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Understanding the Causes & Impact of Drug Scarcity

The reasons behind drug shortages can range from supply and demand, manufacturing and regulatory issues, to discontinuations.

By: Kristin Brooks

Managing Editor, Contract Pharma

Drug Shortages can occur for many reasons and can range from the unknown to supply and demand, manufacturing, regulatory issues and quality problems, delays, and business decisions, such as discontinuations. Even natural disasters, such as a tornado damaging Pfizer’s sterile injectable site in Rocky Mount, NC, can impact supply. Manufacturers provide the FDA with most drug shortage information and the agency works with them to help prevent or reduce the impact of shortages.   
 
Latest Response to Shortages
GENIXUS, a pharmaceutical company focused on acute and critical care medicines, recently launched its KinetiX syringe platform, Rocuronium Bromide Injection. The launch is in response to the recent natural disaster impacting Pfizer’s manufacturing site in NC, and the expected impact on the sterile injectables market as a result. 

Additionally, Nephron 503B Outsourcing Facility, a division of Nephron Pharmaceuticals Corp., a company focused on resolving drug shortage concerns, recently announced the production and availability of 0.5% Albuterol 5 mL, del Nido Cardioplegia Solution 1000 mL, Lidocaine 1% and Succinylcholine products.

According to the American Society of Health-System Pharmacists (ASHP) there are more than 300 shortage bulletins on drugs, biologics, devices, and specific dosage forms.1 The top five active shortages by drug class, according to ASHP, are Antimicrobials, Chemo, CNS, Fluids/Elytes, and Hormones.2
 
According to the FDA’s database of Current and Resolved Drug Shortages and Discontinuations Reported, there are 140 drug products currently in shortage, and 241 permanent discontinuations of certain drug products, with 41 shortages that have been resolved.3
 
Companies are required to notify the FDA of a permanent discontinuance of certain drug products, six months in advance, or as soon as is practical. These drugs include life-supporting, life-sustaining or for use in the prevention or treatment of a debilitating disease or condition, including drugs used in emergency medical care or during surgery.
 
A drug receives Resolved status when the Drug Shortages Staff (DSS) determines that the market is covered, based on information from all manufacturers. The market is considered covered when supply is available from at least one manufacturer to cover total market demand. However, some manufacturers may not have all presentations available and the DSS monitors the supply for these products. 
 
Drug Shortages Highest in a Decade
Ongoing and active shortages are the highest in a decade, according to ASHP, citing the permanent closure of a U.S.-based factory that has created multiple shortages, including an antidote for lead poisoning; chemotherapy drugs are increasingly in short supply, resulting in rationing of care; and the workload required to manage shortages, including changing pharmacy automation and electronic health records, is difficult in the face of staffing shortages.4 Not since 2011 have drug shortages been this high, which at the time saw 237 new shortages.
 
What Are Some Drugs Currently In Shortage?
Pfizer’s Bicillin, a long-acting injectable form of the antibiotic penicillin, is facing a shortage due to increased demand and more diagnoses of syphilis, according to Pfizer, citing an “impending stock out situation” for select Bicillin L-A and Bicillin C-R prefilled syringes. Prefilled Bicillin pediatric syringes were expected to run low by the end of June, and all Bicillin C-R syringes could see shortages in the third quarter of this year. According to Pfizer, inventory is predicted to start recovering in the second and third quarters of 2024.
 
Additionally, Hikma Pharmaceuticals, Teva Pharmaceutical Industries and Sandoz, the generics division of Novartis, have all reported shortages of various doses of amoxicillin, a common antibiotic used to treat a variety of childhood infections. 
 
Hikma is allocating amoxicillin to current customers to meet the planned contracted demand. Sandoz and Teva did not provide a reason for the shortage. Sandoz has amoxicillin 125 mg/5 mL 100 mL bottles, 200 mg/5 mL 100 mL bottles, and 875 mg tablets in 100 count on back order and the company cannot estimate a release date. All other presentations are available in limited supply. 
 
Meanwhile, Teva had amoxicillin 200 mg, 250 mg and 400 mg bottles, in varying doses/counts, previously reported on back order with an estimated release date in mid-June 2023. The 500 mg tablets were on back order with an estimated release date of mid-July 2023. The 875 mg tablets are on back order with a release date anticipated late-July 2023. 
 
