The Windsor Framework introduced new regulations in the UK from 01 January 2025, specifically for the above situation in Northern Ireland for product licensing, labelling, and supply. The MHRA can approve and license medicines in the entire UK (England, Scotland, Wales and NI) and ensure that the same packs of medicines can be supplied throughout. The disapplication of the EU FMD safety features for medicinal products that are authorized and commercialized in NI—as was already the case in Great Britain—is also highlighted [21].

Key Provisions of Windsor Framework

The implementation of Windsor Framework is governed by its numerous provisions which can aid a stakeholder in adapting to the new regulatory requirements. The action for stakeholders is as below:

Licensing

The MHRA authorises all new formulations and medicines that were regulated (Pre-Brexit) under the EU Centrally Authorised Procedure (CAP) for the UK market which are in line with the current definitions of medicines available in UK law.

Category 1: Products such as biotech-derived products, Advanced Therapy Medicinal Products (ATMPs), Orphan Medicines, and New Active Substances are authorised by MHRA based solely on UK law.

Category 2: Products such as Generics, hybrids, biosimilars and products not included in centralised procedure are authorised by MHRA based on either the UK or EU law as applicable.

All PLGBs will be converted into UK-wide licenses and if any MAs hold both PLGB and PLNI, they must withdraw the PLNI immediately.

Northern Ireland Licensing: A NI-only license can be used for UK-wide applications if the MAH is based in NI, called the Unfettered Access Procedure [22].

Parallel Import Licenses (PLPI): Some MAHs who marketed their products in both GB and Europe, possessed Parallel Import Licenses, which allowed MAHs to distribute in the GB while maintaining the same inventory for GB and EU (including NI). These packs will have to possess a ‘UK Only’ statement with a separate inventory for the UK and cannot re-enter the EU market. The GB-only PLPIs will also be changed to UK-wide and distributed including in Northern Ireland [23].

QP Batch Release of Licensed Products

QP personnel must be UK residents, (including in NI) for UK-wide distribution of products. If the QP is based in the EU, then a Responsible Person for Import has to certify that the FMD features on the packs are not registered in EU repositories. Assurance of ‘UK Only’ stickering on all packs entering the UK, effective immediately in GB is mandatory [14].

Authorisation and QP Release of Investigational Medicinal Products

Historically, the markets of Cyprus, Ireland, Malta and Northern Ireland have been dependent on Great Britain for medicinal product supply. The operators of these markets require the manufacturers to have, permanently and continuously, at least one qualified person in the EU or Northern Ireland. The additional burden is now resolved concerning Northern Ireland with the Windsor framework implementation, as all packs available in Great Britain can have easier access to Northern Ireland with the same Qualified personnel for both GB and NI [24].

Paradigm Shift in Northern Ireland

The framework includes a mechanism known as the “Stormont brake” that would enable the NI assembly to temporarily prevent any EU regulations from being imposed in NI, if it appears that the practices are too different and such regulations are hindering NI’s independence from the EU. The Windsor Framework procedure is complicated in nature. In practice, cooperation between regulatory authorities is a more favourable route to ease the travel of goods into Northern Ireland, which in turn will improve the relations between MHRA and EMA [25].

Protection of the EU’s Single Market

The Windsor Framework has also been designed to protect the integrity of the EU’s single market, to which NI will have unique access. The markets of Cyprus, Malta and Ireland are greatly dependent on Great Britain via Northern Ireland. The changing regulation in NI if unmonitored will affect the supply of products that are being supplied via NI. Hence, post implementation of Windsor Framework, products that are entering the EU via NI from Great Britain/other countries will also be scrutinized in customs unless specified as ‘not at risk’ by the EU Joint Committee. Similarly, the Windsor Framework’s complete application and implementation in NI is solely the responsibility of UK authorities acting in NI and not the responsibility of its neighboring European states. This preserves the integrity of the EU’s single market for goods, as well as protecting of public health from counterfeiting, fraud and trafficking [26].

Labelling Requirements

Any pack (excluding the packs being exported from UK) that is to be shipped within the UK from 01 January 2025, must possess a ‘UK Only’ statement and notify MHRA of packaging changes. The inclusion of ‘UK Only’ can be done either by stickering (until 30 June, 2025) or pre-printed on outer cartons [5].

Notification and Approval Process: The updated mock-ups must comply with the MHRA’s Regulation 267 of the Human Medicines Regulations. MHRA has to be notified by any of the following submission routes by 31 December, 2024:

Any regulatory opportunity: As part of another regulatory procedure (such as Type IA variation).

Self—certification: Up to 25 licenses can be self-certified in bulk by submission of mock-ups of products.

