The Trade and Cooperation Agreement and its impact on IP, Pharma and Medical Devices

The final Brexit agreement, the Trade and Cooperation Agreement (the “TCA”) was agreed between the UK and the EU on 24 December 2020. Within this agreement are provisions that set out the standards expected to be recognised (mutually) between the EU and the UK in relation to intellectual property (including SPCs and trade secrets). There are some provisions concerning pharmaceutical regulation and product standards, but overall there is a lack of mutual recognition, with the consequence that, for both pharmaceuticals and medical devices, there are now effectively two separate regimes for the EU and the UK.

Intellectual Property

The provisions on IP match or exceed those for IP set out in the various treaties to which the UK and EU have acceded (such as WIPO, WTO and TRIPS agreements).  These IP standards are to be maintained as a minimum. The cited objectives and scope in relation to intellectual property (see Title V) indicate the aims behind these provisions which are to:

(a) facilitate the production, provision and commercialisation of innovative and creative products and services between [the UK and the EU] by reducing distortions and impediments to such trade, thereby contributing to a more sustainable and inclusive economy; and

(b) ensure an adequate and effective level of protection and enforcement of intellectual property rights.

The provisions are intended to “complement and further specify the rights and obligations of each [of the UK and the EU] under the TRIPS Agreement and other international treaties in the field of intellectual property to which they are parties” and do not “preclude either [the UK or the EU] from introducing more extensive protection and enforcement of intellectual property rights than required under [this section of the TCA] provided that such protection and enforcement does not contravene [those provisions]”. However, there are aspects of current UK and EU IP law, such as the dilution provisions in trade mark law, to which the agreement does not refer, instead referring to the Paris Convention provisions on the protection of well known marks. Whether this will be a point of future divergence remains to be seen.

Both the UK and the EU also have the ability to develop their own exhaustion regimes. The provisions on geographical indications (“GIs”) indicate that a mutual future scheme has not be agreed although a review clause on GIs has, which provides that the UK and EU may (if both parties agree it is in their interests) use reasonable endeavours to agree rules for the protection and domestic enforcement of their GIs.

The UK Government’s Summary document that accompanies the TCA (see here) states that the agreement “includes mechanisms for cooperation and exchange of information on IP issues of mutual interest” and “retains regulatory flexibility for each [of the UK and the EU], enabling the UK to develop an IP system in line with [its] domestic priorities“, thus enabling the UK to diverge where it so requires.

We have already commented on the changes to the UK IP regime in the firm’s guide to Brexit here (see the IP section).

The Regulation of Medical Devices and Medicinal Products

Medical devices: The TCA has a chapter (4) (under Trade – Title I) on eliminating unnecessary technical barriers to trade which deals with conformity of standards. However, this only provides for an approach under which each party can agree that its standards bodies (including those relating to medical devices) will conform with international standards and will work together to influence those and to “foster bilateral cooperation with the standardising bodies of the other Party“.

For medical devices, it had been hoped that there would be at least mutual recognition of conformity assessment under which each of the EU and the UK would recognise the other’s certification bodies. However, as things stand, although Great Britain will continue to accept CE marked medical devices until 30 June 2023 those devices certified by the UK and marked as UKCA (standing for UK Conformity Assessed, as discussed in more detail in our post here), will not mutually recognised by the EU.

Medicinal Products: For medicinal products there is a dedicated annex in the TCA, Annex TBT-2 – Medicinal Products (the “Medicinal Products Annex”), which applies to all medicinal products listed in its Annex C, namely:

  • marketed medicinal products for human or veterinary use, including marketed biological and immunological products for human and veterinary use,
  • advanced therapy medicinal products,
  • active pharmaceutical ingredients for human or veterinary use,
  • investigational medicinal products,

with this list being subject to amended by the UK-EU Partnership Council (the main governing body for the agreement and supplementing agreements).

The aim of the Medicinal Product Annex is to “facilitate availability of medicines, promote public health and protect high levels of consumer and environmental protection in respect of medicinal products”.  To help achieve this aim, the Annex provides for:

  • the mutual recognition of Good Manufacturing Practice (“GMP”) inspections and certificates, meaning that manufacturing facilities do not need to undergo separate UK and EU inspections;
  • the individual inspection, on notice, by the EU or UK of each other’s facilities); and
  • for the suspension of the mutual recognition arrangements.

Further, the TCA also states that the EU and the UK should work together to implement agreed international guidelines and that any changes to either the UK or the EU’s regulation regime should be on 60 days’ notice and be subject to discussion by a Working Group on Medicinal Products, which will be established to enable mutual consultation. This Working Group on Medicinal Products will be under supervision of the Trade Specialised Committee on Technical Barriers to Trade, and will monitor and review implementation and ensure the proper functioning of the Medicinal Products Annex. It is noteworthy that the Medicinal Products Annex is specifically excluded from the TCA’s disputes mechanism, however, through its role in facilitating discussions and functioning as an appropriate forum for issues relating to Medicinal Products, it is hoped that it will be a sufficient mechanism to deal with any concerns.

