III.B.4. Inspection scope

The inspection scope will depend on the objectives of the inspection as well as the coverage of any previous inspections by competent authorities of Member States and whether it is a system or productrelated inspection (a description of the types of inspection, inspection triggers and points to consider for the different types of inspection is provided in III.B.1.).

The following elements should be considered when preparing the scope of the inspection, as applicable:

• information supplied in the pharmacovigilance system master file;
• information concerning the functioning of the pharmacovigilance system, e.g. compliance data available from the Agency such as EudraVigilance reporting and data quality audits;
• specific triggers (see III.B.1.2. for examples of triggers);

It may be appropriate for additional data to be requested in advance of an inspection in order to select appropriate sites or clarify aspects of the pharmacovigilance system.

III.B.4.1. Routine pharmacovigilance inspections

Routine pharmacovigilance inspections conducted on behalf of the EU should examine compliance with EU legislation and guidance, and the scope of such inspections should include the following elements, as appropriate:

• individual case safety reports (ICSRs):
  • collecting, receiving and exchanging reports – from all types of sources, sites and departments within the pharmacovigilance system, including from those firms employed to fulfil marketing authorisation holder’s pharmacovigilance obligations and departments other than drug safety;
  • assessment, including mechanisms for obtaining and recording reporter assessments, company application of event terms, seriousness, expectedness and causality. In addition to examples of ICSRs from within the EU, examples of ICSRs reported from outside the EU should be examined as part of this review (if applicable);
  • follow-up and outcome recording, for example final outcome of cases of exposure in pregnancy and medical confirmation of consumer reported events;
  • reporting according to the requirements for various types of reported ICSRs, including onward reporting to the relevant bodies and timeliness of such reporting;
  • record keeping and archiving for ICSRs;
• periodic safety update reports (PSURs), (as applicable):
  • completeness and accuracy of the data included, appropriateness of decisions concerning data that are not included;
  • addressing safety topics, providing relevant analyses and actions; − formatting according to requirements;
  • timeliness of submissions;
• ongoing safety evaluation;
  • use of all relevant sources of information for signal detection;
  • appropriately applied methodology concerning analysis;
  • appropriateness of investigations and follow-up actions, e.g. the implementation of recommendations following data review;
  • implementation of the RMP, or other commitments, e.g. conditions of marketing authorisation;
  • timely identification and provision of complete and accurate data to the competent authority(ies), in particular in response to specific requests for data;
  • implementation of approved changes to safety communications and product information, including internal distribution and external publication;
• interventional (where appropriate) and non-interventional clinical trials:
  • reporting suspected unexpected serious adverse reactions (SUSARs) according to Directive 2001/20/EC and non-interventional study cases according to Directive 2001/83/EC;
  • receiving, recording and assessing cases from interventional and non-interventional trials (see ICSRs);
  • submission of study results and relevant safety information (e.g. development safety update reports (DSURs) and information included in PSURs), where applicable, PASS or postauthorisation efficacy studies (PAES) submissions, particularly when associated with specific obligations or RMP commitments;
  • appropriate selection of reference safety information, maintenance of investigator brochures and patient information with respect to safety;
  • the inclusion of study data in ongoing safety evaluation;
• pharmacovigilance system:
  • QPPV roles and responsibilities, e.g. access to the quality system, the pharmacovigilance system master file, performance metrics, audit and inspection reports, and their ability to take action to improve compliance;
  • the roles and responsibilities of the marketing authorisation holder in relation to the pharmacovigilance system;
  • accuracy, completeness and maintenance of the pharmacovigilance system master file;
  • quality and adequacy of training, qualifications and experience of staff;
  • coverage and adherence to the quality system in relation to pharmacovigilance, including quality control and quality assurance processes;
  • fitness for purpose of computerised systems;
  • contracts and agreements with all relevant parties appropriately reflect responsibilities and activities in the fulfilment of pharmacovigilance, and are adhered to.

The inspection may include the system for the fulfilment of conditions of a marketing authorisation and the implementation of risk–minimisation activities, as they relate to any of the above safety topics.

III.B.4.2. For cause inspections

The scope of the inspection will depend on the specific trigger(s). Some, but not all of the elements listed in III.B.4.1 and below, may be relevant:

• QPPV involvement and awareness of product-specific issues;
• in-depth examination of processes, decision-making, communications and actions relating to a specific trigger and/or product.

III.B.4.3. Re-inspections

For the scope of a re-inspection, the following aspects should be considered:

• review of the status of the system and/or corrective and preventive action plan(s) resulting from previous pharmacovigilance inspection(s);
• review of significant changes that have been made to the pharmacovigilance system since the last pharmacovigilance inspection (e.g. change in the pharmacovigilance database, company mergers or acquisitions, significant changes in contracted activities, change in QPPV);
• review of process and/or product-specific issues identified from the assessment of information provided by the marketing authorisation holder, or not covered in a prior inspection.

The scope of re-inspection will depend on inspection history. It may be appropriate to conduct a complete system review, for example if a long time has elapsed since the previous inspection, in which case the elements listed in III.B.4.1 may be considered for the inspection scope, as appropriate.