Congress Presses FDA to Do More to Combat Drug Shortages

FDA needs a more concerted effort to address nationwide shortages of intravenous drugs that put patients at risk and threaten public health, according to a group of leading Senators ranging from Republican Orrin Hatch to leading liberal Bernie Sanders. They and their colleagues have expressed dismay about limited supplies of critical, widely used injectable opioids, anesthetics, and sterile IV fluids that continue for months and years. Legislators requested FDA Commissioner Scott Gottlieb, MD, convene an authorized Drug Shortage Task Force and develop recommendations by the end of 2019 to ensure that “appropriate supplies of essential medications are always available."

Evidently, these policy makers believe that FDA can do more to prevent shortages than is indicated in the agency’s annual report to Congress on drug shortages for 2017, or that Gottlieb spelled out in a statement issued May 31, 2018. The annual report indicates that ongoing drug shortages continued to decline from a high in 2012, but that new shortages rose last year, largely due to a devastating hurricane season that ravaged drug production in Puerto Rico, plus the shutdown of a major manufacturer experiencing production difficulties.

Douglas Throckmorton, deputy director of the Center for  Drug Evaluation and Research (CDER), responded to the Senate request with specifics on what FDA was doing to address shortages in IV fluids, pain medications, and EpiPen self-injectibles that raise particular concerns from health professionals. Throckmorton provided specifics on how hurricane damage in Puerto Rico shut down Baxter Healthcare production of saline and dextrose-based fluids widely used to deliver medications intravenously. The storm destruction aggravated already short supplies in IV fluids, and a severe flu season last winter raised demand for these products even more. FDA sought to address the crisis by approving production by other manufacturers, permitting temporary import of saline, and instructing health professionals in the use of alternative products.

Similar action aims to address shortages in opioid analgesics used to treat pain in cancer patients and to manage surgical procedures. Here Throckmorton cites production delays due to changes and upgrades designed to address manufacturing quality issues at Pfizer’s Kansas drug production facility. Other manufacturers, including Akorn Pharmaceuticals, Fresenius Kabi, and West-Ward Pharmaceuticals, have increased their production at FDA’s urging, although Throckmorton noted that expansion of sterile injectible production takes time.

The CDER official also reported that Mylan expects limited availability of EpiPens in certain areas to be a short-term supply issue. FDA is working to address regional supply disruptions and manufacturing issues that have contributed to this situation and encouraging other manufacturers of epinephrine auto-injectors to expand production.

The FDA annual drug shortage report notes that the agency helped to prevent 145 shortages in 2017, a rise from the previous year, by being able to exercise regulatory “flexibility” in authorizing the release of alternative products and importing to alleviate short supply situations. Early notifications from manufacturers of anticipated supply disruptions also is important: FDA reports that it was notified of 520 potential drug and biological product shortage situations by 86 different manufacturers in 2017 and was able to resolve most of these before they created problems, often through expedited review of applications or supplements and early inspections of facilities.

Gottlieb cites manufacturing and product quality issues as the leading cause of drug shortages, along with limited availability in active ingredients, which can affect several drug manufacturers. Only 2% of drug shortages result from a company’s decision to discontinue production of a medicine, he noted, situations that can be related to manufacturing costs, changes in patent life, and product profitability. At the same time, evidence supporting additional uses of a drug can increase demand for a product and put more pressure on supplies. Gottlieb is hopeful that new continuous manufacturing systems and other innovative production technologies will increase manufacturing reliability and prevent quality-related shortages over the long run but acknowledges that the initial cost of investing in such new equipment “presents challenges.”

It may be helpful, the commissioner said, for Congress to expand FDA’s existing authority to require new drug manufacturers to conduct a risk assessment to identify vulnerabilities in their drug supply chains, particularly problems that could lead to a shortage. FDA cannot require a company to produce any drug or to increase production or control distribution, Gottlieb acknowledged, but advance notification and contingency plans can help mitigate the impact of shortages.