues, caused by the VMP under normal conditions of use

ix)any urgent safety issues that occurred during the period covered

  • The evaluation should in particular:
    • indicate whether the safety information remain in line with the cumulative experience to date and the SPC or whether changes should be made to the SPC or other product information, and
    • ascertain whether further investigations need to be carried out, and
    • specify any action recommended and the reasons why
  • Important information received after data lock point
  • Appended latest version of the SPC

The qualified person responsible for pharmacovigilance (QPPV) is responsible for preparing PSURs. It should be noted that a given PSUR should only cover the time period since the last PSUR.

It is strongly recommended that, before submitting the PSUR, the MAH makes sure that all reports from the line listings have been submitted electronically (without duplicate reporting) as described in Part III: Guidelines for Marketing Authorisation Holders, Competent Authorities and the Agency on Electronic Exchange of Pharmacovigilance Information in the EU.

References

 

9. If the medicinal product is not marketed, is the MAH required to submit a PSUR? Rev. July 2015

The MAH is required to submit a PSUR once a veterinary medicinal product is authorised in the EU, even if it is not marketed anywhere in the world.

If the product has not been placed on the market or distributed anywhere in the world during the reporting period, and if no adverse event (either in animals or in humans) was observed in any additional trial (e.g. clinical trial, post-authorisation safety study), PSURs should be in an abridged format. The submission cycle is the same as for full PSURs.

10. How and to whom shall I submit my PSUR? Rev. January 2017

The Agency accepts submissions of signed electronic copies of PSURs e.g. portable document format (pdf) or another searchable format. In addition, simultaneous submission of the PSUR line listings in excel format or other sortable format is encouraged and may be requested for analysis during assessment.

From 1 January 2017 it is mandatory for applicants to use the eSubmission Gateway / Web Client for all veterinary procedural submissions to the Agency, including veterinary PSURs. For more information, including links to guidance on registration with the system, see the Veterinary eSubmission website.

Once the PSUR has been validated by the Agency, copies should be submitted to the agencies of the competent regulatory authorities of Member States and EFTA countries Iceland, Norway and Liechtenstein. The contact details of national competent authorities (NCAs) for PSUR submission are available in the Annex to the standard operating procedure for management of PSURs for centrally authorised veterinary medicinal products, which also includes details of those Member States that may also accept electronic versions of PSURs.

References

11. How will my PSUR submission be handled (timetable)?

Upon validation of a PSUR submission, the PSUR will be assessed by the rapporteur for endorsement by the CVMP. The MAH is informed about the assessment time schedule.

The Agency will inform the MAH in writing of the conclusions of the CVMP. The following may be envisaged depending on CVMP’s conclusion:

  • PSUR is considered satisfactory and no further action is required.
  • PSUR is considered satisfactory. However, additional data are required within a specified timeframe or as part of the next PSUR. If the MAH is unable to submit these data within this timeframe, the MAH must justify the delay and inform the Agency/rapporteur and propose a new submission date.
  • PSUR is considered satisfactory, but a recommendation for a change of the product literature is made. In this case, a variation is needed to implement the conclusion and routinely the MAH will be given the opportunity to comment prior to the decision.
  • PSUR is considered satisfactory. However, a variation is needed and further data may be required.
  • PSUR is not considered satisfactory and further data are required for the MAH to address.

Reference

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