On Friday 30 April 2021 DARQA hosted a webinar on pharmacovigilance: “PV for Non-PV QA”.

During this webinar a presentation was given by Sarah Mills, Senior Manager of Global Quality at PRA Health Sciences (PRA) and based in the UK.

Sarah starts her presentation with an explanation of what pharmacovigilance (PV) is: the promotion of safe and effective use of medicines.

The safety of a product is monitored throughout the life cycle of the product and the safety profile is continuously updated, not only during clinical trials but also post-marketing.

Sarah proceeds with explaining the PV terminology as described in ICH E2A, starting with Adverse Events (AE) and ending with Suspected Unexpected Serious Adverse Reactions (SUSARs).

One or more suspected adverse drug reaction(s) that occur in a single patient at a specific point in time will be reported in an Individual Case Safety Report (ISCR), regardless of how and where the information is obtained. A valid ISCR contains one or more identifiable reporter, a single identifiable patient, the suspected product(s) and one or more Suspected Adverse Reaction(s). In case the SAE is detected during the conduct of a clinical study, the causality should be included (whether an event can be attributed to an IMP). Some special situations should also be reported, e.g. overdose, abuse, off-label use, misuse, medication error, occupational exposure, lack of efficacy and pregnancy.


 Once all the required information is available, the clock starts ticking with regard to reporting timelines (day 0). The ISCR is reviewed and triaged, for instance compared with the Reference Safety Information and in case the SAEs are handled by a CRO, the client (sponsor) may be notified.

Audit aspects to consider here would be the correct calculation of day 0, whether all the required information was available to make a valid case or whether follow up actions were taken, was the case triaged by the PV department correctly and was the client informed appropriately (if applicable).

The ICSR is entered into the PV database and QC’ed and it might need to be medically reviewed, if that’s part of the process.

Audit aspects to consider here would be whether the data entry has been performed in accordance with the guidelines and staff has been trained in following these guidelines, whether the QC-steps have been performed in time and by an independent person, whether the medical review has been conducted appropriately and whether the case has been processed in accordance with the agreed timelines. All steps taken need to be documented appropriately.

The case needs to be finalized and needs to be distributed to the regarding parties, such as the regulatory authorities, investigator sites, ECs etc..  Additional information may be required

 to be queried and all queries need to be followed up. Once query information is received, the case processing process re-starts.  When all information is complete the case can be closed. Cases might be reported individually or as line listings in accordance with a PV master list or algorithms in the PV database.

Audit aspects to be taken into consideration would be to check whether all required updates were done and approved, whether queries were sent to the correct recipients, what process is used to close a case and was the case reported within the required timeframe. All steps taken need to be documented appropriately.

In addition to the audit aspects mentioned before, there are also general aspects about the process that need to be taken into consideration such as data integrity, contractual agreements, regulatory compliance, adequate procedures and their compliance.  

A very important source of information about the expectedness of adverse reactions is the Reference Safety Information (RSI) section in either the IB or the SmPC or a similar document, which is often the focus of an inspection or audit which often results in findings. The RSI should be approved and it should be clear which version of the RSI is approved and used at a certain time points during the conduct of the study.

Aggregate Safety Reports are used to compile all safety information from all sources in a predefined format to be sent to regulatory authorities and is an opportunity for an overall re-evaluation of the safety profile of the product.

An overview of the differences between required pre- and post marketing reporting is provided.

Routine PV is required for all marketed products and processes to ensure this should be in place. The process consists of literature searches, ensuring that the appropriate reports are being generated and distributed, continuous monitoring of the safety profile through using risk management methods and signal detection and other regulatory requirements such as the Pharmacovigilance Safety Master File (PSMF). The PSMF is a key document that should contain information about the PV system and the Quality Management  System and all the vendors used and it is usually reviewed before the start of an audit, if applicable.

The presentation continues with an explanation of some of the concepts mentioned earlier such as literature search, which should be done regularly and documented in accordance with the regarding procedure. The same goes for signal detection which is the processing of AE data resulting from drugs used pre- or post marketing.

PV impacts all departments of a company and all vendors this company is cooperating with. It is therefore important that all employees have at least received a basic PV training.

A lot of (S)AEs are reported by investigator sites. It’s therefore important to review the information generated by the site and the reports/line listings received by the site to assess whether this process is executed as described, to ensure that all the appropriate/current study documents pertaining to the study are used and filed and that the study personnel is sufficiently trained.

Approximately 25 people attended this webinar. In case anyone has questions or would like to provide feedback please contact DARQA via email: Dit e-mailadres wordt beveiligd tegen spambots. JavaScript dient ingeschakeld te zijn om het te bekijken..

The webinar’s recording can be viewed via this link.

Pin It