Pharmacists experience the far-reaching effects of drug shortages on a daily basis. In addition to impacting clinical decision-making, shortage management often requires the marshaling of additional resources. Most importantly, shortages may affect patient care, forcing the delay of medical procedures or requiring that safe, effective therapies be replaced with less effective options. Ultimately, shortages can contribute to medication errors, as clinicians are forced to prescribe and administer unfamiliar agents.
Fortunately, the latest trends, reflected in data collected by the University of Utah Drug Information Service (UUDIS), demonstrate an improvement in the shortage situation, likely due to a renewed focus on product quality by both the FDA and the pharmaceutical industry. Nevertheless, moving forward, greater transparency in drug labeling is necessary to provide pharmacists with the tools to make informed choices in their medication purchasing, thus ensuring the ongoing availability of critical medications.
Defining a Drug Shortage
UUDIS defines a shortage as a supply issue that affects how the pharmacy prepares or dispenses a drug product or influences patient care by forcing prescribers to use an alternative agent.1 The university’s drug information service has been collecting national drug shortage data since January 2001. Voluntary reports of drug shortages are received via a reporting feature on a public Web site (www.ashp.org/shortage) hosted by the American Society of Health-System Pharmacists (ASHP). UUDIS then publishes critical shortage information on the same Web site.
Drug information specialists at UUDIS research each reported shortage to verify that a deficit actually exists. This research includes contacting all manufacturers of a drug reported to be on shortage to determine which National Drug Codes (NDCs) are in short supply at the national level. The manufacturers are asked for a reason for the shortage, as well as an estimated release date. If most manufacturers are experiencing a nationwide shortfall, UUDIS posts information on the ASHP drug shortages Web site, noting which products are affected, which products are available, any specific methods for accessing the product, reasons for the drug shortage, and estimated resupply dates. Also included are any applicable implications for patient care, safety concerns, appropriate alternatives, and management strategies.
UUDIS considers a shortage resolved when all suppliers have all NDCs available again or have discontinued their products. For example, if a supplier has a 10-gram, 2-gram, and 1-gram presentation and has the 2-gram and 1-gram forms available, but not the 10-gram formulation, UUDIS will not consider the shortage resolved until the 10-gram presentation is available again. UUDIS also monitors shortages on the FDA’s drug shortage Web site; typically, UUDIS considers a shortage resolved when FDA announces that the shortage is resolved. Key differences between FDA’s drug shortage Web site and data provided by UUDIS for the ASHP drug shortage Web site are available at http://www.ashp.org/DocLibrary/Policy/DrugShortages/FDA-versus-ASHP.pdf.
The trend toward improvement in the number of new drug shortages is illustrated in Figure 1. Just 68 new shortages have been identified in the first 6 months of 2015, compared with a total of 185 new shortages in 2014 and 140 in 2013, indicating that the rate of new shortages likely is slowing. Note that Figure 1 does not capture ongoing drug shortages, so if a shortage began in 2014 and continued into 2015, it is not counted in the 2015 number. Nevertheless, improvements also are evident with ongoing shortages. The number of active, ongoing shortages is depicted in Figure 2, which also demonstrates a trend toward improvement starting in the first quarter of 2015. For the previous 2 years, the number of ongoing, active drug shortages averaged around 300 in any given quarter. At the end of the second quarter of 2015, the number of active shortages had dropped to 219.
Reasons for Improvement
There are several factors driving this apparent improvement in the number of shortages.
■ Federal Action. The Food and Drug Administration Safety and Innovation Act (FDASIA), signed into law on July 9, 2012, provides additional resources to the FDA, including a requirement for manufacturers to supply advanced notice of drug shortages to the FDA.2 The administration just released the final rule, which requires suppliers to notify the FDA of a permanent discontinuance or interruption in manufacturing that could result in a product deficit.3 These early notifications allow the FDA to work with the pharmaceutical industry to prevent shortfalls. In fact, since 2012, the FDA has prevented over 500 drug shortages.
■ The Drive Toward Quality Improvement. The pharmaceutical industry’s efforts toward enhancing quality also may be a factor in improving the drug shortage situation. While a variety of factors can cause supply shortfalls, such as difficulty acquiring raw materials and poor business decisions, the most frequent cause is manufacturing problems (ie, poor quality control). Thus, improving manufacturing quality is a key step in resolving the drug shortage problem.
■ The ISPE Prevention Plan. The International Society for Pharmaceutical Engineering (ISPE) has been working on a drug shortage prevention plan for several years.4,5 Beginning with a survey in 2012, ISPE identified the lack of a robust quality system as the most common cause of supply disruptions. In 2014, ISPE published a comprehensive drug shortages prevention plan and, in 2015, released a draft of a gap analysis tool for use by the pharmaceutical industry. Manufacturers may choose to use this tool to assess for potential gaps in six specific areas: corporate quality culture, robust quality systems, metrics, business continuity planning, communication with authorities, and building capacity.4
■ Increasing Regulatory Scrutiny. There also is a new focus on quality by pharmaceutical regulators. In January 2015, the FDA launched the Office of Pharmaceutical Quality with the overall mission to “ensure that safe, effective, high quality drugs are available for the American public.” The intent of this new office is to better align quality functions throughout the Center for Drug Evaluation and Research, including inspection, research, and review. The office aims to standardize the quality program over all sites of production and for all classes of drugs (ie, brand, generic, and OTC).6
■ FDA Draft Guidance. In July 2015, FDA issued draft guidance, entitled Request for Quality Metrics: Guidance for Industry for pharmaceutical manufacturers,7 and is accepting public comments until November 27, 2015. The overarching goal of the guidance is to encourage all manufacturers to raise their quality standards; it lists several quality metrics that the FDA will assess, including the rate of lot acceptance and the number of product quality complaints. The intent of the program is to help predict, and possibly prevent, drug shortages, as well as address risk-based inspection scheduling. Risk-based scheduling allows the FDA to inspect facilities that pose the greatest risk more frequently than facilities with a good performance record.
Additional Transparency Needed
Although the state of drug shortages has improved, additional change is needed. Regulatory efforts to use quality metrics to predict and prevent drug shortages are positive; nevertheless, pharmacies require additional transparency to ensure purchasing decisions are based on quality. Pharmacists can review the warning letters and 483 inspection forms that the FDA publishes on their Web site, but these reports typically are heavily redacted. Too often pharmacists are unable to determine which products are manufactured at a specific facility, or, in some cases, to identify which company actually manufactured the product. FDA currently has no plans to publicly release the quality metrics they intend to gather from industry. Current labeling laws do not require that a medication supplier reveal the company that manufactured the product, or even the country of origin.
Further complicating the situation is the practice of contract drug manufacturing, wherein a company may manufacture a product for another supplier, or even multiple suppliers. Many drug labels carry language such as “manufactured for x company,” but do not disclose which company manufactured the product. Congress should act to change the labeling laws to require disclosure of this critical information. Clinicians should have the right to know which company manufactured a product they are prescribing, dispensing, or administering to their patients. FDA also could work to provide more quality information to purchasers of pharmaceutical products.
Overall, the combined efforts of the FDA and industry are slowly improving the drug shortage problem; recent decreases in the overall number of drug shortages support this trend. Nevertheless, additional advocacy supporting transparency in labeling laws is required to improve pharmacists’ ability to make sound purchasing decisions based on quality metrics.
Erin R. Fox, PharmD, is the director of the drug information service at the University of Utah Hospitals and Clinics in Salt Lake City, Utah. She previously served as a clinical pharmacist. Erin received her PharmD at the University of Utah and completed a specialized residency in drug information at the University of Utah Hospitals and Clinics.
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