Drug shortages threaten patient safety
From the July 29, 2010 issue
It’s July, and it’s not just the rising temperature and humidity that’s making this a summer of discontent. Healthcare providers are also feeling the heat from an alarming number of drug shortages of critically important medications. Drug shortages can compromise or delay important drug therapy and result in medication errors. According to reports submitted to ISMP, healthcare practitioners are concerned more than ever before about how frequent drug shortages are adversely affecting patient care and exhausting a tremendous amount of hospital resources to address the growing problem.
While drug shortages have long been a problem in healthcare,(1) the number experienced in the past few months is unprecedented, particularly with high use medications, including emergency drugs, pain medications, and anesthetic agents. Extensive lists of drug shortages are maintained by the FDA (www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050792.htm) and ASHP (www.ashp.org/shortages?WT.ac=hp%5FPopLinks%5FDrug%5FShortages). ASHP’s list, supported by the University of Utah Drug Information Service, is more comprehensive than FDA’s list, which only includes shortages of medically necessary products given their significant impact on public health. A product is considered medically necessary if it is used to treat or prevent a serious disease or medical condition, and there is no other available source of that product or an alternative drug judged by medical staff to be an adequate substitute.(2)
Frustrations are high as healthcare providers experience frequent stock depletion of critical drugs, often without prior notice, and then scramble to devise acceptable and safe alternatives. But using alternative medications, dosage strengths, or dosage forms often requires different dosing, preparation, and administration considerations, which only adds to the complexity of care. This increases the risk of serious errors, especially when the drugs in short supply are high-alert medications.
The HYDROmorphone shortage is a prime example. As recommended in our article on opioid safety (www.ismp.org/Newsletters/acutecare/articles/20070222.asp), many organizations changed from a 2 mg/mL (1 mL) ampul or syringe to a 1 mg/mL (1 mL) ampul or syringe to limit the risk of an overdose. In some hospitals, the switch was initially met with resistance, but perseverance led to success. Then the 1 mg/mL (1 mL) ampuls were unavailable, so hospitals switched to a 1 mg/mL (1 mL) Carpuject prefilled syringe. Now, the Carpuject is unavailable, and the 1 mg/mL (1 mL) ampuls are still in short supply. The only product available in some hospitals is the 2 mg/mL (1 mL) ampuls. If the use of HYDROmorphone is high, pharmacy preparation of 1 mg/mL syringes from the 2 mg/mL ampuls would be difficult. Thus, these hospitals reverted back to the 2 mg/mL concentration, where the risk of an error is especially high given that staff have become accustomed to the 1 mg/mL strength. Now, the 2 mg/mL ampuls are in short supply, which may require hospitals to stock the 4 mg/mL or 10 mg/mL strengths of HYDROmorphone. The risk of a potentially fatal error given these circumstances is unacceptably high.
The propofol shortage offers another example of asking practitioners to quickly acclimate to the use of a new high-alert drug, thus increasing the risk of an error. Propofol has been used outside the operating room for years, so many healthcare practitioners are familiar with its effects, dosing, and administration procedures. In fact, propofol has become the drug of choice within many protocols for procedures. In some locations, the procedures previously performed using propofol must now be performed using an alternative agent for sedation, which may require different prescribing parameters, preparation, storage, dosing, patient monitoring, and recovery from its effects. Requiring the use of an unfamiliar alternate agent for sedation places patients at significant risk for becoming the victim of a harmful medication error.
Our June 17, 2010, newsletter and a recent National Alert Network communication from ASHP and ISMP (www.ismp.org/NAN/files/NAN-201006.pdf) described a similar concern regarding the shortage of EPINEPHrine 1 mg/10 mL (0.1 mg/mL) prefilled syringes for emergency use. Hospital code carts and emergency medical services (EMS) drug boxes both are stocked with these syringes to treat patients in the pre-hospital setting. Because these syringes are no longer available from the sole manufacturer of this product, once emergency personnel run out of the product, they must dilute a concentrated form of the drug before administration. For the vast number of patients in the inpatient setting, these extra steps will cause only minor delays in delivering the drug. However, imagine an emergency medical technician (EMT) caring for a patient in an automobile accident who was thrown from the vehicle into trees and bushes down a dark embankment at 2 a.m. Instead of just grabbing a well-labeled syringe after starting an IV line, the EMT now must pull together various components—syringe, needle, diluent, drug ampul—to prepare the injection. In the past, we’ve received reports about healthcare providers misreading labels on tiny EPINEPHrine ampuls and confusing it with ePHEDrine, or miscalculating a dose based on ratio expressions of 1:1,000 or 1:10,000, often leading to fatal 10-fold overdoses.
