II.B.2. Registration and maintenance

Location:
II.B.
In force from:
31.03.2017

II.B.2.1. Summary of the applicant’s pharmacovigilance system

Article 8(3)(ia) of Directive 2001/83/EC requires a summary of the applicant’s pharmacovigilance system to be included in the marketing authorisation application, which shall include the following elements in module 1.8.1 of the dossier:

  • proof that the applicant has at his disposal a qualified person responsible for pharmacovigilance;
  • the Member States in which the qualified person resides and carries out his/her tasks;
  • the contact details of the qualified person;
  • a statement signed by the applicant to the effect that the applicant has the necessary means to fulfil the tasks and responsibilities listed in Title IX;
  • a reference to the location where the PSMF for the medicinal product is kept.

Applicants for, and holders of simplified registrations of traditional herbal medicinal products are not required to submit a pharmacovigilance system summary, however, they are required to operate a pharmacovigilance system and prepare, maintain and make available on request a PSMF [based on DIR Art 16g(1)].

For other herbal medicinal products, not falling within the scope of the traditional-use registration, the requirements to operate a pharmacovigilance system, to prepare, maintain and make available on request a PSMF and to submit a summary of the pharmacovigilance system apply.

For homeopathic medicinal products registered via the simplified registration procedure the requirements to operate a pharmacovigilance system, to maintain and make available on request a PSMF and to submit a summary of the pharmacovigilance system do not apply [DIR Art 16(3)].

For other homeopathic medicinal products, not falling within the scope of the simplified registration, the requirements to operate a pharmacovigilance system, to prepare, maintain and make available on request a PSMF and to submit a summary of the pharmacovigilance system apply [DIR Art 16(3)].

II.B.2.2. Location, registration and maintenance

The PSMF shall be located within the EU, either at the site where the main pharmacovigilance activities are performed or at the site where the qualified person responsible for pharmacovigilance operates [IR Art 7(1)], irrespective of the format (paper-based or electronic format file). Following European Economic Area (EEA) agreements, the PSMF may also be located in Norway, Iceland or Liechtenstein.

At the time of marketing authorisation application, the applicant should submit electronically the PSMF location information using the agreed format [IR Art26 1(a)], and subsequently include in the application, the PSMF reference number, which is the unique code assigned by the EudraVigilance (EV) system to the master file when the EudraVigilance Medicinal Product Report Message (XEVPRM) is processed (see 1 ). Further to the granting of a marketing authorisation, the PSMF will be linked by the marketing authorisation holder to the EVMPD product code(s). All PSMFs must be registered in the Article 57 database.

Marketing authorisation holders shall continue to ensure that their entries in the Article 57 database for medicinal products for human use are up-to-date, including the information about the qualified person responsible for pharmacovigilance (QPPV), name and contact details (telephone and fax numbers, postal address and email addresses) and PSMF location information [based on IR Art 4(4)]. Upon a change in the QPPV or location of the PMSF information, the Article 57 database shall be updated by the marketing authorisation holder immediately and no later than 30 calendar days, in order to have the information in the Article 57 database and on the European medicines web-portal referred to in Article 26(1) of Regulation (EC) No 726/2004 updated and to allow continuous supervision by the competent authorities [based on IR Art 4(4), REG Art 57(2)(c)] (see 2 ).

The required location information for the PSMF is a physical office address of the marketing authorisation holder or a contracted third party. Where the PSMF is held in electronic form, the location stated must be a site where the data stored can be directly accessed, and this is sufficient in terms of a practical electronic location [IR Art 7(3)].

When determining the main site of pharmacovigilance activity, the marketing authorisation holder should consider the most relevant EU site for the pharmacovigilance system as a whole, since the relative importance of particular activities may vary according to products and fluctuate in the short term. The marketing authorisation holder should have an appropriate rationale for the location decision. In the situation where the main activities take place outside the EU, or where a main site cannot be determined, the location should default to the site where the QPPV operates.

II.B.2.3. Transfers of responsibilities for the pharmacovigilance system master file

The pharmacovigilance system may change with time. Transfer or delegation of responsibilities and activities concerning the master file should be documented (see II.B.4.2. and II.B.4.8.) and managed to ensure that the marketing authorisation holder fulfils their responsibilities. Since a specific QPPV has responsibility for the pharmacovigilance system, changes to the PSMF should also be notified to the QPPV in order to support their authority to make improvements to the system. The types of changes that should be routinely and promptly notified to the QPPV are:

  • Updates to the PSMF or its location that are notified to the competent authorities;
  • The addition of corrective and/or preventative actions to the PSMF (e.g. following audits and inspections). The QPPV should also be able to access information about deviations from the processes defined in the quality management system for pharmacovigilance;
  • Changes to content that fulfil the criteria for appropriate oversight of the pharmacovigilance system (in terms of capacity, functioning and compliance);
  • Changes in arrangements for the provision of the PSMF to competent authorities;
  • Transfer of significant services for pharmacovigilance to a third party (e.g. outsourcing of PSUR production);
  • Inclusion of products into the pharmacovigilance system for which the QPPV is responsible;
  • Changes for existing products which may require a change or increased workload in relation to pharmacovigilance activity e.g. new indications, studies or the addition of territories.

Any recipient QPPV should explicitly accept the following changes in writing:

  • Transfer of responsibility for a pharmacovigilance system to a QPPV.

The QPPV should be in a position to ensure and to verify that the information contained in the PSMF is an accurate and up to date reflection of the pharmacovigilance system under his/her responsibility (see GVP Module I).