By: Jennalynn Fung, PharmD Candidate c/o 2025

Drug shortages are not new; however, their frequency has significantly increased over the years. Dr. Peter Chin-Hong, an infectious disease doctor and professor at the University of California, San Francisco, stated, “[i]t’s something that I’ve seen from time to time since I started practice about 20 years ago, but it’s gotten worse in the last few years.”¹

Shortages can occur for a multitude of reasons, ranging from manufacturing and quality problems to delays, and discontinuations. The Food and Drug Administration (FDA) has even released notices regarding natural disasters, such as their notice of a tornado that had damaged Pfizer’s sterile injectable site in Rocky Mount, North Carolina in August 2023.²

One could even consider a shortage a new “status quo” of the industry, considering the FDA has identified over 100 drug shortages per year since 2007. This number rose to 267 drugs in 2011. In 2022, at its peak, there were 295 drugs in shortage, and many fear that under the current regulatory system, the problem will only grow. In April 2023, the American Society of Health-System Pharmacists (ASHP) reported that 301 drugs were in short supply. In June 2023, ASHP reported more than 300 active drug shortages, the most in nearly a decade.³

The most common drug classes that have experienced a short supply, according to ASHP’s data in Specialty Pharmacy Continuum from April 2023, can be found in Table 1. Central nervous system (CNS) drug shortages are often due to the complex manufacturing required to ensure that injectable medications like fentanyl, morphine, and hydromorphone are sterile. Although the quantity of chemotherapy drugs in short supply is less than those of other drug classes, there are often no available or approved substitutes for chemotherapeutic drugs.

Table 1. Drugs in Short Supply³

Drug class	Quantity of drugs in short supply
All drugs classes	301
CNS	52
Antimicrobials	35
Fluid and electrolytes	30
Hormones	27
Chemotherapy	23

Pharmacists frequently utilize the FDA Drug Shortage database to determine if a specific medication is still in shortage or not. One can search for a drug on the website and the status of the drug will pop up on the right side of the table. There are also sections for discontinuations, therapeutic categories, and updates. Unfortunately, one crucial piece of information that drug companies are not required to reveal is why exactly there is a shortage – that is allowed to be kept as classified information.⁴ The lack of transparency from drug companies jeopardizes pharmacists and pharmacies by forcing them to make inferences from this FDA data that it is a manufacturing problem, without knowing the real and true cause. This makes it more difficult for pharmacies to assist their patients too.

Dr. Erin Fox, a pharmacist and national expert on drug shortages at the University of Utah, mentioned that issues with manufacturing are a primary factor associated with drug shortages.⁵ Issues in manufacturing noticeably increased during the emergence and peak of coronavirus disease 2019 (COVID-19), as the FDA did not conduct overseas inspections due to pandemic legislation, which prevented free travel across borders. The actions that the FDA is currently taking against many manufacturers and their factories are rippling through the supply chain, worsening the shortage post-pandemic.

Fox stated that the manufacturing problem is what happened with many chemotherapy shortages in 2022. For instance, Intas Pharmaceuticals, a pharmaceutical company in India that produces chemotherapy drugs, was inspected by the FDA in December 2022. The agency found a variety of concerns, ranging from microbial contamination risk, poor record keeping, and undefined procedures and controls. As a result, the company was forced to close down in order to resolve the issues. Other companies cannot supply that product difference, thus leading to a deficit in chemotherapy drugs, like cisplatin.

During the shortage, doctors were forced to choose which patients received cisplatin, and who did not. When Intas Pharmaceuticals resumed production following their enforced closure, the pharmacies ordered Cisplatin in bulk to protect their patients. These shortages are changing the way hospitals and pharmacies behave when ordering medication.

