Over the last ten years, the number of drug shortages has increased, straining out health care system. The American Society of Health System Pharmacists (ASHP) and the Food and Drug Administration (FDA) monitor drugs distributions and track drug shortages.
The Food and Drug Administration defines drug shortages as "products used to prevent or treat a serious life-threatening disease or medical condition for which there is not other available source with sufficient supply of that product or alternative drug available."
The ASHP describes a drug shortage as "a supply issue that affects hot the pharmacy prepares or dispenses a drug product or influences patient care when prescribers must use an alternative drug available". Two very different definitions. Drug shortages can happen for a number of reasons, including little to no access to raw materials, issues with manufacturing noncompliance to regulatory standards, along with business and economic variables.
Barack Obama signed the FDA Safety and Innovation Act (FDASIA), which gave the FDA authority to regulate drug shortages. Under this act, manufacturers of biologics and all prescription drugs that are covered must provide notice to the FDA if a delay or interruption in production is foreseen. This act also gives the FDA the right to conduct expedited reviews of drug applications and/or expedited inspections, in an effort to alleviate the burden of a drug shortage.
Drug shortages can lead to rising health care costs, increased safety risks, and an overall burden to health care providers. It can also lead to non-traditional distributors to enter the market, purchase the remaining supply of the drug, and sell to hospitals and health clinics at an inflated price. The alternative drug that would take its place would probably have more side effects than the prior medication along with reduced efficacy.
Although the number of new drug shortages has declined since 2011 as a result of work by many groups, including FDA, shortages continue to pose a real challenge to public health. This is especially the case when the shortage involves a critical drug to treat cancer, to provide parenteral nutrition, or to address another serious medical condition, such as a shortage of blood pressure medications.
Although there has been a leveling off in new shortages over the past few years, CY 2021 has been a challenging year for shortages. FDA has seen manufacturers in the U.S. and abroad continue to experience quality issues as well as struggle with capacity constraints. Additionally, as demand increased for numerous drugs over the last year, FDA has seen additional strain on the pharmaceutical supply chain.
Shortages can delay or deny needed care for patients, creating a potential lapse in medical care. Shortages can also lead prescribers to use second-line alternatives, which may be less effective or pose additional risks compared to the drug in shortage. To prevent these situations from occurring, FDA has used a variety of methods to prevent shortages, working within the statutory and regulatory framework in place and in partnership with manufacturers and other stakeholders. FDA’s investigation into nitrosamine impurities is an example of how the Agency has taken steps to ensure the safety of drug products while also working to both mitigate and prevent future shortages using tools such as expedited reviews and inspections.
In response to a dramatic increase in shortages, the President issued Executive Order 13588 on October 31, 2011, recognizing that “shortages of pharmaceutical drugs pose a serious and growing threat to public health ... endanger patient safety ... burden doctors, hospitals, pharmacists, and patients ... and increase health care costs.” The Executive Order acknowledged the need for a “multifaceted approach” to address the many different factors that contribute to drug shortages. The Executive Order directed FDA to take steps to help prevent and reduce current and future disruptions in the supply of life-saving medicines, including notifications and expedited reviews, as appropriate.
With the enactment of FDASIA on July 9, 2012, the FDA was given important new authorities related to drug shortages. For example, section 1001 of FDASIA amended the FD&C Act to broaden the scope of the early notification provisions by requiring manufacturers of most prescription drugs that are life-supporting, life-sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition (whether approved or unapproved) to notify FDA of a permanent discontinuance or temporary interruption in manufacturing that is likely to lead to a meaningful disruption in supply of the drug in the United States.
The FD&C Act as amended by FDASIA also allowed FDA to require, by regulation, early notification of such discontinuances or interruptions in the manufacturing of biologics.
The FD&C Act as amended by FDASIA requires FDA to send a non-compliance letter to firms that fail to notify FDA in accordance with section 506C of the FD&C Act. FDA sent the first two such letters in 2014, an additional two such letters in 2016, three in 2018, one in 2019, and one in 2021.
Other FDASIA requirements with respect to prescription drug shortages include improving FDA’s internal and external communications about shortages, improving communication between FDA and the Drug Enforcement Administration (DEA) regarding shortages of controlled substances, and developing a strategic plan to enhance FDA’s response to preventing and mitigating drug shortages.
The Coronavirus Aid, Relief, and Economic Security Act (aka CARES Act) was signed into law on March 27, 2020, to aid response efforts to the COVID- 19 pandemic and to ease the economic impact of COVID-19. In addition, the CARES Act amended the FD&C Act to include authorities intended to enhance FDA’s ability to identify, prevent, and mitigate possible drug shortages by, among other things, enhancing FDA’s visibility into drug supply chains.
Specific authorities to enhance FDA’s ability to identify, prevent, and mitigate drug shortages include the following:
• Amendments to section 506C(a) of the FD&C Act to expand the requirement for manufacturers of certain drugs to provide information on permanent discontinuances and interruptions in manufacturing that may lead to a meaningful disruption in supply to FDA.
• Amendments to section 506C(g) of the FD&C Act to require FDA to prioritize and expedite, as appropriate, the review of certain applications and inspections that could help mitigate or prevent a shortage of a drug covered by section 506C(a).
The addition of section 506C(j) to the FD&C Act, requiring manufacturers of drugs described in section 506C(a) of the FD&C Act or of any active pharmaceutical ingredient (API) or any associated medical device used for preparation or administration included in the drug to develop, maintain, and implement, as appropriate, a redundancy risk management plan that identifies and evaluates the risks to the supply of the drug, as applicable, for each establishment in which the drug or API of the drug is manufactured.
Amendments to section 510(j) of the FD&C Act to require drug manufacturers registered under section 510 of the FD&C Act to annually report the amount of each drug that they have “manufactured, prepared, propagated, compounded, or processed” for commercial distribution.
In response to a request in June 2018 from 31 U.S. Senators and 104 members of the House of Representatives, the Commissioner of Food and Drugs established the inter-agency Drug Shortages Task Force to determine the root causes of drug shortages and develop recommendations to address them.
The task force took a comprehensive look at all drivers of drug shortages and identified potential ways to prevent or mitigate them in the future. To ensure FDA did not overlook any drivers or solutions, the task force included not only senior leaders from FDA but also leaders from a number of federal agencies including the Centers for Medicare & Medicaid Services (CMS) and the Department of Veterans Affairs (VA).
Collectively, CMS and the VA provide or pay for prescription medicines for millions of Americans. The Department of Defense, the Federal Trade Commission, and the Office of the Assistant Secretary for Preparedness and Response (within the U.S. Department of Health and Human Services (HHS)) were also represented on the task force.
The task force invited public participation through a public meeting on November 27, 2018; established a docket to receive comments; and invited stakeholders to a series of listening sessions. In October 2019, the task force issued its report Drug Shortages: Root Causes and Potential Solutions that identifies root causes of drug shortages and offers recommendations for government and industry to address them. The report was updated on February 21, 2020, to include a revised economic analysis about production increases and supply restoration after a shortage.
1. https://www.fda.gov/media/159302/download
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3. Second Annual Report on Drug Shortages for Calendar Year 2014. http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UCM443917.pdf
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