As we have previously reported, under the Northern Ireland Protocol of the Withdrawal Agreement between the EU and UK, Northern Ireland (“NI”) has continued to follow the EU rules after the end of the transitional period. In contrast, Great Britain (“GB”) now has a freestanding independent regulatory regime. This means that there are two sets of rules that apply in the UK, and this has led to difficulties with medicines, and other products, moving from GB to NI (the route by which the majority of products reach the market in NI).
In December 2020, the European Commission published a notice that allowed certain flexibilities to be in place through 2021 to ensure there were no medicine shortages in NI (as well as other territories historically dependent on medicines supply through GB). As 2021 concluded, industry – and patients – had been concerned that no long-term solution had been found.
After protracted negotiations, on 17 December 2021, the European Commission put forward proposals to ensure the continued undisrupted supply of medicines from GB to NI. The proposals seek to ensure that patients in NI will have access to life-saving medicines at the same time as patients in the rest of the UK. These proposals also allow time to put in place long-term solutions for the supply of products to NI, and time for industry to adapt to future regulatory requirements and changes.
In parallel, legislation changes have been made in the UK, and the MHRA guidance has been, and is being, updated to reflect the proposals, although they are not yet formally adopted by the EU legislative bodies. Further, the MHRA has stated that there is a reporting obligation on industry to notify the MHRA if the flexibilities applicable to NI will not be used.
There are two parts to the EU package:
- the current grace period will be extended until the end of 2022 (although the MHRA’s position is that this date may be further extended if there is no agreement on the long-term legislative solution);
- legislative proposals amending EU medicines legislation which will be sent to the European Parliament and the Council for approval.
A summary of the key provisions mentioned in the second bullet point is set out below:
Marketing Authorisations (“MA”)
A large area of confusion for companies has been having separate MAs, granted under different regulatory regimes, in different parts of the UK. Linked to this is the relationship between these authorisations and those granted in the EU. To streamline the process, marketing authorisation holders (“MAH”) will be able to choose to apply for a UK-wide national MA in parallel with applications through the mutual recognition or decentralised procedures in the EU. This is likely to be an easier process for applicants than having separate NI and GB MAs. As part of this, it will be possible to use a single leaflet when supplying products in GB and NI and it will not be necessary to have separate packaging.
The MHRA encourages the application of UK-wide MAs. However, this is not possible where products fall under the mandatory scope of the EU centralised procedure or an EU-wide MA has been granted for the product. It will still be the case that centralised MAs will apply in NI, but not in GB, so there will still be situations where separate MAs apply across the UK. To assist with the potential discrepancy, in cases where MHRA grants an MA in advance of grant of the centralised MA, amendments are proposed to Regulation 726/2004 to permit MHRA to authorise the product to be supplied in NI for a bridging period of 6 months.
Under EU rules, batch testing must be conducted in the EU. For products moving from GB (not in the EU) to NI (operating under EU rules) this is not practical. Under the proposals, the batch testing of products for the NI market can be carried out in GB and does not need to be repeated in the EU, provided these products are:
- certified and released by a qualified person (“QP”) located in the EU, NI or GB applying the equivalent standards of quality as the EU; and
- the site of the batch testing is “regularly supervised”, i.e., that it is appropriately licensed and subject to inspection.
Similarly, no manufacturing authorisation or import licences are needed for medicines supplied from GB to NI. As such, medicinal products can continue to be supplied to NI by holders of a wholesale distribution authorisation located in GB provided that:
- products are licensed in NI;
- batches have been certified and released by a QP in EU or UK; and
- batches have undergone batch testing in the EU or UK, and, if QP certified in the EU, products have been imported into GB by the holder of a wholesale distribution authorisation under the supervision of a responsible person.
Such products may only be made available in NI, and are not for onward supply into the EU.
Location of key personnel
The MAH for the UK MA may be located in GB or EU for each of the authorisations that may be relevant in the UK (UK-wide, GB or NI). For applications made through the EMA centralised procedure (applicable in NI), the MAH must be located in the EU.
Under EU rules, the Qualified Person for Pharmacovigilance (“QPPV”) must be located in the EU. This caused difficulties for MAs granted for the NI market. The proposal states that where an application for a NI MA is made through the decentralised and mutual recognition procedures, the QPPV can be located in GB unless the MAH already has a QPPV established in the EU. The QPPV for UK nationally authorised products can reside and operate anywhere in the UK or the EU/EEA. Where the QPPV does not reside and operate in the UK, a national contact person for pharmacovigilance who resides and operates in the UK is required.
Similarly, the proposal states that the QP for manufacturing (batch certification and release) can be located in GB and a UK site of batch release can be nominated on applications for UK national MAs or MAs applicable in NI.
On 1 January 2022, new regulations 167A and 167B were introduced into the UK Human Medicines Regulations 2012. These set out an exemption to the requirement that all medicinal products must have a valid MA by permitting unlicensed supply of medicines to fulfil special patient needs. The new Northern Ireland MHRA Authorised Route (“NIMAR”) provides a route for the lawful supply of prescription only medicines that are unlicensed in NI (where the product is authorised in GB), where no licensed alternative that meets the patient’s needs is available in NI. The MHRA maintains a list of medicines that can be supplied through NIMAR. From 1 January 2022, the listed medicines may be dispatched from GB to NI on the basis of the medicine’s authorisation in GB.
The Falsified Medicines Directive (Directive 2011/62/EU) applies in NI, which means that safety features must be applied to products to be placed on the market in NI. Medicines with an MA valid in NI require a unique identifier (“UI”) and a tamper evident device on each pack. While there is no requirement to apply safety features to products licensed in GB only, MHRA encourages retention of an anti-tamper device.
When a medicinal product leaves the EU, which would include distribution in GB, the UI should be decommissioned, but a derogation has been in place. Under the proposal, the current derogation from the obligation to decommission UIs will continue to apply until 31 December 2024.
The MHRA provides guidance on the implementation of these safety features in the UK. Further discussions on the position from 31 December 2024 are ongoing, and MHRA and the Department of Health and Social Care are carrying out a consultation with industry on the future of the UK system.
Investigational Medicinal Products (“IMP”)
An IMP can continue to be supplied to NI from GB without any additional importation controls, meaning that sites in NI do not require an importation licence, provided that:
- the IMP has been QP certified in the EU/EEA or UK; and
- the IMP is only made available to clinical trial participants in NI (and not the rest of the EU).
QP certification performed in the EU/EEA is acceptable for the supply of IMP to GB, and to NI via GB, provided that an oversight process is in place and that the GB site holds an authorisation for importation of QP certified IMPs from a country on the approved country for import list.