Report to Congress

Drug Shortages for Calendar Year 2021

(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 the Agency) during calendar year (CY) 2021 to prevent or mitigate drug 

shortages1 in the United States (U.S.). 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. 

During the Coronavirus Disease 2019 (COVID-19) pandemic, FDA continues to closely monitor the 

medical product supply chain, which was impacted by the pandemic, 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 2021, 

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 317 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 41, 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. This is especially the case when the shortage involves a critical drug to treat cancer, to 

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

pressure medications. In the past year, 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 as a result of the COVID-19 pandemic, FDA has seen additional 

strain on the pharmaceutical supply chain.

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 our 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.

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 ninth 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 3 for a 

breakdown of CBER’s and CDER’s CY 2021 numbers.
Table of Contents

Introduction................................................................................................................................. 1

Background ................................................................................................................................. 1

Data Sources Used in This Report............................................................................................. 6

Annual Reporting Requirements Per Section 506C-1............................................................. 6

Continued Drug Shortages Efforts in 2021 ............................................................................ 11

Conclusion ................................................................................................................................. 14

A-1 .............................................................................................................................................. 15

A-2 .............................................................................................................................................. 16

A-3 .............................................................................................................................................. 17

A-4 .............................................................................................................................................. 18
1

Introduction

The Food and Drug Administration Safety and Innovation Act (FDASIA) was enacted on July 9, 

2012.3 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 the Agency) to file an annual report to Congress on drug shortages.4 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) 2021;

 

• 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.

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 shortages tracked by CDER quadrupled, from approximately 61 shortages in 

2005 to more than 250 in 2011.

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

4 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 3 

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 ....
2

Figure 1 shows the number of new drug shortages identified by calendar year from 2010 through 

2021. The number of new drug shortages per calendar year has declined from a high of 250 in 

2011 to 41 in 2021.

Figure 1. Number of New Drug Shortages Per Calendar Year, 2010 to 2021.

5

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. As summarized below, 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 

5 This ninth annual report to Congress is the sixth 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 (PHS Act); and biological products 

licensed under section 351 of the PHS Act that are tracked by CBER’s Office of Compliance and 

Biologics Quality, such as vaccines and blood products. See Appendix 3 for a breakdown of CBER’s 

and CDER’s CY 2021 numbers.
3

working to both mitigate and prevent future shortages using tools such as expedited reviews and 

inspections.6

As tracked by CDER, FDA helped prevent 282 drug shortages in CY 2012, 170 shortages in CY 

2013, 101 shortages in CY 2014, and 142 shortages in CY 2015. As tracked by CBER and 

CDER, FDA helped prevent 126 shortages in CY 2016, 145 in CY 2017, 160 in CY 2018, 154 in 

CY 2019, 199 in CY 2020, and 317 in CY 2021.

7

 This is the highest number of shortages 

prevented since 282 were prevented in CY 2012.

Figure 2 shows the number of prevented drug shortages, identified by calendar year, from 2010 

through 2021. 

Figure 2. Number of Prevented Drug Shortages Per Calendar Year, 2010 to 2021.

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

1. 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.”8

 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 

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

7 See supra n. 2.

8 Executive Order 13588, available at https://obamawhitehouse.archives.gov/the-pressoffice/2011/10/31/executive-order-13588-reducing-prescription-drug-shortages.
4

and reduce current and future disruptions in the supply of life-saving medicines, including 

notifications and expedited reviews, as appropriate.

2. The Food and Drug Administration Safety and Innovation Act (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. 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.9

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.10 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.

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

The CARES Act was signed into law on March 27, 2020, to aid response efforts to the COVID19 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 

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

10 Section 506C(f) of the FD&C Act.
5

mitigate or prevent a shortage of a drug covered by section 506C(a).11

• 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. 

4. Inter-agency Drug Shortage 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 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. Departmentof Health and Human Services 

(HHS)) were also represented on the task force.12 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 Solutions13 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. 

11 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).

12 The task force also consulted with officials from the Defense Advanced Research Projects Agency, the U.S. 

Department of the Treasury, and DEA.

