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This coming year could see a combination of regulatory uncertainty and inactivity for the pharma industry, mainly as a result of Brexit.
The main factor will be the United Kingdom’s departure from the existing 28-member state European Union, due to take place on 29 March 2019, almost three years after the country’s voters backed Brexit by a 52/48% margin in a referendum.
Nearly two months before the Brexit deadline day, an EU regulation on the mandatory serialization of drug packaging is scheduled to come into force with a large proportion of pharmaceutical producers and distributors currently looking unlikely to be able to comply with the new rules.
Both events may require the introduction of emergency regulations at the national and EU levels to ensure that patients have continued access to their medicines. This possible rush of temporary rules to protect medicine supplies could be accompanied by a slowdown in activities on more permanent regulatory initiatives.
The European Medicines Agency (EMA), which is not only responsible for the centralized licensing of medicines in the EU but also for providing guidance on existing legislation, will not be working at full capacity for much of next year (1). This is due to its relocation from London to the Dutch city of Amsterdam to ensure that the agency remains based in an EU member state. The move of its offices is forcing the agency to suspend or reduce some operations on preparing the ground for new legislation or improving existing regulations (1).
At the same time, the existing European Commission is completing its five-year term in mid-2019 to be replaced by a new one that could have different regulatory priorities.
Also, in May voters from the 27 remaining member states will be choosing members of a new European parliament (2) who will take their time sorting out alliances and coalition deals before taking on the task of discussing new legislation.
The biggest disruptions are likely to stem from the uncertainties of Brexit, both before it is scheduled to take place and afterwards. In December 2018, four months before the planned departure, it looked possible that the UK could crash out without a withdrawal deal with the EU (3). This would mean that on 30 March 2019 the UK would be considered a third country under the EU’s law without any regulatory ties except those based on the basic trading rules of the World Trade Organization (WTO) (4).
In mid-December 2018, the ruling Conservative party and UK parliament were still split over whether to approve a UK–EU withdrawal deal negotiated by prime minister Theresa May. This deal would allow a transition period until the end of 2020 for the negotiation of a free trade agreement and the implementation of a full Brexit (5).
In a confidence vote on 12 December 2018 among the Conservative party’s 317 members of parliament, close to 40% strongly hostile to the deal opposed the prime minister. This confirmed that the withdrawal agreement would not be supported by a majority in parliament unless May gained further concessions from Brussels.
With approximately 80 million medicines packages a month being traded between the UK-a major centre of drugs production in Europe-and the rest of the EU, pharmaceutical supplies not only in the UK itself but also across Europe would be severely impeded without a withdrawal agreement covering the export and imports of medicines (3). It could also impact wide areas of pharmaceuticals regulation in addition to supplies.
“A ‘no-deal’ Brexit would mean the biggest disintegration of the complex regulated medicines market across Europe in terms of regulation, cross border movement of goods, comparative pricing, and intellectual property,” said Steve Bates, chief executive of the UK Bioindustry Association, representing biopharmaceutical producers, in a blog on 10 December 2018 (6).
Only a few days before, Matt Hancock, the government’s health secretary, had announced more ‘no-deal’ contingency plans. In addition to a previous instruction to pharmaceutical companies to stockpile six weeks supplies, extra storage space would be made available, and shipping routes would be opened specifically for transporting medicines (3).
Amidst fears in the industry about the pan-European effects of a Brexit without a deal, the European Federation of Pharmaceutical Industries and Associations (EFPIA) urged in December the European Commission and the UK to take emergency steps in preparation for a ‘no-deal’ scenario.
“We ask that the European Commission and member states consider every possible measure they can take collectively and with the UK to avoid disruption in the movement of medicines and clinical trial materials across the UK and EU borders,” said EFPIA (7).
Among its suggestions were that medicines and clinical trial materials be temporarily exempted from any new customs and borders checks and the creation of fast-track lanes or priority routes for medicines into ports. Also, it proposed recognition by the EU’s European Air Safety Authority (EASA) of UK air safety certificates to ensure that planes, particularly those carrying medicines, can continue to fly, and the possible exemption of active pharmaceutical ingredients (APIs) as well as other medicines raw materials from border checks (7).
The European Commission may have to relax medicines regulations even before Brexit to remove any unnecessary obstacles to drug supplies. One of these is an EU regulation for the serialization or identification of individual medicine packs, due to be implemented on 9 February 2019 (8).