When considering the confidentiality of information supporting applications for marketing authorisations (“MAs”), regulatory protection of pharmaceutical products, and Supplementary Protection Certificates (“SPC”) it is noteworthy that this is not included in the Medicinal Products Annex, but is included in the IP section (Title V) of the TCA.

  • In relation to regulatory data protection generally, the TCA requires that both the UK and the EU ensure that commercially confidential information submitted to obtain an MA is protected against disclosure to third parties, unless there is an overriding public interest or steps are taken to ensure the data is protected from unfair commercial use.
  • For the regulatory protections of data and market exclusivity, the TCA provides that, subject to any international agreement to which both the EU and the UK are party, and without prejudice to any additional periods of protection which either party may wish to provide for in its domestic law, these regulatory protections will be “for a limited period of time to be determined by domestic law”. This allows each of the UK and the EU to determine the length of such regulatory exclusivities under their own regulatory regimes.
  • For SPCs, the TCA records the agreement of both the UK and the EU to provide for further patent protection to compensate for the impact of regulatory administrative procedures but, again, the length of time is not stipulated.

The effect of these provisions is that they provide some comfort that these valuable forms of protection for medicinal products will be maintained by both the UK and the EU.

For detailed commentary on the new regulatory position for Pharma in the UK, and the impact on IP rights generally, see our series of posts on the HSF Intellectual Property Notes blog here.

Other provisions relevant to the pharmaceutical and medical device industry

The TCA also has provisions relating to the UK’s continued participation in EU programmes and on UK / EU cooperation on “serious cross-border threat[s] to health that are relevant for the pharmaceutical industry.

  • Subject to the UK making financial contributions, Part 5 of the TCA includes agreement on the UK’s continued participation in EU programmes, including the EU’s research and innovation funding programme, Horizon Europe.
  • UK / EU cooperation on serious cross-border threat[s] to health is covered by the TCA including agreement between the UK and the EU on emergency relief in relation to importation requirements, tax and road transport exemptions, and agreement to cooperate in relation to international health security systems.

Future developments

Although tariff free and quota-free trade has been agreed, there is little mutual recognition of regulatory provisions. This may not be the end of negotiations, with automatic reviews every 5 years written into the TCA and termination possible on 12 months’ notice.  See the HSF Brexit blog for further information, and our initial comments here.

Key contacts and authors

Jonathan Turnbull

Jonathan Turnbull
Partner, London
+44 20 7466 2174

Rachel Montagnon

Rachel Montagnon
Professional Support Consultant, London
+44 20 7466 2217

George McCubbin

George McCubbin
Senior Associate, London
+44 20 7466 2764

Priyanka Madan

Priyanka Madan
Associate - London
+44 20 7466 2986

Paediatric medicines in the post-Brexit world

Paediatric Investigation Plans

The legal requirements for UK Paediatric Investigation Plans (PIPs) from 1 January 2021 are set out in the Human Medicines Regulations 2012, as amended by the Human Medicines Regulations (Amendment etc.) (EU Exit) Regulations 2019.

Under the Human Medicines Regulations, results from an agreed PIP must be included in an application for UK marketing authorisation (MA) for a UK application for a relevant medicinal product which is an initial marketing authorisation for the purposes of a global marketing authorisation, or an application for a new indication, new pharmaceutical form or new route of administration in relation to a product which is already subject to an existing UK MA. Continue reading

Clinical trials in the post-Brexit world

Once the UK leaves the EU, it will cease to participate in the European regulatory network for clinical trials, and regulatory responsibilities would shift to the MHRA. The UK government guidance Registration of clinical trials for investigational medicinal products and publication of summary results from 1 January 2021 (1 September 2020) and Guidance on substantial amendments to a clinical trial from 1 January 2021 (1 September 2020) set out the latest position in relation to clinical trials after the transition period ends.

This latest guidance does not address the status of existing approvals for clinical trials (both regulatory and ethics), or whether the UK will seek to align with the EU Clinical Trials Regulation. It is anticipated that further guidance on the requirements of registration and reporting of trials will be to come.

The latest guidance addresses requirements for the sponsor and legal representative for a clinical trial. After the transition period ends, the UK will require the sponsor or legal representative of a clinical trial to be in the UK or country on an approved country list (this will initially include the EU/EEA countries). For ongoing trials, the UK will accept a sponsor or legal representative established in the EU/EEA, and no amendment submission to the MHRA will be required.  Where the sponsor is from the rest of the world, and the legal representative is established in the UK and there are sites elsewhere in the EU/EEA, the sponsor will need to assign an EU/EEA legal representative for these EU/EEA sites.

