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Addressing the Critical Pharmacovigilance Elements for License Application Submission

Syneos Health experts examine what is necessary to build a compliant pharmacovigilance system for any company preparing for a license application submission.

For asset development teams considering a first license application submission in the United States or European Union (EU), or any other region, preparing a business to meet the requirements can be a challenging task.

A license application is one of the most important steps in placing a medicinal product on the market. Failing to submit a compliant application may lead to questions, rejections and/or delays in the approval of an application. Regardless of country or region, regulatory expectations for license applicants tend to be stringent and must be met, as the legal environment shifts from clinical towards post-marketing.

As a business approaches the license application process, there are two critical pharmacovigilance (PV) elements biopharmaceutical and asset development teams must be aware of prior to submission:

  1. Set-up essential structure and processes enabling continuous benefit-risk balance monitoring.  A license applicant is expected to continuously oversee the asset’s risks and put them into the context of existing information on benefits. This benefit risk assessment is performed by collecting data globally from available sources, such as global and local scientific literature, and then periodically assessing this information and notifying authorities when needed. To do so, essential processes need to be set-up for data collection, data analysis and action determination. These include Adverse Drug Reaction (ADR) collection, periodic review of literature and limited signal detection to name a few examples.
  2. Propose prospective mitigation of asset’s risks. Your asset’s baseline safety profile has been determined during controlled clinical trials in a subset of the population. These results are used to outline not only the asset’s benefits but also associated risks. In the post-marketing setting, consideration is given to a more diverse patient population and treatment settings. As such, there might be long-term effects and less common risks to be still characterized within a larger exposed group. Additionally, such factors might negatively influence the benefit-risk balance with increasing potential for administration errors, off-label use, abuse, misuse and overdose when the product is prescribed or administered to a wider population. Routine risk mitigation described in the product information and the prescribing status might not be sufficient to address the asset’s risks. In such scenarios, the company should propose additional strategies for mitigation of the risks, such as educational material or prescriber checklist, to enable the asset’s benefits to outweigh its risks.

Other tasks to consider when preparing for License application submission, i.e. Marketing Authorization Application (MAA), in European Union.

Besides a requirement for Marketing Authorization Applicants to have a legal entity established in the EU, EU law introduces one of the strictest expectations for a PV system. Thus, extra considerations and planning are needed to meet these expectations. ​Teams must consider four additional tasks, enabling compliance with European requirements:

  • Describe the PV system being developed in the Pharmacovigilance System Master File (PSMF) and prepare a Summary of PV System (SPS). The PSMF is submitted to the authorities upon request only. However, the submission dossier must contain the PV System Summary, essentially declaring that the EU requirements have been met.
  • Describe the Risk Management System being proposed for an asset in the EU Risk Management Plan (RMP). The European Medicines Agency (EMA) has published the template which should be followed and includes. The RMP must be included in the submission dossier as well as the Summary of Product Characteristics (SmPC).
  • Appoint an EU Qualified Person for Pharmacovigilance (QPPV) and deputy. The QPPV has a key role in establishing and maintaining your PV System and overseeing the product safety profile. Review and approval of RMP and PSMF/SPS by QPPV is mandatory.
  • Register your company, PSMF location and EU QPPV in the EudraVigilance (EV). During MAA evaluation, EV registration allows ICSR submission of foreign serious cases (where the product is already marketed). The EU country where your PSMF location is registered, will be the supervisory authority for your EU PV System, from which GVP Inspections can be performed.

In terms of ex-EU countries and regions, such as United Kingdom (UK), some accept similar documents to those in the EU MAA dossier, such as the EU RMP, or mimic EU requirements such as the concept of the QPPV, PSMF and RMP. This will ease document preparation for such regions but requires global coordination to ensure adequate consistency via change management. While the license application process is complicated, this level of due diligence is essential for safe pharmaceuticals. Thorough planning and preparation will ensure that your company is prepared to meet the many requirements of this process.

Syneos Health has made patient safety a critical component in the acceleration of biopharmaceutical therapies. If you want to understand how we work to keep patients safe throughout the lifecycle of a product with both standalone and integrated services, get in touch with our safety and pharmacovigilance teams.


Miroslava Matikova
EU Qualified Person for Pharmacovigilance
Syneos Health

Fanny Provost
Principal Qualified Person for Pharmacovigilance Office Specialist
Syneos Health

Zeshan Iqbal
Director Safety & Pharmacovigilance
Syneos Health

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