13 The report is available at https://www.fda.gov/drugs/drug-shortages/report-drug-shortages-root-causes-andpotential-solutions.
6

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).

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 2021, FDA was notified of 777 potential drug and biological product shortage situations 

by 115 different manufacturers.14

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.

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

to FDA’s prompt response to a drug shortage. These two groups have separate functions with 

14 No notifications were received regarding a permanent discontinuance or interruption in manufacturing of an API 

in CY 2021. 
7

respect to drug shortages. First, CDER/OC communicates with DSS on warning letter and 

enforcement action recommendations being reviewed within that office. Second, FDA’s field 

investigators in ORA typically conduct inspections at manufacturing facilities and report on their 

findings. 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 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:

• Identify the extent of the shortfall and determine if other manufacturers are willing and 

able to increase production to make up the gap;

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

manufacturers attempting to restore production;

• Expedite 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;

• Expedite the release of lots of certain licensed biological products regulated by CBER or

CDER;15

• Review requests for extensions of expiration dating;

15 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.
8

• Exercise temporary regulatory flexibility for new sources of medically necessary drugs;

• Work with the affected manufacturers to ensure adequate investigations into the root 

cause of the shortage;

• Work with the Assistant Secretary for Preparedness and Response (ASPR) on their 

efforts under the Defense Production Act (DPA) for development of COVID-19 vaccines

and therapeutics;

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

released even when quality assurance requirements were not met; and

• Establish communication channels with stakeholders and other interested parties.

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

legal authority depending on the severity of the potential shortage and the surrounding 

circumstances. 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 274 submissions in CY 2021.

16

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.17

FDA prioritized 29 establishment inspections to address drug shortages in CY 2021.

18

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 DEA in efforts 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 

16 See Appendix 4 for a breakdown of submission types.

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

granted an expedited review due to a drug shortage.

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

require multiple inspections.
9

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 shortage of a 

controlled substance. To help streamline and improve communications, FDA and DEA 

developed a memorandum of understanding (MOU). The MOU sets forth steps and procedures, 

including identifying contacts, for efficiently tracking and exchanging relevant information.19

DSS has reached out to DEA on three occasions during CY 2021 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 ensure patients have access to safe, effective, and high-quality 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 2021, FDA exercised regulatory flexibility and discretion in 104 instances, affecting 

59 products.20 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, and

19 The MOU is available at https://www.fda.gov/about-fda/domestic-mous/mou-225-15-11.

20 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.
10

- Special instructions were provided to health care 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,21 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 nine non-compliance letters under section 506C(f). In CY 2021, a 

letter was sent to Teva Pharmaceuticals USA, Inc., on January 6, 2021. 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 2021.

The data from CDER’s drug shortage database22 shows that the number of new shortages 

significantly decreased between 2012 and 2016, with 117 in CY 2012, 44 in CY 2013, 44 in CY 

2014, 26 in CY 2015, and 26 in CY 2016. Unfortunately, this downward trend did not continue 

in subsequent years. Two large drug manufacturers closed manufacturing facilities for 

remediation purposes in 2017 and 2018, and these closures resulted in the loss of the 

manufacturing capacity needed for the supplies of numerous drug products. In CY 2017, there 

were a total of 39 new CBER- and CDER-tracked shortages identified; in CY 2018, 54 were 

identified, in CY 2019 there were 51 new shortages, in CY 2020 there were 43 new shortages, 

and in CY 2021 there were 41 new shortages.

23

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

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

22 CDER’s drug shortage statistics can be found at: 

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050796.htm.

23 See Appendix 3 for a breakdown of CBER’s and CDER’s CY 2021 numbers.
11

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

years. FDA identified 97 ongoing CDER-tracked shortages at the end of CY 2013, 74 ongoing 

CDER-tracked shortages at the end of CY 2014, 64 ongoing CDER- tracked shortages at the end 

of CY 2015, 48 ongoing CBER- and CDER-tracked shortages at the end of CY 2016, 41 ongoing 

CBER- and CDER-tracked shortages at the end of CY 2017, 67 ongoing shortages for CY 2018, 

76 ongoing shortages for CY 2019, and 86 ongoing shortages for CY 2020. As of December 31, 

2021, there were 83 ongoing CBER- and CDER-tracked shortages. 