Transparency provisions are also clarified in the latest guidance. From 1 January 2021, those running trials should continue to use existing and established international registers such as ISRCTN registry (UK) or ClinicalTrials.gov (USA). Trials that involve both UK and EU sites, there will be a record in the EU Clinical Trials Register (other than for adult Phase 1 studies). In the UK, a favourable opinion given by a research ethics committee is subject to the clinical trial being registered. The UK will continue to make information UK trials publicly available via the Health Research Authority website and the UK “Be Part of Research” website. A summary of results for UK trials must be published on the public registers where the clinical trial is registered within 6 months of the end of trial (paediatric clinical trials) or within one year of the end of trial (non-paediatric clinical trials). Confirmation that the summary of results has been published should be emailed to the MHRA. The same timeframes apply to the submission of a final report to the Research Ethics Committee of the Health Research Authority.

Importers of Investigational Medicinal Products (IMP) to a UK clinical trial site will require a Manufacturers Licence (MIA). Sponsors will have up to 1 year after the end of the transition period to submit a substantial amendment to the MHRA to include the details of the MIA holder performing the “supply chain oversight” role. No substantial amendment is required if the sponsor retains an existing IMP release site in the UK for an ongoing UK trial but includes an additional EU/EEA site for trials in the EU/EEA only.

 

For more of our Brexit coverage click here.

Julie Chiu

Julie Chiu
Senior Associate (Australia), London
+44 20 7466 2658

Jonathan Turnbull

Jonathan Turnbull
Partner, London
+44 20 7466 2174

Rachel Montagnon

Rachel Montagnon
Professional Support Consultant, London
+44 20 7466 2217

Comparator products in the post-Brexit world

Comparator products for use in bioequivalence and therapeutic equivalence studies for Great Britain are covered in the UK government guidance Comparator products in Bioequivalence/Therapeutic Equivalence studies from 1 January 2021 (1 September 2020). The scope of the guidance only covers applications relating to generic medicinal products (regulation 51 of the Human Medicines Regulations 2012) and applications relating to certain medicinal products that do not qualify as generics (regulation 52 of the Human Medicines Regulations 2012), but the guidance makes clear that the principles may also be applicable for other forms of applications (Regulation 54, 55 and 65C of the Human Medicines Regulations 2012). Comparator products for applications in Northern Ireland continue to be covered by the EU requirements.

Generally, the comparator product used in bioequivalence, pharmacokinetic or therapeutic equivalence studies should be sourced from Great Britain. A non-GB comparator product should be authorised in and sourced from a country that has similar scientific and regulatory standards to the UK. Examples of such countries are the EU/EEA, Switzerland, USA, Canada, Australia and Japan. The non-GB sourced comparator product would normally be expected to be part of the same global marketing authorisation as the reference medicinal product, or marketed in the non-GB country through a licensing arrangement with the entity that currently markets the product in Great Britain.

Where a non-GB sourced comparator product is used, an eligible reference medicinal product must still be referred to in the application for a new medicinal product. If the non-GB sourced comparator product can be shown to be identical to the eligible reference medicinal product, then no further data is required. Identicality can be shown by written confirmation from the MA holder of the comparator product. Otherwise, it must be demonstrated that the non-GB sourced comparator product is representative of the eligible reference medicinal product. The applicant should provide adequate comparative, experimental data or information to justify the relevance of the comparator product and establish an acceptable bridge to the reference medicinal product. This bridging data must always include data from analytical studies that compare the reference medicinal product, the non-GB sourced comparator product and the proposed medicinal product. Comparative data from at least 3 batches of each of the non-GB sourced comparator product and the eligible reference medicinal product are usually expected.

If representativeness between the non-GB sourced comparator product and the eligible reference medicinal product cannot be demonstrated, then bioequivalence and therapeutic equivalence studies will need to be performed in Great Britain between the new medicinal product and the reference medicinal product.

The exact type of data that are required are assessed on a case-by-case basis. If the application relates to a product of a certain type (including products that do not exhibit immediate release of the drug substance, products not for oral administration, products with a narrow therapeutic range or safety margin, products with a risk of serious undesired effects), it is recommended that the applicant contact the MHRA for advice.

Applications for which there is no eligible reference medicinal product are advised to contact the MHRA for advice. Applicants for more complex products are also encouraged to contact the MHRA for advice.

 

For more of our Brexit coverage click here.

