Every marketing authorization holder (MAH) needs a pharmacovigilance system to guarantee the safety of its products.
Within the EU a pharmacovigilance system is defined as a system used by an organization, such as the MAH, to fulfil its legal tasks and responsibilities in relation to pharmacovigilance. It is designed to monitor the safety of authorized medicinal products and detect any changes to their risk-benefit balance. Other regions may mix this up with the Global Safety Database where adverse event reports are entered, assessed, and reported. From an EU PV system perspective, the Global Safety Database is part of the PV system. However, there are more elements included in the PV System including but not limited to the processes to collect, assess and report adverse event reports from all sources, literature searches, regulatory intelligence, aggregate report writing, signal management, Risk Management Plan, the Pharmacovigilance System Master File (PSMF), Safety Data Exchange Agreements (SDEA), SOPs, filing and archiving.
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As part of the pharmacovigilance system, the MAH shall have permanently and continuously at its disposal an appropriately Qualified Person for Pharmacovigilance (QPPV) . The requirements and responsibilities of a QPPV are laid down in article 23 of EU Regulation (EC) No 726/2004) and article 103 of EU Directive 2001/83/EC as amended by new PV Regulation No 1235/2010 and Directive 2010/84/EU.
In addition to the QPPV, many competent authorities not only in the EU Member States but also world-wide are requesting the nomination of a PV contact person at national level.
There are multiple naming conventions described in local regulations and across Pharma companies for such a function, such as but not limited to Local Drug Safety Officer (LDSO), Local Safety Responsible (LSR), Local Safety Officer (LSO), Drug Safety Officer (DSO), Graduated Plan Officer (GPO), local Qualified Person Responsible for Pharmacovigilance (L-QPPV). However, for the purpose of this blog, we will use the term Local Person responsible for Pharmacovigilance (LPPV) and focus mainly on the EU.
Responsibilities of such LPPVs vary from country to country, but in essence it is to ensure the safety of the medicinal product and compliance with the pharmacovigilance guidelines on national level. Therefore, the QPPV together with the LPPVs build the key network in Europe to ensure the Pharmacovigilance system is functioning.
Guidance from Legislation
For the LPPV requirements, the Legal framework is given in Regulation (EC) No 726/2004 and Directive 2001/83/EC as amended by new PV Regulation /EU) No 1235/2010 and Directive 2010/84/EU. Article 104 paragraph 4 of the Directive 2010/84/EU says:
“Notwithstanding the provisions of paragraph 3, national competent authorities may request the nomination of a contact person for pharmacovigilance issues at national level reporting to the qualified person responsible for pharmacovigilance activities.”
Additionally, the GVP (Guideline on Good Pharmacovigilance Practices) Module I provides similar guidance in section I.C.1.1.:
“In addition to the QPPV, competent authorities in Member States are legally provided with the option to request the nomination of a pharmacovigilance contact person at national level reporting to the QPPV. Reporting in this context relates to pharmacovigilance tasks and responsibilities and not necessarily to line management. A contact person at national level may also be nominated as the QPPV.”
So, the detailed requirements for LPPVs in different countries are found in their national legislation.
In the following section we will provide you with some insight into the differences.
Understanding the Local Requirements
Many different requirements exist in the EU. Below we have categorized them into different areas:
- Which country requires an LPPV?
The EU Directive and GvP make the provision of an LPPV is optional (“may request…”, “provided with the option to…”). So, when setting up a pharmacovigilance system, the first question is: for which countries do we need an LPPV? Not all European countries actually require an LPPV? In principal there exists four categories of country-LPPV requirement:
- Countries not requiring an LPPV
- Countries requiring an LPPV
- Countries recommend an LPPV
- Other country requirements
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Some countries require an LPPV based on certain situations like the type of registration (central or national registration), life cycle period (during application, post authorization, post launch) or even language capabilities of QPPV.
A high level “overview, which country require an LPPV based on the PV Inspectors Working group survey from 2020 can be found here: Information on Member States requirements for the nomination of the LPPV.
- At what point in time is an LPPV required?
It is very important to know what point in the product life cycle an LPPV is required. This may be either from submission of marketing application, from marketing authorisation, or from first launch of the product. It may even vary due to the authorization procedure or whether obligations to collect PV data or a Pass study is required (e.g. Czech Republic).
For example, Croatia requires for centrally authorized products LPPVs only when the product is launched, but for all other authorizations, a LPPV is required when the marketing authorization application is submitted.
- Language and country residence:
Many countries require their LPPV to speak the local language(s), and many require that the LPPV resides in the country. If the EU QPPV resides in the country, he or she may also act as an LPPV, provided that he or she speaks the local language, but there may be exceptions to this, so you cannot always assume you do not need an LPPV if you already have a QPPV in that country.
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What qualifications are required?
Another difference is the requirements with regard to education. These range from none or not specified, to trained in PV, qualified to take over the responsibilities as LPPV (e.g. Luxembourg), up to be medically qualified or having access to a person with medical training (the Netherlands) or health professionals, biologists or chemists adequately trained (Cyprus).
- Availability:
Some countries require their LPPVs to have 24/7 availability for authorities (e.g. Germany), some need to be available to health professionals or patients (e.g. Belgium) and some do not have any such requirement.
- Deputy:
Many countries also require a deputy LPPV, who acts as a backup when the LPPV is not available. This ensures business continuity and robustness of the system.
- Waiver:
Based on ProPharma’s experience, some countries may accept waivers for not nominating an LPPV, although required. This varies very much on the type of drug and whether the drug is launched or not. Also, it is recommended to request such a waiver at an early stage after marketing authorization is granted.
Purpose of a LPPV Network
For all marketing authorization holders, it is essential to have a functional PV system in place, which is also organized by having the appropriate LPPVs in place at the right time. Dependent on your business needs and local and regional legislation this can be a very intensive large LPPV network across the 30 countries in the EU or a very tailored approach.;
The main purpose of the LPPV network is to support the Marketing Authorisation Holder to:
- comply with local, regional, and global PV legislation
- implement, oversee, and ensure functioning of the local PV system including local regulatory intelligence, local literature screening, and PV training of MAH’s employees performed
- ensure the benefit risk profile is favorable considering the local differences, e.g., with local risk minimization activities like targeted questionnaires or educational programs
- support the EU QPPV (e.g., with PSMF maintenance)
- be the local contact for PV (e.g., for inspections, recalls, urgent safety restrictions, etc.)
Implement Your QPPV and LPPV Network with ProPharma
ProPharma's large network of experienced QPPVs and LPPVs can support you to implement such an LPPV network while you are planning to approach the EU or any other market in the world. We will tailor the QPPV/LPPV network to your needs regarding product launch, patient exposure, risk minimization activities, type of authorization procedure and local affiliates in the countries. Contact us to speak with one of our QPPV/LPPV Network experts today and tell us how we can help.
