A CDER conversation with Emily Thakur, CDR , United States Public Health Service, Team Leader, Drug Shortage Staff, Center for Drug Evaluation and Research, FDA
There has been some confusion regarding the definition of a drug shortage throughout the pharmaceutical industry and among the public. Adding to the static is FDA’s definition of a drug shortage compared to the definition of a drug shortage by its partners, such as the American Society of Health-System Pharmacists. How can these differences be resolved; are they really that far apart? Let’s look at how CDER’s Drug Shortage Staff focuses on the drug shortages that have a significant effect on public health in the United States.
Tell me how FDA defines a drug shortage
We define shortages as a period of time when the demand or projected demand for a medically necessary drug in the United States exceeds its supply.
Explain “projected demand”
Based on health data, information from suppliers, and by evaluating information from U.S. healthcare transactions, we can anticipate demand and determine if available drug products can meet that projected demand.
How does an FDA partner, such as the American Society of Health-System Pharmacists define a drug shortage?
Both FDA and ASHP closely follow drug shortages however, there are some differences in how we track and report this information. ASHP considers a drug product to be in shortage once the shortage is verified with manufacturers, regardless of whether the product is or is not medically necessary. They also consider a drug to be in shortage when supply issues affect how a pharmacy prepares or dispenses a drug product, or influence patient care when prescribers must use an alternative therapy.
Do the differences in these definitions impact the availability of drugs for consumers?
No – the differences affect how we each define availability and report shortages, but don't affect the availability of drugs for consumers. For example, ASHP may decide to post on their website when one manufacturer’s product is unavailable; while FDA would only post if the total demand is not able to be met by the current manufacturers, regardless if one manufacturer is "down" or currently not producing.
FDA receives information from manufacturers about their ability to supply a product for the market. A product is only listed on FDA’s drug shortage website when it has been confirmed to be unable to meet current demand (i.e. – the quantity of drug available from all manufacturers does not meet the current or projected demand). We do not consider a product to be in shortage if one or more manufacturers are able to supply enough of the product to meet the demand.
In contrast, ASHP’s drug shortage website provides information about which manufacturers have a drug available and which ones do not. If a product is listed on ASHP’s website, it is likely that a consumer will still find the product available from other manufacturers. The numbers and information from ASHP are valid; they track availability -- but they do not serve the same purpose as FDA.
Regardless of the differences between FDA and ASHP, we provide the most updated information possible on our websites about shortages and availability.
Overall, does FDA consider drug shortages a high priority?
Drug shortages are a top priority for FDA. They are a significant public health issue in the United States and we use every tool in our toolbox to find solutions including working with manufacturers to help prevent shortages from occurring or lessen the impact of shortages that cannot be prevented. We have issued a long-term strategic plan that outlines our priority actions, and actions drug manufacturers and others can take to prevent drug shortages.
Our comprehensive strategy recognizes the importance of addressing the underlying causes of shortages, including sustaining manufacturing quality. For example, the plan calls for improving data and response tracking, so we’re working to clarify the roles and responsibilities of manufacturers. We are constantly exploring actions the agency can take alone and in collaboration with other groups to reduce the impact and number of drug shortages.
Why are drug shortages still a critical issue in the United States?
Health care professionals caring for patients need the right drug, for the right patient, at the right time. We want to ensure this important tenet of health care - and not having a product available can be a major road block to treatment. Until drug shortages cease to occur, we will continue to be vigilant in our efforts to prevent them.
What is the major reason for these shortages?
There are a number of reasons why drug shortages can occur. Over half of all drug shortages are due to quality or manufacturing issues, such as the presence of particulates or endotoxins. Production delays at the manufacturer or delays obtaining raw materials and components from suppliers can all cause shortages. Sometimes companies stop producing a drug to make newer, more profitable drugs. With fewer firms making sterile injectable drugs, there are fewer production lines and in this case a shortage can occur if even one of these lines becomes unavailable. Seven manufacturers produce most of the sterile injectable drugs on the market. When one company has a problem or stops making the drug, it is difficult for the remaining companies to increase production quickly and shortages can occur.
Why can’t we just say to industry, “make more of product X?”
It doesn’t work that way – although it would be a lot easier if it did! FDA cannot require a company to make a drug. We can’t tell a company to make more of a drug. We can’t tell them how much of a drug should be distributed, nor can we tell manufacturers where a drug should be distributed. But if a shortage is imminent, we can work with companies to try to minimize its impact. Early and open dialogue between FDA and manufacturers is critical to our success.
How does the agency resolve shortages?
We have a carefully developed process we follow to identify the sources of the shortage and what can be done to prevent or minimize the impact of the shortage. To address the underlying causes, we work with the company to help resolve manufacturing or quality problems. The problems can be what we term “low risk” such as the wrong expiration date on a package. High risk problems can include foreign particles in the drug or sterility issues. We decide how to best address each situation based on its cause and the public health risk associated with the shortage. We work with other firms still able to make the drugs that are in shortage to help them ramp up production, if they are willing. Like I said, we can’t order them to increase production. If needed, we expedite approval of new production lines or new raw material sources. If U.S. manufacturers can’t resolve a shortage immediately and the shortage involves a critical drug, we may look for an international firm that is willing and able to redirect the product to the United States.
How has the Food and Drug Administration Safety and Innovation Act (FDASIA) enhanced our ability to prevent and mitigate drug shortages?
The biggest impact is the requirement that manufacturers must report shortages to us. This has resulted in additional early notifications to the FDA about potential shortages, and we have used that information to prevent shortages. FDASIA has detailed a list of prescription drug and biologic products for FDA to monitor, and requires all manufacturers of these products to notify us of a permanent discontinuance or temporary interruption in manufacturing. The Act also requires FDA to send a noncompliance letter to firms that fail to notify the agency. Other FDASIA requirements involve improving our internal and external communications; improving communication between FDA and the Drug Enforcement Administration regarding shortages of controlled substances; and developing a strategic plan to enhance FDA’s response to preventing and mitigating drug shortages.
How can the public access the latest information on drug shortages?
FDA is working hard to communicate effectively to the public about shortages to provide the most up to date information possible. To enhance communications we launched a new searchable format for FDA’s Drug Shortage website. This should help the public and health care professionals quickly identify drugs in shortage and find information on availability. Additionally, the FDA website now provides sections for new and updated drug shortages, and a listing of drug shortages by therapeutic categories.
We now also have the ability to report a shortage via a web form, and sorting functions to find drug shortages by generic name or status. This is an exciting development. We hope it will increase public access to drug shortage information and lessen some of the frustrations. We are also working on a mobile app that will help communicate drug shortage information to the public in real-time, as well as provide an additional means for the public to notify us about potential shortages.
The number of reported drug shortages has decreased in recent years. How do you think the efforts of FDA and its partners have helped create this trend?
The decrease in shortages has definitely been a combination of our efforts and the work of our partners – particularly the increased number of notifications we receive from manufacturers and health care providers. While our goal is to prevent all shortages, we’re not there yet. The downward trend in shortages, the uptick in notifications, and the increased focus on manufacturing quality are all things we hope will continue.
We are pleased to have seen a great decrease in new drug shortages over the last few years, however, more work needs to be done. Although last year there were less shortages, the United States experienced several critical shortages, like IV saline (intravenous saline solution used to give patients necessary fluids for hydration and other conditions). We will continue to work with industry and other stakeholders to address the root causes of shortages and do what is necessary to prevent them from occurring.