Directive 2010/84/EU and GVP Module I note the following:
Each company must submit a summary of the applicant’s pharmacovigilance system master file (PSMF) which shall include the following elements:
Proof that the applicant has at his disposal a qualified person responsible for pharmacovigilance;
The Member State(s) in which the qualified person resides and carries out his/her tasks; and
The contact details of the qualified person.
The MAH should have permanently and continuously at his disposal a QPPV residing and operating in the EU or EEA with 24/7 availability.
One QPPV per PV system in a company is required, but one single QPPV may have oversight of several PV systems. There could be a qualified deputy also residing in the EEA. The name and contact information must be provided to EMA/member states.
Some member states require a named person/national QPPV, too. This person may or may not be the same as the EU QPPV.
The QPPV should be appropriately qualified, with documented experience in all aspects of pharmacovigilance. If the QPPV is not medically qualified (i.e., an MD), access to a medically qualified person should be available 24/7.
The EU QPPV has multiple responsibilities:
Establishing and maintaining/managing the MAH’s pharmacovigilance system;
Ensuring that a PSMF is in place and up to date (some jurisdictions also have local requirements for the equivalent of a local or regional PSMF, which must be consistent with the EU PSMF);
Ensuring that all ARs (including literature searches) are collected, collated, and accessible at least at one point within the EU;
Preparing ICSRs and synthesis reports (PSURs/PBRERs, RMPs, benefit–risk assessment, etc.) and company-sponsored post-authorization safety/efficacy studies (PASS & PAES);
Evaluating continuously the overall pharmacovigilance system, including in particular, during the post-authorization period;
Having oversight of signal detection and risk management, including PASS/PAES and risk minimization measures (routine and non-routine measures);
Being aware of any new information about benefit–risk assessments for all registered drugs;
Ensuring that any request from the health agency is answered fully and promptly.
Note: GVP Module I specifies “The QPPV may delegate specific tasks, under supervision, to appropriately qualified and trained individuals, for example, acting as safety experts for certain products, provided that the QPPV maintains system oversight and overview of the safety profiles of all products. Such delegation should be documented.”
The QPPV should have oversight of the PV system, including and, therefore, “sufficient authority to influence the performance of the quality system and the pharmacovigilance activities and to promote, maintain and improve compliance,” i.e., authority over:
The organization of the Drug Safety department, processes, tools, and performance/compliance;
The needed measures for signal detection and risk management activities, including benefit–risk assessments;
The decision to take for variations, urgent safety restrictions, and communication to patients and healthcare professionals;
Partnerships.
The MAH, as well, has responsibilities to the following:
Support the QPPV and ensure appropriate processes, resources, communication mechanisms, and access to all sources of relevant information in place for the QPPV.
Ensure full documentation of all procedures and activities of the QPPV.
Implement mechanisms for the QPPV to be kept informed of emerging safety and risk–benefit issues including clinical trials and contractual agreements.
Ensure the QPPV has the authority to implement changes to the MAH’s PV system to maintain compliance.
Ensure the QPPV has input into Risk Management Plans and the preparation of regulatory action in response to emerging safety concerns.
Ensure the presence of back-up procedures (e.g., in case of non-availability of personnel, AE database failure, failure of other hardware or software with impact on electronic reporting and data analysis).
Note: The MAH may transfer/outsource PV activities to another person or organization. A detailed and clear written contract must be in place documenting such transfers and outsourcing. The contracted person or organization should implement QA/QC and allow auditing by the MAH. It is possible to outsource the EU QPPV function but the ultimate responsibility for all PV obligations always resides with the MAH.
Practicalities
The QPPV is a responsible and very challenging position. The person must be involved and have real influence in the safety system of the company. He or she must be knowledgeable and able to discuss, at least at a high level, particularly during a governmental inspection, the PV system in place globally, including standard operating procedures (SOPs); working documents; quality assessment/quality control (QA/QC); databases in use for drug safety, privacy, and security issues; all products marketed in the EEA and where they are sold outside of Europe; global licensing; distribution; co-marketing; agency commitments; compliance status and key performance