Julie Chiu

Julie Chiu
Senior Associate (Australia), London
+44 20 7466 2658

Jonathan Turnbull

Jonathan Turnbull
Partner, London
+44 20 7466 2174

Rachel Montagnon

Rachel Montagnon
Professional Support Consultant, London
+44 20 7466 2217

Biological products in the post-Brexit world

The licensing of biological products (including biosimilars, advanced therapy medicinal products and plasma master files and vaccine antigen master files) from 1 January 2020 is covered by the Human Medicines Regulations 2012, as amended by the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019. The UK government guidance in relation to biological products is provided in the Guidance on licensing biosimilars, ATMPs and PMFs from 1 January 2021 (1 September 2020).

Biosimilars (similar biological products)

Biosimilar products in Great Britain will be regulated by the MHRA according to the same principles that were applicable pre-1 January 2021. Biosimilar products in Northern Ireland will follow the EU acquis and the MHRA will regulate applications from 1 January 2021 onwards.

Applications for biosimilar products made after 1 January 2021 must be made with reference to a product that is a reference medicinal product under regulation 48 of the Human Medicines Regulations 2012, as amended by the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019, which is discussed further in our previous article Marketing Authorisations in the post-Brexit world.

Advanced therapy medicinal products (ATMPs)

After 1 January 2021, ATMPs will be regulated by the MHRA in Great Britain according to the same principles that applied pre-1 January 2021. Northern Ireland ATMPs will continue to be regulated under the EMA’s Centrally Authorised Procedure.

Data, traceability, exceptions from licensing, packaging and post-authorisation requirements that applied in the EU will be transposed into UK law. There will be no changes to the definitions of individual classes of ATMPs, which will continue to be classified as gene therapy medicinal products, somatic cell therapy medicinal products or tissue engineered products.

Plasma Master Files (PMFs) and Vaccine Antigen Master Files (VAMFs)

After 1 January 2021, the MHRA will continue to recognise existing PMFs until further notice. Further guidance will be provided by the MHRA in relation to the future transfer of the supervision of PMFs into a national system. Similarly, until further guidance is provided regarding the future transfer of PMFs to the MHRA database, the data requirements for PMFs will be according to what is currently in place for the EU.

The current guidance from the UK government is that the PMF holder should notify the MHRA of the outcome of annual updates within 4 weeks of the completion date. Similarly, the MHRA should be notified of the submission of variation applications within 4 weeks, and the determination outcome of such variation applications also within 4 weeks.

Applicants wishing to submit a VAMF should contact the MHRA for further guidance.

Batches

The National Institute for Biological Standards and Control (NIBSC) has provided guidance in relation to the certification of batches of immunological medicinal products or medicinal products derived from human blood or plasma products.

From 1 January 2021, EU Directive 2001/83/EC (Article 114) will no longer apply in Great Britain. Instead, NIBSC will be a stand-alone National Control Laboratory. The NIBSC will independently certify batches of biological medicines that are to be used exclusively in Great Britain.

Batches that have an EU Official Control Authority Batch Release (OCABR) certificate issued on or before the end of the transition period will be accepted by Great Britain. After 1 January 2021, samples and documentation relating to batches for use in Great Britain will need to be sent to the NIBSC. NIBSC certification is not required for batches that were manufactured and certified by a country with whom the UK has a mutual recognition agreement (the initial expectation is that these countries will be Switzerland and Israel), though re-examination of the batches by NIBSC is permitted where there are public health concerns. Further information on the procedure for batches that fall under a mutual recognition agreement will be published in the future.

For batch release in the EU, NIBSC continues to offer batch release testing via subcontracting arrangements with a European Official Medicines Control Laboratory. For non-EU/EEA/UK countries, the NIBSC will continue to certify batch releases.

For batch release in Northern Ireland, OCABR certificates will continue to be accepted, without further testing, and a NIBSC certificate will not be required. Where there is no OCABR certificate, the procedure for obtaining a NIBSC certificate in Northern Ireland is the same as the procedure for Great Britain.

Applicants are encouraged to contact the NIBSC to discuss the specific arrangements for their products.

 

For more of our Brexit coverage click here.

Julie Chiu

Julie Chiu
Senior Associate (Australia), London
+44 20 7466 2658

Jonathan Turnbull

Jonathan Turnbull
Partner, London
+44 20 7466 2174

Rachel Montagnon

Rachel Montagnon
Professional Support Consultant, London
+44 20 7466 2217

Marketing Authorisations in the post-Brexit world

New MHRA Brexit guidance was released on 1 September 2020 (and further supplemented in October 2020), after the previous UK Government guidance in relation to pharmaceuticals was withdrawn in January 2020.  The guidance confirms the regulatory steps required for grandfathering of centralised marketing authorisations to ensure that they are replaced by the UK marketing authorisations (UK MAs) at the end of the transition period (referred to as “exit day” or “implementation period completion day – IP completion day”).