Figure 3. Number of Ongoing Drug Shortages Per Calendar Year, 2013 to 2021.

Continued Drug Shortages Efforts in CY 2021

FDA’s COVID-19 pandemic response in CY 2021 included the following activities:

• 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. To 

respond to this risk, DSS requested that manufacturers evaluate their entire supply chain, 

including key starting materials, APIs, packaging components, and finished dosage forms

and continue to communicate on any new issues that arise. 

• The number of new drug shortages has not increased significantly during the COVID-19 

pandemic; there were 41 new drug shortages in 2021, down from 43 in 2020. However, 

during CY 2021, there were shortages of drug products from manufacturers in the U.S.

and abroad, and there continues to be concern surrounding the supply chain and reliance 

on overseas manufacturing. At this time, we are not aware of any new shortages directly 
12

related to the effects overseas of the ongoing COVID-19 crisis. That said, we are 

working closely with our colleagues in foreign regulatory authorities and directly with 

manufacturers to understand what the future impact on supply disruptions might be. We 

are also not aware of shortages caused by restrictions on exports from Asia or other 

regions, although we continue to monitor for any supply impact related to exports of 

pharmaceuticals, raw materials and components. Should the situation change, we would 

rely on our established shortage surveillance programs to inform the public and to 

mitigate the impact of supply constraints as we have been doing throughout the 

pandemic. 

• In CY 2021, we continued to see increases in demand first evident with the onset of the 

pandemic in 2020 as a driver of drug shortages. We base this assessment on the types of 

drug products that went into shortage in CY 2021. As discussed above, manufacturers 

are required to notify FDA of certain permanent discontinuances and interruptions in 

manufacturing. In response to the COVID-19 pandemic, during CY 2021, FDA also 

requested, on a voluntary basis, additional information, including inventory levels, 

production plans, and distribution quantities, to better understand the supply chain. 

Although the manufacturers are not required to provide this information, it has been 

extremely valuable for FDA’s work to prevent drug shortages. 

• Another area of concern during the COVID-19 pandemic is possible impact to drug 

supply due to ASPR’s DPA and government-issued rated orders resulting in shortages or 

displacement of drug products because the U.S. government has required drug 

manufacturers to manufacture COVID-19 vaccines and therapeutics on manufacturing 

lines normally used for other FDA-regulated drugs. We have continued to monitor

approximately 90 different potentially impacted products involving multiple 

manufacturing sites. The issues involve potential finished dosage form (FDF), API, and 

component constraints. Shortages of these drugs are being prevented so far through 

working with the manufacturers on various actions, including qualifying alternate 

manufacturing sites, raw materials, and components, in addition to exercising regulatory 

flexibility and discretion. To accomplish these steps involves DSS coordinating a 

CDER-wide response, including the Office of Pharmaceutical Quality, the Office of 

Generic Drugs, the Office of New Drugs, and CDER/OC. FDA has also continued to 

work closely with the ASPR DPA team on any potential concerns.

• In CY 2021, to increase patient access to critically needed medications in shortage, or to 

prevent potential shortages, FDA leveraged all its regulatory tools. 

- CDER expedited reviews for close to 100 original abbreviated new drug applications 

(ANDAs) and over 100 ANDA supplements. 

- CDER expedited assessments of manufacturing supplements to facilitate the 

manufacturing capacity for COVID-19 therapeutic biologics. 

- CDER exercised regulatory flexibility and discretion in 15 instances to increase 

supplies of critically needed medications. 
13

- FDA issued a guidance for industry for immediate implementation entitled 

“Reporting Amount of Listed Drugs and Biological Products Under Section 510(j)(3) 

of the FD&C Act,”24 to assist registrants of drug establishments in submitting to FDA 

reports on the amount of each listed drug manufactured, prepared, propagated, 

compounded, or processed for commercial distribution, as required by section 

510(j)(3) of the FD&C Act added by the CARES Act. 

