Pharmacovigilance Services: What Each One Does and When You Need It
PSMF, ICSR, PBRER, RMP. Pharmacovigilance comes with a lot of acronyms. Here is what each service actually does, how they connect, and when your company needs them.
By Dr. Upendra K Jain · · 10 min read
A medicine’s safety story does not end on the day it gets approved. In many ways, that’s where it starts.
Clinical trials is limited by design. They involve a few thousand carefully selected patients, for a fixed period of time. Once a product reaches the market it is used by far more people, including older patients, people on several other medicines and groups who were never in a trial at all. Rare side effects often only show up at this stage.
The thalidomide tragedy of the early 1960s showed how devastating a missed safety problem can be, and it shaped the drug safety systems we have today. Those systems is what we now call pharmacovigilance (PV).
If you are a marketing authorisation holder or a clinical sponsor, you have probably noticed that PV comes with a long list of acronyms and even longer list of obligations. This article explains what each service does, how they all connect, and when you actually need them.
What is pharmacovigilance?
The WHO defines pharmacovigilance as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem.
Simply put, a good PV system does four things:
- Collects safety information from every source it can come from
- Evaluates that information, one case at a time and as a whole
- Acts on what it finds, by updating labels, managing risks or informing regulators
- Proves all of the above with documents an inspector can check
The services below follow that same order. It’s easier to understand them as one connected system than as twelve seperate items on a price list.
Step 1: Build the foundation
PV system and database setup
Everything in PV depends on data, and that data needs a validated home. A safety database stores every case, codes it using standard dictionaries such as MedDRA and WHO-DD, and sends reports to authorities in the E2B electronic format.
Our PV system setup service covers implementation of systems like Argus Safety and Veeva Vault Safety, along with validation in line with 21 CFR Part 11. Our AI-enabled safety database can also pull data straight from emails, PDFs, scanned documents and published literature, which means less time spent on repetitive data entry and less mistakes from retyping.
You need this when: you are getting your first product approved, moving away from spreadsheets, or your current system can’t keep up with case volumes.
PSMF and SOPs
The Pharmacovigilance System Master File (PSMF) describes your whole PV system: who does what, which systems are used, where the data sits and how quality is managed. It is a legal requirement in the EU and is covered in GVP Module II. A competent authority can ask for it at any time, and you have just seven days to provide it. So it is definately not a document you want to write at the last minute.
SOPs then turn that description into daily instructions for your team. Our PSMF and SOP service prepares both documents, along with annexes and version control, so they reflect how your company really works.
You need this when: you are applying for a marketing authorisation in the EU or UK, changing your PV service provider, or preparing for an inspection.
Step 2: Collect the safety data
Medical Information Call Centre (MICC)
Often the first person to hear about a side effect is whoever answers the phone. A doctor calls with a dosing question, and halfway through the call a patient’s reaction is mentioned. If that information is missed, you may miss a reportable case too.
Our Medical Information Call Centre is a fully functional, AI-powered service that runs 24×7. It handles medical enquiries, adverse event intake and product complaints from healthcare professionals and patients, with multilingual support and real time escalation of serious issues to the PV team.
You need this when: your product is on the market and you need someone to answer enquiries outside office hours or in several languages.
Literature monitoring
Adverse events are also published in journals, and companies are expected to catch them. GVP Module VI asks marketing authorisation holders to search widely used databases such as Embase and Medline at least once a week, and to look at relevant local journals as well.
Doing this by hand is slow, and most articles that come back from a search turn out to be irrelevant. Our literature monitoring service uses a fully automated AI system for search and article screening, and then our PV experts review what it flags. The machine handles the volume, while a person makes the final call on what counts as a case.
You need this when: you have an authorised product. This applies to older generics too, not only to new medicines.
ICSR case processing
An Individual Case Safety Report (ICSR) is the basic unit of pharmacovigilance. To be valid it needs four things: an identifiable patient, an identifiable reporter, a suspected product and an adverse reaction.
The clock is strict. In the EU, serious cases are generally due within 15 days and non-serious cases within 90 days. In the US, serious and unexpected reactions go as 15-day alert reports. Day zero is the day anyone in your organisation, or your partner, first recieves the minimum information, not the day your safety team opened it.
Our ICSR case processing service covers the complete cycle:
- Intake and triageCases come in from calls, emails, literature and partners. AI-assisted extraction pulls out the key data, and each case is checked for validity and urgency.
- Data entry and codingEvents and medicines are coded using MedDRA and WHO-DD, so that data stays consistent across all cases.
- Assessment and narrativeSeriousness and expectedness are assessed, and a clear narrative is written that explains what occured.
- Medical review and quality controlA qualified reviewer checks the case for accuracy and clinical sense before it goes any further.
- Submission and follow-upThe report is submitted in E2B R2/R3 format, follow-up informations are chased, and the data is reconciled with its sources.
