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Patients' worries about supplies of insulin, as well as other diabetes medications and devices due to Brexit have not, so far, been born out in reality, but the long-term situation remains uncertain as cross-border movement of goods is set to rise, according to experts.

In particular, Northern Ireland puts a fine point on these concerns with difficulties already apparent at border crossings.

Experts also warn patients against stockpiling medicines and related goods, which would in itself create product shortages not directly related to Brexit border issues.

"In some areas the cure is worse than the disease," cautioned Mark Dayan, MSc, Brexit programme lead at the Nuffield Trust.

At only 7 weeks after the end of Brexit transitional arrangements, it is reasonable to assume that the first few weeks are a relatively artificial reflection of the longer-term status quo around the bidirectional trade between the UK and EU.

Concerns around the supply of devices and medicines including insulin are very real to those whose lives depend on it, but in reality, how valid are they?

Back in 2018 when Brexit negotiations were in full-flow, the scene was set when senior officials expressed concerns around insulin supply. Sir Michael Rawlins, who was chair of the Medicines and Healthcare products Regulatory Agency (MHRA) at the time, told the Pharmaceutical Journal that: "We make no insulin in the UK. We import every drop of it. You can't transport insulin around ordinarily because it must be temperature-controlled."

Then a study of tweets posted in 2019 by people with diabetes reflected that these concerns were rife among patients too. At this point the outcome of Brexit 'no deal' or 'deal' negotiations were unknown.

Recently published in JMIR Diabetes on 27 January, the study investigated patients' views around lots of disease-related issues, but of note, the tweets around diabetes product supplies were particularly poignant.

Insulin supply is a key concern for dependent patients because a lack of the replacement hormone can be fatal. The study found that 9% of tweets featured real worries among diabetes patients relating to insulin availability, whatever the outcome of Brexit negotiations.

Tweets emphasised the desperation and fear of some patients. One wrote: "INSULIN - for most of you it is just a medical term, but it is a lifesaver for me and other type 1 diabetics. Do I buy a big fridge to stockpile to make sure I can live while you #brexiters apply for your new blue passport?"

Another wrote: "Diabetics are not sure if their life-saving insulin will run out.So many medications CANNOT BE STOCKPILED!It's a DEATH THREAT from the government and violates our human right to life. #NotoDeathbyBrexit #DyingforBrexit."

Su Golder, PhD, from the University of York led the Twitter study. "UK-based patients with type 1 diabetes were all very worried and scared about supply," she told Medscape UK in an interview. "We don't know if these concerns were real, but the opinion expressed does show how vulnerable these people feel.

"Because insulin is a life-saving drug that needs storing in the fridge, it can't really be stockpiled," she adds.

Nikki Joule, policy manager at Diabetes UK, lends support but also contextualises these concerns. "The worry is understandable, particularly around insulin because people depend upon it for their lives," she said, but added that, "I think much of the concern expressed by people with diabetes is really anxiety and hasn't been borne out by reality, so far at least, and certainly not above and beyond normal short-term shortages that happen, Brexit or not."

Diabetes UK says it has supported Government calls to suppliers of insulin and other diabetes medicines too, asking them to keep 6 weeks of stockin the UK. "Contingency plans comprised alternative routes into the country, extra stock being held on UK soil, and the Department of Health and Social Care (DHSC) ensured those levels of stock with both medications and device companies," said Nikki Joule.

"In fact, we were aware that some companies had threetimes more stock than a 6-week supply, and so far, to our knowledge at Diabetes UK, supply routes seem to be operating well," she added.

The DHSC was always concerned about insulin given how essential it is for people with type 1 diabetes and others who are dependent on insulin, said Ms Joule, and this concern was not only due to the risk of 'no deal' but also for potential disruption due to restrictions or supply issues around COVID-19. "The same actions and contingency plans around supply would need to be taken whether issues were related to Brexit or COVID."

