Brexit Update (again)
It had been hoped by all parties that the mechanism for the UK to leave the EU would be worked out by now as the UK is due to leave on March 29, 2019 – less than three months away. In fact, the situation is in chaos as the proposal made by the UK government and accepted by the EU was rejected by the UK Parliament. The remaining 27 EU countries don’t seem to be in any mood to reopen negotiations.
The main, but not the only stumbling block, is the border between Northern Ireland (UK) and the Republic of Ireland (Eire). But many other issues remain. Whether the UK will really leave in March with “no deal”, as it is called, remains to be seen. However, the EU has a habit of reaching final agreements at midnight before the deadline (metaphorically speaking); that is, a week or so before the deadline date. It is entirely possible that the UK exit will be suspended for 6 months or more and negotiations will continue.
I had planned to write about Brexit again after this was all done but it looks like that will not happen for a while. In addition, the situation with the EMA has also been further clarified.
Status
The EMA move to the new Netherlands office is underway. The definitive headquarters building is not yet ready in Amsterdam so the EMA is leaving London on 1 March 2019 and moving into a temporary building called the Spark Building in Amsterdam. From 4-8 March, the agency will operate using “extended teleworking.” The following week, 11-15 March, the staff will move in and the Spark Building should be up and running. The address of the temporary Spark building, near the mail rail station in Sloterdijk, is:
European Medicines Agency
Orlyplein 24
1043 DP Amsterdam, The Netherlands (NL)
Meetings and visits to the agency will be held there. This building is about ½ the size of the facilities at Canary Wharf so some logistical changes are being prepared.
The official address of the EMA will be the permanent building in the Zuidas business district of Amsterdam and it is expected to be ready in November 2019 is:
European Medicines Agency
Domenico Scarlattilaanlaan 6
1083 HS Amsterdam, The Netherlands
See here for information and maps on these locations including information where mail should be sent after 1 March (two addresses: one for regular mail and one for shipments that require signature). A page for asking questions online to the EMA is also provided. I could not find a new phone number yet. The one online is still the UK Canary Wharf number. Presumably, a new number will be provided before March.
As of the end of December, 2018 the EMA has estimated that 75% of the approximately 900 EMA employees will move to Amsterdam. About 67 have moved already. The biggest issue seems to be finding affordable housing and schools for the staff’s children.
The EMA has said that if 65% of the staff move, it would be largely able to maintain its drug approval and safety monitoring activities though some would be delayed. “Core activities” will be continued with minimal delay or interruption.
Meanwhile the situation in the UK is uglier. The EMA’s lease for the Canary Wharf buildings runs for 21 more years and would cost in rent some £500 million (€574 million, $654 million). Thus the EMA would be paying double rent till then as there seems to be no way to break the lease early. This is now being litigated in the UK courts.
Priorities
The EMA revised its activity list for 2019. There are four “themes” with priorities for 2019 that are noted. Here are some of the key functions with attention to DS and PV matters in italics:
1) Contributing to human health
- Supporting needs of children
- Enhancing ability to react rapidly to public health emergencies
- Minimize the risk of shortages of medications
- Reducing time to patient of novel medications
- “Supporting effective and efficient conduct of pharmacovigilance through product related support as regards planned access to and analysis of real-world data, and conducting planned surveillance using patient registries”
- Incorporate patients’ values and preferences in the review process
- Increase innovation with academia
- “Strengthening pharmacovigilance capability across the network in the fields of signal management and activities directly related to the EMA/HMA Big Data Task Force”
2) Animal Health
- See the document for this information
3) Optimizing operation of the network
- Reinforce the scientific and regulatory capacity and capability of the network
- Strive for operational excellence and effective communication
- Strengthen links with other agencies and stakeholders
4) Contributing to the global regulatory network
- Involving non-EU regulators in inspections of GCP/GMP compliance
- Facilitating effective information-sharing by using international electronic standards for product specific exchanges
- “Increasing product-related information-sharing between regulators responsible for the conduct of clinical trials/pharmacovigilance activities”
- Improving existing mechanisms for sharing/exchanging information with other regulators on products throughout their lifecycle
Various EMA duties and actions will be cut back or suspended temporarily. See guidance for the no Brexit deal scenario issued 4 January 2019.
- Some ICH activities will be cut back with EMA moving to observer status stopping their active participant status
- Most cutbacks and suspensions are only expected to last until 30 June 2019
- The workload of external (EU member state) health agencies has increased, as the EMA is moving some 370 human and veterinary medicines from the MHRA to other health agencies.
- Guideline generation activity is being restricted to urgent public health needs
- Certain non-product related Working Groups will be cut back or suspended till July 2019
- In 2017 the EMA estimated that with over 65% staff retention in Amsterdam it would take about 2-3 years to get back to full speed
The UK and MHRA
On the other side of the coin, the MHRA and the UK are dealing with issues that the MHRA move and Brexit are producing. Many of the preparations are being made as if Brexit will be a “no deal” exit.
- The MHRA is planning to convert (“grandfather”) existing Centrally Approved Marketing Authorisations (CAPs) into UK Marketing Authorisations before 29 March. The MHRA has already assigned product license numbers to these products. If products are not converted to UK marketing authorisations by 22 April 2019 they will no longer be allowed on the market in the UK
- New assessment routes for marketing applications will be put in place including a review of products already accepted by the EMA CHMP as well as an accelerated full assessment in 150 days
- A UK-based QPPV must be in place though a waiver till 2020 will let the EU QPPV function for the UK till then.
- Labeling must be amended by the end of 2021 to meet UK labeling standards for marketed products.
- For clinical trial safety reporting all SUSARs must be reported to the MHRA via UK based IT systems not via the EMA and EudraVigilance
- In regard to safety and PV, the MHRA will have oversight of all activities. All suspected ADRs from industry, PSURs, PASS, risk management plans etc. must be submitted to the MHRA for assessment
See this document for further information on orphan drugs, pediatric investigation plans, importing, fees (£890 for a PSUR assessment, £51,286 for a Pharmacovigilance Major Safety Review) and other issues.
Comment:
Although the EMA and MHRA are putting in high level plans on how the pharmaceutical world will work in the new environment, the devil will be, as always, in the details. And those details, even if proposed and put in place to some degree before March, will need to be worked out and fine-tuned after the EMA and MHRA start work in March. Some of these new proposals will not be put into place if Brexit is delayed, but the EMA is still in Amsterdam whether Brexit occurs or not or is postponed.
So pay close attention to what happens in the next several months. There will be big changes, particularly in the PV and regulatory world and they are not fully predictable now.
