Pharmacovigilance is defined by the World Health Organization (WHO) as the “science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other medicine/vaccine-related problem.” Launching products in new markets presents unique pharmacovigilance challenges. By addressing post-marketing, drug safety monitoring, and compliance requirements, sponsors can navigate pharmacovigilance to ensure the safety and success of their products. We share some insights and tips on navigating pharmacovigilance in Europe and the U.S. 

 

Pharmacovigilance Systems 

The European Medicines Agency (EMA) coordinates the European Union (E.U.) pharmacovigilance system throughout all clinical trial phases. The E.U. pharmacovigilance system operates through the cooperation of E.U. member states, the EMA, and the European Commission (E.C.). The Pharmacovigilance Risk Assessment Committee (PRAC) published its strategy for measuring the impact of pharmacovigilance in 2022. The EMA works closely with several partners, particularly the U.S. Food and Drug Administration (FDA), by sharing information related to drug safety and communicating before decision-making and publication. The FDA Center for Drug Evaluation and Research (CDER) is responsible for handling pharmacovigilance in the U.S. Within CDER, the Office of Surveillance and Epidemiology (OSE) mobilizes medical officers and safety evaluators to manage pharmacovigilance in their field of experience.  

 

1. Diverse Pharmacovigilance Strategies 

Innovative treatment options, e.g., advanced therapy medicinal products (ATMPs), digital therapeutics (DTx), and vaccines developed using advanced tech, require enhanced pharmacovigilance monitoring. Officials from the FDA and EMA reportedly said that ATMPs are complex products that require diverse pharmacovigilance strategies for monitoring post-market safety. As gene therapies may contain biochemical toxicities and cell therapies, biologic toxicities, safety monitoring, and the need for long-term monitoring should consider treatment toxicity, the likelihood of toxicity, how toxicity is measured, and how long the patient is at risk of adverse events (AEs). Of note, elevated safety risks for six approved CAR T-cell medicines and reports of secondary malignancies led EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) to review data (a similar review was conducted in the U.S.). 

 

2. Digitalization on Both Sides

Digitalization and access to new healthcare data, including data from wearables and apps, can improve patient safety, quality of life, and health outcomes through symptom management and the capture and analysis of real-world data. Workstreams at the EMA, FDA, and the U.S. National Institutes of Health (NIH) are connecting with epidemiology, statistics, and computer science experts to develop effective management and analyses of these data streams.

Regulatory agencies are not exempt from digitalization. Starting January 16, 2024, the FDA accepts electronic submissions for expedited and non-expedited post-marketing individual case safety reports (ICSRs) using the E2B(R3) standard endorsed by the International Council for Harmonisation. More recently, on April 1, 2024, the FDA started accepting electronic submissions of pre-marketing (investigational new drug (IND) study or IND-exempt bioavailability (BA)/bioequivalence (BE) study) ICSRs.  

 

3. AI. & Pharmacovigilance in the Lifecycle of Medicines

Note that regulators worldwide have a growing interest in exploring the use of artificial intelligence (AI) in pharmacovigilance. In the fall of 2023, the FDA and EMA launched a working group to explore AI in the lifecycle of medicines.

In post-approval pharmacovigilance, ICSRs, an important data source of potential drug safety issues, are used to report adverse events (AEs) to the FDA and EMA. Due to the massive volumes of electronic healthcare data generated daily, including increasing ICSR volume, advanced methodologies such as AI/machine learning (ML) are being explored to help regulatory agencies like the FDA and EMA process and evaluate ICSR submissions. According to the EMA, regulators will increasingly use insights derived from big data to assess the benefit-risk of medicines, including the real-world setting. The FDA OSE is already using AI to support reviewing and responding to the growing number of AE reports.

The Heads of Medicines Agencies (HMA) and EMA offer online catalogs to help regulators, researchers, and pharmaceutical companies. One catalog is for real-world data sources, while the other is for real-world data studies. By June 2024, the EMA intends to publish a revised version of its good practice guide to help users of the catalogs. 

