Shortage of Relief: Recent Disasters Highlight Multifaceted Drug Shortage Problem
- Nearly a month after Hurricane Maria swept through Puerto Rico, roughly 80 percent of the U.S. territory is still without electrical power.
- The island is home to multiple drug manufacturing facilities that are directly affected by these power outages, and U.S. Food and Drug Administration (FDA) Commissioner Scott Gottlieb has warned that the hurricane may cause shortages for more than 40 different drugs.
- The situation in Puerto Rico makes clear that although new drugs may be and are approved at an increasing rate, the supply of these drugs is not unlimited and can be curbed surprisingly easily by natural disasters or other one-time events.
Texas, Florida and now Puerto Rico are reeling from the devastation inflicted by hurricanes Harvey, Irma and Maria, respectively. Hurricane Maria alone inflicted nearly $100 billion of damage to Puerto Rico and surrounding islands, resulting in more than 75 confirmed fatalities. While many conversations are going on both in and outside the Beltway concerning ways to alleviate Puerto Rico's food and water issues as well as its Medicaid shortfall, the aftermath of Maria has brought another recurring topic to relevance: drug shortages.
Nearly a month after Hurricane Maria swept through Puerto Rico, roughly 80 percent of the U.S. territory is still without electrical power. Besides its citizens, Puerto Rico is home to multiple drug manufacturing facilities that are directly affected by these power outages, many of which are owned and operated by some of the largest drug companies in the world. U.S. Food and Drug Administration (FDA) Commissioner Scott Gottlieb has warned that the hurricane may cause shortages for more than 40 different drugs, and the agency is already utilizing its authority to import at least four of those drugs. Of the 40 drugs in potential or current shortage, about a third are deemed "sole-source," meaning that other alternative drugs are not approved or are typically unavailable to fill the supply chain.1
The situation in Puerto Rico makes clear that although new drugs may be and are approved at an increasing rate, the supply of these drugs is not unlimited and can be curbed surprisingly easily by one-time events, such as natural disasters. Thus, the situation in Puerto Rico begs a three-pronged question: 1) how common are these drug shortages; 2) what can the FDA and others do when there is a shortage; and 3) are those actions enough?
Drug shortages have been a frustratingly consistent problem for healthcare providers and hospital systems, especially in the past five years. From 2011 to 2015, the number of both new and ongoing drug shortages – shortages that last for two years or more – remained static at just shy of 450.2 In the abstract, it's easy to assume that these shortages are temporary and deal with drugs used to treat diseases that affect small populations. However, tours of the FDA's drug shortage database and other drug shortage resources, including ones run by the American Society of Health-System Pharmacists and the University of Utah, show a different situation, one marked by wide-ranging shortages for drugs that are critical for patient care. The current shortage of sodium bicarbonate injection is a perfect example of the complexity of a typical drug shortage and how care for the sickest patients can be quickly comprised.
Sodium bicarbonate, an ironically common ingredient found in your kitchen cabinets as the basis of baking soda, is crucial to counter acidosis, or elevated acidity in blood and body tissues, and is important during advanced cardiac life support care and surgical situations. Because of its common usage, multiple drug companies manufacture the drug. However, two of these companies have the substance backordered due to increased demand and manufacturing delays, which can affect both the sodium bicarbonate itself and the syringes or vials that it comes in, with the third company doling out limited supplies of the drug on back order.3
For medical professionals who commonly use substances such as sodium bicarbonate, the first instinct is to find a substitute drug. However, the most commonly used substitute for sodium bicarbonate is sodium acetate, which takes approximately 15 to 20 minutes to infuse in a patient versus one to two minutes for sodium bicarbonate.4 In an emergency situation, the 10-minute-plus difference in the timing of an infusion could be life or death. Further, looking for quick or adequate alternatives may involve dealing with a different route of administration, concentration or packaging type for a certain drug, or administering a new drug that may be contraindicated in certain patients, all of which can easily result in medication errors and unintended harm. In these all-too-common situations, a drug shortage also tends to be accompanied by an information shortage that provides the basis of this critical problem.
Since 2012, the FDA has, on average, increasingly prevented drug shortages from occurring. Much of the FDA's increased effectiveness is based on authorities granted through the Food and Drug Administration Safety and Innovation Act (FDASIA).5 Among other things, FDASIA requires manufacturers of "life-sustaining" drugs, as well as drugs used in emergency medical care or surgery, to notify FDA at least six months prior to a production discontinuance or interruption. Those that fail to do so will receive non-compliance letters.6 The FDA also allows for the expedited review of pending applications for generic versions of drugs related to drugs in shortage as determined by the FDA.