• During CY 2021, FDA approved 35 original ANDAs and 86 supplemental ANDAs for 

drug products frequently used in hospital intensive care units for treatment of COVID-19 

patients. These approvals help 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.

• CDER launched the Emergency Event Notification Portal and CDER Nexus workflow. 

The new automated external portal for industry helps DSS identify, manage, and track 

potential drug shortages, due to an emergency event, before supplies reach critical levels. 

The new portal gives DSS an opportunity to be proactive in the event of an emergency, 

such as the COVID-19 pandemic. DSS sends out a request for information from industry 

to find out if there is the possibility of a shortage due to an emergency or unexpected 

event. Prior to this new solution, the responses from industry were collected manually. 

Now, the Emergency Event Notification Portal will automate the response collection. 

Required notifications regarding permanent discontinuances and interruptions in 

manufacturing of products regulated by CDER should still be submitted via email at 

drugshortages@fda.hhs.gov or through the CDER Direct NextGen Portal25 at

https://edm.fda.gov/wps/portal/ while such notifications for those products regulated by 

CBER should be submitted to FDA electronically via email at cbershortage@fda.hhs.gov. 

All additional updates to the initial notification should be submitted by email to the 

applicable center (CDER or CBER), not through the NextGen Portal.

• To provide the most current information to patients and caregivers, FDA maintains 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-19.26

• In addition to the efforts described above, FDA continues work to implement the 

authorities and requirements added by the CARES Act (described in the Background 

section) and plans to issue guidance on these topics, including on reporting 

manufacturing discontinuances and interruptions to FDA and risk management plans.

24 This guidance is available at https://www.fda.gov/drugs/drug-shortages/coronavirus-aid-relief-and-economicsecurity-act-cares-act-drug-shortage-mitigation-efforts.

25 The NextGen Portal is available at https://edm.fda.gov/wps/portal/.

26 These lists are available at http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050796.htm and

https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/cber-regulated-products-currentshortages. 
14

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 continue to work towards a more 

robust supply chain. 

The Agency notes that FDA’s response to the COVID-19 pandemic has highlighted the 

following needs that require ongoing work to address fully: 

• 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 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. Such authorities include additional notifications to FDA of manufacturing 

discontinuances or interruptions and a requirement for firms to report the amount of 

drugs they manufacture. 

• 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 2021, there were 41 new shortages, 

and FDA helped prevent 317 potential shortages. While important progress has been made in 

preventing drug shortages from occurring, 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.
15

Appendix 1

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.
16

Appendix 2

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;

(3) (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;

(4) describes the coordination between the Food and Drug Administration and theDrug 

Enforcement Administration on efforts to prevent or alleviate drug shortages;

(5) 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;

(6) lists the names of manufacturers that were issued letters under section 506C(f); and

(7) specifies the number of drug shortages occurring during such calendar year, as 

identified by the Secretary.
17

Appendix 3

Breakdown of CDER’s and CBER’s Shortage Numbers, CY 2021

CDER CBER

New Shortages 38 3

Prevented Shortages 303 14

Ongoing Shortages 79 4

Notifications 744 33

No. of Manufacturers Notifying 98 23

ACTIONS TAKEN TO MITIGATE SHORTAGES

Regulatory Flexibility and 

Discretion

97 0

Expedited Reviews 260 14*

Expedited Inspections 29 0

* This number includes expedited reviews for eight biologics license application (BLA)/BLA 

supplements and six lot-release submissions for CBER-regulated products.
18

Appendix 4

Breakdown of Expedited Reviews by Submission Type

EXPEDITED REVIEWS

CDER NDA/NDA Supplements 36

CDER ANDA/ANDA Supplements 216

CDER BLA/BLA Supplements 8

CBER BLA/BLA Supplements 8*

* This number does not include expedited reviews for the six lot-release submissions for CBER-regulated 

products.