Batch testing medicines
This notice updates businesses on the arrangements that will come into force in the unlikely event that the UK leaves the EU on 29 March 2019 with no agreement in place for the regulation of human medicines. This notice only covers arrangements with reference to:
- batch testing, by manufacturers, of human medicines
- Qualified Person (QP) certification and release, by manufacturers, of human medicines
The July 2018 white paper on the future relationship between the UK and the EU set out the government’s offer to explore the terms on which the UK could remain part of the European Medicines Agency (EMA). The Prime Minister has also set out our desire to ensure that products only need to undergo one series of approvals in one country – this is essential in continuing to get new medicines and devices to patients quickly.
However, we recognise that companies need certainty on the future requirements for batch testing and QP certification and release after the UK leaves the EU and it’s important that we put in place appropriate contingency plans for other potential outcomes from the EU exit negotiations.
Batch testing is the process of confirming every batch of medicine has the correct composition through laboratory tests. QP certification and release is the confirmation that the batch meets the requirements of the Marketing Authorisation (MA) and is suitable for sale and supply or export.
The pharmaceutical sector may also wish to consider other relevant notices, including on IT systems, general life sciences, intellectual property, and other manufactured goods. Further guidance on the future regulatory framework for medicines, including biological medicines, IT systems requirements, manufacturing and import licensing will be published later this year.
Before 29 March 2019
Manufacturers can batch test medicines anywhere in the EU, EEA or other third countries with whom the EU has a ‘Mutual Recognition Agreement’ (MRA) under Article 51(2) of Directive 2001/83/EC (“the Directive”).
For human medicines manufactured in the UK, a UK-based Qualified Person must certify the batch testing and ensure compliance with the MA and Good Manufacturing Practice (GMP) guidelines. These medicines can then be sold or supplied anywhere in the EU or EEA, including the UK, without further certification.
For human medicines manufactured in the EU/EEA, the batch testing and certification or release by an EU or EEA based QP allows a batch of human medicines to be sold in any other EU or EEA country (subject to the requirements of the country), including the UK, without the need for any further certification.
For human medicines manufactured in a third country outside the EU or EEA and imported into the UK through the EU or EEA, batch testing is required within the UK, EU or EEA, unless the medicine has been manufactured in a third country with which the EU has an MRA.
However, a human medicine manufactured in a third country requires a QP based in the UK, EU or EEA to certify that it meets all the required standards and specifications of the Marketing Authorisation, before it can be sold or supplied in the EU or EEA (including the UK).
After 29 March 2019 if there’s no deal
In the unlikely event of no deal, the UK would no longer be part of the EMA.
In order to ensure continuity of supply in medicines however, the UK will continue to accept batch testing of human medicines carried out in countries named on a list set out by the MHRA. On exit day, this list would include EU countries, other EEA countries and those third countries with which the EU has an MRA.
The UK will also continue to accept batch testing of Investigational Medicinal Products (IMPs) – substances being used in medical trials – manufactured in EU and EEA states. There will be no change to the present arrangements for batch testing of IMPs manufactured in third countries.
For human medicines manufactured in the UK, we will continue to require a UK-based QP to certify the batch testing and to ensure compliance with the Marketing Authorisation and GMP guidelines, before these medicines can be sold or supplied in the UK.
For human medicines manufactured in a third country and directly imported into the UK, we will continue to require a UK-based QP to certify the batch testing, as well as to ensure compliance with the MA and with GMP guidelines, before they can be sold or supplied in the UK.
Where human medicines are manufactured in a third country but are imported into the UK from a country on a separate list maintained by MHRA (on exit day, this list will contain EU and EEA countries), we will continue to recognise certification, release and assurance of compliance with the MA and with GMP guidelines, if conducted by a QP based in the listed country, without the need for any further certification.
For human medicines manufactured in a country on the MHRA’s QP list, which have the relevant QP certification, we will continue to recognise certification, release and assurance of compliance with the MA and with GMP guidelines, if conducted by a QP based in the listed country, without the need for any further certification.
The approaches to QP certification of licensed medicines set out above will also apply to IMPs.
