Drug shortages are a significant public health issue that have affected many critically important drugs including chemotherapy treatments, nutritional support preparations, and antibiotics. Drug shortages can result in delaying or denying needed care to patients and may cause practitioners to prescribe an alternative therapy that poses greater risk or that may be less effective for the patient. Drug shortages have interfered with clinical trials, in some cases delaying research on important new therapies.
The year 2011 was a critical one in this public health crisis. After several years of steady increases in new shortage reports, manufacturers, hospitals, and other stakeholders reported an unprecedented number of new drug shortages to the Food and Drug Administration (FDA)—251 in that year alone. That year also marked a turn in the FDA’s ability to assist in mitigating and preventing impending shortages.
Requested in a presidential executive order and then codified into law by Congress in 2012, manufacturers are now required to notify the FDA of impending production disruptions in certain prescription medications. These early notifications give the FDA and manufacturers more time to take actions aimed at preventing disruptions from turning into shortages and mitigating the impact of shortages, should they occur.
Once companies began to increase reporting of anticipated or in-progress production disruptions, the trend in new shortages reversed. Working within the confines of the current statutory and regulatory framework and in partnership with manufacturers and other stakeholders, the FDA helped prevent almost 80 percent of impending shortages in 2013, up from about 45 percent in 2011. As a result, the number of new shortages posted by the FDA fell by over 80 percent from its 2011 peak. But another key data source on drug shortages, the University of Utah Drug Information Service (UUDIS), shows a 47 percent drop in new shortages between 2011 and 2014.
On other measures, the picture seems more confusing. At the onset of 2015, the UUDIS was tracking 301 active shortages, an increasing trend reported in a 2014 Government Accountability Office (GAO) study and later reflected in a Health Affairs health policy brief. Yet during a 2014 Congressional hearing on the topic, the FDA presented statistics showing that the number of active shortages is going down.
These statements reflect the numbers on the FDA drug shortage website, which listed 82 active shortages at the onset of 2015, down from 121 shortages two years earlier. The two organizations, the FDA and UUDIS, work closely together and communicate regularly about arising problems and resolved shortages. Why is it then that their numbers are at different levels and facing diverging trends? In this blog entry, we discuss how the FDA’s list of shortages represents a subset of a broader list of supply disruptions listed by the UUDIS.
The FDA And UUDIS Differ In How They Define A Shortage
The FDA and UUDIS’s active shortage numbers are different because the two organizations have contrasting definitions for what constitutes an active shortage, partly due to the organizations’ objectives and partly due to the data that they have at their disposal. The UUDIS defines a shortage as a supply disruption that affects how the pharmacy prepares or dispenses a drug product or that influences patient care when prescribers must use an alternative agent. In turn, the FDA takes a more macro approach by focusing on the public health impact and the national supply of the drug. In particular, the FDA’s definition of a shortage considers whether the combined supply from all manufacturers in a specific drug market meets historical demand patterns.
The FDA and UUDIS pay equal attention to any given manufacturer’s report that it is experiencing a production disruption with a given drug dose. The two organizations differ in their reporting sources, but they collaborate routinely on shortage reporting by sharing reports. It is at that point that things diverge. After verifying with the affected manufacturer that a national supply disruption exists, the UUDIS will generally list the supply issue as a shortage on the website hosted by the American Society of Health-System Pharmacists (ASHP). In turn, the FDA will conduct further analysis to verify that a market-wide shortage is in place before posting it on its website.
What Does The FDA Consider A Market-Wide Shortage?
To determine whether a market-wide shortage exists, the FDA must first define the relevant market. In making that determination, the FDA considers the clinical implications of the supply disruption in question. For instance, can pharmacists split or combine other doses of the drug to provide the dose in question? Can patients use another version of the drug that contains the same active ingredient?
The FDA generally defines a market on the ingredient-route level (for example, injectable doxycycline). Sometimes, the FDA’s market definition will be more narrow when clinical practice demands it, as in the case of preservative-free injectable methotrexate for childhood cancers, or with controlled release tablets that cannot be split up to make up the right dose.
With a market definition in hand, the FDA evaluates the extent of the reported production shortfall in that market. The FDA uses third-party market research databases to assess the market share of the presentations with supply disruptions as well as those they identified to be in the same market. FDA staff then contact manufacturers of products in the relevant market to collect up-to-date inventory information, rate of demand (units per month), manufacturing schedules, and any changes in ordering patterns. Although manufacturers are not required to provide this information to the FDA, firms have been voluntarily sharing this information and that has greatly facilitated the management of shortages. If possible, the FDA’s drug shortage staff also evaluates product inventory in distribution channels.
