Despite notable successes in preventing and mitigating short supplies of important medicines, the drug shortage crisis still disrupts medical treatment and gives drug manufacturers a bad name. FDA is doing a better job of identifying potential shortage situations and implementing relief strategies, but many supply problems continue to limit treatment options for doctors and patients. A severe shortage in intravenous saline solutions has generated outcries from hospitals, dialysis centers, and physicians. The situation is aggravated by increased hospitalizations due to flu outbreaks. Some states are taking extreme measures for executing felons facing the death penalty due to difficulties obtaining supplies of drugs for lethal injections. Recent vaccine shortages have forced physicians to delay immunizations.
FDA summarized its gains in dealing with drug shortages in a Feb. 5 annual report on actions taken in 2013 to prevent or mitigate shortage situations, as required by the FDA Safety and Innovation Act (FDASIA) of 2012. This reflected the agency’s Drug Shortage Action Plan, issued last October to map out how it would implement the FDASIA provisions that require early notification by manufacturers of potential drug shortages and permit regulatory flexibility to bring substitute products to the market and to permit some troubled products to continue distribution.
As a result of such strategies, FDA was able to report at this week’s hearing before the House Energy and Commerce Committee that it was able to prevent 170 shortages in 2013. Armed with such advance warnings, Douglas Throckmorton, deputy director of the Center for Drug Evaluation and Research (CDER), explained that the agency can look for other manufacturers able to ramp up production to fill gaps; expedite reviews and inspections of alternative producers; and exercise “enforcement discretion” when a compliance action might lead to production halts that could limit supplies. Such actions reflect agency consideration of the potential risks of permitting distribution of a drug with quality problems vs. the benefits to patients in need of treatment.
FDA’s drug shortages annual report outlines a number of specific actions, such as appointing drug shortage coordinators in the Office of Regulatory Affairs (ORA) to oversee CDER and field force activities. CDER addressed shortages by expediting reviews through June 2013 of 62 applications for new generic drugs and for more than 100 supplements for generics, brands, and biological products. The agency also moved quickly to conduct 63 inspections and permitted manufacturers to use release testing and third-party oversight as more flexible ways to ensure product quality.
But while there’s a notable decline in new drug shortages, the number of active shortages remains high – rising from 184 in 2011 to 261 in 2012 and to 288 through June 2013 – an indication that many supply problems don’t have ready solutions. In fact, active shortages tripled between 2007 and 2012, noted Marcia Crosse, healthcare director at the Government Accountability Office (GAO), at the House hearing. GAO confirmed that FDA was doing more to prevent new shortages and advised the agency to improve its information systems to identify risk factors for potential shortages early enough to resolve them. FDA said it was initiating such strategies. And most Republican critics applauded their role in strengthening FDA’s authorities to deal with shortages – instead of beating up on the agency for doing too little too late.
FDA and GAO agreed that ongoing drug manufacturing problems, for both active ingredients and finished products, remain a main factor underlying disruptions in pharma supply chains, particularly for sterile injectibles. Longer-term solutions thus require an industry commitment to quality production of drugs and biologics, noted Ilisa Bernstein, deputy director of CDER’s Office of Compliance, at the CBI Pharmaceutical Compliance conference in January. Bernstein called on pharma companies to invest in new manufacturing facilities instead of trying to patch up old, deteriorating plants. FDA would like to see more redundancy in manufacturing systems to create back-up capacity, as well as identification of additional suppliers “waiting in the wings” to prevent serious shortages. Of course, such investments are costly, and the economics of sterile generic drug production supports lean, efficient production systems, not extra capacity that may not be needed.