HALMED is giving the answers to most frequently asked questions related to the submission of Periodic Safety Update Reports (PSURs) after Croatia’s accession to the EU
1. Who submits PSURs for centrally-authorised medicinal products (CAPs), after 1st July 2013 ?
The marketing authorisation holder for the EU submits PSURs for CAPs.
2. How PSURs for CAPs are submitted after 1 July 2013 ?
3. Who submits PSURs for nationally-authorised products (NAP)* after 1st July 2013 ?
The marketing authorisation holder for Croatia submits PSURs for NAPs.
4. How PSURs for NAPs are submitted after 1st July 2013 ?
PSURs for NAPs are submitted electronically (.pdf) on a CD to the following address: Robert Frangeš Mihanović Street 9 (Sky Office), Zagreb.
5. What is the accompanying documentation that needs to be submitted with PSURs for NAPs ?
The following documents should be attached_
- accompanying letter (in paper format)
- comparison of the Summary of Product Characteristics (SPC) authorised in the Republic of Croatia and reference safety information possessed by the company (in electronic format)
The comparison of the SPC authorised in Croatia and reference safety information possessed by the company should contain the following:
- comparison of reference safety information possessed by the company and SPC authorised in Croatia
- justification of the established differences (i.e. reason for non-compliance, ratio of differences, or the impact on befit/risk ratio)
- measures that will be undertaken by the (or have been undertaken, i.e. submitted an application for variation) with the aim to harmonise the SPC authorised in Croatia with the reference safety information
- date by which MAH will undertake measures (or when did undertake one)
Local qualified person for pharmacovogilance in Croatia declares and undersigns in the accompanying letter that he/she agrees with the content of the attached documentation.
6. What are the deadlines for PSUR submission (independently of the marketing authorisation procedure) ?
PSUR that is related to the period to (including) one year, needs to be submitted within 70 days from the date of data-lock-point (DLP), and PSURs related to the period longer than one year need to be submitted within 90 days from DLP, according to the Art. 31 of the Ordinance on Pharmacovigilance (Official Gazette, No 83/13) (hereinafter: Ordinance), or Guidelines on Good Pharmacovigilance Practice (GVP) Module VII - Periodic Safety Update Report).
7. What are the products that do not need PSUR to be submitted ?
According to the Art. 169 of the Medicines Act (Official Gazette No 76/13) (hereinafter: Act) for medicinal products having a valid authorisation according to the Articles 29, 34, 63 and 68 of the Act, or:
- generic medicinal product
- well-established use
- traditional herbal medicinal product
- homeopathic products registered via a simplified procedure, or according to the Art. 56 of the Ordinance, for medicinal products having a valid marketing authorisation according to the Art. 15, § a) and § b), Art. 19 and Art. 108 of the Medicines Act (Official Gazette, No 71/07, 45/09 and 124/11). The obligation to submit PSUR exists for the above mentioned medicinal products if indicated on the EURD list, or the transition list, according to the Art. 170 of the Act and Art. 31 § 2 of the Ordinance or based on the obligations in accordance with the Art 46 or Art 48 of the Act or based on the Agency’s request related to pharmacovigilance data or due to non-existence of PSUR for the active substance after granting the marketing authorisation (Art. 169 of the Act).
8. Is it necessary to submit a variation for a change in periodicity of PSUR in order to comply with the EURD list ?
For CAPs please see EMA’s Q&As on Practical Transition Measures for the Implementation of the Pharmacovigilance Legislation.
The periodicity of PSURs for NAPs is after 1st July 2013 automatically harmonised with the EURD list, according to the Article 170, § of the Act.
In rare cases where HALMED prescribed periodicity of PSUR in the marketing authorisation, it is necessary to submit an application for a variation for a change in periodicity with the aim to harmonise with the EURD list (does not include those marketing authorisations indicating that PSUR should be harmonised with the EURD list).
9. How is the change in periodicity of PSUR classified ?
The change of the PSUR periodicity is classified as C.I.10 (IAIN variation).
10. If indicated on the EURD list that for generic medicinal product, well-established use, traditional medicinal product or homeopathic product it is not necessary to submit PSUR, is it necessary to submit an application for variation in order to harmonise with the EURD list, which means not to submit PSURs any more ?
No, please see under 8.
11. The active substance is not listed on the EURD list and the periodicity is not defined in the marketing authorisation. What is the PSUR periodicity of submission for that active substance ?
In this case, provision of the Art. 168 of the Medicines Act (Official Gazette, No 76/13) apply, except for medicinal products authorised according to the Art. 29, 34, 63 and 68 of the Act that do not need a PSUR submission.
12. The active substance is transferred from the EURD list to the transition list (List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised). What is the PSUR periodicity for this active substance ?
In this case the PSUR periodicity is determined by the transition list, according to the Art. 31, § 2 of the Ordinance.
13. The authorised medicinal product is composed of more active substances. The periodicity of the combination of these active substances is not listed on the EURD list, but for the substance itself. What is the periodicity for PSUR for those medicinal products ?
In these cases, the periodicity is prescribed by HALMED in the marketing authorisation, or subsequently via notice to the applicant, according to the Art. 169 of the Medicines Act (except for medicinal products authorised according to the Art. 29, 34, 63 and 68 of the Act, for which no submission of PSUR is needed).
If the marketing authorisation holder is not informed about the periodicity of PSUR, PSUR should be submitted according to the Art. 168 of the Act.
14. Are marketing authorisation holders required to submit PSUR for renewal ?
According to the Art. 41 of the Ordinance on granting marketing authorisation (Official Gazette, No 83/13), marketing authorisation holders submit an addition to the clinical overview including the evaluation of the benefit/risk ratio (Module 2.5 Addition to the clinical overview) instead of PSUR and related documents.
*Nationally-authorised products are those authorised via MRP, DCP and those authorised via "strict” national procedure.