This quarterly eNewsletter will keep you informed of news and trends as it relates to pharmacovigilance and patient safety within clinical development. We will also share insights and updates from PRA's pharmacovigilance and patient safety team.

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Edition Highlights:

Signal Management in Pharmacovigilance

One of the fundamental purposes of Pharmacovigilance as a discipline is to provide early warnings (i.e. identification of safety signals) for previously unexpected adverse events for a medicinal product/active substance.

Signal Management, a critical piece in performing safety surveillance, is the process for identifying new safety concerns, or changes to known safety concerns, and any associated action required.

Signal management consists of distinct steps:

Signal management

Detection is the screening of numerous data sources (such as safety database) for identification of potential signals, by the application of both quantitative (statistical methodologies) and qualitative methods.

After a signal has been detected, Validation, Analysis & Prioritization and Assessment will prove whether the signal is in fact real. Once proven, a full assessment using additional data and information is performed.

The Recommended Action can vary from taking no action (but still tracking the signal) or taking action (i.e., Marketing Authorization suspension, stopping of study(ies), label updates, further risk minimization measures, post-authorization study, etc.)

Information Exchange is key to ensuring MAH/Sponsors maintain transparency regarding the safety of the product with all stakeholders (patients/public, Health Care Professionals (HCPs), other MAHs/Sponsors and competent authorities) and to demonstrate continuous active monitoring of products.

Information such as any significant change to the safety profile/benefit risk of a product, and the potential impact on patients, is shared with HCPs and the public.

In the current climate with the Coronavirus pandemic and the need for a viable vaccination, signal management is key in identifying the risks associated with any vaccine in development and once on the market. The process of signal management allows for a rigorous framework for pharmaceutical companies to ensure safety remains a priority and can be monitored effectively.

Within PRA Signal Management activities are offered to our clients by our Patient Safety team lead by Catherine Godefroy, Executive Director (

Always laugh when you can. It is cheap medicine.

Lord Byron, 19th-century English romantic poet

PVS Spotlight | Bobby Azam

Bobby azam
Director, Patient Safety Surveillance

What is your role at PRA?

Provide guidance and consultancy as a SME for signal and risk management related processes, tools, regulatory requirements relevant to PV. Participate in PRA initiatives for the implementation and integration of new or enhanced processes as well as best practices for systems, databases and tools. Manage and oversee a team of 8 Safety Scientists.

What inspired you to join CRO business and what convinced you to stay with PRA?

Well – in retrospect this is down to luck as I was in the right place at the right time. 3 years ago I found myself redundant and crossed paths with PVS leadership, and was subsequently invited to consider a role with PRA. I was lucky enough to work with PRA as the safety CRO on the study I was assigned to about 10 years ago, and remembered this is a positive experience, so I thought why not?

It was definitely one of my best moves – the interview process was seamless, the job sounded interesting and relevant to my existing skills with the definite chance to develop further. So far not only has the role fulfilled as was promised by leadership in PVS, but I have had so much more opportunities such as presenting at conferences and writing articles. Also PRA has given me my first role in Functional Management.

I stay because of the continued supportive leadership in Patient Safety and the wider PVS. The nature of our business keeps the work variable and interesting for me, and I have been developed as promised. Most importantly from my perspective the people I work with are great – every day is a good day at work.

Reference Safety Information (RSI)

What is the RSI?

The RSI should be a list of medical events that defines which reactions are expected for the Investigational Medicinal Product (IMP) being administered to clinical trial subjects (MHRA).

Where to find the RSI?

The RSI is contained in the Investigator Brochure (IB) for products under development or in the Summary of Product Characteristics (SmPC) for authorized products.

Regulation (EU) 536/2014 for example provides a clear definition and regulatory expectation with regard to the RSI in an IB:

  • clearly-identified separate section titled “Reference safety information for assessment of expectedness of serious adverse reactions”
  • presented in form of a table, with events listed per system organ class using preferred terms followed by the frequency of the event

The RSI of a product authorized in the EU can be a table or list of Adverse Reactions (ARs) in section 4.8 ‘Undesirable Effects’ of the related SmPC.

Primary Purpose of the RSI in Clinical Trials (CTs)

From a regulatory perspective, in relation to safety reporting the RSI serves as basis for the expectedness assessment of serious adverse reactions (SARs) for expedited reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) and annual safety reporting by the CT Sponsor. This means whether or not the reaction is an expected side effect of the IMP, thus determining whether it does or does not need reporting in an expedited manner. To be categorized as expected the reaction must be clearly listed in the RSI.

Core Criteria for RSIs in CTs

Core criteria 1
Core criteria 2

PVS Spotlight | Susanne Elsner

Susanne elsner
Associate Director Drug Safety Center EAPA – Subject Matter Expert for RSI

What is your role at PRA?

I am responsible for managing and overseeing the Drug Safety team in Mannheim, Germany including the Managers of Drug Safety Center, Drug Safety Associates and Safety Assistants.

What inspired you to join CRO business and what convinced you to stay with PRA?

I joined PRA 15 years ago as Drug Safety Associate (DSA), attracted by a wide variety of different tasks and interesting career opportunities within Pharmacovigilance and Patient Safety (PVS). During my professional career I’ve learned case processing in safety databases, safety reporting to Authorities, Ethics Committees and sites and I’ve gained an understanding of safety regulatory intelligence and project management. I grew into functional and resource management, and now I’m recruiting DSAs to start or advance their professional career within PVS. I stay at PRA because, as a company, we have a positive impact on the patients we serve and within the PVS team, I’m consistently challenged to grow and advance my career.

Drug Safety Center (DSC): Manila

Located in Makati Business Central District, PRA PVS Drug Safety Center Manila is composed of healthcare professionals, including nurses and pharmacists, providing Asia Pacific time zone coverage.

When the Manila DSC was established, the team initially consisted of 7 DSAs in 2016 and has now grown to 18 DSAs and 2 Safety Assistants. All DSAs have at least 2 years of Safety experience.

The team is gradually and continuously growing and aims to become an essential contributor to the growth of the Safety department in PRA in the coming years.

In addition to the PVS DSC team, there is also one Safety Writer from the Patient Safety group located at the Manila office.

With a cost-efficient location, Manila DSC provides a good quality of work following standard PRA processes, and serves as an additional option for cost-sensitive sponsors.

The Manila Drug Safety team demonstrates effective teamwork and is able to understand and appreciate each other's unique abilities and works well together ensuring quality deliverables.

For fun, the team likes eating a lot, laughing out loud, and getting things done.

Remote working

Interested in learning more about any of the information mentioned here, have a personal interest in pharmacovigilance, or would like more information?

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