Regrettably, we believe the forecast for drug shortages is grim. There is little relief in sight to halt the rapid escalation of shortages in large part because the conditions that lead to shortages are varied and FDA lacks the necessary regulatory authority to proactively manage potential shortages. It is not always clear what causes drug shortages, as drug companies are not required to disclose the underlying reason or notify FDA regarding a decision to stop production unless they are the sole-provider of the product and it is a medically necessary product. Few manufacturers will supply letters to healthcare providers regarding the reason behind the shortage and the anticipated duration, which is very frustrating to healthcare personnel. The drug shortage lists maintained on the ASHP and FDA Web sites attempt to provide a reason for the shortage in very general terms.
Some of the more common reasons for drug shortages include the following:(3)
- Unavailability of bulk and raw materials used to produce pharmaceuticals, of which 80% come from outside the US
- A delay or halt of production in response to an FDA enforcement action regarding noncompliance with good manufacturing practices identified during an inspection
- Voluntary recall of a drug after the manufacturer discovers a problem with the medication, such as inadvertent bacterial or fungal contamination
- Change in the manufacturer or product formulation (e.g., inhalers without chlorofluorocarbons) that delays production
- Manufacturer’s business decision to halt production of a drug due to availability of generic products, patent expiration, market size, drug approval status, regulatory compliance requirements, anticipated clinical demand, and/or reallocation of resources to other products (FDA does not have authority to require a company to continue manufacturing a medically necessary product)
- Manufacturer mergers that narrow the focus of product lines, causing discontinuation of certain products, or move production of a drug to a new facility, causing production delays
- Poor inventory ordering practices, stockpiling before price increases, and hoarding caused by rumors of an impending shortage
- Unexpected increases in demand for a drug when a new indication has been approved, usage changes due to new therapeutic guidelines, or a substantial disease outbreak occurs
- Natural disasters that involve manufacturing facilities or that lead to demands for certain classes of medications to treat disaster victims.
FDA has also reported an ongoing trend with some older sterile injectable products that has resulted in fewer companies making these critical products because they are not as profitable as newer agents. Further, some pharmaceutical companies say they do not want to invest additional resources to gain newly required FDA approval for drugs that were previously manufactured under a grandfather clause without explicit FDA approval. The few companies that continue to make these products use their production lines for multiple products, so scheduling production of the older products is very tight. The production lines are often running at maximum capacity and usually cannot ramp up for increased demand. If there are even slight delays or manufacturing issues, a shortage usually results. Another factor is the low inventory levels maintained in the companies. Shortages develop very quickly when manufacturing stalls for any reason. Capacity and inventory issues are managed by the pharmaceutical companies. FDA can’t require companies to enhance capacity or keep higher inventory levels to help ensure against shortages. However, FDA can facilitate approval of new manufacturers that are willing to make these older drugs, which are vulnerable to shortage.
Whatever the cause, drug shortages have become a key patient safety concern in healthcare today. The urgency of this situation suggests that the current “business as usual” approach is woefully inadequate in every respect; this issue requires a disaster-type response. ISMP and ASHP are interested in co-convening a public meeting and inviting key stakeholders representing FDA, the pharmaceutical industry, healthcare practitioners, regulatory authorities, and medication safety experts to explore and articulate the scope of this problem, and to develop a plan to reduce the occurrence of drug shortages and better manage them when they occur.
In preparation for such a meeting, which ASHP, ISMP, and others are actively pursuing, we encourage you to take a few minutes to complete a short survey on this topic at: www.surveymonkey.com/drugshortages. A copy of the survey appears on page 4 (of the PDF version of the newsletter) for practitioners who do not have Internet access. We need your input to ensure that the unique perspective of each discipline in healthcare affected by drug shortages is heard at any convened meetings on the subject. You can help demonstrate the urgency of the issue and contribute to its resolution by participating in the survey. We will publish the results as well as recommendations for managing drug shortages in a future newsletter. Continued inaction on this issue will undoubtedly result in much more than a summer of discontent.
References: 1) ISMP. Part 1 of our national survey on drug shortages reveals high level of frustration, low regard for safety. ISMP Medication Safety Alert! 2001; March 21. 2) CDER manual of policies and procedures 6003.1: drug shortage management. Rockville, MD. Food and Drug Administration, 2006. 3) Fox ER, Birt A, James KB, et al. ASHP guidelines on managing drug product shortages in hospitals and health systems. Am J Health-Syst Pharm. 2009; 66:1399-406.