Report to Congress

Drug Shortages 

CY 2022 

(Required by Section 506C–1 of the Federal Food, 

Drug, and Cosmetic Act) 
Executive Summary

This annual report to Congress summarizes the major actions taken by the U.S. Food 

and Drug Administration (FDA or Agency) during calendar year (CY) 2022 to prevent or 

mitigate drug shortages1 in the United States. Because drug shortages can pose a 

significant public health threat that can delay, and in some cases even deny, critically 

needed care for patients, drug shortages remain a top priority for FDA. 

FDA continues to closely monitor the medical product supply chain, which was impacted 

by the Coronavirus Disease 2019 (COVID-19) pandemic during 2022, leading to supply 

disruptions or shortages of drug products in the United States. FDA understands the 

significant impact this can have on patient care and is doing everything within its 

authority to help prevent and alleviate these disruptions and shortages. As a result of 

presidential, congressional, and Agency actions, manufacturers are notifying FDA 

earlier than in the past about certain manufacturing interruptions and discontinuances 

that can lead to shortages. These early notifications give FDA additional time to work 

with manufacturers and other stakeholders to identify ways to maintain treatment 

options and prevent a shortage. During CY 2022, FDA’s Center for Biologics Evaluation 

and Research (CBER) and FDA’s Center for Drug Evaluation and Research (CDER) 

worked with manufacturers to successfully prevent 222 drug shortages through the use 

of a range of available tools, including regulatory flexibility and discretion when 

appropriate. During this same period, the number of new shortages tracked by CBER 

and CDER was 49, compared to a peak of 251 new shortages during CY 2011.2 

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, particularly when the shortage has involved a critical drug to treat cancer, to 

provide parenteral nutrition, or to address other serious medical conditions, such as a 

shortage of antibiotics. In the past year, FDA has seen manufacturers in the United 

States and abroad continue to experience quality issues as well as struggle with 

capacity constraints. Additionally, as demand increased for numerous drugs over the 

last several years as a result of the COVID-19 pandemic, as well as an earlier than 

typical flu and respiratory virus season, FDA has seen additional strain on the 

pharmaceutical supply chain.

1 In this report, the phrase “drug shortages” includes shortages of human drug and biological products. 

This report individually refers to shortages tracked by FDA’s Center for Drug Evaluation and Research or 

FDA’s Center for Biologics Evaluation and Research when the context requires distinguishing between 

these Centers.

2 This tenth annual report to Congress addresses all covered drug and biological products, including all 

drugs within the meaning of section 506C(h)(1) of the Federal Food, Drug, and Cosmetic Act. As 

permitted by section 506C(h)(i)(3), FDA included in this definition all biological products licensed under 

section 351 of the Public Health Service Act, except source plasma and those that also meet the 

definition of a “device.” See Final Rule: Permanent Discontinuance or Interruption in Manufacturing of 

Certain Drug or Biological Products, 80 FR 38916 at 38918 (July 8, 2015). See Appendix C for a 

breakdown of CBER’s and CDER’s CY 2022 numbers.
Based on FDA’s experience to date and the data on drug shortages presented in this 

report, the Agency believes that the requirements related to early notification of 

interruptions and discontinuances in manufacturing and FDA’s own actions are helping 

to reduce the threat and impact of drug shortages. FDA will continue to prioritize its

efforts on this important public health issue, working to ensure the availability of 

necessary drugs and biological products for the American public, including adequate 

supplies of drugs needed to treat patients with COVID-19 and other respiratory 

illnesses.
Table of Contents

I. Introduction ................................................................................................. 1

II. Background ................................................................................................. 2

A. Executive Order 13588 – Reducing Prescription Drug Shortages.................. 4

B. FDASIA.......................................................................................................... 5

C. The CARES Act ............................................................................................. 5

D. The Inter-agency Drug Shortages Task Force ............................................... 6

III. Data Sources Used in This Report ............................................................ 8

IV. Annual Reporting Requirements Per Section 506C–1............................. 9

V. Continued Drug Shortage Efforts in CY 2022......................................... 15

A. Incentivizing QMM........................................................................................ 15

B. Expediting the Review of Monkeypox Biologics ........................................... 16

C. Collaborating with Foreign Regulatory Authorities ....................................... 16

D. Responding to COVID-19-Related Shortage Risks...................................... 17

E. Responding to Sudden Increases in Demand.............................................. 17

F. Communicating About Current Drug Shortages........................................... 18

G. Leveraging FDA’s Regulatory Tools............................................................. 19

VI. Conclusion................................................................................................. 20

Definitions of Key Terms............................................................. 1

Section 506C–1 of the FD&C Act................................................ 1

 Breakdown of CDER’s and CBER’s Shortage Numbers for CY 

2022 .............................................................................................................. 1

 Breakdown of Expedited Reviews in CY 2022 by Submission 

Type .............................................................................................................. 1
Page 1

I. Introduction

The Food and Drug Administration Safety and Innovation Act (FDASIA) was enacted on 

July 9, 2012.1 Title X of FDASIA, which addresses drug shortages, took effect on the 

date of enactment and, among other things, amended the Federal Food, Drug, and 

Cosmetic Act (FD&C Act) (21 U.S.C. 301 et seq.) by adding section 506C–1, which 

requires the Food and Drug Administration (FDA or Agency) to file an annual report to 

Congress on drug shortages.2 FDA is submitting this annual report to fulfill its 

obligations under section 506C–1.