Self—certification without initial electronic Common Technical Document (eCTD) submissions: Self- certification process can be followed by the updating eCTD sequence. The sequence should be updated within 31 December, 2025 after initial self-certification [27].

Joint EU/UK Packs: The Joint EU/UK packs cannot be released into the UK market from 01 January, 2025. However, existing packs in the market can be sold until their expiry date. Any content relevant to EU market must be removed from the cartons, and a common inventory can be maintained for leaflets and foil [5].

Removal of the EU Falsified Medicines Directive (FMD)

As of 01 January 2025, NI will come under the MHRA, so any packs that are coming into the UK will not require FMD features as it is a requirement of EMA. The safety regulations which are covered by UK law, such as inclusion of the batch number, expiration date and other packaging requirements, remain unmodified. However, inclusion of a 2D Barcode (which meets the global ISO/IEC standards) can still be continued if not uploaded to any European repository system. The anti-tamper packaging feature will be encouraged [5].

Supply Route—Green and Red Lane System

The Windsor Framework has created a streamlined UK internal market scheme, also known as the ‘green lane’, for goods remaining in the UK (trade between GB and NI). Goods that are at risk of entering EU single market (e.g.: Ireland) must pass through red lane, which includes comprehensive checks and controls. The new approach is based on data sharing, labelling of selected items and monitoring so that the single market in EU is protected and a uniform supply is maintained throughout the UK-wide [28].

The Northern Ireland MHRA Authorised Route (NIMAR)

The Windsor Framework will not have an impact on NIMAR’s ability to operate and support the importation of pharmaceuticals into NI. From 01 January 2025, upon commencement of the Windsor Framework, it is estimated that NIMAR will no longer be required to support the supply of medicines to NI as a Green Lane is established for the trade of goods between the UK and NI, However it is still effective in cases of any product shortage or unavailability of NI compliant pack [29].

Advertising and Promotion of Products

The advertising and promotion of products will be monitored by MHRA as per the Blue Guide across the entire UK.

Using the same advertisement for both UK and EU is advised to be avoided. However, the UK-audience should not be misled and the material has to be compliant with UK Summary of Product Characteristics (SPC) and should fulfill Part 14 of Human Medicines Regulations. The MHRA looks into any complaints such that no materials that are misleading, and those which fail to comply with UK’s legal requirements are withdrawn immediately. Complaints can be made as per the Blue Guide of MHRA [27, 30].

Pharmacovigilance

All MAHs, irrespective of license category, must send all UK-wide ICSRs and serious non-UK ICSRs that comply with the reporting requirements of MHRA from 01 January, 2025.

Qualified Person for Pharmacovigilance (QPPV): It is mandatory to have a QPPV in UK, if he/she is established in the EU, then a National Contact Person (NCP) must be appointed in UK [31].

Pharmacovigilance System Master File (PSMF): It must comply with MHRA and follow the UK submission metrics.

Category 2: PSUR submission is not mandatory to MHRA, if available in EMA repository systems. However, ICSRs have to be submitted to MHRA.

QPPV: A QPPV for both EU and UK are necessary. However, if a QPPV has already been appointed in the EU, MAH can appoint a National Contact Person (NCP) for UK.

PSMF: For a product registered in MHRA, PSMF must comply with MHRA metrics primarily. However, in cases of ambiguity MAHs can also refer to EMA regulations [31].

Pediatric Requirement

The Pediatric Applications for medicines that transferred from the EU to UK on 01 January 2025, will also be affected if they are still under registration. Pediatric Investigational Plans (PIPs) are a mandatory requirement for new marketing authorisation applications in the UK. Any product whose PIP/waiver opinion is available at the EMA will be acknowledged by MHRA for the authorisation of products. However, variations are to be filed wherever applicable based on the UK’s PIP requirements. PIPs under Category 1 products will be governed by UK law, while those under Category 2 by UK law or EU law as applicable [22, 32].

Variation

The products authorised under CAP will not be applicable from 01 January, 2025, in NI. The variations pending in these products along with any transfer of MAs to MHRA will have to be applied again in MHRA as applicable. The pending variation in PLGB applications will be automatically applicable UK-wide. Previously, if the product was authorised by the EMA in NI, the goods required a variation to be filled in MHRA, to secure the Unfettered access route, which will no longer be required [33].

The descriptive analysis of actions required from a Stakeholder to market in UK is provided in Fig. 1.

Figure 1

Action for Stakeholders on Windsor Framework Implementation.

The Evaluation of Windsor Framework

The implementation of Windsor Framework in NI is outlined using 2 aspects, Pre-implementation i.e., the scenario until 31 December, 2024 and the Post-implementation changes which has commenced from 01 January 2025, as referred in Table 1.

Table 1 Comparative Study of Windsor Framework Implementation in Northern Ireland (NI).