Dr. Michael Ganio, PharmD, pointed out that Intas is a contracted manufacturer for Accord Pharmaceuticals, making this inspection even more concerning. “When you see smoke, there’s probably fire,” Dr. Ganio said to Specialty Pharmacy Continuum.⁶

COVID-19 lockdowns in China also impacted the global supply.⁷ In April 2022, a GE HealthCare factory in Shanghai that produced iodine-based contrast media was shut down due to stringent Chinese COVID-19 policies. The United States (US) healthcare system felt the impact of this closure immediately, with many doctors scrambling to find the dye so that they could perform scans for their patients. Dr. Andrew Shuman, a head and neck surgeon at the US Department of Veterans Affairs, told CNN Health that this impacted veterans overnight – medical practitioners who were depending on the dye to evaluate conditions like cancer or heart disease were unable to, inevitably forcing some physicians to make some difficult decisions on who should receive the radiographic tests.⁸

The increase in these recent shortages, though, is less related to COVID-19 and may be more attributed to the low-profit margin of generic drugs; companies are less likely to see a profit in these medications and may decide to discontinue production, even if demand is still high. The Association for Accessible Medicines found that generic drugs account for 90% of all prescriptions filled, yet they only represent about 20% of the drug spending in the US.⁹ The decline in profits that generic manufacturers face is why so many companies have had to file for bankruptcy or close entirely. For example, Athenex, a company in the injectable generic market, filed for bankruptcy and closed its physical locations in New York, which directly impacted the hospital’s pharmacy supply.

Many larger manufacturers play a crucial role in the pharmaceutical supply chain. One example being Akorn Pharmaceuticals which closed down for good in February 2023, which impaired the healthcare system severely. This company was responsible for producing 75 different generics.¹⁰ The pharmacy of a hospital (name, undisclosed) in New York City was impacted directly by their closure; the supervisor for the pharmacy stockroom stated that the lack of Akorn products made delivering quality patient care all the more difficult. To combat this, the pharmacy has scrambled to find suitable substitutions for these newly discontinued products. For example, lidocaine 2% gel, which is utilized in the operating room trays for surgery, is no longer made, warranting the use of lidocaine 4% cream when necessary. However, for most trays, the section designated for Akorn’s product is simply empty. Similarly, viscous lidocaine hydrochloride solution no longer comes in unit-dosed cups. Instead, the pharmacy must send this medication to Safecor Health, a company that provides unit-dose repackaging and other services to hospital pharmacies that do not have the correct equipment to perform these services themselves. Large bottles of the solution are repackaged into unit dose cups sterilely. Other substitutions for Akorn products are listed in the Table 2.

Table 2. Akorn Drug Discontinuations and Substitutions

Akorn drug discontinuation	Substitute/alternative
Lidocaine 2% gel	Lidocaine 4% cream
Viscous lidocaine hydrochloride solution (cups)	Safecor compounding of unit-dose vups
Fluorescein injection	Trypan blue ophthalmic solution Fluorescein ophthalmic strip
Calcitriol	Paricalcitol

Shortages in antibiotics also directly impact patient health and care. Due to the high possibility of antibiotic shortages, hospitals, and pharmacies will carry multiple different drugs in case they need to be substituted. However, every time a person takes an antibiotic, they increase their likelihood of developing bacterial resistance. Taking a multitude of antibiotics also increases the possibility of more side effects, drug interactions, and errors. When patients are not treated with the appropriate medication, they have worse health outcomes. This not only goes for antibiotics. For example, a study done by Vail et al. found that there was a 3.7% increase in mortality rate amongst those treated with sepsis when there was a shortage of norepinephrine.¹¹

How can drug shortages be better managed in the future? The FDA wrote their tenth annual Report to Congress on Drug Shortages about how to prevent this significant public health threat in 2022. In it, they write that “manufacturers are notifying FDA earlier than in the past about certain manufacturing interruptions and discontinuances that can lead to shortages. These early notifications give FDA additional time to work” on preventing extenuating circumstances for pharmacies and patients, alike.¹² In the FDA report’s conclusion, the agency states that they will work on gaining better insight into the supply chain by increasing their communication with manufacturers and other partners involved in the pharmaceutical process. Manufacturers will also be expected to improve their current operations by increasing preparation, safety, and sterility.¹²

Congress is also currently trying to address this issue; they want to pass legislation that will grant the FDA the ability to require drugmakers to alert them of increasing demands for certain drugs.¹³ This could improve the supply of drugs that are over the counter, like children’s pain relievers and antibiotics, which frequently spike during winter during the flu and cold season. Other lawmakers want the quantities of resources needed to create in-demand drugs to become public information as well.