Specifically, this report:

• Provides a background on drug shortages and FDA’s efforts to address them; 

• Responds to the specific issues listed under section 506C–1;

• Includes analyses that reflect data collected and evaluated by FDA’s Center for 

Biologics Evaluation and Research (CBER) and FDA’s Center for Drug 

Evaluation and Research (CDER) during calendar year (CY) 2022; 

• Summarizes some important ongoing activities FDA believes will help address 

drug shortages in the future; and 

• Includes a list of definitions in one appendix, as well as three additional 

appendices that include the statutory language regarding annual reporting on 

drug shortages and a breakdown of data supplied by CBER and CDER, at the 

end of this report.

1 Pub. L. 112-144, 126 Stat. 994 (July 9, 2012).

2 Section 506C–1 of the FD&C Act initially required the annual report on drug shortages to be submitted 

to Congress “not later than the end of each calendar year.” To meet this deadline, the annual reports 

submitted to Congress presented data and information on drug shortages gathered during the first three

quarters of the calendar year. The 21st Century Cures Act, which was enacted on December 13, 2016, 

amended section 506C–1 to require that 

[n]ot later than March 31 of each calendar year, the Secretary shall submit to the Committee 

on Energy and Commerce of the House of Representatives and the Committee on Health, 

Education, Labor, and Pensions of the Senate a report, with respect to the preceding 

calendar year, on drug shortages . . . 
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II. Background 

Drug shortages can have serious and immediate effects on providing needed therapies 

to patients, therefore preventing shortages is a priority for FDA. At the height of the 

drug shortage crisis, the number of new drug shortages tracked by CDER quadrupled, 

from approximately 61 shortages in 2005 to more than 250 in 2011.

Figure 1 shows the number of new drug shortages from CY 2010 to CY 2022. The 

number of new drug shortages per calendar year has declined from a high of 250 in 

2011 to 49 in 2022.

Figure 1. Number of New Drug Shortages Per Calendar Year, (from CY 2010 to CY 

2022).3

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, particularly when the shortage has involved a critical drug to treat cancer, to 

provide parenteral nutrition, or to address another serious medical condition, such as a 

shortage of antibiotics. Although there has been a leveling off of new shortages over 

3 This tenth annual report to Congress is the seventh to include reporting for both drug and biological 

products, which include all drugs within the meaning of section 506C(h)(1) of the FD&C Act; other 

products tracked by CDER’s Drug Shortage Staff, such as certain therapeutic biological products licensed 

under section 351 of the Public Health Service Act; and biological products licensed under that same 

section that are tracked by CBER’s Office of Compliance and Biologics Quality, such as vaccines and 

blood products. See Appendix C for a breakdown of CBER’s and CDER’s CY 2022 numbers.
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the past few years, CY 2022 has been a challenging year for shortages. FDA has seen 

manufacturers in the United States and abroad continue to experience quality issues 

and struggle with capacity constraints. Additionally, there were dramatic and rapid 

changes in demand for some products used to treat infectious diseases such as 

COVID-19, respiratory syncytial virus (RSV), and seasonal influenza, which has placed 

additional strain on the pharmaceutical supply chain and made it harder for FDA and 

manufacturers to avoid drug shortages.

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. 

As summarized below, FDA has used a variety of methods to prevent shortages, 

working within the statutory and regulatory frameworks in place and in partnership with 

manufacturers and other stakeholders. FDA’s investigation into nitrosamine impurities 

serves as an example of how the Agency has continued to take steps to ensure the 

safety of drug products while working to both mitigate and prevent future shortages by 

using tools such as expedited reviews and inspections.4 

In CY 2022, FDA worked with manufacturers to successfully avoid a large number of 

drug shortages, helping to prevent 222 shortages. For a comparison to recent years, 

FDA helped prevent 199 shortages in CY 2020 and 317 in CY 2021.5 For information 

on FDA’s historical prevention of drug shortages, see Figure 2, which shows the 

number of drug shortages prevented by FDA from CY 2010 to CY 2022. 

4 See https://www.fda.gov/drugs/drug-safety-and-availability/information-about-nitrosamine-impuritiesmedications. 

5 See supra n. 2.
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Figure 2. Number of Prevented Drug Shortages Per Calendar Year (from CY 2010 

to CY 2022). 

Many actions, including the following four, are helping FDA address drug shortages: 

• Executive Order 13588 – Reducing Prescription Drug Shortages

• The Food and Drug Administration Safety and Innovation Act (FDASIA)

• The Coronavirus Aid, Relief, and Economic Security Act (CARES Act)

• The inter-agency Drug Shortages Task Force

Each of these elements will be addressed in turn. 

A. Executive Order 13588 – Reducing Prescription Drug 

Shortages

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.”6 

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—including expediting reviews, as appropriate, and requiring 

manufacturers to provide advance notice of manufacturing discontinuances that could 

6 Executive Order 13588, available at https://obamawhitehouse.archives.gov/the-pressoffice/2011/10/31/executive-order-13588-reducing-prescription-drug-shortages. 
Page 5 

lead to a shortage of certain drugs—to help prevent and reduce current and future 

disruptions in the supply of life-saving medicines.

