Statement from Douglas Throckmorton, M.D., deputy center director for regulatory programs in FDA’s Center for Drug Evaluation and Research, on the agency’s response to ongoing drug shortages for critical products
Among the biggest challenges health care providers and patients face are shortages of medically necessary medications. These shortages greatly impact patient treatment options and require practitioners to make difficult decisions that can compromise care, such as rationing supplies or using less desirable, but more readily available, alternative therapies. The FDA also understands the impact and concern these shortages may have on patients and we want to reassure them that their care will continue to be our priority. Ensuring access to the drugs patients need means finding creative responses to shortages while also addressing the root causes of the shortage issue. The FDA’s role is focused on working with manufacturers, using all of our authorities to help prevent and mitigate drug shortages of medically necessary products used to prevent or treat a serious or life-threatening disease or medical condition.
As Commissioner Gottlieb recently explained and we detailed last week in our 2017 annual report to Congress on drug shortages, the FDA does everything possible within our statutory authority to help address drug shortages. For example, using a range of available tools, the FDA’s Center for Drug Evaluation and Research worked with manufacturers to prevent 145 drug shortages in 2017. Still, there were 39 new shortages that occurred during 2017, and although this number is far lower than the peak of 251 new shortages in 2011, we recognize that many of these shortages have been for critical drug products and that they are having a tangible impact on patients.
While many of the shortages that occurred in 2017 have been resolved, unfortunately there are some that we are still working with companies to resolve. Further, there have been new shortages that have occurred in 2018 that require our immediate and consistent attention to help minimize their impact and bring them to a resolve as quickly as possible. Today, we want to provide updates on several specific shortages that we know have had a significant impact on the medical community and patients: the shortages of IV fluids, opioid analgesics (pain medications) and EpiPen. It’s important to underscore that we know that there are other medically necessary drugs in shortage, and we’re continuing to prioritize our ongoing work to address all shortages of these drugs given the impact on the public health.
IV fluid shortage
The 2017 hurricane season devastated Puerto Rico and impacted many of the drug and device manufacturers on the island. Among them was Baxter Healthcare Corporation. Baxter is a major manufacturer of sodium chloride-based (saline) and dextrose-based fluids for IV infusion, which, for example, are critical for mixing drugs for use in health care settings and are also used to keep patients hydrated. While IV fluids were in short supply before the hurricane and the FDA had been working with various manufacturers since 2014 to help improve the supply and address rising demand, the hurricanes compounded the pre-existing shortage situation leading to significant challenges in care across the country. After the hurricanes, the FDA quickly began working in partnership with Baxter and other manufacturers to consider ways to get ahead of the inevitable and significant impact on the existing shortage situation. With the support of other manufacturers, and after careful evaluation of the inspection history of specific manufacturing sites around the world, we worked with manufacturers to temporarily import IV fluids approved in other countries. We also expedited review of product applications from other manufacturers that would help with the shortage and add capacity to this market.
But even though the FDA quickly took these and other important steps, in the months following the hurricanes, many hospitals throughout the U.S. and abroad experienced serious shortfalls of these essential products. A particularly challenging flu season added to the concerns with IV fluid availability. The products’ scarcity forced health care professionals and facilities to use less desirable alternative therapies – for example, in some instances it required them to manually “push” drugs to patients through syringes instead of an IV drip, stretching already thin resources for medical staff at the bedside of patients.
After much work and a great deal of collaboration with a wide range of stakeholders, these IV fluid shortages are beginning to improve. Baxter is now producing at significantly higher levels. Other companies, including ICU Medical, B. Braun Medical, Laboratorios Grifols and Fresenius Kabi, are also producing critically-needed saline, many of which received expedited FDA reviews of their applications and supplements to add capacity and additional supply. In addition, six different manufacturing sites continue to temporarily import saline, which is helping to meet patient needs until the shortage completely resolves and approved IV fluid products can meet all demand.
While we are encouraged by the improvements in supply, there is still much work to be done as we carefully monitor the progress.
Injectable Opioid Analgesic shortage
In 2017, we also saw a manufacturing-related shortage of injectable opioid analgesics (pain medications), including hydromorphone, morphine and fentanyl which, among other things, are used for the treatment of cancer patients or during surgical procedures as well as for the care of other critically ill patients. These are highly potent, yet effective, drugs that are given directly by health care providers to help manage serious pain while patients are in the hospital or other inpatient medical settings. Part of our strategy to address this shortage includes enlisting the support of other companies who make these products to help close the gap on the demand so that health care providers can continue to provide appropriate and effective treatments for the patients who need them.
Shortages of these particular drugs were caused by production delays due to a number of changes and upgrades at a Pfizer facility in Kansas. The shortage has been further exacerbated by recent issues related to manufacturing quality at the same facility. As Pfizer works through these challenges, the FDA has remained in constant communication with the company regarding these shortages. While Pfizer currently expects that delays will continue until 2019, we are working with them to increase supplies before then. One of the actions taken to help mitigate the impact of the shortage was that Pfizer recently coordinated with the agency to release some of the products that were on hold due to potential quality issues to distribute them with instructions for the safe handling and use to help mitigate any risks to patients.
We are also working with other companies that manufacture FDA-approved injectable analgesics, which have agreed to increase their production, including Akorn Pharmaceuticals, Fresenius Kabi USA and West-Ward Pharmaceuticals. However, it is taking time for these companies to produce enough product to cover the shortfall in the market. We will continue to share updates on our website as this situation progresses.
EpiPen supply
Another recent product supply issue that has been of particular concern involves EpiPen, which is a continuously evolving and fast-moving issue. Many patients rely on self-injectable epinephrine products, such as EpiPen, to reverse life-threatening reactions to bee stings or other allergies for either themselves or for their children. We recognize the anxiety that is felt when access to these products are not guaranteed, and we want to assure the public that we are doing everything we can to address supply issues with the brand product. The FDA also reminds health care providers, pharmacists and patients that there are alternative epinephrine products that can be used safely and effectively.
Multiple factors, including regional supply disruptions and manufacturer issues, have contributed to EpiPen’s limited availability in certain areas in the U.S. The FDA has been working closely with Mylan regarding the status of EpiPen production supply and has been in contact with the other manufacturers of epinephrine auto-injectors regarding their supply status. Mylan established a customer service number, which we have posted on our website, to help pharmacies and patients locate EpiPens if necessary. Based on Mylan’s information, the FDA anticipates the issue to be short-term. Information on other approved epinephrine autoinjector products can also be found on our website.
Nearly half of all Americans take at least one prescription drug in a given month, and nearly four billion drugs are ordered each year, according to the Centers for Disease Control and Prevention. By comparison, the number of medicines in short supply may seem small, but we know that each one can be essential to the life or well-being of a patient who needs it.
These examples help illustrate some of the many ways the FDA is helping to mitigate and prevent drug shortages, often with a mix of industry cooperation, regular communication and the flexible use of the FDA’s regulatory authorities. When we are given appropriate notice by manufacturers of a pending supply disruption, the FDA can better use our strategies and tools to help protect the public by preventing and mitigating expected shortages.
We stand committed both in our mission as a public health agency and in service to the care of American patients to do all that we can to help mitigate the impact of drug shortages.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.