In summary, the granted marketing authorisations issued centrally by the European Medicines Agency (EMA) will automatically convert to UK MAs, following which some further supporting data will need to be submitted, unless the holders opt out of the scheme. Pending applications which have already been submitted to EMA by the end of the transition period will either be determined in parallel by the Medicines and Healthcare products Regulatory Agency (MHRA) or will be put “on hold” until the EMA’s Commission for Medicinal Products for Human Use (CHMP) issues a positive decision which can be relied upon by MHRA. From 1 January 2021 any new applications for UK MAs based on an abridged procedure will need to rely on “eligible” Reference Medicinal Product, as explained further below.

Market Authorisations (MAs)

From 1 January 2021, the MHRA will be the only medicines and medical devices regulator in relation to products being marketed in the UK, taking over the EMA’s previous functions.

An MA is required in order to market pharmaceuticals within the EU. MAs are currently obtained either nationally (whether by a national authorisation procedure or via the European authorisation routes, the decentralised procedure (DCP) or mutual recognition procedure (MRP), that involve the Heads of Medicines Agencies (HMA) or using the centralised procedure. The centralised procedure gives the granting authority, the European Commission, the power to grant a single marketing authorisation (in the guidance referred to as either centralised Marketing Authorisations or Community Marketing Authorisations) (CMAs) for the whole of the European Union, Iceland, Norway and Lichtenstein. This is in contrast to the other procedures that result in individual member states authorising the medicines for use in their own territory. Products which obtain authorisation via centralised procedure are referred to as Centrally Authorised Products (CAPs). The centralised procedure is optional for some medicines but compulsory for others (such as medicines derived from biotechnology processes). The EMA is the European body responsible for the scientific evaluation of CMAs. Following a positive recommendation from the EMA, which is usually followed by the European Commission, it takes around two months for the European Commission to approve a medicine.

Grandfathering of Centrally Authorised Products (CAPs)

At the end of transition period, any existing CMA will automatically (without a fee) convert to a national UK MA and be issued with a UK MA number. This is termed “grandfathering” and such MAs are referred to in the guidance as “converted EU MAs”. The MA holder (MAH) is not compelled to accept the converted EU MA and can opt out by notifying the MHRA in writing by the end of 21 January 2021. However, to support the ongoing regulation of these converted EU MAs, the MHRA requires certain “baseline data” to be submitted by the MAH within a year of the end of transition. The detailed list of information which the MAH must submit for each converted EU MA in accordance with the applicable regulatory provisions and guidance on how to submit the application is available here.

On 26 October 2020 the MHRA issued a further guidance in the form of a letter to industry setting out the actions each MAH ought to take to ensure the grandfathering process runs smoothly, which include reviewing the list of currently authorised CAPs and advising of any errors or omissions, advising the MHRA on any CAPs that the MAH does not want to be converted and advising of the marketing status of each product.

Reference Medicinal Products (RMPs)

A RMP is a medicinal product which has been granted an MA (either via procedures resulting in a national MA or via the centralised route) on the basis of a complete dossier (with the submission of the quality, pre-clinical and clinical data as required by the Directive 2001/83/EC). A generic or a biosimilar can apply for an MA without submitting such a full suite of information but by submitting a so-called “abridged application” instead which can be a faster and cheaper route. If the MAH seeks authorisation using an abridged application, they will have to identify in their application form the RMP which has been authorised in the EEA and is used as a comparator in the abridged application.

A difficult issue is what happens to granted MAs and pending MA applications (MAAs) for generic or biosimilar medicines which are based on the data from a RMP where that RMP was not granted by the UK national route or where the UK was not the Reference Member State (RMS). In this situation, the underlying data for the RMP will be held by the EMA or other relevant non-UK authority that was used as the RMS and will no longer be available to the MHRA after 31 December 2020.

The MHRA guidance confirms that granted MAs (whether obtained nationally or via the centralised procedure) for products which are based on a RMP authorised in the EU remain valid after 31 December 2021 (and, for CMAs, they will convert to converted EU MAs, as described above). The guidance also states that pending MAAs based on a RMP authorised in the EU will remain valid (and will be dealt with in accordance with the guidance for pending applications as described below).

From 1 January 2021 any applicant that would like to apply to the MHRA for an MA using an abridged procedure (ie, based on RMP) will be able to do so if it falls within the definition in regulation 48 of the Human Medicines Regulations 2012, as amended by the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019, that is an RMP which:

(i) has been authorised under Regulation 49(1)(a) of the Human Medicines Regulations 2012 (the provision which governs the grant of UK MAs), or

(ii) had a CMA prior to 31 December 2020 but where the MAH opted out of the conversion to a UK MA.