B. FDASIA

With the enactment of FDASIA on July 9, 2012, 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. In addition, the FD&C Act, as amended by 

FDASIA, allows FDA to require, by regulation, early notification of such discontinuances 

or interruptions in the manufacturing of biologics.7

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.8 FDA 

has sent ten such letters, including one in 2022.9

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.

C. The Coronavirus Aid, Relief, and Economic Security 

(CARES) Act

The 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 

7 See section 506C(i)(3) of the FD&C Act; see also 21 CFR 600.82 and 80 FR 38915 (July 8, 2015).

8 Section 506C(f) of the FD&C Act.

9 See https://www.fda.gov/drugs/drug-shortages/drug-shortages-non-compliance-notification-requirement. 
Page 6 

manufacturers of certain drugs to provide information to FDA on permanent 

discontinuances and interruptions in manufacturing that may lead to a meaningful 

disruption in supply.

• 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).10

• 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.

These amendments took effect on September 23, 2020. 

D. The Inter-agency Drug Shortages Task Force

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 interagency 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 several 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. Departmentof Health and Human Services (HHS)) were 

10 Note that an amendment to the FD&C Act in 2017 also required the Agency to prioritize an abbreviated 

new drug application for a drug that had been included on the drug shortage list under section 506E of 

the FD&C Act. See the FDA Reauthorization Act of 2017, Pub. L. 115-52 at s. 801 (Aug. 18, 2017).
Page 7 

also represented on the task force.11 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 Solutions12 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. Although the work of the task force concluded with the report and the task 

force itself no longer meets, FDA regularly meets internally to monitor and discuss 

potential and ongoing shortages.

11 The task force also consulted with officials from the Defense Advanced Research Projects Agency, the 

U.S. Department of the Treasury, and DEA.

12 The report is available at https://www.fda.gov/drugs/drug-shortages/report-drug-shortages-root-causesand-potential-solutions. 
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III. Data Sources Used in This Report

The data used to fulfill the reporting requirements of section 506C–1 of the FD&C Act 

are collected by several program areas within FDA. For instance, tracking the data for 

reporting requirements related to drugs and biological products (the number of products 

in shortage) is within the purview of CBER’s Office of Compliance and BiologicsQuality 

(CBER/OCBQ) and CDER’s Drug Shortage Staff (DSS). CBER/OCBQ and DSS track 

information about drug shortage notifications and their sources (and, therefore, the 

number of reporting manufacturers).

In contrast, section 506C–1 reporting requirements related to FDA’s expedited review 

are tied to specific submissions by manufacturers that are experiencing production 

disruptions or by manufacturers that are adding or expanding their production 

capabilities to address a specific shortage. CBER’s and CDER’s offices reviewing 

these submissions track which reviews and related inspections they have expedited as 

a part of a larger set of activities related to their review of submissions.

Other section 506C–1 reporting requirements for this report relate to instances of 

regulatory flexibility and discretion. These specific instances, all requiring separate 

regulatory and scientific evaluations and justifications, are tracked by CBER/OCBQ and 

CDER’s Office of Compliance (CDER/OC).
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IV. Annual Reporting Requirements Per Section 506C–1 

Section 1002 of Title X of FDASIA added section 506C–1 to the FD&C Act, requiring 

FDA to file a report to Congress on drug shortages for each calendar year.

The statutory requirements for this congressional report and the data addressing those 

requirements are as follows.

Requirement 1: Specify the number of manufacturers that submitted a notification to 

the Secretary of HHS under section 506C(a) during such calendar year.

For CY 2022, FDA was notified of 1,293 potential drug and biological product shortage 

situations by 150 different manufacturers. FDA continues to see a greater adherence to 

notification requirements, with an increasing number of manufacturers notifying FDA 

annually about potential shortage issues.

Requirement 2: Describe the communication between FDA’s field investigators and 

CDER/OC and DSS, including FDA’s procedures for enabling and ensuring such 

communication.

Field investigators in CDER/OC and FDA’s Office of Regulatory Affairs (ORA) are 

crucial to the Agency’s prompt response to a drug shortage. These two groups have 

separate functions with respect to drug shortages. First, CDER/OC communicates with 

DSS on the recommendations being reviewed within that office about warning letters 

and other regulatory or enforcement actions; this communication helps determine if 

there may be an impact on supply and if additional steps should be taken to mitigate a 

potential shortage when possible. Second, ORA’s field investigators typically conduct 

inspections at manufacturing facilities and report their findings to CDER. For example, 

if the investigators identify actions or activities during an inspection that may have a 

detrimental impact on product availability, information regarding the observations and 

the products manufactured can be relayed to CDER immediately so that DSS can begin 

to assess the supply situation for those products. These procedures are critical to 

FDA’s efforts to prevent and mitigate a potential drug shortage.

To facilitate communications between ORA and FDA’s medical product centers, which 

include CBER and CDER, ORA issued Field Management Directive (FMD) #15 in July 

2012. FMD #15 established drug shortage coordinators in ORA so that each FDA field 

district would have a District Drug Shortage Coordinator who serves as the point of 

contact between ORA and FDA’s medical product centers. The District Drug Shortage 

Coordinator is responsible for notifying the relevant FDA center of any issue identified 

during an inspection or other field activities that has the potential to lead to a product 

shortage. Also, FMD #15 clarified communication roles, responsibilities, and 
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expectations between ORA and the centers related to potential and current product 

shortage situations. In addition, consistent with section 704(b)(2) of the FD&C Act, 

added by the CARES Act, DSS routinely receives access to the Form FDA 483 

presented to drug establishments.

