Shortages are growing because of disruption caused natural disasters and ingredient supply issues, as well as increased demand for certain drugs.
Over the last five and half years, more drug shortages have occurred and more shortages have lasted more than a year, according to a recent report from IQVIA Institute for Human Data Science. The report found that more shortages continue to be report than resolved.
“The issue of drug shortage is front and center for manufacturers, providers, and, in particular, patients,” David Gaugh, interim president and CEO of Association for Accessible Medicines (AAM), said in a press release. “The IQVIA Institute’s new report highlights several important factors leading to shortages, including the critical role that unsustainable reimbursement plays in causing and contributing to these shortages.”
According to IQVIA, as of June 2023, there are 132 molecules in the U.S. market with active shortages, impacting a range of therapy areas including pain/anesthesia, oncology, central nervous system, and infectious disease. Shortages tend to be in generic (84%) and injectable drugs (67%) and are more frequently multi-source. For the currently active shortages, 75% have been active for more than a year and 58% have been ongoing for more than two years.
Key drivers of shortages, the report found, include natural disasters, active or inactive ingredient supply issues, as well as disruptions to packaging materials can all contribute to manufacturing supply issues.
IQVIA has also found that shortages of GLP-1 drugs for diabetes and weight loss increasing, which is being driven by increased demand. Since the launch of Wegovy (semaglutide) in 2021, new prescriptions are up 181% for diabetes GLP-1s and 257% for obesity GLP-1s as increasing awareness of these medicines has increased patient demand. Novo Nordisk, the manufacturer of Wegovy, indicated in May 2023 that it was limiting supply of lower doses of Wegovy used as starting doses to ensure adequate supply of higher doses for existing patients.
IQVIA suggests that new data the shows that GLP-1 therapies prevent cardiovascular events will likely increase demand. Last month, Novo Nordisk released data from the SELECT trial showing that Wegovy cuts the risk of serious cardiovascular events by 20%.
According to the ASHP drug shortages database, semaglutide products Ozempic (for diabetes) and Wegovy (obesity), tirzepatide product Mounjaro (diabetes), liraglutide product Saxenda (obesity), and dulaglutide product Trulicity (diabetes) are all experiencing shortages.
Oncology Shortages Continue
Shortages of chemotherapies are often due to inspection disruptions or pharmaceutical companies leaving the market. The COVID-19 pandemic impacted the FDA’s ability to properly inspect facilities that manufacture prescription drugs and the regulatory agency is now working through its backlog.
For example, earlier this year, Insta Pharmaceuticals, an India-based company manufacturers the three generic cancer products that are distributed through Accord Healthcare, experienced quality issues at end of last year. Among the findings of an FDA inspection are that Insta’s test procedures and laboratory control mechanisms were not followed and that procedures for quality control were not followed.
Specifically, carboplatin and cisplatin have been particularly impacted by shortages beginning in February 2023. Shortages of cancers drugs, including carboplatin and cisplatin as well as methotrexate, began in early 2023. Carboplatin is used to treat patients with ovarian cancer; cisplatin is used to treat advanced ovarian cancer, testicular cancer, and bladder carcinoma. Methotrexate is used to treat leukemia, as well as breast, skin, head and neck, lung and uterine cancer. According to the ASHP drug shortages database, both carboplatin, cisplatin, and methotrexate continue to experience shortages.
A survey by the National Comprehensive Cancer Network in June 2023 found that 93% of cancer centers have faced shortages of carboplatin and cisplatin. Many indicated that that supplies have reached a critical level. All of the centers surveyed are still able to treat patients who need cisplatin without any delays or claim denials. But for carboplatin, that number dropped to only 64% of centers that are able to keep all current carboplatin patients on the regimen.
When the NCCN repeated the survey in September, cancer centers reported that the shortages were getting better, but were not fully resolved. Additionally, there were other medications at risk of shortage, including 66% reporting a shortage of methotrexate, 55% for 5-flourouracil, 45% for fludarabine, and 41% for hydrocortisone.
“The manufacturing complexity associated with some oncology medicines and highly commoditized prices have reduced the number of active manufacturers in many molecules over a period of years,” the IQVIA authors wrote. “Competitive pressures have most often created markets with high concentration, where one or just a few companies have a majority of the market, limiting the resilience of the market to any unexpected disruptions.”
Also contributing to the shortages is that carboplatin can be a substitute for cisplatin, Erin R. Fox, Pharm.D., associate chief pharmacy officer, Shared Services, University of Utah Health and adjunct professor, University of Utah College of Pharmacy, said in an interview in June. “Cisplatin and carboplatin are used for so many different cancers as a backbone of standard of care in many cancers,” she said. “There are a large number of patients that are affected.”
The shortage crisis could be become worse as a new law takes effect. The Drug Supply Chain Security Act now requires pharmaceutical manufacturers to implement electronic interoperable exchange, verification, and tracing for all drug products. This became effective Nov. 27, 2023.
The ramp up of these policies could cause a spike in drug shortages, suggested an August 2023 white paper by the Association for Accessible Medicines (AAM). “It is unknown how many generic manufacturers are prepared for this..,” the authors of the AAM report wrote. “And those manufacturers that are fully ready will be asked to supply additional volumes to cover shortfalls when supply may already be constrained.”
The AAM report suggested several solutions to ensuring a sustainable generic drug market, including: