Advantages of QPPV Outsourcing in the EU/EEA

Regulations and Responsibilities of a QPPV

For the marketing of a medicinal product in the EU and the European Economic Area (EEA), a Market Authorization Holder (MAH) has to appoint a Qualified Person responsible for Pharmacovigilance (QPPV). They are in charge of establishing and maintaining a pharmacovigilance (PV) system, overseeing the safety profiles of MAH’s products & coordinating any necessary actions in accordance with the PV legislation.

The EU regulations Medicinal Product Directive (MPD) (Directive 2001/83/EC (Article 104) and Regulation (EC) No 726/2004 (Article 23)) describe the legal basis of QPPV requirement. A MAH shall appoint a QPPV that resides and operates in the EU and is responsible for the fulfillment of the following core tasks:

• Implementing and managing a pharmacovigilance system – in accordance with the legal requirement and GVP – that collects, evaluates, and processes information about adverse reactions to medicinal products.
• Overviewing medicinal product safety profiles and any emerging safety concerns.
• Coordinating necessary regulatory actions in response to the emerging safety concerns.
• Maintaining detailed records of suspected adverse reactions and drafting and submitting Periodic Safety Update Reports (PSUR) and Risk Management Plans (RMPs) to national Competent Authorities (CA) and the EMA.
• Being aware of any conditions and obligations deriving from the Marketing Authorization release, including risk minimization measures, and of any commitment taken on by the MAH to ensure the product safety.
• Be permanently (24/7) available for information requests from national CAs or the EMA, and the contact point for inspections.
• Providing CAs with any further information relevant to the benefit-risk evaluation, such as Post-Authorization Safety Studies (PASS) results.
• Back-up procedures in the case of QPPV absence and be accessible through the QPPV’s contact details.
• Summary of the PV system and the Pharmacovigilance System Master File.

The MAH has to operate a pharmacovigilance system for the fulfilment of its pharmacovigilance tasks. A summary of the pharmacovigilance system should be provided along with the application for marketing authorization. The mentioned summary includes:

• Proof about the availability of a QPPV and their contact details;
• Member States in which the qualified person resides and carries out their tasks;
• A statement that the MAH has in place the necessary means to fulfill its obligations;
• The location of the pharmacovigilance system master file (PSMF).

Pharmacovigilance System Master File (PSMF)

The pharmacovigilance system master file (PSMF) is a detailed description of the pharmacovigilance system used by the MAH with respect to one or more authorized medicinal products. The PSMF is not a part of the Market Authorization Application (MAA). It should be permanently available for inspection and should be provided within 7 days to the Competent Authorities if requested.

The PSMF has to describe the PV System and its aspects like an organizational structure of the MAH (including the position of the QPPV), the sites where the PV functions are undertaken covering individual case safety report collection, evaluation, safety database case entry, periodic safety update report production, signal detection and analysis, risk management plan management etc., delegating activities, links with other organizations & contractual agreements, and the quality system, at the current time.

Finally, it also covers the education, experience, and contact details of the QPPV. The QPPV oversees the PV system’s compliance with the Good Pharmacovigilance Practices (GVP), which you can find on the EMA website.

Product safety profile & Emerging safety concerns

The current European pharmacovigilance legislation defines signal and risk management as ‘a set of pharmacovigilance activities and interventions designed to identify, characterize, prevent or minimize risks relating to a medicinal product, including the assessment of the effectiveness of those interventions’ (Directive 2010/84/EU). MAHs shall ensure that continuous monitoring of the safety of their medicinal products and signal detection through multiple sources are duly and timely fulfilled, their product information is up to date, and the authorities are informed of any new information that might have an impact on the marketing authorization. For this, the PV system should include Standard Operating Procedures (SOPs) describing how the relevant safety information is collected, analyzed, and processed, and how MAH liaises with the Local Authorities.