Requirement 3: List the major actions taken by the Secretary to prevent or mitigate 

drug shortages.

Mitigation efforts begin once FDA confirms that a shortage exists or may occur. The 

actions FDA can take to prevent or mitigate a shortage include, as appropriate, the 

following:

• Identifying the extent of the shortfall and determine if other manufacturers are 

willing and able to increase production to make up the gap;

• Expediting FDA’s inspections and reviews of submissions submitted by affected 

manufacturers attempting to restore production;

• Expediting FDA’s inspections and reviews of submissions from competing 

entities who are interested in starting new production or increasing existing 

production of products in shortage;

• Expediting the release of lots of certain licensed biological products regulated by 

CBER or CDER;13

• Reviewing requests for extensions of expiration dating;

• Exercising temporary regulatory flexibility for new sources of medically necessary 

drugs;

• Working with the affected manufacturers to ensure adequate investigations into 

the root cause of the shortage;

• Working with the Assistant Secretary for Preparedness and Response (ASPR) 

on (1) their efforts under the Defense Production Act (DPA) for the development 

of COVID-19 vaccines and therapeutics and (2) supply chain activities;

• Developing risk mitigation measures to allow individual batches of a drug product 

to be released even when quality assurance requirements were not met; and

13 FDA may require manufacturers to submit for review, as well as for confirmatory testing, samples of 

any lot of any licensed biological product, together with the protocols showing the results of applicable 

tests when deemed necessary for the safety, purity, or potency of the product. See 21 CFR 610.1 and 

610.2.
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• Establishing communication channels with stakeholders and other interested

parties.

Depending on the severity of the potential shortage and the surrounding circumstances, 

FDA can use one or more of these mitigation tools or seek to develop other options 

within its legal authority. When selecting specific tools, FDA continues to work with 

manufacturers to tailor their responses to the specific situations. As a part of these 

actions, FDA also frequently communicates available information about a potential 

shortage or existing shortage to affected stakeholders and monitors the shortage until it 

has been resolved.

List the number of applications and supplements for which the Secretary expedited 

review under section 506C(g)(1) during such calendar year.

FDA expedited the review of 199 submissions in CY 2022.14

List the number of establishment inspections or re-inspections related to mitigation 

or prevention of a shortage that the Secretary expedited under section 506C(g)(2) 

during such calendar year.15

FDA prioritized 30 establishment inspections to address drug shortages in CY 2022.16

Requirement 4: Describe the coordination between FDA and DEA to prevent or 

alleviate drug shortages.

If a drug at risk of shortage is a controlled substance, FDA works closely with the Drug 

Enforcement Administration (DEA) to prevent or mitigate the shortage. Among other 

duties, DEA is responsible both for setting aggregate limits on the amount of certain 

controlled substances that may be manufactured and for allocating to each 

manufacturer a specific percentage of the aggregate limit (a quota). This tight control 

over such controlled-substance products requires FDA and DEA to coordinate when a 

shortage of a controlled substance is looming. For example, FDA may work with DEA 

to enable a manufacturer to increase its allotted quota of a controlled substance if this 

step would help avoid a shortage of the product.

Recognizing this need, FDASIA amended the FD&C Act to include provisions on 

improved coordination and communication between FDA and DEA regarding a potential 

14 See Appendix D for a breakdown of submission types.

15 This includes prioritized inspections or site reviews for new applications or supplements that 

were granted an expedited review due to a drug shortage.

16 Note that not all submissions to FDA require inspections, but some submissions may involve multiple 

sites that require multiple inspections.
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shortage of a controlled substance. To help streamline and improve communications, 

FDA and DEA developed a memorandum of understanding. This memorandum sets 

forth steps and procedures, including identifying contacts, for efficiently tracking and 

exchanging relevant information.17 DSS has reached out to DEA on 20 occasions 

during CY 2022 regarding potential shortage situations.

Requirement 5: Identify the number of (and describe) instances in which FDA 

exercised regulatory flexibility and discretion to prevent or alleviate a drug shortage.

FDA’s first priority is to help ensure patients have access to safe, effective, and highquality drugs even when a drug is in shortage. FDA’s preferred solution to any shortage 

situation is to help ensure that there is a supply of approved drugs and biological 

products sufficient to meet patient demand that also meet the appropriate quality, 

safety, and efficacy standards. However, FDA recognizes that there can be risks to 

patients if treatment options are not available for critical conditions.

The Agency understands the importance of using appropriate tools within its legal 

authority for certain situations in order to prevent or mitigate a shortage situation. In 

certain shortage situations, the temporary exercise of regulatory flexibility and discretion 

has proven to be an important tool in helping to alleviate a drug shortage and to ensure 

access to treatment options for patients in critical need.