 

4. Identifying & Filling Gaps

Conduct a thorough gap analysis early to identify disparities between existing internal processes and the drug safety monitoring requirement of the EMA and FDA. Additionally, there might be capability gaps for various reasons. ATMPs, novel drugs, and new methods in drug development require talent with the right expertise, skill in pharmacovigilance, and ability, e.g., to define the risk profile of newer, highly individualized treatments like chimeric antigen receptor (CAR)-T cell therapy. Sponsors need talent with skills in writing standard operating procedures (SOPs) and setting up pharmacovigilance systems, which, in Europe, must be in place from the time of the market authorization filing.

In Europe, a nominated Qualified Person responsible for pharmacovigilance (QPPV) is personally responsible for the safety of the human pharmaceutical products that the company markets. A designated person is required inside each region; e.g., a U.S.-based company with a European market authorization must have a QPPV in Europe and also at the country level (a regulatory requirement in France and Spain). Requirements vary from country to country, from a request to know a local language to more stringent criteria where a QPPV holds legal responsibilities. 

 

5. Safety Database & Quality Management System

To ensure compliance with post-marketing surveillance requirements, maintain a robust quality management system (QMS) and establish the safety database. Clearly define roles and responsibilities to ensure compliance, e.g., adhering to FDA submission requirements. A TFS HealthScience Case Study describes the challenges and steps taken to successfully transition from clinical to post-approval for a sponsor planning to secure approvals in the U.S. and E.U.

An oncology sponsor, amid a late-stage development program involving multiple studies, had clinical safety data across multiple contract research organization (CRO) databases. On the verge of its first product approval, despite understanding the U.S. and E.U. Pharmacovigilance framework, the sponsor lacked the necessary resources and expertise to fulfill its regulatory obligations. It relied on TFS’s proficiency and experience to facilitate the complex transition, which allowed the sponsor complete oversight of its product’s safety profile. This oversight translates to valuable safety insights to meet regulatory requirements, allowing the product to support patients across the U.S. and E.U. 

 

6. Precision Pharmacovigilance

With the advent of personalized medicine, sponsors need to consider that pharmacovigilance must shift from traditional approaches. Silva et al. discuss the integration of pharmacogenetics in enhancing drug safety, demonstrating how genetic profiling helps predict drug responses and adverse reactions12. Unlike small molecule drugs, novel treatments, such as CAR-T-cell and curative gene therapies, require a change in pharmacovigilance expertise. As pharmacogenomics is not broadly introduced in the P.V. routine, sponsors can anticipate regulatory requirements for precision pharmacovigilance in the future. 

 

7. Patient Centricity

Sponsors should be aware that the shift to patient-centricity in clinical research poses challenges for pharmacovigilance. A lack of an established definition of patient-centricity or a general standard framework for patient-centric approaches hampers identifying pharmacovigilance’s role in patient-centered outcomes delivery. The FDA established MedWatch, its medical product safety reporting program for healthcare professionals, patients, and consumers. When appropriate, MedWatch publishes safety alerts for FDA-regulated products such as prescription and over-the-counter medicines, medical devices, and combination products. 

 

TFS HealthScience Drug Safety and Pharmacovigilance 

TFS HealthScience is a leading global mid-size CRO that partners with biotechnology and pharmaceutical companies throughout their clinical development journey. 

TFS HealthScience pharmacovigilance experts set up, manage, and optimize the product safety needs of our customers throughout the entire clinical development and post-marketing journey. When outsourcing some or all of your program’s pharmacovigilance activities, efficient, high-quality processes are necessary to ensure the collection, management, and analysis of all safety data. Integrating these services into your technical systems is equally essential so that you have complete oversight of your safety data. Not just in Europe and the U.S., TFS provides end-to-end global pharmacovigilance services tailored to your needs.

Visit our TFS HealthScience Drug Safety and Pharmacovigilance website to learn more about TFS’s expertise in pharmacovigilance, or connect with a TFS representative today!