QH Regulatory Updates

EU-UK Trade & Cooperation Agreement

QHC Administrator QH Regulatory Updates , ,

(First published 28 December 2020, updated 31 December 2020).

The Trade and Cooperation agreement between the European Union and the United Kingdom published on 24 December 2020 identifies particular areas of interest to pharmaceutical and healthcare sectors. The following brief guide describes the overall structure of the agreement and identifies/directs to specific topics, but it should not be considered a full precis, analysis or advice of the 1246-page document. There is also discussion of some scientific elements which are excluded from the agreement.

Overall Agreement Structure

The Agreement comprises 7 Parts covering:

  • The Agreement comprises 7 Parts covering:
  • Common and Institutional Provisions
  • Trade, Transport, Fisheries and Other Arrangements (including intellectual property, transport of goods)
  • Law Enforcement and Cooperation on Crime
  • Thematic Cooperation (including health security)
  • Programme Participation and Finance
  • Dispute Settlement and Horizontal Provisions
  • Final Provisions

Each Part is divided into topics called Titles, designated by roman numerals.

The seven Parts are supported by 49 Annexes, of which the following are particularly relevant to the pharmaceutical and healthcare sectors:

  • Annex ORIG-1 to -5: product origin (page 415)
  • Annex TBT-2: medicinal products (page 492)
  • Annex TBT-3: chemicals (page 504)
  • Annex TBT-4: organic products (page 507)
  • Annex SERVIN-1 to -6: services and professional recognition (page 530)
  • Annex ROAD -1 to -3: Transport of goods by road (page 800)

There are also a series of Protocols (each subdivided into Titles, designated with roman numerals, and Annexes) relating to tax, administration and social security.

Science

At the outset, there is acknowledgement that agreement about the UK access to European programmes could not be finalised within the negotiating timetable. The intent of both parties to progress these is documented, including one of which seeks to encourage future cooperation in science programmes. There appears to be sufficient confidence in this aspiration that a draft has been included in the appended joint declarations allowing UK to participate in (among others) the Horizon Europe Framework Programme for Research and Innovation (Draft Joint Declaration Article 1.b & 1.c, page 16; Article 4, page 18; Article 5, page 19). It is expected that this will form the basis for subsequent agreement. Details of Horizon funding and finance arrangements up to 2027 are set out in this 26-page document. The first healthcare mission priority within the Horizon programme is cancer. Although the UK will participate on an equal footing, it will only have observer status on the Joint Research Centre Board of Governors and will not participate in the European Innovation Fund (Draft Joint Declaration Article 6, page 21).

[At present, the UK will no longer participate in the Erasmus programme for academic exchange, which starts a new 7-year cycle in 2021. Existing UK participants may complete their current assignment. Non-EU countries can participate in the scheme (subject to financial contribution) but this is not currently envisaged by the UK government, which has independently flagged its intention to establish a system for global academic exchange (the Turing Programme)].

Pharmaceuticals & Healthcare

From the outset, there is agreement to cooperate on measures which address antimicrobial resistance (Article SPS.17, page 51) by control of antibiotic use.

Considering cross-border health security, the UK may ask for access to the EU Early Warning and Response System (EWRS) and the UK may be invited to participate in committee(s) which address such hazards, but these would be limited to the specific need and would not continue in perpetuity (Article HS.1, pages 362-363).

Annex ORIG (pages 415-486) covers the requirements for rules of origin. This may be relevant to pharmaceutical and healthcare product packaging materials and also to the materials used in the manufacture of the products themselves. Of particular relevance in this section is Note 5 (pages 417-419) which provide definitions for manufacturing processes which are used in the pharmaceutical and healthcare sectors. Similarly, Notes 6 and 7 (pages 419-422) cover definitions of woven materials which may be relevant to medical dressings. Based on the established 2017 Harmonised System on rules of origin, medicines and pharmaceuticals are specifically listed on page 419 (considering definitions of purity), with a Change of Tariff Sub-Heading for pharmaceutical products on page 430 and a Change of Tariff Heading for medical or surgical instruments on page 468. In general, there is a maximum limit of 50% on the ex-works product value attributable to all costs of components obtained outside the stated country of origin.

Annex TBT-2 covers Medicinal Products (pages 492-503): including GMP, quality, inspections and national statutory authorities.

Shipping and Transport of Goods

Goods for humanitarian purposes, which include medical, surgical and laboratory equipment, are allowed to pass through a country’s customs without import duties, taxes or other restrictions, if they are to be re-exported without material change (Article CUSTMS.16, page 71/72). Such goods may also be carried by transport without normal licence (Article ROAD.6, page 248-249).

Distribution of pharmaceuticals is covered in Reservation No. 13 (pages 675-676).

Intellectual Property

Protection of intellectual property, including medicinal products, is covered in TITLE V: Intellectual Property pages 125-147. In particular, patents are covered in Section 4: Patents, pages 136-147.

Future arrangements will be channelled through the Working Group on Medicinal Products which will operated under the supervision of the Trade Specialised Committee on Technical Barriers to Trade (article INST.3: Working Groups, page 15).