During CY 2022, FDA exercised regulatory flexibility and discretion in 87 instances, 

affecting 76 products.18 Examples of situations in which FDA exercised regulatory 

flexibility and discretion to prevent or mitigate a shortage are listed below:

• FDA exercised temporary regulatory flexibility and discretion for medically 

necessary products that presented quality issues. For example:

- Filters were supplied with a product to remove particulate matter,

- Extra testing for product quality or identity was completed before releasing the 

product into the marketplace,

- Third-party oversight of production was instituted to monitor quality issues, 

17 This memorandum, MOU 225-15-11, is available at https://www.fda.gov/about-fda/domesticmous/mou-225-15-11. 

18 One instance of regulatory flexibility may affect more than one product. Conversely, a shortage of one 

product may involve multiple instances of regulatory flexibility to mitigate the issue. For this year’s report 

and moving forward, the methodology will include instances when FDA has exercised regulatory flexibility 

and discretion to carve out products from Import Alerts. When FDA implements a product carve-out to an 

Import Alert, FDA stipulates additional controls to balance any particular concern with importing such 

products. 
Page 13

and

- Special instructions were provided to healthcare professionals and patients.

• FDA exercised temporary regulatory flexibility and discretion with respect to the 

continued distribution of a drug product to mitigate or resolve a drug shortage 

while FDA reviewed a supplement for a proposed change to address a problem 

with the drug product.

• FDA exercised temporary regulatory flexibility and discretion with regard to new 

sources of medically necessary drugs, including FDA-registered foreign sources, 

in rare instances when all alternative approaches were exhausted.

Requirement 6: List the names of manufacturers issued letters under section 

506C(f).

Under section 506C(f) of the FD&C Act, if a manufacturer fails to provide notification of 

a discontinuance or interruption in manufacturing as required by section 506C, FDA 

must issue a letter to that manufacturer stating that the notification requirement was not 

met. The manufacturer is required to respond to FDA’s letter within 30 calendar days, 

providing the reason for noncompliance and the required information on the 

discontinuance or interruption. Within 45 calendar days of issuing the letter, FDA is 

required to post a copy of the letter and any response received on FDA’s website,19 with 

appropriate redactions to protect trade secrets or confidential commercial information, 

unless FDA determines that the letter was issued in error or, after review of the 

manufacturer’s response, that the manufacturer had a reasonable basis for not notifying 

FDA as required.

Since 2014, FDA has issued 10 non-compliance letters under section 506C(f). FDA sent 

the first two such letters in 2014, an additional two such letters in 2016, three in 2018, 

one in 2019, one in 2021, and one in 2022.20 In CY 2022, a letter was sent to the

Bristol-Myers Squibb Company on February 2, 2022. The letter sent by FDA and the 

response received from the manufacturer are available on FDA’s website. 

Requirement 7: Specify the number of drug shortages occurring during 2022.

19 Links to letters of non-compliance with notification requirements are available at

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm403902.htm.

20 See https://www.fda.gov/drugs/drug-shortages/drug-shortages-non-compliance-notificationrequirement. 
Page 14

The data from CDER’s drug shortage database21 show that the number of new 

shortages significantly decreased over time. There was a record high of 251 new 

shortages in 2011.22 Since the enactment of the notification requirement under section 

506C(a) of the FD&C in 2012, there has been an overall trending decrease of new 

shortages. Despite a slight increase in numbers over the past few years, notifications 

have continued to help prevent shortages. There were 43 new drug shortages in CY 

2020, 41 new drug shortages in CY 2021, and 49 new drug shortages in CY 2022.

23

Another data point to note is the number of ongoing shortages yet to be resolved from 

previous years. As of December 31, 2022, FDA had identified 86 ongoing CDER- and 

CBER-tracked shortages. This number has continued to remain steady over the past 

couple years; there were 86 ongoing shortages for CY 2020 and 83 ongoing shortages 

for CY 2021. 

Figure 3. Number of Annual Ongoing Drug Shortages Per Calendar Year (from CY 

2013 to CY 2022). 

21 CDER’s drug shortages can be found at 

https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm. 

22 See Figure 1 for CBER’s and CDER’s new shortages per calendar year.

23 See Appendix C for a breakdown of CBER’s and CDER’s CY 2022 numbers.
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V. Continued Drug Shortage Efforts in CY 2022

In CY 2022, FDA worked diligently to address and prevent drug shortages, including 

implementing actions to, among other things, incentivize the use of quality management 

maturity (QMM) practices, expedite the review of monkeypox-related biologics, and 

collaborate with foreign regulatory authorities. These and other efforts, which are 

addressed below, have helped ensure the adequate supply of essential products, even

during this time of heightened demand, and represent the dedicated efforts of review 

staff from many offices within FDA.

A. Incentivizing QMM

CDER worked to establish a program to incentivize drug manufacturers to invest in 

QMM. QMM practices help drug manufacturers reduce the likelihood of supply chain 

disruptions (caused by a decreased supply or an increased demand) and lead to 

reduced costs, increased customer satisfaction, and greater operational efficiencies. 

CDER’s specific QMM accomplishments in CY 2022 include the following:

• CDER completed two pilot programs that evaluated best practices and 

developed frameworks to distinguish levels of QMM. 

• CDER published a white paper on QMM,

24 which highlighted the benefits of the 

program to different stakeholders (patients, providers, payors, purchasers, 

pharmacies, and pharmaceutical manufacturers) and identified key 

considerations that impact program development. 