It is worth noting, if the “eligible RMP” is a converted EU MA, the MAH has 12 months to submit the baseline data to the MHRA which could, arguably, cause delays when assessing an MAA using an abridged procedure which relies on that “eligible RMP”. Schedule 7 of the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 gives the MHRA the power to request the MAH of a converted EU MA to submit the baseline data before the 12-month deadline.

Where there is no eligible RMP (for example, the RMP has a national MA from another EU Member State), generic and biosimilar companies will need to file a complete set of regulatory data to the MHRA in order to obtain a new MA.

Pending applications for Centrally Authorised Products

Applications under the EMA’s centralised procedure which are still pending on 1 January 2021 will be determined by the regulatory route chosen by the MAH and the stage of the procedure the application was at on that day. Essentially, the applicant has two options:

(1) to apply to the MHRA for what the guidance describes as an “in-flight assessment” in parallel with the application for a CMA. In that case the applicant submits the same application to the MHRA as has been submitted to the EMA. The MHRA will take into account any assessment that has already been reported on or before 1 January 2021 and the MHRA will tailor its assessment to any outstanding issues and reach a decision as soon as practicable (the guidance suggests a 60-day process); or

(2) to wait for the positive opinion of the CHMP and to apply to the MHRA using the new reliance route (which is not further described in the MHRA Brexit guidance). The application will then be determined when the decision by the European Commission regarding CMA has been confirmed.

In both cases, the applicant will need to submit an application and supporting dossier to the MHRA accompanied by all iterations of the CHMP assessment report, since the MHRA does not hold the supporting data for applications made to the EMA. Procedures that have been completed with a positive opinion from the CHMP and are awaiting a European Commission decision will be determined “as soon as practicable” by the MHRA; in other cases, the MHRA will need to make an assessment, the timetable of which will vary depending on the stage the EMA assessment has reached. More detailed guidance dependant on the stage of the assessment before the EMA is available here.

Renewals and variations

Converted EU MAs will be treated as if they were granted on the date the corresponding CMA was granted. The renewal date will stay the same. If renewals were submitted through the MRP or DCP and no decision was rendered before 1 January 2021, the MHRA will ensure the renewal process is concluded and processed appropriately, and there will be no need to resubmit the application. From 1 January 2021 the requirements for renewal submissions remain the same as currently required by the EMA and the MAH should continue to submit renewal applications to the MHRA 9 months before they expire (or 6 months in relation to conditional MAs).

In relation to variations to converted EU MAs, the general rule is that MHRA will not consider variations until the MAH submits at least a “minimal initiating sequence” and related documentation. The date on which these are received is referred to as the “data submission date”. The MHRA will consider the variation before the data submission date only in limited circumstances. These include: (1) if a variation is necessary on urgent safety grounds, or (2) if it is necessary to maintain supplies of a particular medicinal products to patients in Great Britain (England, Wales and Scotland); or (3) if there are other reasons to consider the variation in such timeframe. The approach to assessing the variations in the regular timeframe (ie, after the data submission date) depends on the type of variation (whether it is a minor Type IA or IB variation or a major Type II variation) and the stage the application (ie, whether the application to vary was submitted before or after 1 January 2021 and whether the variation had reached positive CHMP opinion by then).

A handy guide of MHRA’s approach to handling variations to converted EU MAs which were pending as at 1 January 2021 can be accessed here.

The procedures applicable to variations to purely national MAs, detailed under Chapter IIa of Variations Regulation (EC) No 1234/2008, will become incorporated into UK law at the end of the transition period and will apply to pending and new applications to purely national UK MAs. They can be found in the new regulation 65C and Schedule 10A to the Human Medicines Regulations 2012. Detailed guidance on how the MHRA will assess variations to national MAs is available here.

Conditional MAs

The MHRA will introduce a national Conditional Marketing Authorisation scheme for new medicinal products from 1 January 2021. The scheme will have the same eligibility criteria as the EU scheme and is intended for medicinal products that fulfil an unmet medical need, such as where the medicine is for serious and life-threatening diseases where no satisfactory treatment methods are available or where the product offers a major therapeutic advantage. Conditional MAs may be granted where comprehensive clinical data is not yet complete, provided sufficient evidence of safety and efficacy is submitted to the MHRA to conclude that the risk-benefit balance of the medicinal product is positive. Conditional MAs will be valid for one year and will be renewable annually.

Prioritising Access to New Medicines and new assessment routes

The MHRA is introducing changes designed to streamline the assessment procedures and reduce the time needed for the approval of a novel medicine. In the newly published guidance dated 27 October 2020, the MHRA foreshadows a new interactive toolkit which will use the expertise of the MHRA and other partners in the wider UK healthcare system, such as NICE, with further information to be published by December.

