What is Pharmacovigilance?

The book description reads as follows:

“Science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem.”

Once you read it, the sentence on its own probably doesn’t tell you much about what your duties as a Marketing Authorization Holder (MAH) are. This page can help you understand what PV requirements you need to meet as a MAH to be compliant with regulations and avoid getting into trouble with inspectors.

This page is intended as a concise summary for those unfamiliar with the different EU and global PV requirements. If you want to take a deep dive into the regulations and legislation, you will do best following the references in the endnotes.

If you are a PV professional or are PV aware, you may find it more useful to learn about how we innovate and modernise the world of Pharmacovigilance: see pages Automation or About us.

Our guide covers following PV terminology:

Pharmacovigilance System
Master File (PSMF)

Risk Management Plan

Literature Monitoring

Signal Management

European Union Qualified Person For Pharmacovigilance (EU QPPV)

ICSR MANAGEMENT

Local Contact Person for Pharmacovigilance

Disclaimer: The below serves to provide free information and educate and shall be seen as a quick point of reference and overview of different PV obligations MAHs need to meet. By no means should it be interpreted as a professional advice or a full description of relevant legislation and guidelines.

Pharmacovigilance System Master File (PSMF)

You will probably have heard of this since you landed on a PV company website. Pharmacovigilance System Master File (PSMF) is the one guiding document defining your entire PV system in EU. It describes all processes and structures the MAH has in place to ensure compliance with GvP and EU legislation. You’ll need to maintain and update the document regularly in order to run your PV operations, and upon request, make available to regulatory agencies for review.

When you’re applying for a Marketing Authorization, you’ll need to provide a summary of the PSMF. Best to put the document together prior to submitting the MA application. As part of the summary, you will name your European Union Qualified Person for Pharmacovigilance. Typically, the PSMF shall be located where the EU QPPV resides (or alternatively, at the location where PV activities are performed).

Do you need some help with putting the PSMF together? We’re here for you.

European Union Qualified Person for Pharmacovigilance (EU QPPV)

If you plan on or are selling a medicinal product in the EU, you will need an experienced Pharmacovigilance expert with perfect knowledge of the EMA guidelines and EU PV directives to assume the role of Qualified Person for Pharmacovigilance.

Basically, this is the regulator’s main PV contact point on your behalf, whose responsibility is to oversee the PV system (as defined by the PSMF) and of course provide input relevant to safety of your products.

You need to name your EU QPPV when you’re submitting the MA application, this information is provided in the PSMF summary as part of the submission. So, you should make sure you have the right person for the job before you submit the application.

The QPPV needs to be properly qualified in Pharmacovigilance, with thorough knowledge of GvP and PV regulations, and has to reside in EEA (incl. Norway, Iceland, and Liechtenstein).

If you don’t have the EU QPPV role covered in-house, you can easily sub-contract the position to Tepsivo and one of our QPPVs.

Risk Management Plan

Side by side with the PSMF summary, a Risk Management Plan (RMP) needs to be submitted as part of your MA application dossier. As you can probably guess, the document should describe how risks are to be managed. Over the lifecycle of your product, the RMP needs to be updated either at the request of the EMA/NCA or with new information that can significantly affect the product’s safety profile.

The RMP is a comprehensive document containing parts on the safety specification, pharmacovigilance plan, plans for post-authorization efficacy studies, and risk minimization measures. It takes expert knowledge and some time to put it together.

Do you need help compiling the Risk Management Plan? We’ll be happy to work on this with you.

ICSR Management

Collection and reporting of side effects or potential side effects to the medicinal products on market is a key responsibility within Pharmacovigilance the MAHs have. For the purposes of this quick overview, we simplify this activity under Individual Case Safety Report (ICSR) Management but there are differences between ICSRs, Adverse Events, Adverse Drug Reactions, or other similar reports.

Basically, you need to ensure you have a good system in place to capture all suspected adverse reactions, store it, validate as an ICSR, and submit to EMA and other regulatory agencies. The sources can be different, mainly differentiating between unsolicited and solicited reports.

Typical sources for unsolicited reports can include consumers communicating via medical enquiries (website, phone…), company representatives, healthcare professionals, social media (and anywhere on internet), scientific literature (see below), and many other occasional sources from about anywhere you can think of.

Solicited reports are typically from organized data collection programs, such as clinical trials, non-interventional studies, named patient use programs, compassionate use, surveys, and other similar systems.

So, what happens once a suspected adverse reaction that can be related to your product arrives? You need to validate it as an ICSR and see if it is in fact a reaction that has a causal relationship with the product. It gets a little more complex than this, but to put simply, the report needs to meet 4 minimum criteria: identifiable reporter(s), identifiable patient, suspected substance(s)/product(s), and suspected adverse reaction(s).