These arrangements will continue until the government considers any further change is necessary. We are committed to working with industry ahead of any such changes to the arrangements outlined in this technical notice which might impact supply chains and manufacturing processes, and to giving at least two years notice of the introduction of any changes, in order to allow industry to fully prepare for their implementation.
What you would need to do
In the unlikely event of the UK leaving the EU with no deal, there are different implications for the pharmaceutical sector, depending on whether they are selling human medicines onto the UK, EU or EEA market.
To ensure continuity of supply in medicines, we would continue to accept batch testing of human medicines done in certain countries included on a list which will be set out by the MHRA. We would apply the same approach to QP certification and release as we do now.
The EMA has published guidance on its website as to the approach EU and EEA countries will take to human medicines that are batch tested and certified and released by a UK based QP if there’s no deal.
Ensuring blood and blood products are safe
The purpose of this notice is to set out to UK blood establishments, hospital blood banks, manufacturers of blood products and members of the public, the actions they should consider in the unlikely event that the UK leaves the EU in March 2019 with no agreement in place.
Before 29 March 2019
The EU has a common set of quality and safety standards for blood supply – including the collection, testing, processing, storage and distribution of human blood and blood components. The standards are primarily used by blood establishments, hospital blood banks and the Medicines and Healthcare products Regulatory Agency (MHRA), the regulatory authority.
In the UK, these standards are set out in the Blood Safety and Quality Regulations 2005. This transposed Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003, its associated amendments and relevant implementing legislation.
The UK is largely self-sufficient in the supply of blood and blood components. We occasionally export rare frozen red blood cells (usually fewer than 10 units a year) to EU and non-EU countries. We import from the EU per year around 6.5% of plasma units issued in the UK.
As this area is devolved the UK Government is currently engaging and consulting with the devolved administrations to establish a framework for UK-wide this policy area.
After 29 March 2019 if there’s no deal
If there’s no deal, the EU Blood Directives would no longer apply to the UK. Arrangements for sharing blood, blood components and information with EU partners would be based on the UK’s status as a third country.
Blood establishments importing blood or blood components from the EU for transfusion would be required to add a description of activity to cover import to their blood establishment authorisation.
To export blood or blood components to the EU, establishments may need to certify that any products comply with EU standards. However, EU countries should be aware of the EU Commission position for such imports, and should note that these products will need to be tested in conformity with the Union testing requirements. In both cases, it is recommended that the MHRA is consulted prior to importing or exporting blood or blood components to or from the EU.
If there’s no deal, the current blood safety and quality standards for blood and blood components would not change. The Blood Safety and Quality Regulations 2005 would be retained in UK law under the EU (Withdrawal) Act powers. The new regulation would maintain the current standard of blood quality and safety on exit day and enable updates to be made to the blood safety and quality standards to respond to emerging threats and changing safety, quality standards and technological advances.
We are engaging with blood establishments, the MHRA and devolved administrations to ensure that there is day one operability for blood safety and quality. We are currently, consulting with the devolved administrations to ensure that there is flexibility to update the safety and quality standards to respond to emerging threats and changing safety, quality standards and technological advances.
Blood establishments, blood banks and manufacturers of blood products
Blood and blood components from the UK would continue to conform to the current EU testing requirements (Directive 2002/98/EC4). They would also meet with the equivalent standards (Directive 2004/33/EC5) of quality and safety as implemented by the UK Blood Safety and Quality Regulations 2005.
To import blood or blood components into the UK from any country, including EU/EEA countries, you would need to ensure that each unit of blood and blood component imported continue to be prepared in accordance with standards equivalent to the EU standards (which have been transposed into UK law) and requirements set out in the Annex to Commission Directive 2005/62/EC and meets the standards of quality and safety equivalent to those we currently have implemented. These standards are also set out in Part 5 of the Blood Safety and Quality Regulations 2005.
To export blood or blood components from the UK to any EU/ EEA country, you would also need to ensure that each unit of blood and each blood component exported continues to conforms with the EU testing requirements (Annex IV, Directive 2002/98/EC4) and meets the equivalent standards of quality and safety (Annex V to Directive 2004/33/EC5).