The regulation, introduced under the EU’s Falsified Medicines Directive (FMD) of 2011 to combat counterfeiting of drugs, stipulates that each medicine should carry specific identification and safety features by the February deadline (8). These include a two-dimensional barcode with a machine-readable data matrix that can be accurately decoded using common scanning equipment.
In preparation for the legislation, medicine manufacturers are having to modernize their packaging lines and adopt new software and communications systems for transferring labelling information to data repositories at national and European hubs. These hubs are connected to a network of wholesalers and pharmacies and other dispensing points across the 32 EU and non-EU states taking part in the scheme (9).
By December 2018, it was evident that while all countries in the scheme would have repositories and hubs with connections to the European hub up and running by the deadline, there will be large numbers of pharmaceutical companies, mainly small-to-medium enterprises (SMEs), which will not be ready by February.
“Pharmaceutical producers, especially SMEs, are running out of time,” explained Bart Vansteenkiste, global life-sciences business development manager at Domino Printing, a UK-based serialization specialist in printing and coding, when speaking with Pharmaceutical Technology Europein December. “Only around 30–40% of packaging production lines in the European pharmaceuticals sector are currently ready for the legislation.”
“According to the text of the legislation, if a medicine pack does not have a compliant label by 9 February 2019, it can’t be dispensed by the pharmacist,” he continued. “It seems unlikely that the European Commission will allow serious shortages to occur because of non-compliance by pharmaceutical manufacturers. Something like a system of fines may have to be introduced to make medicine producers gradually compliant.”
Medicines for Europe, the Brussels-based trade association for generic and biosimilars manufacturers, has called for emergency action to help SMEs struggling with the high costs of updating packaging lines.
“We urgently ask the member states to communicate clear guidance on how they will deal with any actor that would not be able to comply with the FMD as of the deadline,” an association spokesperson told Pharmaceutical Technology Europe.
Meanwhile, the relocation of the EMA has forced the agency to reorganize its activities so that it can focus on the core areas of authorization of new and existing medicines and their variations and safety monitoring during their life cycles. The agency has warned that it could lose as much as 30% of its 900 staff as a result of its move to Amsterdam, where initially it will be accommodated in temporary offices (1).
Well before its relocation, due to be completed by 29 March 2019, the agency has cut back on work in areas such as international activities, guidelines, working party activities, and stakeholder interaction (1).
EMA had estimated that it would be able to resume full operations in mid-2019. But now this resumption may have to be extended well into the second half of the year. “In the latter half of 2019, EMA will gradually reintroduce previously suspended/reduced activities in line with priorities in the (European medicines regulatory) Network’s strategy to 2020,” an EMA spokesperson told Pharmaceutical Technology Europe. “We aim to fully resume our international activities by the end of 2019.”
The EU’s regulatory activities in pharmaceuticals should return to a level of normalcy in 2020, but it may take longer to make up for the ground lost in 2019.
1. EMA, “EMA Brexit Preparedness Business Continuity Plan-Phase 3 Implementation Plan,” EMA/701082/2018 (London, 9 October 2018).
2. European Parliament, “Facts and Figures on European Parliament Elections” (Brussels, 20 August 2018).
3. UK Department of Health & Social Care, “EU Exit-Human Medicines Supply in a March 2019 ‘No-Deal’ Scenario: An Update” (London, 7 December 2018).
4. European Commission, “Brexit: European Commission Implements ‘No Deal’ Contingency Action Plan in Specific Sectors,” Press Release (Brussels, 19 December 2018).
5. European Commission, “Draft Agreement on the Withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union,” TF50(2018)55 (Brussels, 14 November 2018).
6. BIA, “CEO Update,” BIA Blog (London, 10 December 2018).
7. EFPIA, “Brexit: Protecting Medicines Supply in Europe in a ‘NoâDeal’ scenario. The Need for Urgent Action by the European Union,” Position Paper (Brussels, 10 December 2012).
8. European Commission, “Delegated Regulation (EU) 2016/161 Laying Down Detailed Rules on the Packaging of Medicinal Products for Human use,” (Brussels, 2 October 2015).
9. European Commission, European Medicines Agency, Heads of Medicines Agencies (HMA), “Letter to Stakeholders Regarding the Implementation of Safety Features under the Falsified Medicines Directive 2011/62/EU” (Brussels, October 2018).
Pharmaceutical Technology Europe
Volume 31, Number 1
When referring to this article, please cite it as S. Milmo, "A Year of Possible Regulatory Upheaval and Paralysis," Pharmaceutical Technology Europe 31 (1) 2019.