Health and Pharmaceutical Professional Services

Although service industries are not the focus of this Agreement, the provision of healthcare and pharmaceutical professional services is covered in a series of Reservations. These appear to cover service areas which do not conform with the Agreement terms for:

  • investment liberalisation (Articles SERVIN.2.2 & SERVIN.2.3, page 79),
  • cross-border trade (Articles SERVIN.3.3 & SERVIN.3.4, page 84),
  • most favoured nation treatment (Article SERVIN.2.4, page 80),
  • senior management and boards of directors (Article SERVIN 2.5, page 80), performance management (Article 2.6, page 80) or
  • legal services (Article SERVIN.5.49, page 115)

but which may be subject for improvement in subsequent negotiations.

Of particular relevance are:

  • Reservation No. 3 – health and pharmaceutical professional services  (pages 563-574; pages 658-661; pages 721-722)
  • Reservation No. 10 – health and social services (pages 731-732),
  • Reservation No. 13 –health and social services (pages 604-608; page 675)
  • Reservation No. 17 – energy related activities (pages 691-693).

Queen’s House Consulting will continue to offer services to the pharmaceutical and healthcare industries in the areas of pre-clinical pharmaceutical development, technical assessment for pharma start-up and follow-on investment/due diligence, regulatory authoring, pharmaceutical and healthcare strategy and systems analysis. Please contact Queen’s House Consulting to discuss your particular needs.

Accelerated assessment of COVID-19 products

QHC Administrator QH Regulatory Updates , , ,

Regulatory health agencies around the world have responded to the COVID-19 pandemic by offering accelerated review of applications related to detection or treatment of the disease, while providing assurance that scrutiny of product quality and patient safety would not be compromised. Such a position is understandable, given the global impact of the disease and the public expectation that nothing should impede developments to minimise the human, economic and social cost.

The regulatory stance has some interesting implications for potential pharmaceutical manufacturers and marketing authorisation holders. Those with products which are relevant to the management of SARS CoV-2/COVID-19 could benefit from accelerated review, as would individuals and society as a whole. However, health agency resources are finite, which prompts three observations yet to be widely considered:

  • Accelerated review of COVID-19 related applications will probably delay the review of non-COVID-19 related applications. Over the short- to mid-term, this could defer the availability of treatment for patients with other, non-COVID-19, conditions no less than the prioritisation of hospital beds to severely-ill COVID-19 patients deprives other patients of critical care.
  • If accelerated review is possible for COVID-19 applications without compromising product quality or patient safety and without delaying other applications, then it may be possible to establish a routine accelerated review process for all applications.
  • While maintaining that product quality and patient safety will not be compromised, the hazard from COVID-19 may allow for greater risk when assessing risk-benefit, than for other non-COVID-19 medicinal products. This may be easier to justify for COVID-19 patients who are already critically-ill, but presents interesting philosophical questions when comparing COVID-19 and other conditions which have not progressed to critical illness but may have the potential to do so.

The above three scenarios are not accusations; the response of all parties involved in tackling the COVID-19 challenge has been to find solutions as quickly and as safely as possible, in the context of data available at the time. Rather, these scenarios highlight the unchanged responsibility of developers.

Accelerated review is dependent on the applicant (whether academic institution, public sector provider or commercial company) ensuring the quality and safety of  product throughout the pre-licensing development programme from concept to market. Notwithstanding the perceived urgency, the developer needs to maintain a critical scrutiny of their data and underlying assumptions continually, in order to minimise risk at the regulatory review stage and in the clinic.

Queen’s House Consulting can offer independent review to support that critical scrutiny, acknowledging that the developer is most expert in that field. A detached view can challenge assumptions and interpretations, either confirming an already-robust package of data, or prompting enhancement of the eventual regulatory process. If you are a developer and would like to explore such a service, please contact Queen’s House Consulting to discuss your particular needs.

Organs, Tissues, Cells and Brexit

QHC Administrator QH Regulatory Updates

The UK Government Department of Health and Social Care has published advice that existing quality and safety standards for work with human organs, tissues and cells will be retained,  when the UK leaves the EU. Arrangements also cover the possibility of the UK leaving the EU without a deal. This means that facilities working with these materials can continue to follow existing quality and safety procedures.

However, after UK leaves the EU, it will no longer be party to the Single European Code or the EU Coding Platform, so UK establishments will not be included or required to use them. Any UK facility working with tissues or cells which are moved in or out of the EU will require approval of import/export licences from the UK Human Tissue Authority. For movement of reproductive cells, authorisation will be needed from the UK Human Fertilisation and Embryology Authority. There will be a 6-month grace period for users to comply with the new requirements.

The UK government has drafted three statutory instruments, covering Human Tissue, Organs for Transplantation and Human Fertilisation and Embryology, to ensure that these arrangements remain codified in UK law after departure from the EU. These may need to be amended or revoked, depending on the final outcome of negotiations between the UK and the EU.

NOTE: Arrangements for the UK departure from the EU are subject to change. This summary is not binding. Please use the embedded links the official UK websites for the most current and definitive information.