However, the FDA's most direct response to drug shortages thus far has been to determine and approve new foreign manufacturing sources for importation. (As an aside, drug importation, which is the process by which FDA-approved drugs manufactured overseas are brought into the U.S., is not interchangeable with drug reimportation, the currently illegal process of reimporting FDA-unapproved, U.S.-manufactured drugs for sale in other countries and a policy option associated with the current drug-pricing debate.) Although drug importation sounds like an obvious solution to this issue, it's not so simple. In order to draw medications from an alternate manufacturing facility, the manufacturer has to submit an application and a listing of the drugs that it is equipped to make, and in many cases the FDA enters into cooperative agreements with foreign governments to ensure that the substances being imported into the U.S. conform with public safety and quality laws.7 The FDA also must ensure that these manufacturers can develop a sound shipping plan for these drugs and that they are able to adequately communicate information about their drugs to patients and providers.8
All of these steps take time, but in many cases foreign importation remains one of the most viable solutions. In the aforementioned case of sodium bicarbonate injection, the FDA granted an Australian pharmaceutical company importation rights for the drug, albeit on a direct order basis only. It was FDA Commissioner Gottlieb's instinct to use the agency's authority to expedite the importation of certain drugs from a hurricane-affected company's alternate manufacturing facilities outside of Puerto Rico, which seems effective in the short-term despite the additional registration and oversight steps required to ensure the process' success.
As discussed previously, the FDA's discretion and abilities to combat drug shortages have been increased by Congress, and the agency has done an admirable job of reducing drug shortages over time. However, the FDA is still limited in its abilities to shift existing resources from one affected group to another and in what it can compel manufacturers to do under its current enforcement discretion. Further, while the incidence of non-acute drug shortages has dropped, especially since 2012, shortages of drugs used in emergency medicine has gone largely unchanged despite these provisions, indicating that there is still a great deal of work left to be done.
In addition to implementing and expanding FDA's existing tools, stakeholders have proposed several other alternative methods of reducing drug shortages. One possible way is by expanding the use of compounding pharmacies during acute drug shortages. Traditionally a state-regulated activity, compounding involves a licensed pharmacist or licensed physician combining, mixing or altering drug ingredients to form new medications, which can be helpful if ingredients of a particular drug are available but the FDA-approved formulation from a licensed manufacturer utilizing those ingredients is in shortage. However, although the process is regulated9, compounded drugs are technically not FDA-approved, are unable to be produced in bulk without prior authorization of the ingredients and do not necessarily carry with them the FDA's seal of quality, which can lead to situations such as the fungal meningitis outbreak at the New England Compounding Center in 2012.
Two further solutions include 1) tapping into, expanding or modifying the Strategic National Stockpile, a national repository of antibiotics, life-support medications and medical surgical items for resupplying state and local public health agencies during emergencies, and 2) using FDA's authority to extend the expiration dates of medications so that existing supplies of drugs may be stored for longer periods for future use. Both of these programs, while benefiting from years of implementation, are currently limited to larger-scale emergency situations such as natural disasters, the nature of which tend to be far different than the recurring drug shortages felt by the medical community in general. And, as noted by the FDA's own 2013 "Strategic Plan for Preventing and Mitigating Drug Shortages," many drug shortages are caused by quality and contamination issues during the manufacturing process, which makes the development of incentives for quality manufacturing and advanced metrics to identify manufacturing issues before they occur a potential solution not to be ignored.
As has been shown in the resolution of past drug shortages, much of the work to combat these shortages is through communication – not only between the FDA and manufacturers/suppliers but also between healthcare entities, including hospitals, health systems, community health centers and disaster relief services – to fuel coordination of resources. As more information on drug shortages becomes available, the FDA, given its jurisdiction over drug shortage issues, should at the very least have the ability to expand its drug shortage database to include information on alternate sources of drugs in shortage and therapeutic alternatives to these drugs if they exist, which is something that other drug shortage databases provide. In addition, the FDA should also maintain and empower its Drug Shortages Task Force, created under FDASIA, to develop the aforementioned FDA strategic plan on drug shortages in order to continue to develop and implement innovative solutions to drug shortages both preventatively and as they arise in emergency situations.
Ultimately, the aforementioned solutions to expand FDA's authorities regarding drug shortages must be combined with increased communication with and between manufacturers and suppliers so that patients and providers are put first when addressing these shortages in affected communities.
1 Florko N., "FDA Allows Importation Of Four IV Drugs After Hurricanes, Three Are In Shortage," InsideHealthPolicy.com, Oct. 10, 2017.
2 U.S. Government Accountability Office, "Drug Shortages: Certain Factors Are Strongly Associated with This Public Health Challenge," July 7, 2016.
4 Neavyn M.J., Boyer E.W., Bird S.B., Babu K.M., "Sodium Acetate as a Replacement for Sodium Bicarbonate in Medical Toxicology: a Review," Journal of Medical Toxicology, September 2013; 9:250-254.
5 Public Law 112-144.
6 21 U.S.C. 356(c).
7 21 U.S.C. 360(i).
9 21 U.S.C. 353(a).
Information contained in this alert is for the general education and knowledge of our readers. It is not designed to be, and should not be used as, the sole source of information when analyzing and resolving a legal problem. Moreover, the laws of each jurisdiction are different and are constantly changing. If you have specific questions regarding a particular fact situation, we urge you to consult competent legal counsel.