In the United States in recent years, interruptions in access to SLDs have hindered MDR TB and XDR TB treatment. CDC does not formally monitor SLD supplies, but TB control officials in local and state health departments request assistance from CDC when they encounter difficulties with drug procurement. Since 2005, CDC has received reports of difficulty obtaining each of the following SLDs: streptomycin, cycloserine, ethionamide, rifabutin, amikacin, capreomycin, and kanamycin. Shortages of rifampin also have been reported, and, in the past 2 months, a national shortage of isoniazid has developed (1). Shortages of MDR TB medications have been experienced by most U.S. TB programs that have diagnosed and reported MDR TB cases. In 2010, most (130 [73%] of 178) of these reports of SLD shortages involved sterile injectable antibiotics essential for the treatment of MDR TB. Since September 2011, the availability of injectable SLDs for MDR TB treatment has been precarious. Kanamycin is no longer produced in the United States, streptomycin has been intermittently unavailable because of increased international demand, and capreomycin and amikacin have been available on an intermittent basis in only small amounts because of manufacturing problems and lack of raw materials.

Drug shortages in the Unites States have become increasingly common. In 2005, a total of 61 impending drug shortages were reported to FDA; in 2010, there were 178. FDA maintains a website to alert the public of drug shortages and their causes (4). A recent FDA review of medical product shortages underscored the complexity of the problem, identifying poor drug quality leading to product recalls as the most common cause for a shortage. Difficulties procuring raw materials and components also were problems. Early notification to FDA can help prevent some impending shortages. For example, in 2010, of 178 drugs with impending drug shortages, FDA was able to prevent shortages of 38 (21%); in 2011, 195 shortages were prevented (5,6), and, as of November 1, 2012, shortages of at least 150 drugs had been prevented in 2012 (Jouhayna Saliba, PharmD, Center for Drug Evaluation and Research, FDA; personal communication; 2013).

As with any drug shortage, SLD shortages can contribute to adverse outcomes such as delays and interruptions in treatment, the need to use potentially less effective treatment regimens, prolonged infectiousness and increased transmission of drug-resistant TB in the community, the further development of drug resistance, and worse outcomes for patients (7). Additionally, drug shortages lead to rationing, increased drug costs, and inefficient use of staff time, and increase the risk for medication errors because regimens must be adjusted, leading to confusion over drug administration schedules, adverse reactions, and interactions (8).

In March 2011, the Federal Advisory Council for the Elimination of Tuberculosis, which provides recommendations for TB elimination to the U.S. Department of Health and Human Services, formed a workgroup to design strategies for improving SLD access. In November 2011, a recurrent bimonthly national forum of 60 TB experts (including members of the Federal Advisory Council for the Elimination of Tuberculosis, state TB controllers, members of the CDC-funded Regional Training and Medical Consultation Centers, patient advocacy groups, and personnel from CDC and FDA), convened by National Jewish Health to discuss clinical and programmatic issues specific to MDR TB and XDR TB, assessed the findings of the NTCA survey and data from FDA and CDC in the context of case presentations. Potential solutions for improving continuity of SLD supplies were suggested by the TB experts present, although no report resulted from the meeting; these proposed solutions included the sharing of drugs in short supply among state and local TB programs, centralized drug stockpiling, obtaining drugs from foreign manufacturers when not available in the United States, and having CDC be responsible for a nationally centralized IND application protocol for certain drugs to expedite access to these drugs for all U.S. patients. Currently, CDC is responsible for nine IND protocols and is developing such a proposal for clofazimine, an SLD.

The findings in this report are subject to at least one limitation. Because of the low response rate (54%) to the NTCA survey, the results might not be representative of the nation’s experience with SLD shortages generally.

On July 9, 2012, the FDA Safety and Innovation Act of 2012 was signed into law. In the law, Congress provided FDA with authorities to combat shortages of drug products in the United States and imposed requirements on manufacturers regarding early notification to FDA of issues that could lead to a potential shortage or disruption in supply of a product.

In October 2011, Executive Order 13588 directed FDA and the U.S. Department of Justice to take action to combat drug shortages, protect consumers, and prevent deliberate price inflation (9). Maintaining access to SLDs will require the collaboration of CDC (because of its role as the central component of the national TB program), FDA, and other partners, including the Global Drug Facility, the Treatment Action Group, local and state health departments, national and international health professional societies, and the pharmaceutical industry. To report information about shortages or supply issues, manufacturers can send updates by e-mail to drugshortages@fda.hhs.gov. State and local health departments, health-care professionals, and patients also are encouraged to notify FDA of shortages, using the same e-mail address.