Notes From Brexit: HPRA-Stakeholder Engagement Event Held on 31st Aug 2017

A seminar hosted in Dublin by the Health Products Regulatory Authority (HPRA) heard that a key priority for its post-Brexit strategies is to safeguard against disruption to Irish patients’ access to medicines.  The event, which was attended by over 300 representatives from the biopharma, medtech and life sciences sector, discussed the concerns of different stakeholder groups given the unique context for Ireland in the Europe-wide medicine regulatory environment. Among the organisations speaking at the event were Biopharmachem Ireland, Medicines for Ireland, the Animal and Plant Health Association, IDA Ireland and IBEC, as well as European industry representatives.  Each organisation shared their views on the potential issues Brexit may present in their respective fields.  The key message from the speakers was that while Brexit undoubtedly creates challenges, there are opportunities for IE in all aspects and that IE very much remains open for the healthcare industry.

From the perspective of the HPRA, engagement with the stakeholders allows them to focus their efforts on maintaining the authorisation and supply of existing products, working closely with companies and their fellow regulators across Europe.

Speaker: Dr Lorraine Nolan, Chief Executive, HPRA

There are distinct issues that face Ireland in any post-Brexit scenario: “Whilst the eventual outcomes of the Brexit negotiations are unknown, it is clear that there are potentially significant implications for Ireland with its shared market place with the UK.  This, combined with the fact that Ireland is a small market, can place pressures on the availability of certain products for the Irish market.  The HPRA’s priority is to ensure Irish patients will continue to have access to required medicines post-Brexit. Today’s event is about discussing these and other Brexit-related issues with key stakeholders in the sector.”

“The HPRA has established an internal working group which has already started planning for all possible eventualities and outcomes that may occur when the UK withdraws from the EU market.  It is the HPRA intention to regularly engage with industry representatives and individual companies to offer guidance and support to ensure the continued availability of their products to Irish patients.  They have already begun surveying the industry in relation to their intentions regarding marketing their products post-Brexit and this provides very useful information for planning purposes.

The HPRA has also announced that it will increase its contribution to the European assessments of human and veterinary medicines, in conjunction with other Member States, to minimise the impact of the loss of the UK’s significant contributions to the system.  It has begun planning and identifying its future resource requirements with the support of the Department of Health and the Department of Agriculture, Food and the Marine.

Regardless of the nature of the final negotiated UK exit, the HPRA stated that it is imperative to maintain close links with the UK’s medicines agencies in the future given the proximity of the two markets and the many shared stakeholder companies.  Good working relations and engagement between the UK and the European regulatory network will be beneficial to all parties.

Speaker: Rita Purcell, Deputy Chief Executive, HPRA

The HPRA has established an internal working group under the direction of Rita Purcell, Deputy Chief Executive, to ensure that the HPRA are prepared for the UK’s withdrawal from the EU.

At the end of March this year, the United Kingdom (UK) notified the European Council that it intends to withdraw from the European Union (EU).  Together with other Member States and the European Medicines Agency (EMA), the HPRA is preparing to ensure that they continue to deliver on their patient and animal health remit even if the UK fully exits the current systems on 29 March 2019.

The UK continues to play a full role within the European regulatory network during the ongoing discussions in relation to its withdrawal from the EU.  Although the eventual outcomes of these negotiations are unknown, there are potentially significant implications for the European network as a whole and particularly for Ireland with its shared market place.

Protecting the availability of medicines for Irish patients and the integrity of our market are key strategic aims of the HPRA’s Brexit-related activities while also optimising their role within the European regulatory network and maintaining their strong working relationships with UK colleagues. In relation to veterinary medicines, the HPRA recognises the challenges facing Irish agriculture and the impact of Brexit on the availability of veterinary medicines in Ireland.  The HPRA is committed to increasing its contribution to the EU network through assessment of centralised and decentralised marketing authorisation applications, being available to carry out inspections and expanding its role in medical devices.

A major priority for the HPRA is to ensure the availability and the continued uninterrupted supply of human and veterinary medicines and medical devices in Ireland.  The HPRA will provide support to marketing authorisation holders (MAHs) to maintain the availability of medicines and is available to meet with and discuss issues with MAHs, as required.

