Solutions?

Solutions to the drug shortage are elusive, mostly because we do not understand the causes.

There are of two types of solutions. — mitigating and preventive. Only the first has received much attention or action. However, the second invites imaginative new procedures that could transform the industry. See more below.

But to manage or prevent shortages, first we need to MEASURE them! to understand what exactly they are!

Canada lists drugs in short supply but it is not measuring the rate, duration, frequency, or nature of the drug shortages through time. A 2017 IPF report compared Canada’s tracking with that of other nations. Without this information, it is difficult to fully understand its nature, impact and causes. Out of frustration, our team published the first ever measurement of the Canadian drug shortage with the C.D. Howe Institute on 5 June 2018. For a summary, see here.

The US FDA has published annual reports on shortages since 2012 (e.g., 2018 is here). But as far as I know it is unique. With numbers and duration of shortages spiking, the US FDA public consultations on 27 November 2018 reviewed 19 recommendations from a coalition of healthcare groups that were published by ASHP. This late 2023 report also offered some suggestions: Christina Jewett, Possible ways to ease drug shortages, New York Times, 19 December 2023. Policy solutions were described in Brookings in March 2024.

In January 2020, UK admitted that it did not even maintain a national list of shortages, while the European Medicines agency is trying to create a single database for shortages in the EU. Switzerland has such a list. In the same month, China announced that it will create a list.

In early 2020, the European Association of Hospital Pharmacists released their report on shortages for 2019 with recommendations. The pressure of COVID-19 and worsening of drug shortages by  early April 2020 caused several to argue for solutions to fix the already longstanding problem (for example  Choo et al., in Mayo Clinic Proceedings). In November 2021, the American company Vizient launched End Drug Shortages Alliance, to search for solutions. In June 2023, the Association for Accessible Medicines, launched a White paper. Drug shortages: causes and solutions, June 2023.

The tracking lists are all likely to have different criteria for inclusion of shortages, but they are much better than nothing–and they would be useful as comparisons with Canada’s shortages — and for getting to the bottom of the problem.

Mitigating solutions — these are intended to help decrease the effects of the drug shortage. They may be helpful, but they are “inside the box.”

