4 Ways to Brexit-Proof your Pharmacovigilance System
With six months until the United Kingdom (UK) leaves the European Union (EU) and the threat of a ‘no deal’ growing, what will pharmacovigilance (PV) look like come 23:00:01 GMT on Friday 29th March and, most importantly, what should companies have in place to prepare for it?
Ever since Article 50 was triggered in March, last year, companies have been having to make a best guess as to what PV in the UK and EU may look like in the future. While both the European Medicines Agency (EMA) and Medicines and Healthcare products Regulatory Agency (MHRA) have released many a guidance and Q&A document, they have been very black and white regarding the UK as a ‘third-country’ following Brexit, which may well not be reflective of the kind of deal that the UK may end up with. For instance, whilst not binding on anyone, in July 2018 UK Parliament voted by 305-301 that the UK should remain part of the EMA, which suggests a desire (on one side at least) to maintain the status quo for the pharmaceutical industry.
As such, we may have situations as disparate as remaining part of the EMA, with nothing ultimately changing, to crashing out with no deal come next March with subsequent chaos and confusion. Most likely is some sort of withdrawal agreement being struck in the next couple of months and the cliff edge being avoided in favour of a gradual transition over an additional 21 months. However, with the mantra “hope for the best, prepare for the worst” running through our minds, what should PV departments make sure they have in place?
Here, we take a look at four key areas where contingency plans, if not already being worked on, should be urgently put in place. These are top level, relatively simple, areas to ensure compliance in the event of a cliff-edge. Where they lead further down the line, for example moving whole departments, is a much bigger strategic challenge.
1) Qualified Person for Pharmacovigilance (QPPV) and Deputy
As it stands, the position of QPPV must be fulfilled by someone residing within the European Economic Area (EEA) and the EMA has confirmed that this will also be the case for the deputy, in the event of Brexit [1]. As such once the UK leaves the EU QPPVs and their deputies will no longer be able to be based here. Furthermore, the MHRA has confirmed that a local UK QPPV would need be established on day one, although those without a current UK presence will have until the end of 2020 at the latest to do so [2]. Companies may choose to have the EU QPPV take on responsibility for UK MAs until the UK QPPV can be established.
With the potential for an extended transition period the need to transfer responsibility may not be necessary immediately but there should at least be a strategy in place for how the transfer will be managed. It is a particularly sensitive situation as some of the 140+ UK based QPPVs may find themselves without a position in the new structure. Even if a new role can be found for them, such as fulfilling the new requirement of local UK-QPPV, it would inevitably be a demotion from being responsible for PV across Europe.
As it is not 100% guaranteed that the QPPV won’t be able to be based in the UK, companies may not want to jump the gun and preemptively replace their most senior and experienced PV staff. Contingency plans will differ from company to company, depending on size and set-up, but some considerations may be:
- Utilising existing network of EEA based offices and local QPPVs. Already familiar with the product(s) and PV system, they should easily be able to step into the EU QPPV role with minimal disruption and at short notice.
- Directly hire an EEA based consultant who would be able to take on the QPPV role and spend the next six months training them on company products(s) and and PV system. If a withdrawal agreement is reached, and the QPPV can remain in the UK for at least an extra 21 months, the consultant can either be released or their newly acquired knowledge of the company can be utilised to help with the longer-term strategic planning for the position. There may be significant recruiting effort in this position identifying a suitably qualified candidate willing to take up such an insecure contract.
- Engage a service provider to guarantee the provision of an EEA based QPPV in the event it is needed at short notice. This takes the headache out of identifying a candidate, ensures continued compliance and is also likely to be able to scale to other PV activities as needed. However, it is likely to come at significant cost.
Smaller companies may need to think especially hard about the best approach to take and the impact on their 2019 budgets. Engaging consultants or services providers may be costly in the short term and the potential for needing a new local UK QPPV in the long term is another senior headcount to take account of.
