VII.C.6. Quality systems and record management systems for PSURs in the EU network

Location:

VII.C.

VII.C.6.1. Quality systems and record management systems at the level of the marketing authorisation holder

Specific quality system procedures and processes shall be in place in order to ensure the update of product information by the marketing authorisation holder in the light of scientific knowledge, including the assessments and recommendations made public via the European medicines web-portal, and on the basis of a continuous monitoring by the marketing authorisation holder of information published on the European medicines web-portal [IR Art 11(1)(f)].

It is the responsibility of the marketing authorisation holder to check regularly the list of EU reference dates and frequency of submission published in the European medicines web-portal to ensure compliance with the PSUR reporting requirements for their medicinal products (see VII.C.3.). Systems should be in place to schedule the production of PSURs according to:

the list of EU reference dates and frequency of PSURs submission; or
the conditions laid down in the marketing authorisation; or
the standard PSUR submission schedule established according to DIR Art 107c(2) for products authorised before 2 July 2012 (for centrally authorised products) and 21 July 2012 (for nationally authorised products) as applicable (without any conditions in their marketing authorisation or not included in the list of EU references dates and frequency of submission or not affected by the derogation established in [DIR Art 107b(3)]); or
ad hoc requests for PSURs by a competent authority in a Member State or the Agency.

For those medicinal products where the submission of an RMP is not required, the marketing authorisation holder should maintain on file a specification of important identified risks, important potential risks and missing information in order to support the preparation of the PSURs.

The marketing authorisation holder should have procedures in place to follow the requirements established by the Agency for the submission of PSURs.

The QPPV shall be responsible for the establishment and maintenance of the pharmacovigilance system [DIR Art 104(e)] and therefore should ensure that the pharmacovigilance system in place enables the compliance with the requirements established for the production and submission of PSURs. In relation to the medicinal products covered by the pharmacovigilance system, specific additional responsibilities of the QPPV in relation to PSURs should include:

ensuring the necessary quality, including the correctness and completeness, of the data submitted in the PSURs;
ensuring full response according to the timelines and within the procedure agreed (e.g. next PSUR) to any request from the competent authorities in Member States and the Agency related to PSURs;
awareness of the PSUR and assessment report conclusions, PRAC recommendations, CHMP opinions, CMDh positions and European Commission decisions in order to ensure that appropriate action takes place.

The record retention times for product-related documents in Module I also apply to PSURs and source documents related to the creation of PSURs, including documents related to actions taken for safety reasons, clinical trials and post-authorisation studies, relevant benefit information and documents utilised for the calculation of patient exposure.

VII.C.6.2. Quality systems and record management systems at the level of the European Medicines Agency

The application of the Agency’s quality system (see Module I) should support compliance by the Agency when fulfilling its tasks and responsibilities for the management of PSUR procedures and EU single assessments.

The Agency should have in place a process to technically validate the completeness of PSUR submissions.

Line listings and summary tabulations from the EudraVigilance database utilised to support the PSUR assessment should be created using reports by means of the EudraVigilance data analysis system.

Effective communication and circulation of PSURs and related documents is crucial for the successful completeness of the procedure; therefore processes have to be in place for the circulation of documents between the Agency, marketing authorisation holders, the Commission and the competent authorities in Member States. Where applicable, the procedures should establish the necessity for quality checks with the aim to remove any information of a personal or commercially confidential nature.

Written procedures should reflect the different steps to follow for the maintenance of the list of EU references dates and frequency of submission of PSURs published by the Agency in the European medicines web-portal (see VII.C.3.).

Prior to the publication of summaries of PSUR assessment reports in the European medicines webportal (see VII.C.7.) the appropriate personnel at the Agency should adhere to the procedures established for web publication of documents produced by the Agency or competent authorities in the Member States.

All records related to PSURs created by the Agency’s staff members, experts or consultants are the property of the Agency and all PSURs and related documents received are in the custody of the Agency. Both types of PSURs records (created or received by the Agency) are subject to the Agency’s overall control via the PSUR repository set up according to the provisions laid down in REG Art 25a.

The Agency’s policy on records management (EMEA/590678/2007)23, provides the basis for a consistent, sustainable and efficient records management program and it has been developed in accordance with the commonly recognised international standard for records management, “ISO 15489-1:2001 Information and documentation – Records management24”. According to the records classification stated by the Agency’s policy, PSURs would be considered business, legal, evidential and research/historical value records.

The record retention times for product-related documents in Module I also apply to PSUR- system related documents (e.g. standard operating procedures) and PSUR -related documents (e.g. PSURs, assessment reports, the data retrieved from the EudraVigilance database or other data used to support the PSUR assessment).

VII.C.6.3. Quality systems and record management systems at the level of the competent authorities in Member States

Each competent authority in the Member States shall have in place a pharmacovigilance system [DIR Art 101] for the surveillance of medicinal products and for receipt and evaluation of all pharmacovigilance data including PSURs. For the purpose of operating its tasks relating to PSURs in addition to the pharmacovigilance system the national competent authorities in Member States should implement a quality system (see Module I).

Competent authorities in the Member States should monitor marketing authorisation holders for compliance with regulatory obligations for PSURs. Additionally, competent authorities should exchange information in cases of non-compliance and take appropriate regulatory actions as required.

No PSUR assessment at EU level is foreseen for purely nationally authorised products authorised in only one Member State; therefore the national competent authority in the Member State where the medicinal product is authorised should have procedures in place for the assessment of PSURs related to those medicinal products.

The procedures established by the national competent authorities in Member States for the performance of the EU single assessment of PSURs, should be in line with the procedures established by the Agency for the coordination of PSUR assessment in the EU regulatory network (see VII.C.4.). These procedures should establish effective communication across the EU regulatory network and the actions to be taken regarding the variation, suspension or revocation of the marketing authorisation following the PRAC recommendations, CHMP opinion, CMDh position and European Commission decision as applicable.

The procedures established by the Agency for the use of the PSUR repository to support the single assessment, should be followed by the national competent authorities in Member States.

Where tasks related to PSUR procedures are delegated to third parties, the national competent authorities in Member States should ensure that they are subject to a quality system in compliance with the obligations provided by the European legislation.