To assist with this the HPRA has requested MAHs which hold a marketing authorisation in Ireland for a medicinal product for human use, where the UK is the RMS or a CMS, to respond to a survey.  The survey seeks to identify any products where supply and availability may be interrupted in the event of the UK withdrawing from the EU and to ensure that plans are in place to proactively address this.  The HPRA would like to thank MAHs who have already submitted their responses to this survey (currently 30% of MAH’s) and to ask those who have not yet submitted their responses to submit them as soon as possible to article50changes@hpra.ie.

The HPRA have indicated that for products where IE are currently CMS and UK are RMS, the HPRA would encourage companies to change to IE as RMS.  There will not be any HPRA associated fees for this change.

MAHs which hold a marketing authorisation in Ireland for a veterinary medicine, where the UK is the RMS, have also been surveyed to ascertain the likelihood of products being withdrawn from the market and MAHs’ preferences with respect to products that are currently marketed in joint packaging for the Irish and UK markets.

Recognising the considerable contribution currently made by the UK to the work of the European medicines network, the HPRA is ready to assume a greater role in EU regulatory activities post-Brexit as may be required.  The EMA has established working groups to operationalise agreed principles and rules for re-distribution of the centralised workload, see EMA: United Kingdom’s Withdrawal from the European Union (Brexit’). The CMDh has also published information for marketing authorisation holders of nationally authorised products; see CMDh: information on Brexit.  Similar information from the CMDv will be published shortly on the HMA website.

The HPRA already plays a significant role in the European Medicines regulatory network.  HPRA representation in the EMA’s committees and working parties’ mirrors that of the larger agencies in Europe.  The HPRA are highly regarded, holding leading positions including chair of the Committee for Medicinal Products for Veterinary Use (CVMP) and vice-chair of the Pharmacovigilance Risk Assessment Committee (PRAC).

The HPRA have a strong profile in terms of assessment work, ranking in the top 2 in the veterinary medicines assessments over the past 10 years and ranking in the top 10 in Europe for human medicines post authorisation work.  HPRA inspection activities are recognised as providing a strong regulatory environment in Ireland and are heavily relied on for inspection of sites on behalf of the EMA.

The HPRA is fully committed to further increasing its contribution, particularly in human and veterinary medicines assessments and have already begun to plan for this, including identifying the need for increased resources, which is supported by the Department of Health and Department of Agriculture, Food and the Marine.

Companies wishing to discuss any aspect of their operations related to the UK’s withdrawal from the EU should submit their queries to customerservice@hpra.ie clearly indicating whether the query relates to human medicines, veterinary medicines or inspections.

Speaker: Sergio Napolitan, representing the organisation Medicines for Europe

Medicines for Europe began over 20 years ago, as the European Generics Medicines Association (EGA) with the goal of representing the emerging generic industry, and later growing to include biosimilar medicines to its portfolio.  As the pharmaceutical industry and the healthcare environment within which it operates have evolved, so has our Association.

The generic industry now supply over 56% of all medicines in Europe, and over the last ten years, generic medicines have increased access to medicines by over 100% in 7 key therapeutic areas.  For the treatment of high blood pressure alone, almost 50 million patients are taking generics each day, and 20 million people across Europe are now being treated for diabetes with generics.

Technological advances and innovation have had a massive impact on the pharmaceutical industry. The industry has responded to this opportunity with biosimilar medicines.

More recently, the industry has expanded into value added medicines aimed at optimizing, rethinking and reinventing existing medicines based on known molecules, addressing unmet medical needs of patients through improved care delivery systems.

The major priority for the Medicines for Europe Group is to work with the HPRA to ensure the availability and the continued uninterrupted supply of generics, biosimilars and value added medicines into Ireland.  There are challenges e.g. many of these medicines share joint packs with the UK and IE is a small market.  The HPRA anticipate that joint packs will still be permitted even when the UK exit the EU and officially become a third country, as long as the joint pack complies with EU regulations.  Patient access to medicines in the IE market is the main focus, so there will be pragmatic solutions put in place, however, the solutions will need to align with legislation.