Any MAHs currently using service providers should conduct their own due diligence that their QPPV plan is robust and will meet MAH requirements. If your QPPV is currently based in the UK, request details of who your new EEA based QPPV will be early and that you are happy with their experience and qualifications. Also check how many EEA based QPPVs the service provider has and how many PV systems that your new QPPV will be overseeing. You don’t want to find out later that one person has been given more QPPV positions than they could possibly manage because the service provider themselves didn’t have robust enough contingency plans and staffing levels.
One final note, whatever your plans and changes in QPPV, make sure details are updated in Article 57 database!
2) Pharmacovigilance System Master File (PSMF) Location
Again, the EMA’s current position is that the PSMF will continue to need to be located in the EEA [1], either at the site where the main PV activities are performed or at the site where the QPPV operates. Where the PSMF is held in electronic form, the location stated must be a site where the data stored can be directly accessed, and this is sufficient in terms of a practical electronic location [3].
The simplest approach is to amend the location of the PSMF to the office your new EU QPPV is based at, or that of the PV service provider.
As with the details of the new QPPV, ensure the Article 57 database is populated with the new location.
3) Eudravigilance
For MAHs, the QPPV should remain as the organisation’s representative in Eudravigilance. Therefore, MAHs using Eudravigilance should ensure these details are amended if the QPPV is changing.
If the old QPPV was the only holder of EudraVigilance Individual Case Safety Report (ISCR) and/or EudraVigilance eXtended Medicinal Product Dictionary (XEVMPD) knowledge evaluation certificates and will be leaving the company, make sure that the new QPPV holds these certificates, or someone else within the department has been trained in advance of the switch. There are limited numbers of ICSR knowledge evaluation courses being run between now and next March so this is something that should be booked as a matter of urgency, if it will be needed.
4) Regulatory Submissions
Regulatory submissions to the EMA should continue as usual following Brexit. For example, ICSRs should still be submitted via Eudravigilance, periodic safety update reports (PSURs) via the PSUR repository and, as previously mention, QPPV and PSMF data via the Article 57 database.
But what of submissions to the MHRA, which may lose all access to these systems from 29th March 2019? The MHRA has confirmed that those documents would now also need to be submitted directly to it [4]. In order to facilitate this the MHRA have also stated that:
“We would have our own processes and systems to manage UK human medicines and devices regulatory activities. To do this, some new systems are being developed for March 2019.”
With this very vague description of what to expect, coupled with the inevitable complexities and overruns of any information technology (IT) project, it is very difficult to know what to put in place to prepare for this. With more details expected by the end of the year, there may be fewer than three months for MAHs to react to the new systems and put in place processes for using them. However, MHRA’s existing eSUSAR tool, for small and non-commercial sponsors to submit Suspected Unexpected Serious Adverse Reactions (SUSARs) from clinical trials, is a very simple and user-friendly system and suggests that the MHRA can be adept at not over complicating things.
At the very least additional PV and IT resource should be factored in for the first half of 2019, to test and implement processes to allow used of the new system(s). Furthermore, the need for regulatory submissions to another authority, especially ISCRs, would call for an increase in PV headcount (or process efficiency) to compensate for the extra time needed. How much headcount won’t become clearer until the new systems are unveiled and we’ve had a chance to see how quickly submissions can be made on them.
These are just four compliance issues which should have contingency plans in place, in the event of a cliff-edge Brexit on 29th March 2019. There are clearly lots of strategic and commercial issues for companies to consider, that might have long-term repercussions for the location and make-up of PV departments in the EU and UK. However, maintaining PV compliance is imperative while the dust settles and the future becomes clearer for the whole industry.
Drive Phase PV is a pharmacovigilance consultancy and provider of pharmacovigilance services, supporting patient safety throughout the life-cycle of our clients' products. Contact us to discuss Brexit planning for you PV system. Whether via re-configuring your PV system or delivery of EEA based QPPVs, we deliver a tailored packaged to seamlessly fit to your company structure and strategy.