• CDER hosted a QMM public workshop25 (2,000 global attendees) that shared 

learnings from the pilot programs and provided an opportunity for FDA to solicit 

feedback. Ninety-nine percent of over 400 attendees who responded to a 

workshop poll believed that purchasers of drug products or APIs should “consider 

the QMM of the facility that manufacturers them.” 

• Peer-reviewed journal articles on a quality benchmarking study26 (based on 

24 This white paper, “Quality Management Maturity: Essential for Stable U.S. Supply Chains of Quality 

Pharmaceuticals,” is available at https://www.fda.gov/media/157432/download. 

25 This workshop, “Quality Management Maturity Workshop,” is available at 

https://www.fda.gov/drugs/news-events-human-drugs/quality-management-maturity-workshop-05242022. 

26 This article, "Benchmarking the Quality Practices of Global Pharmaceutical Manufacturing to Advance 

Supply Chain Resilience,” is available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589742/. 
Page 16

collaboration with Dunn & Bradstreet and the University of St. Gallen) and 

lessons learned from QMM pilots27 (domestic finished dosage form and foreign 

active pharmaceutical ingredient pilots) were published. 

• An FDA advisory committee28 met and voted unanimously in favor of CDER 

establishing a QMM program, and work is actively ongoing.

B. Expediting the Review of Monkeypox (mpox) Biologics

In late May 2022, following reports of mpox in the United States, FDA/CBER worked 

with its HHS partners to expedite the submission of a manufacturing supplement, 

originally planned for fall 2022, to FDA to facilitate increased production of JYNNEOS, 

Smallpox and Monkeypox Vaccine, Live, Non-Replicating, for prevention of smallpox 

and mpox disease in adults 18 years of age and older determined to be at high risk for 

smallpox or mpox infection. After receiving a supplemental application from Bavarian 

Nordic, the manufacturer of JYNNEOS in May 2022, FDA immediately expedited its

review, which included an inspection of the manufacturing facility in Denmark, which 

took place between July 1 and July 8, 2022. 

Following completion of the inspection, FDA finished its evaluation of the required 

information to validate product quality, determined that the vaccine met its quality 

standards, and approved the supplemental biologics license application for JYNNEOS 

on July 26, 2022. Given the emerging public health need, FDA facilitated advance 

shipments of manufactured doses to the United States, and additional doses 

manufactured at a facility in Europe were distributed and administered in the United 

States to help address the mpox outbreak.

C. Collaborating with Foreign Regulatory Authorities

During CY 2022, there were shortages of drug products from manufacturers in the 

United States and abroad, and there continues to be concern surrounding the supply 

chain and reliance on overseas manufacturing. FDA continues to work closely with its

colleagues in foreign regulatory authorities and directly with manufacturers to 

understand what the future impact on supply disruptions might be. FDA is not currently 

aware of shortages caused by restrictions on exports from Asia or other regions, 

although the Agency continues to monitor for any impact on supplies related to exports 

27 This article, “Lessons from CDER’s Quality Management Maturity Pilot Programs,” is available at 

https://link.springer.com/content/pdf/10.1208/s12248-022-00777-z.pdf. 

28 Information on this Pharmaceutical Science and Clinical Pharmacology Advisory Committee Meeting is 

available at https://www.fda.gov/advisory-committees/advisory-committee-calendar/november-2-3-2022-

pharmaceutical-science-and-clinical-pharmacology-advisory-committee-meeting. 
Page 17

of pharmaceuticals, raw materials, and components. Should the situation change, FDA

would continue to rely on its established relationships with its foreign counterparts to 

inform the shortage surveillance programs to inform the public and to mitigate the 

impact of supply constraints. 

D. Responding to COVID-19-Related Shortage Risks

The COVID-19 pandemic has increased the risk of shortages due to sudden increases 

in demand for drugs used in hospitalized patients, particularly the most critically ill. In 

fact, in CY 2022, based on an assessment of the types of drug products that went into 

shortage, FDA noticed an increase in demand for certain drugs used to treat COVID-19 

and other infectious diseases, especially in children. 

To respond to this risk, in CY 2022, DSS requested that manufacturers not only 

evaluate their entire supply chain (including key starting materials, APIs, packaging 

components, and finished dosage forms) but also communicate about any new issues 

that arise. In addition, even though manufacturers are required to notify FDA of certain 

permanent discontinuances and interruptions in manufacturing, as discussed above, 

FDA also, in CY 2022, requested, on a voluntary basis, additional information from 

manufacturers (including inventory levels, production plans, and distribution quantities) 

to better understand the supply chain. Although the manufacturers were not required to 

provide this information, it has been extremely valuable for FDA’s work to prevent drug 

shortages.

Due to the forward-leaning actions mentioned above, the number of new drug shortages 

has not increased significantly during the COVID-19 pandemic; there were 49 new drug 

shortages in 2022, slightly up from 41 in 2021. In addition, during CY 2022, FDA 

expedited the review of and approved 36 original abbreviated new drug applications 

(ANDAs) and 73 supplemental ANDAs for drug products that may be used in managing 

patients with COVID-19. These approvals have helped ensure the adequate supply of 

these essential products during this time of heightened demand and represent the 

dedicated efforts of review staff from many offices within FDA.