She also noted that stock problems are unlikely for many diabetes medicines such as metformin or gliclazide, because they are made by a large range of companies in the UK.

The default 'no deal' scenario never came to pass, and the EU-UK Trade and Cooperation Agreement was signed on December 24, 2020.

In an interview with Medscape UK, Mr Dayan explained some of the new processes and challenges underpinning the movement of medicines and devices, including those for diabetes, across borders between the European Union (EU) and UK.

Essentially, concerns prevail around customs and regulatory processes, including medicines' safety alert systems.

Since January 1, 2021, customs processes around the logging of import and exports declarations, as well as new permits and details have been required by hauliers to enable movement between countries.

In terms of diabetes-related products moving into the UK from the EU, the border checks and customs declarations required by UK authorities facilitate a smoother flow of goods into the UK than vice versa.

"Right now, things are relatively under control," said Mr Dayan, adding that companies have some concerns, but this does not seem to have led to more shortages than normal. He pointed out that this reflected several years of work by the DHSC and companies in trying to negotiate the best way forward.

To minimise any difficulties associated with Brexit, the UK has provided various grace periods for products entering the UK from the EU, explains Mr Dayan. "For example, deferral on customs forms for 6 months at the UK border, and a 2-year grace period for regulatory issues. Most relevant are the border-to border easement measures, so the UK is accepting batch testing certificates until 2023."

Some arrangements are more mutually beneficial than others and facilitate trade. "The trade and cooperation agreement that came out on Christmas Eve contains mutual recognition for Good Manufacturing Practice (GMP) for medicines, and EU inspection certificates are still accepted here in the UK," Mr Dayan highlights.

"Unfortunately, many of the easements applied by the UK are not reciprocated by the EU," he pointed out.The safety of medicines databases does raise some concerns, Mr Dayan says. When it left the single market, the UK also left behind its right to submit or receive safety alerts and data from the EU systems for pharmacovigilance (EudraVigilance) or devices (EudaMed). "The danger is that we are, as a result, less well informed about emerging or potential problems with drugs and devices on the market," says Mr Dayan.

Alone, the UK has a smaller population to report safety issues than the EU, and safety issues become more visible with higher patient numbers. However, he points out that reporting systems in the EU and US should mean any safety issues or anomalies are visible but the UK will not necessarily have direct access to these databases. "I'm not overly optimistic about this changing. I'd like to have seen more on this in the trade agreement."

The complex situation in Northern Ireland, which is subject to the Northern Ireland protocol (to overcome the need for a border between the Republic of Ireland, which is still part of the EU, and Northern Ireland, which is no longer part of the EU, there is an arrangement whereby there is effectively a border check down the Irish Sea) is challenging and promises to continue to be so.

"The situation around regulatory switch overs in Northern Ireland is making it far more difficult for companies to move medicines from the mainland,"Mr Dayanremarks.

This will remain a live issue, with Cabinet Office Minister, Michael Gove, recently requesting an extension to the existing grace period beyond April.Mr Dayanhighlights that this reflects genuine concerns around the situation there. "For medicines, Northern Ireland has effectively stayed in the EU, and the movement of medicines from the UK [mainland] faces similar hurdles as shipping them anywhere on the continent. This is certainly an area where there is more risk."

The UK is only 7 weeks into Brexit and many companies gave January a wide berth, avoiding the borders for fear of confusion and delays. As a result, cross-border controls have run relatively smoothly to date. The next few months might paint a different picture with volumes of trade at borders picking up.

With all of the UK's insulin imported from the EU, concerns are not without foundation. Supplies are all sourced from EU-based manufacturing and distribution centres, with the main providers being Sanofi (France), Novo Nordisk (Denmark), and Lilly (various EU locations).

But Mr Dayan explained that despite all the UK's insulin supply being imported, insulin supply from the large pharma companies is less risky than medicines made by smaller firms. "These companies might be less capable of dealing with Brexit-related changes around operating across different markets," he said.