You need this when: you have any product generating cases, whether it is on the market or in a clinical trial.
Step 3: Make sense of the data
Medical review
A coded case isn’t the same as an understood case. Medical review brings in qualified healthcare professionals to check ICSRs and narratives, look at trends and support benefit-risk assessments. Is the event plausible for this drug? Is there another explanation for it? Those are medical questions, and a software can’t be left to answer them alone.
Signal management
One case rarely tells you much, but a pattern across many cases might. A signal is information suggesting a new possible link between a medicine and an event, or a new aspect of a known one, that deserves a closer look.
Under GVP Module IX, the process moves through detection, validation, analysis and prioritisation, assessment and recommendation for action. Statistical methods such as disproportionality analysis help to find unusual reporting patterns. It is important to remember that a statistical signal is not proof that the drug caused the event. It is just a reason to investigate further.
Our signal management service works with tools such as Empirica and VigiLyze, and also handles tracking and regulatory communication.
You need this when: you hold an authorised product. Signal management is an ongoing duty, not a one time project.
Aggregate reports
Aggregate reports step back from single cases and ask a bigger question: does the product’s benefit still outweigh it’s risks? Each of these reports have its own purpose and audience:
| Report | Used for |
|---|---|
| PSUR | Periodic benefit-risk evaluation for authorised products in the EU, under GVP Module VII |
| PBRER | The ICH E2C(R2) format for periodic benefit-risk evaluation, used in many markets |
| PADER | US FDA periodic report: quarterly for the first three years after approval, then annual |
| DSUR | Annual safety report for drugs in clinical development, under ICH E2F |
| ASR | Annual safety report for clinical trials, where a regional requirement applies |
Good reports take time, because they pull data from cases, literature, signals and sales figures. Our aggregate reports team prepares, reviews and quality checks them so that deadlines don’t catch you out.
Step 4: Act and report
Risk Management Plans
Every medicine has risks. A Risk Management Plan (RMP) sets out what is known and unknown about a product’s safety, how you will learn more, and how you will keep the risks low. In the EU it has a safety specification, a pharmacovigilance plan and risk minimisation measures, as described in GVP Module V. Some products in the US need a REMS, which FDA requires when labelling alone isn’t enough.
An RMP is a living document that needs updating as new information comes in. Our Risk Management Plan service supports both EU-RMP and REMS preparation, and looks after the plan through it’s lifecycle.
You need this when: you are filing a new marketing application in the EU, or when a regulator asks for one after a safety concern.
Global submissions
Every authority has their own gateway, format and local rules, whether it is EudraVigilance in Europe, FAERS in the US, PMDA in Japan or PvPI in India. A rejected report that isn’t corrected in time can end up late, so it is neccessary to monitor acknowledgements and not just assume that everything went through.
Our global submissions team handles E2B submissions, gateway configuration and region-specific filings, which is especially useful if your product is sold in many countries.
Step 5: Stay inspection ready
Compliance and audit support
Inspectors want evidence that your system works, not only that it exists. GVP Module I sets out the quality system expected, Module III covers inspections, and Module IV covers audits. Late cases, weak SOPs, missing reconciliation and unmanaged partner agreements are all findings that can be avoided with regular checks.
Our compliance and audit service covers compliance monitoring, inspection preparation and CAPA management, so you can find the gaps before an inspector does.
PV training
Anybody in your company could hear about an adverse event, including sales reps and customer service staff. If they don’t know what to do with that information, your reporting clock may already be running without anybody knowing. Our PV training programs cover GVP and ICH E2E, and include train-the-trainer workshops so that knowledge stays within your team.
Do you need all of this at once?
Probably not. It depends on where your product is today:
- In clinical development: safety database, ICSR processing, medical review and DSURs
- Approaching approval: PSMF, SOPs, an RMP, and a system that is ready on day one
- On the market: literature monitoring, MICC, signal management and periodic reports on top of the above
- Preparing for an inspection: a gap assessment, CAPA management and refresher training
Some companies outsource their whole PV function, while others only need help with one activity. Either arrangement can work, but remember that outsourcing the work does not outsource the responsibility. The marketing authorisation holder stays accountable, so choose a partner who’s systems and people you can check yourself.
Where AI fits in, and where it doesn’t
Case volumes keep growing, and much of the work is repetitive. That is why we use AI across MICC, literature monitoring and safety database operations, where it reduces manual effort and speeds up the workflow.
But AI does not replace expert judgement in our process. Causality, medical significance and regulatory decisions still need qualified people who can explain there reasoning to an inspector. We think that is the right balance for patient safety.
How Indivirtus can help
Indivirtus has worked with 800+ clients across 64+ countries, and our PV services are built around the regulators you actually deal with, including the EMA, US FDA, MHRA, PMDA, DCGI and WHO-UMC. You can use the complete system or just the one piece you are missing.
Not sure where your PV system stands? Talk to our drug safety team or explore our full range of pharmacovigilance services.