E. Responding to Sudden Increases in Demand

Although the majority of drug shortages are linked to quality and GMP issues, some 

drug shortages are a result of increased demand. FDA generally does not receive 

notice or adequate information from drug manufacturers regarding sudden increases in 

demand (in contrast to drug shortages driven by a disruption in supply) that, if received,

would position the Agency to assist in preventing or mitigating drug shortages driven by 

that increase in demand. 
Page 18

During the COVID-19 public health emergency and the recent confluence of respiratory 

illnesses, including COVID-19, RSV, and seasonal influenza occurring at the same time,

there have been substantial increases in demand for many products needed to treat 

patients, resulting in shortages of some of these products, such as amoxicillin oral 

suspension. In addition, prior to the COVID-19 pandemic, FDA identified several 

demand-driven drug shortages, which FDA was not aware of until after they occurred. 

This delay has impacted FDA’s ability to respond. 

With advance notice of increases in demand that the manufacturer anticipates that it will 

likely be unable to meet, FDA may be able to take proactive steps to prevent or mitigate 

demand-driven drug shortages.

F. Communicating About Current Drug Shortages 

In CY 2022, FDA communicated with industry in multiple ways (such as by publishing 

guidances and posting an up-to-date list of drugs and biological products that the 

Agency has determined to be in shortage) to provide information about current drug 

shortages. In particular: 

• In November 2022, FDA issued the immediately-in-effect guidance for industry 

Compounding Certain Beta-Lactam Products in Shortage Under Section 503A of 

the Federal Food, Drug, and Cosmetic Act29 to help alleviate the shortage of 

amoxicillin for oral suspension. The guidance, which is geared for certain drug 

compounders, is intended to enable a greater supply of antibiotics like amoxicillin 

that are in shortage until manufacturers are able to meet the full demand. 

• In July 2022, FDA issued the guidance for industry Changes to Disposable 

Manufacturing Materials Questions and Answers30 about making changes to 

applications regarding disposable manufacturing materials (e.g., sterilizing filters, 

single use systems). The limited availability of these materials during periods of 

increased demand (e.g., public health emergencies or natural disasters) can 

affect the availability of sterile drugs and biological products. The guidance 

provides recommendations to applicants in determining the appropriate reporting 

category to communicate changes to disposable manufacturing materials.

• In May 2022, FDA issued a draft guidance for industry, Risk Management Plans 

to Mitigate the Potential for Drug Shortages,

31 intended to help manufacturers 

develop, maintain, and implement, as appropriate, risk management plans to 

29 This guidance is available at https://www.fda.gov/media/163367/download. 

30 This guidance is available at https://www.fda.gov/media/160300/download. 

31 The guidance is available at https://www.fda.gov/media/158487/download. 
Page 19

proactively assist in the prevention of human drug product and biological product 

shortages. 

• To provide the most current information to patients and caregivers, FDA posts a 

public, up-to-date list of drugs and biological products that the Agency has 

determined to be in shortage, including those related to COVID-19.32

G. Leveraging FDA’s Tools to Address Shortages

To increase patient access to critically needed medications in shortage or to prevent 

potential shortages, FDA leveraged available tools (including the authorities and 

requirements added by the CARES Act (which are described in section II.C of this 

report)). For example, CDER:

• Expedited its reviews of approximately 80 original ANDAs and over 70 ANDA 

supplements. 

• Expedited its assessments of manufacturing supplements to facilitate the 

manufacturing capacity for COVID-19 therapeutic biologics. 

• Exercised regulatory flexibility and discretion in 85 instances to increase supplies 

of critically needed medications. 

32 These lists are available at https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm and

https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/cber-regulated-products-currentshortages. 
Page 20

VI. Conclusion 

Drug shortages remain a significant public health issue in the United States and a top 

priority for FDA, particularly during the COVID-19 pandemic. While important progress 

has been made in preventing many drug shortages from occurring, FDA continues to 

work to ensure that patients in the United States have access to the medicines they 

need and to ensure a more robust supply chain. 

The Agency notes that its response to the COVID-19 pandemic has highlighted the 

following needs that require ongoing work to be fully addressed: 

• Need to gain better insight into the supply chain. Interruptions or problems in 

the drug supply chain can create or worsen drug shortages. As mentioned 

earlier in this report, the CARES Act includes authorities and requirements meant 

to enhance FDA’s ability to identify, prevent, and mitigate possible drug 

shortages by improving the Agency’s visibility into the drug supply chain. While 

such provisions do include a requirement for manufacturers to notify FDA of API 

manufacturing discontinuances or interruptions and a requirement for firms to 

report annually the amount of drugs they manufacture, manufacturers are not 

required to notify FDA of increases in demand that they are unlikely to be able to 

meet without meaningful shortfall or delay. 

• Need to increase the resilience of the supply chain. Redundancy in the 

supply chain (as opposed to reliance on a single facility or geographic region) 

increases agility and potential solutions to alleviate shortages that occur due to 

regional or localized supply disruptions and that could ultimately create or 

exacerbate a drug shortage. For example, if a manufacturing facility needs to 

temporarily close, or its operations are curtailed by factors such as travel 

restrictions, quarantines, or social distancing requirements, it is important to have 

alternative facilities available to manufacture the drug or its API. In addition, as 

noted above, the CARES Act includes a provision requiring certain 

manufacturers to develop a redundancy risk management plan that identifies and 

evaluates the risks to the drug supply at establishments manufacturing the drug 

or its API. 

