Goodbye to DDPS and Hello to PSMFs

New Pharmacovigilance legislation (Regulation (EU) No 1235/2010 and Directive 2010/84/EU) was adopted by the European Parliament and European Council in December 2010. The aim of the legislation is for better pharmacovigilance and better health protection and promotion.

The legislation is the biggest changes to the regulation of human medicines in EU since 1995. It has significant implications for applicants and holders of EU marketing authorizations. The EMA is responsible for implementing much of the new legislation, effective from July 2012.

Scope of Changes:

1. Authorization requirements: Say goodbye to DDPS (Detail Description of Pharmacovigilance Systems) and hello to PSMFs (Pharmacovigilance System Master File). All MAHs will need to create PSMFs and continuously update them.

2. Risk Management Plans:  All applicants submitting an initial MAA after 2 / 21 July 2012 irrespective of the legal basis of their MA application are required to submit an RMP. This includes generic MA applications.

• For pending initial marketing authorisation applications on 2 / 21 July 2012 which do not contain an RMP, there is no obligation to submit an RMP during the course of the evaluation procedure.
• For those MAs granted before 2 / 21 July 2012 with an existing RMP, the MAH should continue to operate and update the risk management plan.
• As set out in the Commission Implementing Regulation, the new format and content for RMPs shall apply from 10 January 2013 to new or updated RMP submitted as of that date. The template for the RMP will be updated and this is expected to be available around September 2012.
• Marketing authorisation holders (MAHs) are reminded that a summary of the RMP will be published on the European medicines web-portal for the centrally authorised medicinal products and on the national medicines web-portals for the nationally authorised medicinal products. This requirement also applies to existing medicinal products with an RMP.
• Its not required for  a traditional–use registration and homeopathic medicinal products registered via the simplified registration procedure.

3. Post-Authorisation safety studies (PASS) : The new procedures for submission and assessment of non-interventional PASS protocol, substantial amendments and final study results as provided for in Articles 107n to 107q of Directive 2001/83/EC only apply to PASS studies which have been imposed after 2 / 21 July 2012 as a condition to the marketing authorisation. Such studies shall be identified in the RMP. For the CAPs, they will also be incorporated in the Annex II of the marketing authorisation. For the CAPs it means non-interventional PASS imposed through a Commission decision issued after 2 July 2012 including those with an opinion which may have been adopted in the months just before July 2012. For NAPs, it is anticipated that it will be reflected in the national decision to the marketing authorisation.

4. Periodic Safety Update Reports (PSUR) and EURD list:

The single assessment procedure involving only nationally authorised medicinal products will not start in 2012. The EMA will communicate further information in 2013.

The procedure for the different types of products is summarized below:

• For a single centrally authorised medicinal product (i.e. for a substance or combination of active substances contained in only one medicinal product which is centrally authorised), any PSUR submitted as of 2 July 2012 will follow the new procedure involving the PRAC as detailed in the GVP Module VII.
• For several centrally authorised medicinal products containing the same active substance or combination of active substances and where the submission dates are harmonised, the single assessment procedure involving the PRAC will be followed.
• From when the EURD list becomes binding, where centrally and nationally authorised medicinal products contain the same active substance or combination of active substances, the single assessment procedure involving the PRAC will be followed.
• Where nationally authorised medicinal products containing the same active substance or combination of active substances are authorised in more than one Member State and follow already the current worksharing scheme (WS), please refer to HMA website where arrangements for the assessment of these PSURs is provided until the single assessment procedure involving the PRAC is implemented.
• For nationally authorised medicinal products containing the same active substance or combination of active substances and which are authorised in more than one Member State but which are not covered by the current WS scheme, the assessment of the PSUR remains at an individual national level until the single assessment procedure involving the PRAC is implemented.

Please note that for purely nationally authorised medicinal products identified by the MAH as not authorised in more than one Member State, the assessment of the PSUR will remain at an individual national level as it is outside the scope of the single assessment procedure defined in the legislation.

As set out in the Commission Implementing Regulation, the new format and content of PSUR shall apply from 10 January 2013. The transitional period will apply according to the PSUR submission date and not to the data lock point. PSURs with submission date after the transitional period has elapsed should follow the new format and content established in the Commission Implementing Regulation.

5. Literature monitoring: As per the plan for implementation of the pharmacovigilance legislation by the EMA published on the EMA website, the monitoring of selected medical literature for certain active substances will not start in July 2012.

6. Product Information and the black symbol: The intention is to update the QRD templates for CAPs and NAPs that will include all the new requirements in the summary of product characteristics (SmPC) and package leaflet (PL) including:

• The black symbol and standard statements for products subject to additional monitoring.
• The statement to encourage the reporting of suspected adverse reactions for patients and healthcare professional applicable to all medicinal products.

Considering that the black symbol has to be selected by the European Commission after recommendation from the PRAC, the updated QRD templates will be published only after the selection of the symbol.
The selected symbol and standard statements will have to be included in the SmPC and PL of the medicinal products subject to additional monitoring. It is expected that the introduction of the black symbol will require the submission of a variation.

Further Information: Pharmacovigilance