Speaker: Loretto Callaghan Novartis Ireland Limited, Chair of IPHA’s Regulatory Affairs Advisory Forum

The Irish Pharmaceutical Healthcare Association (IPHA) represents the international research based pharmaceutical industry in Ireland.  Their members include both manufacturers of prescription medicines and non-prescription or consumer health care medicines.  IPHA engages with national policy so that the healthcare needs of patients are met with valued, innovative medicines.

IPHA’s primary concerns are to ensure that

• Patients in Ireland have access to medicines and continuity of supply.
• Patient safety timely reporting of SAE’s
• Maintenance of supply chain operations in compliance with FMD.

From a regulatory perspective, the MAH for all MA’s authorised in IE needs to be resident in the EEA.  Many IE MA’s are currently held by UK MAH, therefore there is a substantial amount of work to be done in order to ensure that all MA’s are transferred in sufficient time to allow continuity of supply.

In addition, many medicinal packs are joint IE/UK packs.  It is envisaged that joint IE/UK packs can remain, as there is already some divergence and compromise between the agencies with regards to the packs, however joint packs can only remain if the UK comply with EU labelling requirements.

From a PV perspective – After UK leave EU, they will become a third country, therefore it will be imperative in terms of patient safety that the UK continue to meet EU safety reporting requirements.  In addition, the QPPV will need to be resident within an EEA country, therefore if the current QPPV is resident in the UK, that person will either need to relocate, or be replaced.

From a supply chain perspective, for marketed products the UK will be subject to the same requirements in terms of a third country, so import of product from the UK to IE would require a Manufacturers Importers authorisation.  QP release will need to done in the EU, so UK QP’s will either need to re-locate or be replaced.

For CTA’s the EU legal rep will need to be changed from the UK to an EU country and in addition supply of IMP in line with EU GMP requirements will need to be maintained.

Each MAH is currently identifying individual impact and risks of Brexit in terms of medicinal product/supply chain and developing solutions as appropriate.

From an Irish industry perspective, where UK are currently MAH or RMS, industry needs to be working to close out UK procedures before March 2019.  Transfer MA to EU country and change to an RMS within the EU.  Industry needs to look at every aspect of their business including supply chain, QP, QPPV, joint packs etc.  Early communication with HPRA on different situations is vital.

IPHA ‘asks of HPRA

• Continue close partnership
• Timetable for transition arrangements to HPRA as RMS etc. considering sufficient lead times
• HPRA resource planning
• Flexible and practical solutions within the legislation
• Agree critical product list and work with EMA and European regulatory network to ensure that needs of Irish patients and industry are met.

Speaker: Sandra Gannon, Joint Chairperson and Spokesperson of medicines for Ireland, and General Manager of Teva Ireland

The way Ireland procures and supplies medicines is outdated and no longer fit for purpose.  Medicines for Ireland is an organisation founded and motivated by a strong desire to fix this problem.  Globally and in Ireland, the presumption of automatic access to innovative medicines is no longer guaranteed. The supply of medicines requires radical reform so that patients can access life-saving and life-enhancing treatment vital to their well-being.  Achieving reform in this critical area of patient care is a core objective of the organisation.  Medicines for Ireland are committed to working with key stakeholders to effect real change and reforms that ensure Irish patients receive the best medical treatment in the most affordable way.

The implications of Brexit in terms of patient access to medicines lead to uncertainty and potential regulatory divergence.  The greater the divergence, the more cost implications and documentation will be required by companies.  In particular, supply of low volume/low value medicines in IE is largely dependent on sharing of batches/packs with the UK.  Without this option, supply of certain medicines in IE would be unsustainable.

For the licencing of generic products the reference product needs to be authorised in the EEA.

In addition, there is currently unfettered access of goods/people between manufacturing sites in ROI and NI.  Any restrictions on movement of people or goods will have implications for companies with faciilites in both jurisdictions.  It is anticipated that there will be an impact on pricing and parallel trade.

Speakers: Matt Moran Director of Biopharmachem Ireland, Mr Tommy Fanning Head of Biopharmaceuticals & Food at IDA Ireland and Mr Arnold Dillon Brexit Campaign Lead, IBEC

Biopharmachem Ireland is the leading representative body for the biopharma and chemical sector in Ireland.  Their member company’s research, develop and manufacture biopharmaceutical products, ingredients and general chemical material.

