Assessment of Periodic Safety Update Reports for Nationally Authorised Products in 2013/2014 - Cover note
List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised
1. Introduction
The new Pharmacovigilance Legislation establishes the EU single assessment of Periodic Safety Update Reports (PSURs) for medicinal products subject to different marketing authorisations and containing the same active substance or the same combination of active substances whether or not held by the same marketing authorisation holder (Article 107e (1) of Directive 2001/83/EC).
To allow this EU single assessment, the frequency and dates of submission of PSURs for products authorised in several EU Member States that contain the same active substance or the same combination of active substances have been harmonised and published on 1st October 2012 in the list of Union reference dates and frequency of periodic safety update reports, also called the “EURD list”[1], in accordance with Article 107c (4) and (7) of Directive 2001/83/EC.
In February 2012, the European Medicines Agency (EMA) published a plan[2] for the implementation of the new Pharmacovigilance Legislation requirements. Following the December 2012 EMA Management Board meeting, the single assessment of active substances or combination of active substances contained in both centrally and nationally authorised products (NAPs) will start in April 2013, corresponding to the entry into force of the EURD list. However, the single assessment of active substances or combination of active substances contained in NAPs only (including products authorised through Mutual Recognition, Decentralised and National procedures), will not start in 2013.
2. Legal implication
In accordance with Article 107e (1) of Directive 2001/83/EC, the PSUR EU single assessment shall be performed for all active substances and combination of active substances included in the EURD list. However, considering the Management Board’s decision not to perform the single assessment procedure in 2013 for NAPs only, the concerned active substances and combination of active substances with a Data Lock Point (DLP) falling in 2013 have had to be temporarily removed from the EURD list and transferred to a separate “transitional list” (see below for further information).
Given that the prioritisation for 2014 will only be confirmed at the December 2013 EMA Management Board meeting and in view of increasing predictability for stakeholders in terms of management of PSURs for NAPs in the short term future, the scope of the active substances and combination of active substances removed from the EURD list has been extended to those with a DLP falling until 31 August 2014.
To oversee the active substances and combination of active substances temporarily removed from the EURD list and support stakeholders in planning PSUR submission requirements, the EU medicines regulators decided to expand the scope of the Member States PSUR Work Sharing list, and to rename this list as follows:
“List of substances under PSUR Work Sharing scheme and other substances contained
in Nationally Authorised Products with DLP synchronised”
This list constitutes a transitional list (until the single EU assessment for NAPs starts) and should be legally interpreted as a “coordinated” national request addressed to Marketing Authorisation Holders (MAHs) in accordance with Article 107c (2) of Directive 2001/83/EC.
Taking into account that the DLPs included in the EURD list have been carefully allocated to the active substances and combination of active substances following a risk based approach, and considering that Marketing Authorisation Holders (MAHs) should have already planned the preparation and the submission of the PSURs accordingly, it is envisaged that PSUR submissions should be requested via this list, in line with the DLPs originally published in the EURD list, i.e. in 2013 until 31 August 2014, as appropriate.
3. Consequences for removing the substances and combinations concerned from the EURD list
The PSURs of the active substances and combination of active substances temporarily removed from the EURD list will continue to be assessed at national level and through PSUR Work Sharing (PSUR WS) whenever possible (i.e. Member States collaboration without formal adoption through the PRAC), in order to avoid duplication of assessment between Member States.
Statement on PSUR cycle included in the marketing authorisations
The transitional “List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised” has been developed by the EU Regulatory Network as a request for PSURs submission to support public health interest until the single assessment for NAPs is operational.
Such request also applies to products for which a statement referring to the EURD List has been included in their marketing authorisations: considering that the active substances and combination of active substances are not in the EURD list any longer, this statement becomes temporally inapplicable until these substances and combinations are moved back into the EURD list once the single assessment procedure starts. As a consequence, no variation to remove the statement, or the substances, from the EURD list is required.
In case however a product containing an active substance or combination of active substances temporally removed from the EURD list includes an explicit condition providing for a specific frequency or PSUR submission date instead of a cross reference to the EURD list in its marketing authorisation, PSURs shall be submitted in accordance with this particular condition instead of following the transitional “List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised”.
For the estimated small number of marketing authorisations of medicinal products that are not subject to the derogation laid down in Article 107b (3) of Directive 2001/83/EC, this condition can only be overruled through the appropriate variation to either remove, or amend it in line with the EURD list in anticipation of the future inclusion of the active substances and combination of active substances.
Products referred to in Article 107b (3) of Directive 2001/83/EC should not be impacted by these changes since by default they do not require submission of PSURs. However, as explained in the EURD list introductory cover note[3], PSURs may be requested in a harmonised manner through the EURD list for reasons related to safety concerns or due to lack of PSURs but such conditions equally apply for the transitional list. Therefore, such requirements have been reflected in the “List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised”.