This summary has been prepared by Queen’s House Consulting, which provides consultancy services to the pharmaceutical and healthcare industry. Please contact Queen’s House Consulting to discuss your particular needs.




Medicines and Brexit

QHC Administrator QH Regulatory Updates

As the United Kingdom (UK) departure from the European Union (EU) approaches the target date of 29 March 2019, both the UK Medicines and Healthcare Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have updated their guidance to pharmaceutical companies.

Generally, these guidance notes are mirror images, with the common underlying message that any functions performed under the auspices of UK’s current membership of the EU will no longer be recognised in Europe or the UK after Brexit, particularly in the event of departure without a negotiated deal. Non-manufacturing functions currently performed in the UK must be transferred to individuals/facilities within the EU or the European Economic Area (EEA). Those functions currently performed in Europe will need to be replicated in UK, in order to maintain supplies of medicines from the EU. While MHRA provides a transition period until the end of 2020 for such establishment in UK, it appears that EMA will apply this requirement immediately after 29 March 2019.

The most public of these changes is the relocation of EMA offices themselves from London to Amsterdam. After some delays, the interim “SPARK” offices in Amsterdam are now fully-operational; however, the relocation of staff and procedures will limit meetings and product certificates from now until 14 March 2019.

As these circumstances mainly relate to medicines which are already approved in the EU, this is primarily an administrative change, albeit costly for UK-based companies. In contrast, medicines currently supplied in the UK under a European (EMA) product marketing authorisation will require new marketing authorisations licenced by MHRA. Pragmatically, MHRA have provided guidelines on “grandfathering”, whereby a new UK marketing authorisation may be generated on the basis of a pre-existing (pre-Brexit) EU licence. However, there are likely to be long-term cost implications for companies to maintain these additional marketing authorisations only for the UK.

Both EMA and MHRA are adopting a risk-based approach to facilities inspections, while establishing their rights to require EU inspection of UK sites and MHRA inspection of European sites.

During this period of transition, consistent and coherent regulatory submissions, specifications and batch testing are needed to ease pharmaceutical manufacturers’ interaction with both UK and EU agencies. Queen’s House Consulting can provide   authoring and checking services for Pharmaceutical and Non-Clinical packages, helping to deliver the additional workload resulting from Brexit. Please contact Queen’s House Consulting to discuss your particular needs.

NOTE: Arrangements for the UK departure from the EU are subject to change. This summary is not binding. Please refer to the official UK and EU websites for definitive information.




EMA and MHRA prepare for BREXIT

QHC Administrator QH Regulatory Updates

The European Medicines Agency (EMA) has published plans to relocate from London to Amsterdam when the U.K. leaves the European Union in March 2019. The limited time means that preparations have started for a two-phase transfer to a new purpose-built headquarters, even though Italy has questioned the process by which Amsterdam was chosen. As the new Netherlands facility will not be ready in time, EMA will first relocate to temporary offices, before a second move to their permanent home. By the end of February 2018, progress towards the establishment of both buildings was delayed, according to the  tracking tool .  

While the set-up of new offices presents logistical challenges, the availability of EMA staff to support and progress the development of new medicines may also be delayed, while new European personnel are recruited and trained to replace the outgoing UK experts. At the same time, staff at the UK MHRA will be surrendering their role as a reference member state for EMA regulatory submissions. Their focus will either be a new possible mutual recognition process with Europe or the creation of systems which secure the continued supply of existing EMA-registered medicines in the UK.

In such circumstances, the need for well-presented regulatory submissions has never been more important. A dossier which is easy to review will progress through the system faster than one which is confusing or ambiguous. Queen’s House Consulting can help you negotiate this workload leading up to Brexit, offering regulatory authoring of Pharmaceutical and Non-Clinical modules, whether for pre-meeting packages or full product marketing authorisation applications. Please contact Queen’s House Consulting to discuss your particular needs.




EMA issues first Q&A about Brexit Impact

QHC Administrator QH Regulatory Updates

The European Medicines Agency has issued its first set of questions and answers about the impact of Brexit on companies based in the United Kingdom. In most instances, if the U.K. ceases to be a member of the European Economic Area (EEA) on 20 March 2019, then:

  • UK companies will need to operate through companies located within the EEA;
  • Pharmacovigilance and product release will have to be performed by companies within the EEA;
  • Active ingredients, bulk drug substances and final drug products which are manufactured in the U.K. will be treated as imports with regard to provision within the European Union;
  • Small and medium sized enterprises (SME) will only be eligible for EMA SME Benefits if they operate through an SME within the EEA and both U.K. and EEA entities meet the definition of an SME.

Although these Q&A reflect the current legislation, the actual outcome will all depend on the final settlement terms agreed by EU and U.K. governments. If an existing or new structure can be utilised to keep the UK under the EEA umbrella, then many of these potential barriers will disappear. As any arrangements are likely to be reciprocal, affecting pharmaceutical companies based inside and outside the EEA, negotiations may lead to a greater concensus than is apparent at the start.

Queen’s House Consulting is based in U.K. and will continue to offer its services to clients inside and outside the EU. Please contact Queen’s House Consulting to discuss your particular needs.

To read the EMA Q&A, click here.




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