Biopharmachem Ireland is committed to providing a receptive environment for a strong and progressive industry in Ireland.  With the support of industry, Ireland can position itself as a centre of excellence for innovation and development in biopharmaceutical and chemical supply, thereby becoming the location of choice for the launch of new products.

IDA (Industrial Development Authority) Ireland is the agency responsible for the attraction and development of foreign direct investment in Ireland.

IBEC (Irish Business and Employers Confederation) is the largest and most active business representation organisation in Ireland.

Brexit offers many opportunities to encourage manufacturing companies looking to locate in the EU to consider IE as their first choice for FDI, however there are challenges to the manufacturing industry e.g.

• UK lowers corporate tax rate, aggressive competition for FDI.
• Funding for research: A significant amount of funding for research comes from the EU, majority of IE research is partnered with research parties in the UK.
• Impact of regulatory divergence/relationship between UK and EU.
• Much guidance is ICH based – where will be UK be in relation to this? Will there be a greater role for the Pharmaceutical Inspection Co-operation Scheme (PICS?).
• It is unclear where UK will be regarding certification (EDQM).
• Where will the UK stand in relation to REACH guidance (addresses the production and use of chemical substances, and their potential impacts on both human health and the environment)?
• The impact of Brexit on the manufacturing industry will depend on the supply chain of companies to varying degrees – varying dependence on the exposure to the UK and the degree of regulatory divergence.

Opportunities

• Many manufacturing companies currently looking to locate into the EU are considering IE as their first choice due to English speaking population.
• The fact that Ireland is considered a hub for manufacturing industry (chemical and biological, CMO, CDMO).
• Regulatory environment in IE is considered excellent in global terms.
• IDA have had many enquiries from manufacturers, packagers looking to locate from the US/UK to an EU country.
• All the top 10 global pharma companies have a presence in IE.
• Cost competitiveness and Tax competitive position of IE.

Need to look at all contingencies now and plan for a ‘hard’ Brexit and support IE companies to allow them to benefit from Brexit.

Speaker: Eugene Smith Chairman of APHA

The Animal and Plant Health Association is the representative body for manufacturers and sole distributors of animal health (veterinary medicines) and plant health (plant protection/agrochemical) products in Ireland.  These industries play a vital role in providing high quality food at an economic cost whilst protecting the environment.

There are challenges facing Irish agriculture and the impact of Brexit on the availability of veterinary medicines in Ireland.

• Currently the UK are RMS for greater than 30% of all veterinary medicines registered in EU.
• Animal population much smaller in IE, so we benefit from MRP.
• Dual Labelling (IE/UK packs account for 75% of all VMP.
• Vital to try and ensure Brexit will not mean divergence of labelling (common culture and seasonality).
• Many VMP manufacturing sites are in the UK – will be subject to import regulations to import into IE.

Closing HPRA remarks

• HPRA key priority for its post-Brexit strategies is to safeguard against disruption to Irish patients’ access to medicines.
• HPRA are experienced at dealing with ‘third countries’ outside of the EU, so the situation is already familiar when UK becomes a ‘third country’.
• Up until March 2017, many MAH’s were still asking UK to be RMS, this number has decreased significantly.
• Each company needs to check where they are with their products and ensure all regulatory activities are completed before change of RMS, MA transfer. Currently the UK are RMS for 30% of medicinal products and perform many regulatory inspections on behalf of other European agencies.
• HPRA resource will be increased significantly – more RMS function, scientific advice function, inspection function etc.
• HPRA are currently in discussion with MHRA and EU regulatory network as to how best to manage portfolio’s.
• It is not clear currently whether MHRA can remain as joint assessor of notified bodies with the HPRA – impact on medical device industry.
• Medical device industry facing dual challenges of Brexit and new medical device regulation.
• HPRA intend to work with companies to develop pragmatic solutions to industry, however legislation may trump pragmatism if there is a hard Brexit and regulatory divergence emerges.
• HPRA will work to reduce the administrative burden and cost of regulatory actions due to Brexit (e.g. no cost for change of RMS from UK to IE, bulk transfer authorisations).
• Early two-way communication is essential between companies and HPRA so that any specific companies’ issues/circumstances are resolved in as pragmatic and efficient way as possible.