To address shortages, including those related to the COVID-19 pandemic, FDA is 

working with manufacturers and other partners to help prevent shortages from occurring 

and to mitigate the impact of shortages that cannot be prevented. Early and open 

dialogue between FDA and manufacturers is critical to the success of this work. 

Because of important presidential, congressional, and FDA actions, FDA has been able 

to learn of possible shortages before they occur and take steps to prevent or mitigate 

them. During CY 2022, there were 49 new shortages, and FDA helped prevent 222 

potential shortages. Important progress has been made in preventing drug shortages 
Page 21

from occurring, and FDA continues to work to ensure that patients in the United States 

have access to the medicines they need. This report reflects FDA’s commitment to 

continue its important work to prevent and mitigate drug shortages.
Appendix A Page 1 

Definitions of Key Terms

Drug Shortage: A drug shortage means a period when the demand or projected 

demand for a drug within the United States exceeds the supply of the drug.

Biological Product Shortage: A biological product shortage means a period when the 

demand or projected demand for a biological product within the United States exceeds 

the supply of the biological product.

Meaningful Disruption: A meaningful disruption means a change in production that is 

reasonably likely to lead to a reduction in the supply of a drug or biological product by a 

manufacturer that is more than negligible and affects the ability of the manufacturer to 

fill orders or meet the expected demand for its product. A meaningful disruption is not 

an interruption in manufacturing due to matters such as routine maintenance and does 

not include insignificant changes in manufacturing so long as the manufacturer expects 

to resume operations in a short period.

Significant Disruption: A significant disruption means a change in production that is 

reasonably likely to lead to a reduction in the supply of blood or blood components by a 

manufacturer that substantially affects the ability of the manufacturer to fill orders or 

meet expected demand for its product. A significant disruption does not include 

interruptions in manufacturing due to matters such as routine maintenance or 

insignificant changes in manufacturing so long as the manufacturer expects to resume 

operations in a short period.

Life Supporting or Life Sustaining: Life supporting or life sustaining is used to 

describe a drug or biological product that is essential to, or that yields information that is 

essential to, the restoration or continuation of a bodily function important to the 

continuation of human life.
Appendix B Page 1 

 Section 506C–1 of the FD&C Act

SEC. 506C–1. ANNUAL REPORTING ON DRUG SHORTAGES.

(a) ANNUAL REPORTS TO CONGRESS.— 

Not later than March 31 of each calendar year, the Secretary shall submit 

to the Committee on Energy and Commerce of the House of 

Representatives and the Committee on Health, Education, Labor, and 

Pensions of the Senate a report with respect to the preceding calendar 

year on drug shortages that— 

(1) specifies the number of manufacturers that submitted a notification 

to the Secretary under section 506C(a) during such calendar year;

(2) describes the communication between the field investigators of the 

Food and Drug Administration and the staff of the Center for Drug 

Evaluation and Research’s Office of Compliance and Drug 

Shortage Program, including the Food and Drug Administration’s 

procedures for enabling and ensuring such communication;

(A) lists the major actions taken by the Secretary to prevent or 

mitigate the drug shortages described in paragraph (7);

(B) in the list under subparagraph (A), includes— 

(i) the number of applications and supplements for which 

the Secretary expedited review under section 

506C(g)(1) during such calendar year; and

(ii) the number of establishment inspections or 

reinspections that the Secretary expedited under 

section 506C(g)(2) during such calendar year;

(3) describes the coordination between the Food and Drug 

Administration and theDrug Enforcement Administration on efforts 

to prevent or alleviate drug shortages;

(4) identifies the number of and describes the instances in which the 

Food and Drug Administration exercised regulatory flexibility and 

discretion to prevent or alleviate a drug shortage;
Appendix B Page 2 

(5) lists the names of manufacturers that were issued letters under 

section 506C(f); and

(6) specifies the number of drug shortages occurring during such 

calendar year, as identified by the Secretary.
Appendix C Page 1 

Breakdown of CDER’s and CBER’s Shortage 

Numbers for CY 2022

CDER CBER

NUMBER OF SHORTAGES

New Shortages 48 1

Prevented Shortages 210 12

Ongoing Shortages 81 5

Notifications 1267 26

Number of Manufacturers Notifying 133 17

ACTIONS TAKEN TO MITIGATE SHORTAGES

Regulatory Flexibility and Discretion 85 0

Expedited Reviews 193 11*

Expedited Inspections 30 0

* This number includes expedited reviews for six biologics license application 

(BLA)/BLA supplements and five lot-release submissions for CBER-regulated 

products.
Appendix D Page 1 

Breakdown of Expedited Reviews in CY 2022 

by Submission Type

Submission Type Expedited Reviews

NDA/NDA Supplements (CDER) 36

ANDA/ANDA Supplements (CDER) 149

BLA/BLA Supplements (CDER) 8

BLA/BLA Supplements (CBER) 6*

* This number does not include the expedited reviews for the five lot-release submissions for CBERregulated products.
This report was prepared by FDA's Center for Drug Evaluation and 

Research and FDA’s Center for Biologics Evaluation and Research. 

For information, please contact:

U.S. Food and Drug Administration

10903 New Hampshire Ave.

Silver Spring, MD 20993-0002

This report is available on FDA’s home page at https://www.fda.gov/.