Intended for healthcare professionals


Crisis in the supply of medicines

BMJ 2019; 367 doi: (Published 04 October 2019) Cite this as: BMJ 2019;367:l5841

Linked Opinion

Securing regular medications is a lottery every month

Linked Letter

Brexit and medicine shortages: evidence from trade data

  1. R E Ferner, honorary professor of clinical pharmacology1,
  2. J K Aronson, clinical pharmacologist2,
  3. C Heneghan, professor of evidence based medicine2
  1. 1Institute of Clinical Sciences, University of Birmingham, Birmingham, UK
  2. 2Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  1. Correspondence to C Heneghan carl.heneghan{at}

Drug shortages have complex causes and important clinical and economic consequences

Shortages of medicines may harm patients by depriving them of treatment or forcing them to use different products.1 Pharmacists cannot legally substitute alternatives without consulting prescribers and may have to refer patients back to their clinician. Errors are also more likely when doctors prescribe unfamiliar medicines and when patients take them—a shortage of lomustine in France led to unintentional overdoses when a different product was substituted.2

The prospect of Brexit has raised concerns about possible UK shortages of medicines. However, shortages are already common globally. Australian prescribers face critical shortages of 56 medicines3; around 5% of licensed medicinal formulations are unavailable in Belgium4; in 2018 there were 769 shortages in the Netherlands5 and the French regulatory agency managed 871 shortages, compared with 405 in 20166; and in the US 213 drugs are currently in short supply.7 In the UK over 900 formulations have been in short supply at some point since 2014, for periods of weeks to months, some indefinitely; current shortages include hormone replacement therapy, oral contraceptives, and antiepileptic drugs.8


The causes of shortages are often complex. Active ingredients for European products are made at 4420 sites in India, 2794 in China, 1936 in Europe, and 599 in the US.9 Medicines are cheaper to make in developing countries, but disruptions to infrastructure are more likely, distant factories are difficult to inspect frequently, and long supply chains are fragile. Changes in clinical practice guidelines can cause unexpected surges in demand. Even when demand can be forecast, the supply chain may fail to match it.

Occasionally, the causes are clear. For example, months of shortages followed a power failure at a French blood products factory.10 An international shortage of angiotensin receptor blockers resulted when products contaminated with potentially carcinogenic nitrosamines were withdrawn.11 Since three quarters of UK medicines arrive through Channel crossings, any customs restrictions after Brexit will probably cause major delays.12


Shortages have clinical consequences. They cause treatment delays, distress to patients, inefficiencies,13 and medication errors and can affect any category of medicines.14 The problems worsened from 2014 to 2018, according to surveys of European hospital pharmacists.15

Shortages also have economic consequences. The price of a medication may increase if it is in short supply or demand increases, as is currently happening. In England, the number of items prescribed per head of the population each year increased from 14.8 in 2006 to 20 in 2016.16 The UK Drug Tariff sets NHS payments to community pharmacies for generic medicines. When a pharmacy cannot buy at or below the tariff price because of shortages, the Department of Health may pay pharmacies a concessionary supplement.17 The number of concessions rose from 282 in 2016-17 to 709 in 2017-18,16 at an estimated cost to the NHS of £160m (€180m; $197m).18

Parallel trading, in which medicines can be imported from a European country and immediately exported to another, complicates matters.19 The incentive is profit, based on price variations and fluctuations in exchange rates.


Shortages are unlikely to diminish while there are global fluctuations in the supply of medicines. We should therefore strive to make the NHS resilient.

Key generics could be manufactured locally to reduce the NHS’s reliance on market forces. That would mean establishing facilities that met the UK’s stringent regulatory requirements for good manufacturing practice. We could not manufacture products protected by patents without approval from patent holders.

The UK Department of Health and Social Care, anticipating shortages after a no-deal Brexit, has exhorted companies to increase their stocks and intends to establish an “express freight service.”20 Stockpiling21 is still incomplete,22 and stockpiled medicines may be sold elsewhere before they go out of date. The department has also signed a contract with two manufacturers to provide intravenous and peritoneal dialysis fluids, previously not included in the essential medicines buffer stockpile23 set up in 2010: the buffer now contains around 500 essential medicines.24

Following the Association of the British Pharmaceutical Industry’s call for a temporary restriction on parallel exports from the UK to the EU to preserve supplies,25 the UK government has banned wholesalers from exporting 24 critical drugs, to counter speculative trading.26 However, the effect on imports is uncertain; supply problems may be worse,27 and costs may increase.28

The UK proposal to establish “serious shortage protocols”29 should be encouraged. If the health minister agreed that a shortage was serious and exceptional, pharmacists, under protocols developed in collaboration with clinicians, would be empowered to dispense substitute formulations.

Until these problems are solved, doctors and patients must contend with drug lists that have unpredictable and increasingly frequent gaps. Sometimes alternatives will be identifiable, but there will often be therapeutic and financial costs.


We thank Anthony Cox from the University of Birmingham for helpful comments.


  • Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: REF is adviser to The BMJ for the series on therapeutics, and until recently a member of the Birmingham, Sandwell and Solihull area prescribing committee. CH is editor in chief of BMJ Evidence-Based Medicine, receives funding support from the NIHR, and is an NIHR senior investigator. He is director of the Centre for Evidence-Based Medicine (CEBM), which jointly runs the EvidenceLive Conference with BMJ and the Overdiagnosis Conference with some international partners, which are based on a non-profit model. JKA is an associate editor of BMJ Evidence-Based Medicine and a member of the CEBM.

  • Provenance and peer review: Commissioned; externally peer reviewed.


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