Additionally, the MHRA plans on introducing an accelerated procedure and reach its opinion on MAAs within 150 days of filing an application. The accelerated assessment will be available for good quality new MAAs for both new and existing active substances as well as orphan designations. Interested applicants should contact the MHRA in advance of submitting the application.

The assessment process will run in two phases totalling 150 days and MHRA will provide an opinion on approvability of the product by day 150.

The Rolling Review is a new route for MAAs based on on-going regulatory input and feedback to ensure the applications can be approved as efficiently as possible. Applications for any new active substances based on a submission of a “full dossier”, including biological applications, are eligible for a rolling review. If any questions are raised during assessment, the applicant will be given the opportunity to update the modules prior to final submission.

MAA referrals under Article 29 of Directive 2001/83/EC

Article 29 referrals are triggered on the grounds of a potential serious risk to public health when a consensus cannot be reached between Member States on the outcome for an MAA which has been evaluated using either the MRP or DCP. In cases of such disagreement, the RMS may refer the matter to the EMA. Under an Article 29 referral, the CHMP would normally issue an opinion on the issue referred within 60 days of the start of the procedure. This opinion is then usually adopted by the EMA and sent to the European Commission that issues a binding decision. In relation to Article 29 referrals that remain pending on 1 January 2021, the MHRA guidance states that if either a positive or negative opinion has been issued by the CHMP but no final decision was issued by that date, the MHRA will either grant or refuse the application with regard to that opinion. If no opinion has been reached by 1 January 2021, the MHRA will complete the assessment as a national procedure.

Active Substance Master Files (ASMFs) and Certificates of Suitability (CEPs)

An ASMF is a set of documents that protects the valuable confidential intellectual property of the manufacturer. It must contain all the scientific information relating to the active substance of the medicine in question and is submitted to support a MAA or a MA variation. A CEP certifies compliance of the active pharmaceutical ingredient (API) with the requirements laid down in the relevant monograph of the European Pharmacopoeia.

The MHRA will continue to accept ASMFs and CEPs from 1 January 2021 in both new national initial MAAs and in MA variation applications, with the guidance suggesting that an ASMF ought to be prepared in accordance with the CHMP guidelines. However, the UK will no longer participate in ASMF worksharing procedures with EU Member States, so the EU/ASMF/XXXXX reference numbers won’t be applicable to UK national applications from 1 January 2021.

CEPs are not affected by the UK leaving the EU as they are issued by the European Directorate for the Quality of Medicines and Healthcare and there will be no change to the relevant procedures.

Steps to be taken once you have been issued a converted EU MA

Once an MAH has been issued with a new converted EU MA, they will have 24 months from 1 January 2021 to establish and register a Great Britain presence for the converted EU MA, which includes submitting:

(i) the name and address of the MAH or their representative;

(ii) the Great Britain MA number; and

(iii) the name and address of the product manufacturer for batch release.

A change of MAH from a company out of the UK to one established in the UK requires submission of a Change of Ownership application. Before one is submitted, the MHRA will ask MAH for details of a UK contact.

The MAH will then have further 12 months to ensure all stock released to market is in compliant packaging, which may require the labelling and/or patient information leaflet (PIL) to be amended to take account of this new information. Some changes, such as changing the name and address of the MAH and/or the manufacturer for batch release, will be suitable for self-certification under the Better Regulation of Medicines Initiative (BROMI) scheme. If changes are more extensive (eg, new changes to the pack design), then the MAH will need to submit the artwork for full assessment to the Product Information Quality Unit.

Multi-country packs are medicinal products that are labelled to allow their placing on the market in several Member States with the same packaging. The MHRA will continue to allow multi-country packs, provided that the entirety of the information is UK-compliant.

Recognition of EC decisions for 2 years from 1 January 2021

The guidance published on 27 October 2020 states that the UK will adopt decisions taken by the European Commission in relation to the approval of new MAs in the centralised procedure for two years from 1 January 2021. The MAH should provide to the MHRA all information that was provided to the EMA during the licensing procedure, including all iterations of the CHMP report and the final CHMP opinion. The UK will also have the power to take into account MA decisions of EU Member States when considering applications for MAs for products that have been approved in decentralised or mutual recognition procedures. Similarly, the MAH should provide to the MHRA all information that was submitted to the RMS, including the RMS assessment report and end of procedure notification.

For more of our Brexit coverage click here.

Monika Klajn

Monika Klajn
Senior Associate, London
+44 20 7466 7604

Jonathan Turnbull

Jonathan Turnbull
Partner, London
+44 20 7466 2174

Rachel Montagnon

Rachel Montagnon
Professional Support Consultant, London
+44 20 7466 2217

UK Government launches consultation on role of MHRA post-Brexit and confirms commitment to underwrite Horizon 2020 funding

The UK Government has today launched a consultation on the role of the Medicines and Healthcare products Regulatory Agency (MHRA) post-Brexitseeking views on how the MHRA legislation and regulatory processes would have to be modified in the event of the UK not securing a deal with the EU after the UK’s exit, with no Implementation Period“. As the consultation closes at 11.45 pm on 1 November 2018, time is short for making a response.

Also today, the Government has released an overview of the UK’s relationship with the EU’s Horizon 2020 science and innovation funding programme including a link to the portal where those with current funding can submit data which will be used to guarantee funding post-Brexit.

MHRA Consultation

  • This consultation was promised in the no-deal technical notice on medicines, clinical trials and medical devices, discussed in our blog post of 29 August 2018. It is expressed to be set in the context of “the UK not securing a deal with the EU after the UK’s exit, with no Implementation Period“, i.e. a “cliff edge” no-deal scenario, with no transitional period. However, if the EU Withdrawal Agreement (which sets out the terms on which the UK leaves the EU and is currently being negotiated between the UK and the Commission) is concluded on the terms that have so far been declared as agreed between the negotiators, then there would be a period until the end of 2020 when the UK would still effectively be part of the EU, despite technically having exited at 11pm on 29 March 2019.
  • A direct link to the consultation can be found here.  More detail on the consultation, including the specific areas being covered, can be found in the Consultation Introduction. As the introduction to states, “the overall approach in no-deal is for the MHRA to be a stand-alone medicines and medical devices regulator, taking any decisions and carrying out any functions which are currently taken or carried out at EU-level. This would include decisions on Marketing Authorisation (MA) applications which are currently authorised through the Centralised Procedure, paediatric investigation plans and orphan status, as well as pharmacovigilance responsibilities“. The consultation also asks for comments on clinical trials issues.
  • The introduction recommends that you read the Draft Statutory Instrument (SI) text, Impact Assessment and Consultation Annex before responding. The Draft SI text relates to statutory instruments that will be needed to update the Human Medicines Regulations 2012, the Medicines for Human Use (Clinical Trials) Regulations 2004, the Medicines (Products for Human Use) (Fees) Regulations 2016, and the Medical Devices Regulations 2002.
  • Response to the consultation is in the form of an on-line survey. Each section of the survey is optional, so you can limit your response to the sections you are interested in.

Horizon 2020 funding

  • Following on from the no-deal technical notice on Horizon 2020 funding which was issued with the other life sciences related notices in August (here), the UK Government has published an overview of the UK’s relationship with Horizon 2020, followed by a Q&A, which aims to clarify the UK’s eligibility to participate in Horizon 2020 – here. Current UK recipients of Horizon 2020 funding are invited to provide data about their projects on a portal managed by UK Research and Innovation (UKRI) (linked on the same page), so that the UKRI has the information it needs in order to underwrite the guaranteed payments if this becomes necessary.
  • As we previously stated in our blog post: If there is ‘no deal’, the Government says it has taken steps to provide continued support for research and innovation currently being funded through this EU project fund. The Government will guarantee funding in most cases, for the full duration of the project, where the funding relates to successful bids submitted by UK participants before the UK exits the EU. Funding will only be for UK participants however. Where UK participants are leading consortia of non-UK parties and would normally be distributing the Horizon 2020 funds, the Government will seek to discuss with the EU Commission how best to address this. In it’s no-deal notice, the Government said it was considering what other measures may be necessary to support UK research and innovation in the event that the EU’s funding is no longer available. Looking beyond 2020, the notice said that “the UK remains committed to ongoing collaboration in research and innovation and wants to work with the EU on a mutually beneficial outcome“.

Contacts

Jonathan Turnbull

Jonathan Turnbull
Partner
+44 20 7466 2174

Rachel Montagnon

Rachel Montagnon
Professional Support Consultant, London
+44 20 7466 2217

Striking a balance on parallel imports

In an article published in the latest edition of CITMA Review, Joel Smith and Emily Bottle comment on the Court of Appeal’s recent judgment in Flynn Pharma Ltd v DrugsRus Ltd [2017] EWCA Civ 226.

This case examined how a balance can be struck between a trade mark owner’s ability to enforce its rights and the fundamental principle of free movement of goods, applying the law in detail to an unusual pharmaceutical fact pattern. Lord Justice Floyd’s detailed analysis of the scope of Article 36 TFEU is a very useful summary of the case law in this area. He confirms that trade mark owners can enforce their marks against imported goods that they did not place on the market and over which they have no control, even where the imported goods are identical goods produced by the same manufacturer.

For the full article, see here.

Author

Joel Smith

Joel Smith
Head of IP - UK
+44 20 7466 2331

Emily Bottle

Emily Bottle
Associate
+44 20 7466 2525