There is an inherent challenge in bringing Pharmacovigilance expertise into the development phase of medicinal products for the first time, especially for small pharmaceutical companies. Even in some large organizations, the weight of the established practices has resulted in a dichotomy between safety management in the pre-marketing and in the post-marketing phase, with many negative impacts. The terminology that is used tells a lot about the existing mindset: many companies still refer to Drug Safety for pre-marketing activities, and Pharmacovigilance for post-marketing activities, while these terms are synonymous. There is in fact an unbreakable continuum of safety expertise between all phases of a product development from pre to post-marketing; both require having dedicated Pharmacovigilance (or Drug Safety) experts.
There are several drivers for this challenge:
Focusing on patient safety is
a core value of the Health Care Professionals part of the Clinical Research team. All individuals contributing to the design and execution of the clinical program are very attentive to patient safety. Often, these teams do not see the immediate added value of bringing PV representatives into the development strategy and activities. There is a deep feeling of caring enough and knowing enough about patient safety without bringing PV onboard.
Bringing PV into the product development activities may challenge the responsibilities of the clinical development team. It is not always easy to share the ownership of patient safety with newcomers in the group, or with PV responsibles who have not had the time yet to demonstrate their expertise and the added value they can bring to the group.
Small organizations are built based on lean models, and PV is usually not at the top of the list of building blocks for a starting company in the development phase. The focus will instead be on insourced or outsourced HR, Finance, Legal, Quality, Clinical and Preclinical Research, Medical Affairs and Vendor Management resources, for example.
These are several key arguments in favor of bringing PV into the drug development phase:
Theoretically, there is a potential conflict of interest for a clinical researcher to care at the same time, with the same attention and without bias, to efficacy and safety. All Clinical development individuals have a genuine vested interest in the success of their programs and an overwhelming majority avoid this potential conflict without difficulties. In rare circumstances, the passion and drive to develop products that save lives and cure severe diseases can influence how the world of data is seen and interpreted. An external contribution from PV experts might prove useful to ensure an unbiased view on a safety risk in these exceptional situations.
The world of drug safety has become very complicated and subtle, requiring highly specialized expertise to manage. Pharmacovigilance is not anymore about reporting individual cases or aggregate reports. It is about establishing ongoing processes to monitor an always evolving benefit/risk profile, with a well-established safety governance model across the enterprise, and a solid underlying process for signal detection and management.
Pharmacovigilance contributions are essential for the development or the review of key study documents and processes such as Protocol, Investigator’s Brochure, Core Development Safety Label, DSUR/IND reports, Study Management Plan, Study Management Team activities, Safety Signaling Plan, etc. In a very outsourced world, a good oversight of PV activities performed by vendors is always beneficial.
Bringing the PV team early into the development phase team will create a critical continuum of safety expertise on the company’s product, with positive impacts during its whole lifecycle. It will help establishing the best governance model for safety data interpretation, and maximize the compliance to complex regulations. A true partnership with shared ownership of patient safety across the company will facilitate the development program execution and best position the product for a very successful approval and launch.
JP Clement, MD
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