On January 1, when the transition period ended, many companies responded to the anticipated pressures and extra administrative needs of Brexit by avoiding the border altogether. "However, at some point this will recover, and as trade volumes increase it might get more difficult. We need to start thinking about the longer-term, for example, around the introduction of new products and long-term cost implications," he cautions.

People building their own personal stockpiles of medicines is the greatest concern stressed by both Mr Dayan and Ms Joule, and more widely. "It isn't a good idea for patients to stockpile because that will create shortages. If people start stockpiling generally then it could apply to other types of medicines and be a greater problem than the effect of Brexit itself," Mr Dayan says.

Most devices, notably continuous glucose monitors (CGM) and goods such as testing strips and sensors, are largely made and supplied by the EU. Exceptionally, the Abbott FreeStyle Libre is made in the UK, and digital interventions likeLow Carb Programare also produced in the UK.

Supply of testing strips or sensors for CGMs might be more challenging than medications, especially ones that need frequent changes such as sensors that require replacement every 7 days.

In early January, people reported a problem obtaining sensors for a Medtronic pump, Ms Joule said, explaining that it actually turned out the delay was with the delivery firm and related to documentation rather than anything to do with the company directly. "This has been resolved now," she says.

Mr Dayan identifies that a key issue for devices is the validity of the manufacturer's CE mark. For UK firms wishing to export their devices to the EU, they would have needed to switch their CE (ConformitEuropenne) mark to an EU regulator prior to January 1, he said. "A UK regulator would not now be able to grant them a CE mark for export to the EU. These firms also have to work through many new customs and border checks for export to the EU that do not reflect the grace period that the UK is applying."

In theory, there is a UK equivalent of the CE mark known as theUKCA(UK Conformity Assessed) marking, which came into effect on January 1, 2021. It is a novel UK product marking that is used for goods being placed on the market in Great Britain (England, Wales, and Scotland). It is not yet widely used in practice. "It covers most goods which previously required theCE marking," says Mr Dayan. However, he adds, there is a grace period until mid-2023 when the UK will still accept EU-granted CE markings.

At the completion of the grace period, new devices made in the EU will need to obtain a UKCA marking as well as an EU CE mark. "This has the potential to increase costs at many steps," Mr Dayan points out.

Costs are predicted to increase once the grace period has passed and new checks, and a higher volume of checks, will need to be implemented.

Various studies have tried to work out the costs of having a free trade agreement versus being in the single market. One studyshowed a significant 5% increase in costs. "Given the NHS spends around 20 billion annually on medicines, that would require an extra one billion pounds," says Mr Dayan.

However, many medicine prices are resistant to price fluctuations due to a set drug price tariff, and a voluntary scheme that caps medicine costs, he explains."Companies are more likely to decide it is unprofitable to supply the UK anymore."

But insulin is unlikely to be affected, he stressed. "Lack of supply due to cost is unlikely to be an issue for insulin, which is a bulk product the UK is very willing to pay for."

However, for higher profit margin items, or at the other extreme, generic medicines where the profit margin is very low, firms might stop supply and this could lead to shortages, he adds. This happens quite regularly despite Brexit, he explained, and has happened more frequently since the EU referendum, probably due to the fall in the value of the Great British pound, which makes some products less profitable."For generic products, we would probably just pay more for them."

But the biggest concern will not be for medicines already on the market, but for new ones, said Mr Dayan. "The UK might be a lower priority market for new products. This tends to happen with smaller markets compared with the EU or US large markets."

Firms might not invest time and resource in a market that has lower returns. However, noted Mr Dayan, size might not be the only consideration. "I suspect the UK will try to use its regulatory system to remain an attractive place to introduce new medicines," he asserts.

"The MHRA granted approval to the COVID-19 vaccines quickly and the UK might be able to offer accelerated routes as an incentive."

More:
Diabetes Product Supply Is This the Calm Before Storm Brexit? - Medscape

This entry was posted on February 19, 2021 at 6:48 am and is filed under Diabetes. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |