The Qualified Person for Pharmacovigilance in the EU
There is sometimes a bit of misunderstanding about what the Qualified Person for Pharmacovigilance (QPPV or QP) is and does. In this post,I will attempt to clarify the situation.
The Qualified Person was initially defined in Directive 2001/83/EC.
“As part of the pharmacovigilance system, the marketing authorisation holder shall have permanently and continuously at its disposal an appropriately qualified person responsible for pharmacovigilance in the EU (QPPV)” Article 104
It was later expanded and defined in Volume 9A which has since been further defined by the Good PV Modules modules 1 and 2.
Here, then, is a basic summary of the QP requirements.
There must be a QP and a deputy in place when any Marketing Authorization Holder (MAH) has approval to market a product in the EU/EEA. In fact, it is necessary to specify the QP in the actual submission dossier of the MA to the EMA. Thus the QP must be identified at the time of submission and a pharmacovigilance (PV) system must be in place at submission even if it is not yet being used.
If a company does not yet have an MA or a submission and is just doing clinical trials there is no requirement for a QPPV. This is a point that is not always understood.
The QP and deputy must be permanently and continuously available and reside in the EU/EEA (note that this does not include Switzerland). The QP should be a senior person reporting at a high level in the management structure of the MAH with a clear reporting structure though this is not always the case.
The QP should have a formal written contract and there should be an SOP clearly defining the QP’s roles, functions and responsibilities. These responsibilities include the oversight, structure, performance and maintenance of the PV system in the MAH. This includes:
- Establishing and maintaining the MAH’s PV system(s). The word “systems” here does not mean just “computer systems” but the entire PV/drug safety functioning of the MAH.
- Ensuring that Quality Control (QC) and Quality Assurance (QA) mechanisms are in place to keep the MAH in compliance.
- SOPs and Working Documents covering PV are in place, up-to-date, trained on and actually followed.
- Metrics & KPIs on expedited and aggregate reporting and other key operational functions are tracked.
- A quality management system (QMS) is in place which includes audits, inspections, Corrective Action, Preventive Action plans (CAPAs) as needed and that they are actually put in place and completed.
- Ensuring that promises made to the health authorities in regard to safety are kept.
- Ensuring that PV training is done in the drug safety/PV department as well as anywhere (everywhere) else in the company (or vendors, third parties etc.) where safety matters may arise
- Ensuring that written agreements with other companies (including business partners, vendors, other third parties) are in place regarding safety and oversee their work.
- Have authority and sign off on Risk Management Plans (RMPs). The QP usually signs off on PSURs and DSURs also.
- Ensure that signal detection and trending mechanisms are in place.
- Ensuring that all suspected adverse drug reactions ADRs received by the MAH are collected and collated and accessible at one or more points in the EU.
- Ensuring that ICSRs, PSURs and Post-Authorization Safety Studies (PASS) cases and any other safety commitments are reported appropriately to the competent authorities (CAs).
- Ensuring the continuing evaluation of the benefit/risk analyses of all products.
- Maintaining an overview of the safety profiles and any emerging safety issues on company products.
- Have access to and ensure that the Pharmacovigilance System Master File (PSMF) is in place, accurate and up to date.
- In regard to the IT systems for PV, there must be a validated database/IT system.
- Ensuring that the appropriate persons are in place and trained to capture AEs.
The MAH (the company) in turn has responsibilities that it must fulfill:
- Set up the QP and deputy with one QPPV per PV system.
- Support the QPPV and ensure that appropriate processes, resources, communication mechanisms and access to information are in place such that the QPPV receives all relevant information he/she needs.
- Ensure full documentation of all QPPV procedures and activities.
- Implement mechanisms for the QPPV to be kept informed of emerging safety and risk-benefit issues.
- Ensure that the QPPV has the authority “influence the performance of the Quality System and the PV activities of the MAH”. That is he/she must be empowered.
- Ensure that the QPPV has input into Risk Management Plans & the action taken in responses to CAs on safety concerns.
- Ensure the presence of back-up procedures (e.g. personnel, AE database failure, failure of AE database & other safety related hardware or software).
- Track the compliance of the whole PV system periodically (e.g. audits).
- Notify the QPPV early in the process when the MAH is acquiring another company/product etc.
The person who is the QPPV must be:
- Appropriately qualified in the theoretical and practical knowledge of PV. This is not further defined and thus leaves a lot of leeway.
- Experienced in all areas of PV
- Must work and reside in the EU/EEA (i.e. Norway, Iceland, Lichtenstein)
- Registered with the EMA (as is the deputy)
- Available 24/7 – either the QPPV or deputy
- Be a single point of contact for PV issues
- Available for PV inspections
- Have access to a physician if the QPPV is not a physician
The QPPV may delegate tasks. If so, this should be done in writing and an oversight system for the out-sourced function be put in place. The QPPV (and MAH) still maintains responsibility for delegated tasks.
The EMA and MHRA (in a 2010 presentation by one of the Expert Inspectors) have made clear, however, that they will look very closely at delegated or out-sourced QPPVs. Broadly speaking, the CAs will not look kindly on a person (e.g. in a CRO) who functions as the QPPV for more than two or three companies at any time. It is felt that the job is so large, even in smaller or generic companies, that no one can handle all the responsibilities for more than 2 or 3 companies at a time. The MAH out-sourcing the QPPV must ensure that:
- This person is appropriately qualified and has worked in PV
- The relationship “will work in practice”
- The QPPV can implement necessary changes to the PV system
- The system will still function if the contract with the out-source company is terminated or it goes out of business or if there are mergers or acquisitions.
Finally, some countries in the EU have established national QPs whose jurisdiction is only in that country. This is in addition to the EU/EEA level QPPV. Sometimes these national QPs are out-sourced and sometimes they are company employees. They may or may not directly report to the EU level QPPV. In any case, clear SOPs and responsibilities must be in place in written SOPs that define the system(s). The company/MAH must verify in each member state what local requirements are necessary such as a QP in order to market a product.
The QPPV is a major responsibility that all MAH’s in the EU must fulfill and fulfill well. This is not a routine job but one that must be done well. Although safety issues may arise less in smaller or generic companies, the potential for a safety issue (or safety crisis) always exists and it is at these times that the QP becomes an important player. Similarly, during government inspections the QPPV will also play a major role. Thus the QP should be sufficiently senior, have authority, responsibility and the appropriate “power”. Although not necessarily a physician, it is wise that the QP have some level of medical training and experience. It is an important job and should be so treated.