Manufacturers of blood products
You should comply with Directive 2002/98/EC for the collection and testing of human blood and human plasma, for use in manufacture of blood products.
Members of the public
These changes would not affect the safety, quality or supply of blood and blood components in the UK as the current standards would be maintained.
How medicines, medical devices and clinical trials would be regulated
Submitting regulatory information on medical products
The purpose of this notice is to inform MHRA (Medicines and Healthcare products Regulatory Agency) stakeholders of what they’ll need to do to continue to submit regulatory information to us in the unlikely event of a no-deal scenario.
Before 29 March 2019
We’re currently a part of the EU regulatory networks for medicines and medical devices. These regulatory networks have shared processes and systems.
You can submit information into one place for it to be shared around all EU and EEA countries.
The shared systems, in the case of human medicinal products, include, but are not limited to:
- CESP (common European submission portal)
- EMA (European Medicines Agency) gateway
- Common repository
- PSUR (periodic safety update report) repository
- PedRA (paediatric record application)
- EudraCT and the new CTR (clinical trial regulation) portal
- Article 57 database
- EudraLink and EudraMail
For medical devices, shared systems include, but are not limited to, the European Databank for medical devices (EUDAMED).
Shared systems also exist for other products, such as the EU common entry gate (EU-CEG) for tobacco products, e-cigarettes and refill containers.
After 29 March 2019 if there’s no deal
If there’s no deal, the UK would no longer be part of the EU medicines and medical devices regulatory networks. The sharing of these common systems, and the associated exchanges of data, between the UK and EU/EEA countries would end.
We would have our own processes and systems to manage UK human medicines and devices regulatory activities. To do this, some new systems are being developed for March 2019.
Implications for MHRA stakeholders
You would need to submit regulatory information relating to human medicines and devices directly to us.
We would have a national portal(s) for you to submit regulatory information into. The following types of information would be submitted via a portal (not an exhaustive list):
- marketing authorisation (MA) applications
- periodic safety update reports (PSURs)
- paediatric investigation plans (PIPs)
- clinical trial applications
- qualified person for pharmacovigilance (QPPV) and pharmacovigilance system master file (PSMF) notifications
- individual case safety reports (ICSRs) and subsequent transmission of anonymised single patient reports (ASPRs)
- device registration
- e-cigarette notifications.
For applications that you plan to submit to both the EU and the UK (for example, a MA for both EU and UK markets), you would need to submit the information separately through EU systems and our portals.
We’re following the below principles in developing independent processes and systems for regulatory activities.
- We would minimise impact on stakeholders, where possible. For example, we would continue to accept EU application forms and EU standards for submission, where possible. We would continue to accept the eCTD (electronic common technical document) for submission of regulatory documents relating to an MA.
- We would avoid unnecessary complexity, for example by following existing processes.
- We would have systems up and running for March 2019. They would then be developed further over time.
Development of new systems
We’ll provide communications and guidance on the new processes and systems ahead of March 2019, so that you are able to use them from day one. We’ll communicate as soon as possible and intend to do this later this year.
We’ll need some of our stakeholders to help us test our systems before March 2019, and where, required, we’ll also provide training.
If you need to change your own systems to work with our new portal(s), we plan to provide notice and guidance to help you do this later this year.
If your organisation will continue to be an EU stakeholder
UK organisations should be able to continue interacting with the EU regulatory network as per EMA guidance and EU guidance.
Quality and safety of organs, tissues and cells
The purpose of this notice is to set out to organisations, businesses and members of the public the actions they should consider taking, to ensure continued access to and use of organs, tissues and cells, including reproductive cells, in the unlikely event that the UK leaves the EU in March 2019 with no agreement in place.
Negotiations are progressing well and both we and the EU continue to work hard to seek a positive deal. However, it’s our duty as a responsible government to prepare for all eventualities, including ‘no deal’, until we can be certain of the outcome of those negotiations.
Before March 2019
The EU has a common set of standards to ensure the quality and safety of:
- organs for transplantation, and
- tissues and cells for human use, including reproductive cells
The UK regulatory frameworks set high standards and are taken from a number of EU directives. These regulations cover issues such as obtaining, testing, processing, storing and tracing organs, tissues and cells.