  1. Advance reporting of future shortages —  legislated as “mandatory” since Feb 2015–however, in Canada reporting is not always practised in advance, and it is not always penalized when it fails. This solution would give patients, pharmacists, and doctors warning to start looking for alternatives. It does not fix the shortage. The Netherlands set up such a centre in 2017 after a shortage of thyroxine. Australia began considering it in April 2018. By 2020, one Notre Dame researcher determined that these mandates to enhance transparency help shorten and prevent shortages. (The report). In May 2023, Florida legislators introduced a bipartisan bill to force manufacturers to notify if they observed increase in demand. In November 2023, Sweden announced heavy fines for companies failing to report.
  2. Restriction of pharmacy supplies. For many years, pharmacists have used the technique of distributing a limited number of products, leaving the rest as “balance owing.” This was a tried and true way of protecting scant supplies for everyone. During COVID-19 in March 2020, the restriction to 30-day supply became a province-wide recommendation in most Canadian jurisdictions, but it was criticized because the pharmacists continued to charge a dispensing fee for each month’s supply (making it three times higher for a 3-month supply). Rather than reducing or abolishing the dispensing fees, pharmacists insisted on keeping their fees. They appeared to be gouging vulnerable people. The result was a public outcry and for political reasons, New Brunswick followed by Manitoba, Newfoundland and Labrador overrode the recommendation of pharmacists and abolished the 30-day restriction. BC left the decision up to pharmacists. Worried about angering pharmacsits, Ontario, which had made the decision to limit dispensing, decided to cover the cost of the extra dispensing fees, but announced it would soon abolish the limitations. By June, Health Canada then urged Canadians to ask for no more than their usual quantity of medication. In early 2024, when Ozempic became popular for weight loss causing a global shortage, Ontario limited access to the drug for those with diabetes.
  3. Extending time between doses of vaccine. The sharing principles are the same as in #2–allowing more people to get a protective first dose with the extant supply.
  4. Alternatives and Substitutes. Some sites offer suggestions as to which drug(s) to use instead of the one(s) in short supply. Along these lines, in March 2016, the U.S. FDA, offered to speed up applications to manufacture drugs which currently have only one supplier. But fast-tracking can result in danger and/or legal action, as for example in the US meningitis outbreak of 2012 that led to a jail-term for a pharmacist, and accusations of misuse of funds in Guyana, both in 2017. During COVID-19 Canada made a list of 19 drugs essential to managing patients in ICU and sought information about other sources. Together with the USA it also allowed for compounding of approved medications — and in Canada’s case allowed for compulsory licensing.  In June 2020, a new health care technology company, Scripta Insightsannounced patient access for a tool to uncover affordable substitutes for drugs that might be in short supply or too expensive. It requires giving an email address and limiting requests to one per patient. The tool is here.  Owing to COVID-19 European Medicines Agency announced that it would be drawing up critical medicines lists to help with future crises–but it must also be said that such lists help manage the more mundane shortages. During the baby formula shortage in 2022, the House of Representatives voted to reduce tariffs on foreign supplies.
  5. Ethical decision making to help decide who gets what when drugs are in short supply. See for example, this pediatric advice, which appeared in early 2016. Again, it does not fix the shortage; it only helps to manage it. In March 2019, when Merck, the only maker of BCG for bladder cancer drug, was confronted with a shortage it decided to ration supplies globally according to the prior quantities ordered. In June 2020 and the COVID-19 pandemic, similar ethical guidelines were established.
  6. Fast tracking approvals of substitutes and “sole-source” products. The US FDA implemented this process in March 2016  See here and here. In late 2022, US COngress passed a bill to improve these mechanisms. See here. In the midst of the longstanding shortage of ADHD drugs, the FDA approved generic versions of Vyvanse in late August 2023. Some argue that the experience may lead to reform of the system for approvals.
  7. Extending shelf life or tolerating limits on contaminants. In early 2021, during COVID-19, FDA extended the shelf life of immunoglobulin. IN 2022, the FDA allowed an antidiabetes drug found to contain certain levels of  a carcinogen to remain on the shelf in order to avoid shortages.
  8. Importation, compounding, and commercial products to “optimize” use of supply chain. Each crisis provokes more responses along these lines as it did following Hurricane Maria in fall 2017. See for example, here and here; see also this new web-based tool announced for December 2017. In April 2018 FDA issued new guidelines for bulk-buying compounding components. But imports in one place can aggravate shortages in another. New laws in US would permit importation of “cheaper Canadian drugs” (as if Canada has such an industry!)..but they raise fears of worsening shortages here.
  9. Export bans. During COVID-19 India and UK both implemented bans on the export of certain drugs during the crisis to protect supplies at home. In the worldwide Ozempic shortage of 2023, Germany considered an export ban on its product.
  10. Political activism; raising awareness. Drug shortages seem boring and attract little media attention until a “story” can be created. This website attempts to raise awareness.  In mid 2019, nurses in South Africa threatened to release their mentally ill patients unless solutions can be found. Meanwhile nurses in Swaziland threatened a strike simply to draw attention to the issue and doctors in Sri Lanka staged a 1-day strike in August 2019.
  11. Sharing networks. An original project to compare shorages with overstock was touted to help 75% of shortages in Saudi Arabia in July 2019. As of late 2019, the EMA has been attempting to coordinate efforts and share information in measuring and understanding shortages across the EU (also here).
  12. Stockpiling. Attempted in certain jurisdictions such as the Netherlands in November 2019,the US in 2022, and the EU in 2023. But it works only if the drugs are available, and if they retain their effectiveness over time. Recommended by Brookings in June 2023.

Preventative solutions — these are intended to help prevent drug shortages.

  1. Enhanced transparency in drug supply system. In 2022, one Notre Dame researcher show that reporting mandates helped reduce shortages in number and duration. More transparency is needed, especially around GPOs and contracts. Along these lines a bipartisan bill was introduced in May 2023 to force drug companies to notify FDA of increased demand.
  2. Creation and maintenance of Essential Medicines Lists (EML) to establish the most important drugs and to make a commitment to stocking them at all times. Vulnerable drugs identified; alternate sources would be recognized in advance prior to a crisis. Canada does not have an EML. See here. In 2017, new policies with commitment to maintaining essential medicines promises to end shortages in Gambia and in Korea (see also here). But why are such policies mostly reserved for developing nations only? In early 2019, a group of American pediatric oncologists also called for an EML to help manage life-threatening shortages of cancer drugs for children. With the advent of COVID-19 in early 2020, many countries scrambled to identify “essential” drugs that were vulnerable to shortages– e.g., Canada developed new additions to its Tier 3 list which had been little used up to that point and issued requests for information about them; USA went into agreement with Phlow Corp to produce a stockpile of a dozen drugs. These lists are very far from comprehensive, but they are a start….and they demonstrate loud and clear the importance of having an essential medicines list before there is a crisis.
  3. Study and control of the appropriate price for generic drugs–some argue that prices are too low to make the drugs profitable; some argue that generic prices soar inappropriately taking advantage of shortages. Bulk buying has become popular to generate cost-savings — but this mechanism, together with the effect of large American Group Purchasing Organizations, may drive the cost of drugs so slow that companies will stop making them. Manufacturers in India in 2017 cautioned against this measure — reminding consumers that strict control could be a disincentive to continue making drugs or devices, by late 2019 the price regulator responded by allowing a 50% increase in the prices of 21 essential medications. In 2019, Pakistan limited prices, but drug makers  blackmailed the country by threatening to withhold essential medicines.  See news of FDA’s guidelines for bulk buying in compounding industry. A variant on this theme from the Brookings Institute in June 2023 suggests manufacturers should be given incentives to keep making sterile generics.
  4. Forcing manufacturers to respect the “duty to supply” clause of their licences. So far this angle has not worked, the  US Supreme Court refused to hear the arguments of Jennifer Lacognata and the widow of William Schubert that companies have a duty to supply (see Consequences) This result affirms the idea that “medicine manufacturers have no legal duty to continue selling medicines when they want to stop.” Such a duty to keep selling “would compete far too fundamentally with the essential premise of the American free enterprise system.” William M. Janssen in Am J Law and Medicine 2014 40:330-92. But at what cost?  See also #11 below.
  5. Consider creating new pharmaceutical manufacturing entities and methods to increase domestic supply. Could they be nationally owned? Former CPSO President Dr. George Miller agrees. See his post at this site. This solution was also suggested by HIV patients for Zimbabwe in 2017. But the new entities could also be private non-profits. A New York Times report in early 2018 suggested that a group of American hospitals would start their own company. Much subsequent reporting suggests that it was only to reduce costs, rather than maintain supply. [See also here from September 2018 and Abelson and Thomas, 18 January 2018.] Nevertheless, Civica RX, as it is called continues to grow, its stakeholders being hospitals and large HMO’s (read July 2019 update here); the first drug was released in early October 2019 and by the end of that year at least eight other medications were being shipped. In March 2019, a startup in the Netherlands proposed a digital platform, called Pharmaoffer, for raw materials to eliminate the middle man and reduce costs and time invested in seeking supplies. Calls for a public pharmaceutical system in USA began in 2019 and continue in 2023, but they are criticized for being “socialized.” Another generic entity was founded by Medivent Health in Chandler, AZ in early 2020. And also in January 2020, Azure in Ireland proposed to make and stock the 173 generic items that are in shortages. In later 2021, a hospital in the Netherlands also proposed to make its own essential medicines (See here). In 2022, a team in Denmark reported in Nature, on a new method of producing vinca alkaloids from yeast– a proof on concept that can help add to the usual method of extraction from plants. Why doesn’t Canada get busy and start making the drugs we need and exploring new ways of doing so? (see also 7 below). In late 2022 Greek and German doctors began calling for greater European production and the US Congress passed a bill intended to encourage greater domestic production; the EU is inclined to respond.
  6. Encouraging more competition between manufacturers and more manufacturers, and expediting approvals, two US bills introduced in early 2017 and supported by group purchasing organizations. This mechanism would deal with the single supplier problem that, for example, characterized the Epipen shortage of 2018 (see here and here and here). They failed. A similar bill was reintroduced in March 2019. An October 2018 study explains how the vendor kickbacks used by American GPO’s leads to a monopsony, putting manufacturers out of business: the “solution” for more competition would be to repeal the “safe harbour provision” of the 1972 Anti-Kickback Statute that has allowed these firms to dominate the market. And when drugs are all gone in the USA, you can be sure that they are hard to find in Canada.
  7. New manufacturing technologies to introduce flexibility and efficiency in the supply system that would answer to increased demand. See for example single-use bioprocessing systems (military technology 2018 report here and here), or MIT’s portable machine announced in April 2016. In 2019, Merck announced that it was testing a just-in-time delivery system to match manufacturing quantities to the market. Other new technologies have been inspired by shortages see e.g. Burns re hemophilia Factor VIII.  In 2022, Nature reported on an exciting new genetic engineering method to encourage yeast cells to make vinca alkaloids — anti-cancer drugs that had been in short supply.
  8. Track quality issues. Since manufacturing problems are the cause most frequently cited by industry, in 2017 the US FDA proposed to track quality issues more closely. But this plan is opposed by the pharma industry.
  9. Working with industry to lower prices on select drugs, a policy used in UAE since 2011.
  10. Greater collaboration between the generic and innovator pharma industries. Some promise in this direction came in early 2018 and Health Canada is participating. See announcement of IGDRP here.
  11. Model pharmacies. In early 2019, Pakistan announced a plan to develop well-stocked model pharmacies in regional centres to which manufacturers must send stocks of all their drugs. This works only if the drugs are available.
  12. Legal controls. In May 2019, Belgium passed a law to prevent drug companies from selling their products outside the country. This strategy is related to #3 above.
  13. Eliminating trade barriers. This possible solution became prominent during COVID-19 but would be helpful at all times.  See here.
  14. Awards. The US FDA created the Drug Shortage Assistance Award circa 2016 to provide public recognition to drug companies and manufacturers who have demonstrated a commitment to preventing or alleviating drug shortages of medically necessary drugs. See also here

Above all, to solve the drug shortage problem we need to understand its Causes.