New Study Highlights Escalated Dangers of Generic Drug Shortages

Frequent shortages of generic drugs are not uncommon, but a newly released report demonstrates the serious clinical implications of nationwide shortages on patients with life-threatening conditions.

The study, published in JAMA, examined the association between the 2011 US norepinephrine shortage and mortality among adults with septic shock, and used the findings as a case study to indicate a need for improvement in preventing potentially deadly drug shortages, especially of generic injectables.¹

In 2011, 251 drug shortages occurred, 73% of which were generic sterile injectables that served as treatments for sepsis, cancer, and other life-threatening illnesses. In February 2011, the FDA announced a severe nationwide shortage of norepinephrine, the first-line vasopressor for treatment of hypotension in septic shock, due to production interruptions at 3 drug manufacturers.¹

Researchers conducted a study to evaluate the norepinephrine shortage’s impact on patient care. The analysis was restricted to 26 hospitals that experienced a shortage, and the researchers focused on determining whether hospital admission for septic shock during this time was associated with increased chances of death. There were 1961 patients admitted during the shortage quarter. The researchers found that mortality increased from 35.9% during nonshortage quarters to 39.6% during shortage quarters, with a difference of 3.7%¹

Norepinephrine use, which is recommended in international guidelines as a primary treatment of septic shock, declined by more than 20% from baseline during the time of its shortage in the hospitals evaluated. The study’s results revealed a strong and consistent trend between the periods of norepinephrine shortage and increased death in patients with septic shock.

Generic sterile injectable drugs are especially susceptible to shortage because of their short shelf life. The FDA reports that most shortages for these medications are a result of quality problems during manufacturing, such as contamination by microorganisms, glass or metal particulate, drug crystallization, and impurities detected in the product. Additionally, relatively low profit margins for generic drugs hinder manufacturers from increasing production, which leads to shortage vulnerability.²

A report from a World Health Organization advisory group meeting analyzed data on shortages, low price, and low profit margin to determine whether there was a link between shortages and low prices. They determined that “price disparities and medicine shortages raise questions about the health of the generic market,” noting that with few competitors, even small disruptions can incite widespread shortages.³

A 2016 US Government Accountability Office report investigated drug shortages from 2010-2015. The analysis found a consis- tently high number of ongoing shortages over the years, although the number of new shortages has generally declined. Even so, sustained drug shortages could increase thousands of deaths per year, as fewer drug options may force providers to ration care or rely on less effective drugs.⁴

The researchers offered broad solutions aimed at addressing and preventing the impact of drug shortages on patient care and outcomes, including either a shift in focus toward risk mitigation or major restructuring of the industry and its regulation. Some of the specific solutions suggested include an early warning FDA sys- tem, rapid changes to clinical guidelines, quality seal of approval, expanded stockpile, and production requirements.

REFERENCES

1. Vail E, Gershengorn HB, Hua M, et al. Association between US norepinephrine shortage and mortality among patients with septic shock. JAMA. Published online March 21, 2017. doi: 10.1001/jama.2017.2841.

2. US Government Accountability Office (GAO). Public health threat continues, despite efforts to help ensure product availability. GAO website. gao.gov/products/ GAO-14-194. Published February 10, 2014. Accessed March 30, 2017.

3. Fair Pricing Forum: Informal Advisory Group Meeting report. website. www.who. int/medicines/access/fair_pricing/ReportFairPricingForumIGMeeting.pdf. Published March 2017. Accessed March 30, 2017.

4. US Government Accountability Office (GAO). Certain factors are strongly associated with this persistent public health challenge. GAO website. gao.gov/products/ GAO-14-194. Published July 7, 2016. Accessed March 30, 2017.