Pharmacovigilance Through Mergers and Acquisitions

PHARMACOVIGILANCE THROUGH MERGERS AND ACQUISITIONS

By Tom Nichols

Mergers and acquisitions (M&A) are an everyday part of the pharmaceutical industry. Whether it involves acquisitions of companies (complete or partial) with the integration of departments, or ‘just’ the sale of assets, M&As are something that we will all have to deal with at some point in our careers. There is no one-size-fits-all approach to pharmacovigilance (PV) during M&A activities, and they are mainly driven by the wider commercial approach being taken by the companies involved. This article looks at some of the key considerations involved.

Such is the ubiquity of M&A, Good Vigilance Practice (GvP) Module I ‘Pharmacovigilance systems and their quality systems’ specifically mentions it: “When a marketing authorisation holder intends to expand its product portfolio, for example, by acquisition of another company or by purchasing individual products from another marketing authorisation holder, the QPPV should be notified as early as possible in the due diligence process in order that the potential impact on the pharmacovigilance system can be assessed and the system be adapted accordingly. The QPPV may also have a role in determining what pharmacovigilance data should be requested from the other company, either pre- or postacquisition. In this situation, the QPPV should be made aware of the sections of the contractual arrangements that relate to responsibilities for pharmacovigilance activities and safety data exchange and have the authority to request amendments.”1 The FDA also recognise it as an area that should not detract from the successful completion of PV activities: “When inspecting firms undergoing corporate transitions, determine that written procedures have been appropriately updated to ensure that the surveillance, receipt, evaluation, and reporting of PADEs remains in a state of compliance.”2 Although there is this regulatory requirement to be involved as soon as possible in the due diligence process, in reality this often doesn’t happen, and PV departments are having to fight reactively. The key words here I think are the QPPV having the “authority to request amendments” to the contracts and safety data exchange agreements (SDEAs). This shouldn’t just be dropped on PV departments and expect them to pick up the pieces. However, the best way to avoid this happening is to proactively foster relationships with the wider business and senior decision makers, so everyone is aware of this in advance. Much more difficult to try and amend things after the event, even if you are given authority by your company. While this article will focus on some of the practical considerations involved in M&A, changing a PV system is not just a series of faceless processes and systems being updated. The human aspect is, if anything, more important. Even though processes and systems are drummed into us, I have never seen a PV system that doesn’t also lean on human knowledge. Even down to the mundane “where can I find this document?”. The PV changes can be sold to people as development opportunities, but it’s very difficult to come up with the advantages of potential redundancies or having to relocate. Even the importance of development opportunities can take a bit of time and distance to understand and appreciate, as I can personally attest. It is vital to manage engagement and communication throughout, as both key messages and staff moral can be undermined without it. Differences in view between ‘the company’ and staff on the ground can often not be more different. It is also important to be aware of differences in work culture and employment rights around the world (for example, between the EU and US), so attitudes may be quite divergent. The following table provides just a few, high level, key considerations for when you approach any merger or acquisition. For all these, you must remember that PV does not work in isolation. Liaison with regulatory is essential for Eudravigilance updates and with Legal

for safety data exchange agreements (SDEA) etc. Consideration also needs to be given to resourcing and the extent to which there is the internal expertise to manage the various strands of the project. It may be possible to deliver certain elements in-house but have to bring in external expertise for others. It is as important to know what you don’t know in these situations, as it is to know what you know!

Strategy

Timelines It’s very easy, and common, for ‘strategy’ to be thrown around as a necessary buzz word without actually doing what it is meant to do. It needs to be decided in advance and inform every other decision that is made. It’s not getting stuck in the detail of ‘how’ but it’s a picture of where you want to get to. “We’re going to integrate PV” is not a strategy. “We are going to centralise global PV activities, while retaining affiliate expertise to fulfil local obligations” is. Different companies’ PV departments will have different working relationships with other departments and some may have been hard won. The strategy should guide you but not be restrictive to the point of ending up with a poorer PV system. For example, you may want everything to be subsumed into Company A’s system but find that Company B has an objectively better way of working with their regulatory team. Rather than throw the baby out with the bathwater, can you roll that way of working out across the new organisation? Timelines are very rarely exclusively driven by PV. The sooner the PV team is involved in the process then the more realistic the timelines can be.

Business Continuity

It is essential to ensure business continuity and maintain patient safety standards throughout the integration. Consider what regulatory activities are due during the transition period. For instance, do PBRER requirements lead to a prioritisation of certain actives being migrated in the database first, or left until last as manual production minimises risk? Safety Database The future use and the integration of different databases must be considered. • Future case processing strategy and structure (i.e. central processing vs affiliate processing) • Migrations: • Duplicates • Configurations • Data structure (i.e. different databases, R2 vs R3) • Conventions • Training • Archiving • Audit trails

Safety Data Exchange Agreements

SDEAs are difficult to manage, especially in big companies. A poll on a previous webinar suggested that both legal and PV manage contracts (i.e. not a single repository of information), so this can immediately lead to confusion over amendments and changing requirements. For example, there may be different formats and requirements depending on age, which involved party’s template was used etc. Eudravigilance Updates to EXtended EudraVigilance Medicinal Product Dictionary (XEVMPD) entries, following licence transfers, and changes in Eudravigilance company IDs or Gateway settings need to be considered before activities can be safely and successfully transferred.

Pharmacovigilance System Master File (PSMF) The PSMF will feed from the overall strategy, but how will multiple PV systems be maintained, in the short-term at least? Does a cut-over to a single, integrated, PSMF need to be rapidly developed? It’s a general good tip to not lose sight of existing open CAPAs ,or forget historical instances, when bringing new products or companies on board.

References

1 Good Vigilance Practice (GvP) Module I ‘Pharmacovigilance systems and their quality systems’ 2 FDA CHAPTER 53 - Postmarketing Surveillance and Epidemiology:

Human Drug and Therapeutic Biological Products

Tom NIchols

PIPA President