Ensuring a network of local PV experts

In the EU, this inevitably means that an established network of national or local persons responsible for pharmacovigilance is required. The MAH has the responsibility to ensure that the appropriate qualified persons are in place to ensure consistent regulatory intelligence surveillance. Consequently, they need to meet the minimum requirements of the national competent authority, and also have adequate experience and expertise to fulfill the role. These local PV experts shall ensure that all local requirements such as local literature monitoring, collection and processing of safety information, local Risk Management Plans and implementation of Risk Minimization measures, local regulatory intelligence, submissions, response to national Authorities’ requests etc., are always completed as per the current local regulations.

A pharmacovigilance contact person at national level reports to the QPPV. Reporting in this context relates to pharmacovigilance tasks and responsibilities and not necessarily to line management. Hence, the QPPV must ensure appropriate oversight of all local and ongoing pharmacovigilance activities across the entire global pharmacovigilance system, and notification receipt of local requirements’ changes to assess the impact on central processes.

Advantages of QPPV Outsourcing

Now that we have discussed the core activities of the QPPV, it is clear that establishing and maintaining a PV system for a medicinal product in the EU/EEA requires a great deal of expertise and a network of local experts rarely feasible to be kept in-house. Also, considering the continuous changes in an ever-evolving regulatory environment, well-implemented specialized outsourcing in PV can drive significant benefit for the organization, including:

1. Expertise and infrastructure

The first of the advantages of QPPV Outsourcing in the EU/EEAA through a specialized QPPV outsourcing partner is a team of skilled experts, experienced in working with various PV systems of different clients and several medicinal products. Therefore, the staff is familiar with all pharmacovigilance aspects to conduct PV services in a proper, compliant, and standardized manner. The IT infrastructure in the form of databases, backup systems, and quality management systems is also established. Hence, the MAH gains access to both the experienced talents and the technology and tools, to ensure efficient and compliant delivery of pharmacovigilance services.

2. An established global network

End-to-end PV outsourcing means trusting your PV system to a partner with readily available resources as part of an already established network of regional and local persons responsible for pharmacovigilance. This also means outsourcing the dealing with safety information sources in local languages, and it facilitates compliance to member state-specific regulations due to knowledge & experience. Business continuity is ensured as back-up resources are always available.

3. Cost-effectiveness and flexibility 

The PV activities of a medicinal product usually have fluctuating periods of work intensity. The MAH can reduce management costs via outsourcing where PV demands are low. Also, in such a competitive and demanding environment, MAH can obtain cost-effectiveness by keeping the number of resources to recruit, manage, and/or train to the minimum. Engaging with external PV experts provides flexibility to respond to varying workloads by allowing up- or downscaling of activities without investing in training, infrastructure, or networks. Access to already set-up and validated tools, such as safety database, is also a factor that significantly reduces the costs.

4. Scaling operations according to pharmacovigilance needs

The level of services that a QPPV outsourcer can offer varies. A larger pharmaceutical company with a basis outside of the EU/EEA may just be looking for a QPPV that handles PV activities in Europe while maintaining its PV system and SOPs. A well-trusted service provider can provide you with fit-for-purpose PV models and customize its PV solution to completely meet your needs and benefit from the advantages of QPPV outsourcing in the EU/EEA.

5. Improved strategic decisions

When a benefit-risk strategy for each product is effectively implemented, PV can drive competitive advantage by improving the product’s safety profile and further enhance the business objectives. PV experts focus on medical and safety outcomes generating significant business insights to make informed decisions.

For companies that prefer partial outsourcing, PV services may include:

• RMP development and maintenance;
• PSUR development and maintenance;
• Quality Management system support (SOPs’ development);
• Safety Database testing;
• International and local literature review;
• Benefit/Risk monitoring;
• PV training;
• PV regulatory intelligence;
• QPPV network (e.g. EAEU or UK QPPV)
• Audit preparation.

6. QPPV outsourcing for a new MAH

If you are a new potential MAH in the MAA process, QPPV outsourcing may prove especially useful for achieving the necessary documentation to support your application. A great starting point is performing a gap analysis to determine which aspects you can develop in-house and what you want to outsource. In case your product isn’t approved by the EMA, you have no idle investments in an unnecessary pharmacovigilance system. As the Market Authorization Holder is ultimately responsible for the post-market surveillance and QPPV activities, combining outsourcing of market authorization and QPPV is an even more integrated approach when marketing a drug in the EU/EEA.