When the ICSR is validated, the public needs to know. You should submit the ICSR to EMA (specifically to EudraVigilance, the EU database on suspected adverse reactions) and other regulatory agencies depending on your geography.

Also, you need to ensure you maintain records of the ICSR and other reports that come in. Typically, PV systems use a “safety database” for managing the overall ICSR management activities, from the moment of a report coming in, to its submission to regulatory agencies.

The ICSR management can easily become the most time-consuming activity of all your PV processes. You will do best to use a system that can streamline the entire process and shave off as much unnecessary workload as possible. Yes, we can help… Reach out.

Literature Monitoring

Once you’ve applied for your Marketing Authorization, you are required to regularly and frequently monitor scientific literature to identify any potential safety relevant information. Scientific literature is an important source of possible adverse reactions and so it takes a crucial part of the overall PV process. Basically, we can split the process in two main parts: global and local literature screening.

For the so-called global literature monitoring, as MAH, you should systematically review publications in widely used databases such Medline or Embase; once a week will do it. If a causal relationship between the given drug and a suspected adverse reaction is identified, the relevant article shall be assessed, and the potential individual safety case report processed.

What we call as local literature screening is a little trickier. In every country where your product is authorized, you should thoroughly monitor all local language journals that are not referenced in the “global” databases. For this, clearly, you’ll need to have a local PV expert with knowledge of the local language, and of course the relevant academic journals in their country.

Literature Monitoring can be a time-consuming activity and you will do best to adapt digital solutions to help ease the process. If you are present across global markets and need local PV support with the medicinal journals, the Tepsivo network of local PV experts across 150+ countries may just be the right solution. Reach out to us and see how we can take care of your literature duties.

Local Contact Person for Pharmacovigilance (LCPPV)

Local literature screening obligations in each country where your product is approved is not the only responsibility you will have as a global organization. Several EU countries and many other countries around the world require the appointment of a Local Contact Person for Pharmacovigilance (LCPPV). Sometimes, the terminology is different, it can be a Local QPPV, Local Safety Officer, or some other name; it all more or less means the same thing.

A Local Contact Person for PV takes on a similar role as the EU QPPV, but logically has that responsibility locally in their country. This should be the key contact point between you and the respective National Competent Authority regulating your product(s) locally. They should know the local language, reside in the country (not always necessary), and have perfect knowledge of the PV regulations in their country.

Don’t worry, you don’t need to start hiring employees everywhere around the world. We can appoint a LCPPV in 150+ countries of the world on your behalf.

What is more? We can manage the full global operations in a completely automated way via our in-house services delivery platform, where we can also look after your internal resources at your affiliates. Don’t be surprised if you can’t compare this offer to other solutions, we’re the only ones doing it this way.

Just contact us and we can provide this to you.

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Furthermore, in some countries, the LCPPV role is legally required. In other countries, it’s simply good practice to have someone in country responsible for PV in that market.

The requirements on this role and their responsibilities also differ country by country. If you don’t want your head spinning having to figure what exactly you need to do and where, you should take advantage of a concise regulatory intelligence reporting, using data from all competent authorities.

See our page about Automation or reach out.

Signal Management

Once your products are on the market, it’s important to keep an eye on their safety profile and how it evolves over time. Following a thorough signal management process throughout the product’s life cycle is a crucial part of a complete pharmacovigilance system, and it needs to be defined in the PSMF, as well.

As a MAH, you’re responsible to monitor all safety relevant information and determine whether there are any new risks relevant to your product. You should review individual case safety reports (ICSRs) and aggregate data from all PV activities including scientific literature and other sources.

Typical process would go from signal detection to validation and assessment of a potential emergent safety issue. But there is no one-size-fits-all process for signal management.

You should consider the relevant sources for your product, frequency of routine signal assessment, signal prioritization, among many other factors.

And from a practical standpoint, you would be well-advised to assess whether a routine manual process or an advanced tech-enabled data mining and statistical analysis is most fitting for your situation.

Do you need expert advice on your signal management process and activities? Just reach out.

Aggregate Reports

Similar to your signal management activities, as you monitor the evolution of your product(s) safety profile, you should evaluate any new safety information in a periodic aggregate report.

In the EU and in many other countries, this is called Period Safety Update Report and it should include an aggregate info on all safety relevant information in a given time period. The frequency largely depends on how new the product is.

And yes, we can take care of your responsibility to put together and submit these periodic reports.

Let’s have a chat

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Feel free to drop us a message and we will contact you right away.

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