Assistant Director-General
External Relations and Governance – WHO
Medicine shortages are being discussed more frequently in the media, but WHO has been fol-lowing the topic for several years. Could you provide some background?
Shortages occur for different reasons, but the increasing number of climate and other health-related emergencies often leads to large and unexpected spikes in demand. Another concern is that there are around 40 countries globally that monitor medicines shortages, but we still have many regions where information is not available and where shortages are likely to be occurring. In those cases, a shortage that goes undetected can quickly lead to a stockout, with serious negative impact on public health systems.
WHO and national medicines regulatory authorities, mainly from industrialized countries, have been following the problem. The number of shortages increased drastically during the COVID-19 pandemic, with a complex landscape, including unprecedented problems such as border closures preventing trade of materials. Shortages are not new, but the pandemic has spotlighted the issue. Outside of pandemics and emergencies, WHO focuses on shortages of medicines that are included on the WHO Model List of Essential Medicines, which is a list considered to be necessary for basic health system functioning. A review of current data sources suggests that up to 20% of medicines currently in shortage are on this list of Essential Medicines.
The problem is serious, and it is important to understand that there is not a one-size-fits all solution to shortages. The technical, manufacturing and clinical implications vary from medicine to medicine. Reporting and monitoring of shortages by WHO and national regulatory authorities, including Swissmedic, may not be popular in a commercial sense, but timely aware-ness and action is critical to avoid a complete stockout. Recent data reviewed by WHO from a large national market suggests that up to 40% of shortages could be resolved without significant negative impact depending on the context and actions taken.
Has the situation become worse since the COVID-19 Pandemic?
Since 2021, the number of medicines reported to be in shortage affecting two or more countries has increased by over 100%. While this increase sounds alarming, there are two sides. One is that we are getting better at reporting and monitoring, so are likely to be finding more shortages that were not reported prior to the COVID-19 pandemic. The other is that the pan-demic had an impact on supply chains where there can be a whiplash effect as corrections move forward. This can take significant time to correct, and in some cases, even years.
Are there some medicines that are more susceptible? Can you provide examples?
Shortages are dynamic and can occur at any time for any product, but some medicines have chronic problems, such as older antibiotics and some injectable medicines. There are cases where manufacturers of older antibiotics have left the market because of pressures to reduce prices to levels that are not commercially viable. For injectable medicines, the manufacturing process is more complex, and it can be difficult to ramp up manufacturing to compensate for a problem. Shortages can occur unexpectedly for several reasons, including a manufacturer that discontinues production, a quality related recall and surges in demand, to name just a few. Not all of these can be predicted.
What are the potential solutions?
Each shortage is different. In some cases, there are short term solutions while others require longer term action. The shortage can have a broad impact or can be limited to a small group of patients. Two examples that highlight the problems and the different solutions required are paediatric tuberculosis (TB) medicines and certain diabetes medicines being used for weight loss.
Tuberculosis medicines are older medicines, and they treat a patient base of around 10 million people annually, which is a relatively small market. There are shortages of several adult products that have been ongoing for approximately a year, but shortages of pediatric TB medicines have a longer history. Treating children with TB is a patient base of roughly 1 million per year, divided across around 25+ high burden countries. This was always a small and commercially fragile market to sustain, but in 2014, a change in clinical guidelines left pediatric patients without an appropriate treatment on the market. The solution in that case was a market shaping activity with support from UNITAID, WHO and other partners to incentivize the development of new products, including a sustainable price structure and a procurement agency to manage demand planning. This type of long-term solution is not always necessary, but in this case was important. The work on TB remains ongoing and includes Swiss companies, who are engaging in manufacturing and research into newer and more sustainable treatments.
Another example is a group of diabetes medicines known as “glucagon-like peptide 1 receptor agonist” products. They are more commonly known by their brand names, such as Ozempic and Wegovy. Demand went up by nearly 200% when they were approved for weight loss in addition to their initial use for diabetic patients. The resulting shortage for diabetic patients is significant, and many cannot be easily switched to another medicine. This shortage, considering the very high demand for the product, has also led to substandard and falsified medicines entering markets. WHO issued an alert in January of this year to that effect. Several regulatory agencies have also issued alerts on falsified products and legal actions are underway to locate and stop all such manufacturing and distribution.
What are examples of WHO’s work in this area?
WHO works with medicine regulators and major procurement agencies to anticipate shortages. Using applications developed by WHO that harvest publicly available information, we monitor for shortages of Essential Medicines. We particularly monitor for medicines that are affecting multiple countries. The data that we gather is kept confidential and only provided to regulatory authorities. WHO also works with regulatory agencies and government procurement agencies to build capacity, including detecting and responding to shortages.
Does WHO work with industry on this problem?
There are ongoing discussions with WHO and industry associations about developing means to improve forecasts for Essential Medicines as well as approaches on predicting shortages in countries where visibility is extremely limited. There is no one-size-fits all solution, but governments have started working with national industry members to increase inventories of certain products. For low- and middle-income countries, the options are more limited.
Do we often talk about substitution? In what cases is it possible? What are the issues in-volved?
Regulatory authorities are the ones to give advice in a specific country, including whether to substitute with a clinically appropriate alternative or an alternative supply source. These are generally short-term solutions and are not always possible. A clinically appropriate alternative may be available in some cases, but depending on the nature of the substitution, it may not be suitable for all patients. Using an alternate supply source means a rapid market authorization from the national regulatory authority for a new supplier. The regulator in each country is the one to make these decisions and recommendations, considering the national context. Questions for them might include how broadly a particular medicine is used, the risks of using a clinically appropriate alternative, clinical capacity to manage an alternative in cases of specialized treatments, or the risks of an unknown supplier.
If nothing is done, will the market self-correct?
No, history is fairly clear that measures to reduce the negative impact of shortages require co-operation between industry members, regulatory agencies, large procurers and others.
How is it that we hear that health care costs are too high, while some medicines are commercially difficult to maintain due to price pressures?
There are estimates in the global medicines market that predict a growth of around 6% per year; however, most of this growth comes from new, patented medicines, where many are highly specialized and expensive. For older generic products, there are situations where pricing policies can have unintended consequences if they are not implemented well, including prices that are not sustainable. Depending on several factors, including a company’s manufacturing capacity, a medicine with low profitability may be a lost opportunity cost for more commercial-ly viable products, leading to discontinuations.
While a price on a national market is managed at national level, there are also initiatives to promote regional cooperation on pricing policies to reduce the risks of unintended consequences. Improved communication with manufacturers on forecasting models can support multi-country price negotiations, particularly when they consider the variability of purchasing power of countries. Preliminary market consultation with the private sector, innovative contracting and joint procurement schemes are a few examples of such collaborative activities.
Some people suggest that the confederation should coordinate the production of medicines and vaccines to ensure its autonomy. What’s your opinion on the subject? for vaccines, for “simple” “low-tech” drugs, using the latest technologies? There are strategies to diversify the supply chain for medicines that are being considered by several countries. Regulators, including Swissmedic, do already intervene in certain cases to support manufacturers in managing a specific shortage. In terms of shifting to centralized government-coordinated procurement and contracting versus other models, there are many factors that impact the success of a particular model, and WHO would encourage thorough assessments be made if a shift is being considered. Manufacturing technologies that facilitate rapid scale up of production during emergencies are also promising, but each use case is different and needs to be assessed according to the context of the medicine.