ADHD medication scarcity adds to questions on US supply chain
Ben Hargreaves looks into why ADHD medicines are still suffering shortages nearly a year after first being announced. The problem has emerged due to surging demand for the medication, but also amid a situation where other medicines are in shortage, pointing to greater, structural issues.
Drug shortages are generally not a common occurrence across the pharmaceutical industry. Considering the complexity of the supply chains involved, the manufacturing expertise required, and the difficulties facing the generics industry, the fact that there are not more shortages is a feat by itself. The US FDA released its report on drug shortages during 2022, and found that drug shortages were markedly lower than ten years prior. In 2011, there was a high of 250 new drug shortages, while the figure in 2022 was 49. However, the agency admitted that 2022 had been “a challenging year for shortages.”
When drug shortages occur, one of the crucial factors is the demand behind the treatment in question. This is why 2022 marked a serious event for the FDA, as the shortages in question were treatments used by millions of citizens; most prominently, medicines for the treatment of attention deficient hyperactivity disorder (ADHD). In October 2022, the FDA announced that there was a shortage of amphetamine mixed salts, more often known by the brand name Adderall. Nearly a year later, the supply is still disrupted, and the agency is reporting that many manufacturers of the product are still struggling to meet demand.
Background to shortages
According to the FDA, the current crisis began with Teva experiencing “ongoing intermittent manufacturing delays”. The company is the biggest manufacturer of ADHD medication for the US market, and this caused immediate problems for the supply of medicine to patients. As the agency stated, there are other manufacturers that are able to produce amphetamine mixed salts, but their combined capacity is insufficient to meet total market demand. As for what the manufacturing issues were, a representative for Teva did not respond to a request for comment. However, it is known that other manufacturers have struggled, with Takeda also citing ‘manufacturing delays’ for the shortage of its Vyvanse (lisdexamfetamine) ADHD drug.
The actual process for the manufacture of ADHD medication is further complicated by the fact that the active pharmaceutical ingredient (API) is a controlled substance. As a result, the manufacturers of ADHD medication are provided a quota by the Drug Enforcement Administration (DEA). To receive a higher amount of the API for manufacture, the companies producing the medication are required to request an adjustment to their quota to manufacture beyond their specified allocation.
There have been suggestions that these quotas have been partially responsible for the current shortages, but this has been refuted by the DEA. At the end of last year, the administration stated: “According to DEA’s data, manufacturers have not fully utilised the APQ for amphetamine in support of domestic manufacturing, reserve stocks, and export requirements for the past three calendar years 2020, 2021, and 2022.”
The DEA also added that it is able to adjust the aggregate production quotas (APQ) during the course of the year, dependent on demand. However, it had concluded that the APQs for the relevant APIs were ‘sufficient’ to supply the market for medical needs, reserve stocks, and export requirements for 2023.
An issue of demand
The principal driver, subsequent to the manufacturing challenges, has been the escalation in demand for ADHD medications. According to IQVIA, the use of ADHD medicines grew by 11% over the last five years. Rather than emerging as a broad trend across age demographics, Trilliant Health found that this has been driven by the 22-44 age group, wherein prescriptions increased by 58.2% from 2018 to 2022. This increased demand meant that, when Teva encountered issues in manufacturing, there was a subsequent pressure felt by other manufacturers to provide alternatives to make up the shortfall, which caused other products to lack inventory.
One of the drivers of this growth was the COVID-19 pandemic, when telehealth services provided an alternative and more streamlined means for individuals to receive prescriptions for ADHD medicine. During the pandemic, some of the rules for prescribing such medication were relaxed to ensure that patients still had access to treatments. One such rule was no longer requiring an in-person medical evaluation. This is still in place, but the DEA is now looking to reinstate the need for an in-person evaluation to receive a prescription for ADHD medication.
The boom in online prescription for medication saw the DEA take selective action to crack down on perceived wrongful filing of prescriptions. One such example was the DEA’s statement alleging that Truepill Pharmacy, which supplied telehealth companies, had dispensed “controlled substances that were not issued for legitimate medical purpose in the usual course of professional practice.”
A problem for the long-term
The issue over supply of ADHD medication is still ongoing. According to the FDA, a number of suppliers expect inventory to return to normal in the coming months. However, Aurobindo Pharma USA states that its own supply will not return to previous levels until December 2023. Epic Pharma also noted that supply was constrained, citing a shortage of API to manufacture the product.
In a statement on the FDA’s website, Teva states: “Teva is manufacturing and distributing consistent with historic levels. We continue to see unprecedented demand.” Several of Teva products are still estimated to recover later this year, while the status of a number of other products is listed as “allocating available supply.”
The reality is that meeting unexpected demand has no simple solution. The generics industry is one marked by fine margins, and reallocating capacity to other medicines within a production facility may not be immediately possible. This is why COVID-19 occasioned a broader range of shortage than just ADHD medicines. Among the other treatments that have experienced supply issues are antibiotics and some cancer treatments.
Both of these medications are urgent and have life-threatening consequences for patients if a secure supply is not achieved, and yet there also remain ongoing problems for both. In May, the American Cancer Society (ACS) put out a notice announcing that chemotherapy drugs are increasingly in short supply. Karen Knudsen, CEO of ACS, highlighted the severity of the situation: “A number of the drugs included in the shortage don’t have an effective alternative. As first-line treatments for a number of cancers, including triple-negative breast cancer, ovarian cancer, and leukaemia often experienced by paediatric cancer patients, the shortage could lead to delays in treatment that could result in worse outcomes.”
On antibiotics, Pfizer stated as recently as June that supply of the antibiotic Bicillin L-A for paediatric patients could run out at the end of June. Further, the company noted that shortages of such products will likely continue into 2024.
It is for these reasons that the US is undergoing a crisis in confidence in its supply chain for essential medicines. The issues in the supply chain, which ADHD medications are now a part of, have led to greater calls to onshore, or ‘reshore’, manufacturing within the US. However, there is no easy solution – there has to be sufficient profit to make it worthwhile to businesses, especially in low-margin areas, such as the generics industry. Teva’s recent announcement, as one of the largest producers of generics - that it plans to cut back on its generics business - only highlights the difficulties in the area, and raises the likelihood that events like the shortage of ADHD medications will emerge again in the future.