UK organisations such as hospitals, stem cell laboratories, tissue banks and fertility clinics that undertake licensable activities working in this area are regulated by:
- the Human Tissue Authority (HTA) for organs, tissues and cells other than reproductive tissues and cells
- the Human Fertilisation and Embryology Authority (HFEA) for reproductive tissues and cells
At present some organs, tissues and cells move between the UK and EU countries, but also between the UK and non-EU countries (third countries).
Only a small number of organs are shared with EU and non-EU countries:
- 22 organs from deceased donors came into the UK from the EU in 2017/18
- 26 organs left the UK in 2017/18, with 19 going to the EU and 7 to non-EU countries
Tissues and cells (for example bone, heart valves and corneas) are imported from and exported to EEA countries less often than they’re imported and exported from and to countries outside the EEA.
The UK imports donated sperm, primarily from commercial sperm banks in the USA and Denmark. Approximately 4,000 samples were imported from the USA and 3,000 samples from Denmark in 2017, as well as a small number from other EU countries. Imports of eggs and embryos are far less common (usually fewer than 500 a year) and come mostly from EU countries.
After March 2019 if there’s no deal
If there’s no deal, the EU Organ Directives and EU Tissues and Cells Directives would no longer apply to the UK. UK law already implements the EU directives, so the safety standards would not change. The UK would, however, become a ‘third country’ and the law would be amended under the EU (Withdrawal) Act to reflect this change.
UK licensed establishments working in this area, such as hospitals, stem cell laboratories, tissue banks and fertility clinics would continue to work to the same quality and safety standards as they did before exit but some would need new written agreements with relevant EU establishments. UK licensed establishments that import or export tissues or cells from EEA establishments would need to make written agreements with those EEA establishments to continue importing or exporting these products post-exit. However, this will for the most part be a minimum burden on industry.
For example, UK licensed establishments that already hold an import licence to import tissues and cells from third countries will be able to use their existing written agreements with third country organisations as a template.
What you would need to do
Members of the public
These changes will not affect the availability of organs or the safety or quality of organs, tissues and cells in the UK as the current standards will be maintained.
Organs for transplantation
NHS Blood and Transplant (NHSBT), which is the organisation responsible for organ donation and transplantation in the UK, is currently working with the UK regulator for organs, the HTA, to ensure that appropriate written agreements are in place with EU organisations to allow organ exchange to continue post-exit. Transplant centres do not need to take any further action.
If there’s no deal, on 29 March 2019 the UK would meet the current EU safety and quality standards for organs, and these would be traceable from donor to recipient and from recipient to donor.
After exit day, the UK and EU countries would consider each other as third countries. The EU directive 2010/53/EU allows for organ exchange between EU countries and third countries. Organisations that currently exchange organs can make written arrangements to ensure organs can still move between the UK and EU countries.
Tissues and cells for human use, including reproductive cells
If there’s no deal, on 29 March 2019 tissues and cells from the UK would meet the current EU safety and quality standards.
After exit day, the UK and EU countries would consider each other as third countries. The EU directives 2004/23/EC and 2015/566 allow for written agreements to be made to import and export tissues and cells for human use between EU countries and third countries. The details of what these written agreements cover are set out in EU directive 2015/566. Licensed establishments that import or export tissues or cells would need written agreements with the relevant EU licensed establishments to continue importing and exporting. UK licensed establishments that already hold an import licence to import tissues and cells from third countries can use their existing written agreements with third country organisations as a template. Licensed establishments are recommended to consult the HTA and HFEA for more information. Further information on the agreement process will be published in November.
The government continues to plan for all negotiation outcomes, and will make the necessary changes to national regulations to maintain day one operability for the import and export of organs, tissues and cells in the unlikely event there is no agreement between the UK and the EU.
This Article draws on information published by the UK Department foe Exiting the EU “UK Government’s Preparations for a no deal scenario” August 2018. UK public sector information is reproduced pursuant to the Open Government Licence The Legal Materials contain UK public sector information licensed under the Open Government Licence v3.0. The Licence is available at http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/ (the UK Licence).
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