The future of drug shortages in this country does not look bright – all things considered, it seems that shortages will only grow more and more frequent. The supply depends on a complex interplay of factors such as regulatory changes, supply chain improvements, manufacturing innovations, and global events. Efforts to address drug shortages may involve regulatory reforms, incentives for manufacturers, and investment in diversified supply chains. While collaboration between healthcare professionals, manufacturers, regulators, and policymakers is key to mitigating the impact of drug shortages on patient care, the problem remains that there are simply not enough manufacturers to satisfy current patient demand.

References

1. Ricciulli V. Why are there so many drug shortage in the US? Public Good News. Published July 25, 2023. https://publicgoodnews.com/2023/07/25/drug-shortages-us-ozempic-amoxicillin-mounjaro/.
2. Drug Shortages. U.S. Food and Drug Administration. Updated January 5, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/drug-shortages.
3. Shaw G. Drug Shortages Reach 10-Year High: ASHP Report. Specialty Pharmacy Continuum. Published 2023. https://www.specialtypharmacycontinuum.com/Policy/Article/06-23/Drug-Shortages-Reach-10-Year-High-ASHP-Report/70318.
4. Notifying FDA of a discontinuance or interruption in manufacturing of finished products or active pharmaceutical ingredients under section 506C of the FD&C Act. U.S. Food and Drug Administration. Published April 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/notifying-fda-discontinuance-or-interruption-manufacturing-finished-products-or-active.
5. Barrón-López L, Hastings D. Prescription drug shortages make treatment decisions difficult for doctors and patients. Transcript. PBS News Hour. Published July 4, 2023. https://www.pbs.org/newshour/show/prescription-drug-shortages-make-treatment-decisions-difficult-for-doctors-and-patients.
6. Banks MA. FDA allows cisplatin imports. Specialty Pharmacy Continuum. Published June 16, 2023. https://www.specialtypharmacycontinuum.com/Online-First/Article/06-23/FDA-Allows-Cisplatin-Imports/70628.
7. Rowland C. Covid shutdowns in China are delaying medical scans in the U.S. Washington Post. Published May 11, 2022. https://www.washingtonpost.com/business/2022/05/11/medical-scans-dye-shortage/.
8. Christensen J. New drug shortages in the US increased nearly 30% in 2022, Senate report finds. CNN. Published March 22, 2023. https://www.cnn.com/2023/03/22/health/drug-shortages-senate-report/index.html.
9. 2020 Generic Drug & Biosimilars Access and Savings in the U.S. Report. Accessible Meds. Published 2020. https://accessiblemeds.org/resources/reports/2020-generic-drug-biosimilars-access-and-savings-us-report/.
10. Attachment I – List of Human Products. U.S. Food and Drug Administration. Published May 4, 2023. https://www.fda.gov/media/167863/download?attachment.
11. Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H. Association Between US Norepinephrine Shortage and Mortality Among Patients With Septic Shock. JAMA. 2017;317(14):1433-1442. doi:10.1001/jama.2017.2841
12. Drug Shortages CY 2022. U.S. Food and Drug Administration. Published 2022. https://www.fda.gov/media/169302/download?attachment.
13. Chairs Rodgers and Guthrie announce legislative hearing on drug shortages. Press release. Legislative proposals to prevent and respond to generic drug shortages. Energy and Commerce Committee. Published September 7, 2023. https://energycommerce.house.gov/posts/chairs-rodgers-and-guthrie-announce-legislative-hearing-on-drug-shortages.

Published by Rho Chi Post