Also, Lilly’s Mounjaro, indicated for weight loss in diabetes, and Novo Nordisk’s Wegovy (semaglutide) an injectable drug indicated for weight loss in obesity, are both experiencing shortages that are expected to last at least through September 2023.
 
While Lilly did not provide a reason for the shortage, increased demand is to blame. Short supply of Mounjaro at the 10mg dose are expected to last through September 2023. While issues with the 7.5mg, 12.5mg and 15mg doses are expected to be resolved by the end of July.
Lilly had estimated resupply dates for Mounjaro 10 mg/0.5 mL, 12.5 mg/0.5 mL, and 15 mg/0.5 mL prefilled pens on intermittent back order through July 2023.
 
Go Deeper: GLP-1 Demand Fuels Growth in Pharmaceutical Manufacturing Capacity
 
Meanwhile, Novo Nordisk also has Ozempic on shortage due to increased demand. Novo Nordisk has discontinued Ozempic 0.25 mg and 0.5 mg dose strength in the 2 mg/1.5 mL presentation but the 0.25 mg and 0.5 mg dose strength in the 2 mg/3 mL presentation is available. The company has Ozempic 2 mg dose (8 mg/3 mL prefilled pens) in limited supply and the company estimates this will continue through mid-August 2023.
 
For Wegovy, the company has taken measures to increase production capacity, however the supply is not anticipated to meet demand for the 0.25 mg, 0.5 mg, and 1 mg dose strengths. Novo Nordisk has Wegovy 0.25 mg/0.5 mL, 0.5 mg/0.5 mL, and 1 mg/ 0.5 mL prefilled pens in limited supply and estimates this situation will continue through September 2023. The 1.7 mg/0.75 mL and 2.4 mg/0.75 mL prefilled pens are available, however there may be periodic shipping delays due to high demand. 
 
Of increasing concern, the FDA has reported that there is a current shortage of injectable cisplatin, carboplatin and dexamethasone sodium phosphate, commonly used in chemotherapy regimens, for which there are limited alternatives, particularly for ovarian, testicular, breast, lung and head and neck cancers.
 
Intas Pharmacuticals’ plant in Gujarat, India, a major producer of cisplatin and carboplatin, halted operations in December 2022 following a failed inspection by the FDA citing 11 violations, including quality control. 
 
In an effort to help with shortages, the FDA is overseeing the release of batches of these drugs from Intas and allowing the temporary importation of drugs from Qilu Pharmaceuticals in China. Analysts estimate the shortage may linger through 2023 and potentially longer.
 
Pending FDA Response
The FDA has recently been asked to answer questions by the House Committee on Energy and Commerce regarding inspections of foreign pharmaceutical manufacturing plants, namely in China and India, with concerns that the U.S. is overly reliant on sourcing from foreign manufacturers with repeated violations of FDA safety regulations.
 
FDA Commissioner Robert Califf has a deadline of August 1, 2023 to respond to the committee’s questions. Specifically, the House committee is asking for information regarding the number of regulatory actions the FDA has taken against non-compliant foreign facilities, and specific actions the FDA has taken. Foreign inspections are becoming increasingly imperative as the FDA has recently allowed the “temporary import of otherwise unapproved drugs” from these countries.5
 
Quality failures at foreign plants have also led to a record number of recalls. In 2022, the pharmaceutical industry saw the most units recalled than in the past six years, with 567.3 million, a 114% increase over the 264.6 million units recalled in 2021, according to data from the recent Sedgwick 2023 State of the Nation Recall Index report. 
 
Read More: Pharmaceutical Recall Trends to Watch in 2023
  
According to the FDA’s annual Report on the State of Pharmaceutical Quality, there were 912 recalls across 166 manufacturing sites in 2022.
 
References:
1.     https://www.ashp.org/products-and-services/database-licensing-and-integration/ashp-drug-shortages
2.     https://www.ashp.org/drug-shortages/shortage-resources/drug-shortages-statistics
3.     https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm
4.     https://www.ashp.org/drug-shortages/shortage-resources/drug-shortages-statistics
5.     https://www.hsgac.senate.gov/hearings/drug-shortage-health-and-national-security-risks-underlying-causes-and-needed-reforms/

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