Once this analysis is complete, the FDA may determine that the current supply of the drug from all producers meets the historical or anticipated demand. In the background, the FDA is monitoring the situation, working with the manufacturer(s) to mitigate the issue and in many cases engaging in efforts to prevent the supply disruption from becoming a market-wide shortage. However, the FDA will not post a shortage if competing manufacturers provide evidence that they have sufficient inventory to cover the existing shortfall. Similarly, the FDA will not post a shortage if the affected manufacturer or competing manufacturers say they are ramping up production and are meeting all demand.
Since not all supply disruptions lead to market-wide shortages, the FDA drug shortage list is a subset of the UUDIS list posted on the ASHP’s website. On the same note, not only will the UUDIS often post when the FDA is not posting, but the UUDIS may keep the FDA-listed shortages on their list long after the FDA no longer considers them market-wide shortages. In general, the UUDIS will wait to delist an issue until all presentations or forms of the drug are back on the market. This is due less to a lack of access to information, and more a reflection of UUDIS’s primary purpose intent to support pharmacists and clinicians when they have to adjust health care delivery practices in managing patient care.
Contemporary practices that utilize electronic medical records, computerized inventory systems, and barcoding incentivize stocking just a few presentations of a given medication. These practices make it important for pharmacists to know which specific product presentations are widely available and which are not; therefore the UUDIS will wait for all relevant presentations to be back in supply before delisting a shortage.
Differences In How The FDA And UUDIS Classify A Supply Disruption As A Shortage
Injectable vancomycin is a great case study in when and why the FDA and the UUDIS have differences in reporting shortages, and what one should and should not infer from a drug’s absence on the FDA’s list. The UUDIS has had vancomycin on the ASHP drug shortage website since 2009 because of short supply of various presentations, mainly larger vial sizes. The UUDIS considers this a shortage because pharmacies must change the way they prepare the medication when the larger vial sizes are not available. Pharmacies are also at risk of not following federal guidance, such as the United States Pharmacopeial (USP) 797, if they must use multiple small vials to make a single dose, justifiable in a public health emergency, but not desirable.
The drug was not listed on the FDA’s website until late 2014, which some have incorrectly interpreted as insufficient engagement on the FDA’s part. Following standard procedures for tracking a potential shortage of a medically necessary drug, the FDA was already closely monitoring the situation but did not post vancomycin until late 2014 because overall supplies of the same ingredient-route alternatives were still keeping up with demand.
During that time, the UUDIS could not report any hospitals that were completely out of stock of vancomycin in some form, although many had to change the way they prepared doses when the larger vials were not available. The situation changed in the fall of 2014 when one vancomycin manufacturer notified the FDA of anticipated delays in production, and another issued a recall of the product. This resulted in a market-wide shortfall that manufacturers would not be able to address quickly, so the FDA posted the vancomycin shortage on its website.
The FDA Works On Many More Supply Disruptions Than Listed On Its Website
Drugs listed on the FDA’s website are only a small subset of all the drugs on which the FDA’s drug shortage staff works. Ever since manufacturers began reporting production disruptions to the FDA, an increasing number of shortage interventions occurred before a market-wide shortage took place. In 2013 alone, 80 percent of impending shortages never ended up on the FDA’s website because manufacturers, in coordination with the FDA, took actions to ramp up production to a level that would keep total supply equal to total demand. We expect that the vast majority of these same supply disruptions reported to the FDA ended up on the UUDIS’s list but were never posted on the FDA’s list because a market-wide shortage was not in place.
When Should One Look At The FDA’s Versus ASHP’s Website?
The FDA and UUDIS/ASHP are committed to providing timely communications about new and ongoing shortages. The organizations collaborate routinely on shortage reporting by sharing shortage reports on a daily basis and by linking to each other’s websites. However, as described in the table posted on both websites, the organizations ultimately have different objectives and different capabilities. As a result, they are the go-to website for different sets of stakeholders:
- The drug list on the FDA’s drug shortage website is intended for the public as an indicator of active market-wide shortages. The list does not reflect the full scope of supply disruptions that the FDA is actively engaging in or monitoring.
- In turn, the ASHP website is very useful in helping pharmacists and clinicians manage the supply disruption at hand, whether the supply disruption is market-wide or not. The UUDIS provides information about which specific product presentations or versions are in short supply as well as evidence-based alternatives if no product is available.
The differences between the FDA’s list and the list on the ASHP website are straightforward: the former lists only market-wide shortages, while the latter lists any supply disruption that forces pharmacists and clinicians to adjust their health care delivery practices.
To learn more about FDA’s role in mitigating and preventing drug shortages, we refer readers to the FDA’s Strategic Plan for Preventing and Mitigating Drug Shortages, which includes extensive background on what the Agency is currently doing in this arena. Information about the ASHP’s advocacy for solutions to the drug shortage problem can be found on the ASHP’s website.