4. Description of the “List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised”
This list constitutes an extension of the PSUR WS list established in the context of the PSUR WS project developed under the auspice of the Heads of Medicines Agency. The “List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised” has been built using the same format as the former PSUR WS list, which has been used over the past years and well understood by stakeholders.
The list includes:
• The active substances and combination of active substances which have been following the PSUR WS scheme with DLPs as of 1st December 2012, together with their procedure number (including the P-RMS[4]). These are marked as “Work Sharing” in the column “Substances under PSUR Work Sharing scheme or Others”;
• The active substances and combination of active substances which originate from, but have been removed from the EURD list with a DLP falling between 1 April 2013 and 31 August 2014, and which have not been following the PSUR WS scheme; as well as the active substances and combination of active substances previously included in the “Synchronisation list” with a DLP falling between December 2012 and March 2013, i.e. before the EURD list becomes binding in April 2013. These are marked as “Other” in the column “Substances under PSUR Work Sharing scheme or Others”.
Special notes on the following columns:
• Column “EU-HBD/EURD”: the EU HBD allocated to the active substances and combination of active substances which are currently enrolled in the PSUR WS scheme and those transferred from the former Synchronisation list follow the format YYYYMMDD, as it was agreed with the relevant stakeholders when the project started. However active substances and combination of active substances previously included in the EURD list have a date following the format: DD/MM/YYYY.
• Columns “DLP” and “Next DLP”:
o The format of the DLPs may differ between active substances and combination of active substances: the format YYYYMM has so far been used for those included in the PSUR WS scheme, and those which have been transferred from the former Synchronisation list. However active substances and combination of active substances transferred from the EURD list have a DLP set on a specific day of the month as previously agreed by the EU Regulatory Network, and follow the format: DD/MM/YYYY.
o Any recommended DLPs following the ones included in the column “DLP” which fall before the 31st of August 2014 are indicated in the column “Next DLP”.
o In order to avoid confusion for stakeholders, the columns specific to the PSUR WS assessment timetables have been removed from the “List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised”.
· Column “Submission of PSURs by”: provides the deadline for the submission of PSUR in accordance with the DLPs indicated in the list. The PSURs should be submitted within 70 or 90 calendar days following these DLPs depending on the PSUR submission frequency for a given active substance or combination of active substances[5]. However National Competent Authorities can request a shorter timeframe if considered relevant.
• Column “Are PSURs required for products referred to in Articles 10(1), 10a, 14 and 16a of Directive 2001/83/EC as amended?”: such products are by default subject to a derogation from submitting PSUR, except if required by a competent authority on the grounds laid down in Article 107b(3)b. The substances can be marked as follows:
o “No, except if required nationally by a competent authority”: by default, PSURs are not required. However this does not undermine the right for a competent authority to request a PSUR at any time in accordance with Article 107c (2) of Directive 2001/83/EC. Such request will be made at national level.
o “Yes”: PSURs for some products subject to derogations are required on the grounds laid down in Article 107b (3) b of Directive 2001/83/EC. The need for PSURs was agreed within the EU Regulatory Network while building the EURD list, as it was thought such a list would constitute a pragmatic way to request the reports in a harmonised manner throughout the EU, and would help provide predictability for MAHs in terms of preparation and submission of PSURs.
• Column “Substances under PSUR Work Sharing scheme or others”: such column allows differentiating the active substances and combination of active substances currently following the PSUR WS scheme to those which do not. Active substances and combination of active substances may change status from “Other” to “Work Sharing” whenever a P-RMS has been allocated.
Note on the Synchronisation list: This list was used to build the EURD list, which includes DLPs from 1st
April 2013, date when it becomes effective. However the synchronisation list contains DLPs falling before that date and will therefore continue to drive the PSUR submission for the active substances and combination of active substances concerned until DLP 31st March 2013. In view of simplification and in order to reduce the number of published lists including active substances and combination of active substances, the synchronisation list has been removed from the PSUR Work Sharing Webpage of the HMA website (http://www.hma.eu/343.html), and all related active substances and combination of active substances which DLPs fall before the EURD list becomes binding have been transferred to the “List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised”, where they are marked as “Other”.
4
[1] EURD list EMA webpage: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000361.jsp&mid=WC0b01ac058066f910
[2] “Plan for implementation of the pharmacovigilance legislation by the European Medicines Agency” EMA/64750/2012: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500121837.pdf
[3] List of European Union reference dates and frequency of submission of Periodic Safety Update Reports, EMA/606369/2012: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/10/WC500133157.pdf
[4] CMDh Best Practice Guide For Transitional Arrangements For PSUR Work Sharing, CMDh/283/2012 http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/CMD_subgroups_working_groups/PSUR/CMDh-283-2012-Rev00-2012_11.pdf
[5] Good Vigilance Practice Volume VII on PSUR (EMA/816292/2011): http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500129136.pdf