DRUG SHORTAGES

FDA’s Ability to 

Respond Should Be 

Strengthened

Report to Congressional Requesters

November 2011

GAO-12-116

United States Government Accountability Office

GAO
 United States Government Accountability Office 

Highlights of GAO-12-116, a report to 

congressional requesters 

November 2011 

DRUG SHORTAGES 

FDA’s Ability to Respond Should Be Strengthened 

Why GAO Did This Study 

In recent years, nationwide shortages 

of prescription drugs have increased, 

preventing patients from accessing 

medications essential to their care. The 

Food and Drug Administration (FDA), 

an agency within the Department of 

Health and Human Services (HHS), 

established a Drug Shortage Program 

with a mission of helping to prevent, 

alleviate, and resolve shortages. FDA 

receives information about shortages 

from manufacturers, though this 

reporting is generally voluntary, as well 

as from the American Society of 

Health-System Pharmacists (ASHP). 

ASHP tracks nationwide shortages for 

its members through a partnership with 

the University of Utah Drug Information 

Service (UUDIS). 

GAO was asked to review trends in 

shortages and examine FDA’s 

response. In this report, GAO 

(1) reviews trends in drug shortages, 

(2) describes FDA’s response, and 

(3) evaluates FDA’s ability to protect 

public health through its response to 

drug shortages. GAO analyzed UUDIS 

data, interviewed officials from FDA, 

health care professional associations, 

and industry, and also examined 

relevant statutes, regulations, 

information, and documents. 

What GAO Recommends 

Congress should consider establishing 

a requirement for manufacturers to 

report to FDA any changes that could 

affect the supply of their drugs. In 

addition, FDA should enhance its 

ability to respond to drug shortages, for 

example, by developing an information 

system to manage data about 

shortages. HHS outlined actions it 

plans to take that are consistent with 

GAO’s recommendations. 

What GAO Found 

The number of drug shortages has grown substantially since 2006. In total, 1,190 

shortages were reported from January 1, 2001, through June 20, 2011, 

according to UUDIS data. From 2006 through 2010, the number of drug 

shortages increased each year. A record number of shortages were reported in 

2010, and 2011 is on pace to surpass 2010’s record. Sixty-four percent of 

shortages involved drugs that were in short supply more than once. On average, 

shortages lasted 286 days (over 9 months). Over half of shortages reported from 

January 1, 2009, through June 20, 2011, that UUDIS identified as critical—

because, for example, alternative drugs were not available—involved generic 

injectable drugs. Certain therapeutic classes (such as anesthetic, oncology, and 

anti-infective drugs) were among those most often in short supply. 

Drug Shortages Reported January 1, 2001 through June 20, 2011, by Year 

0

50

100

150

200

250

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Number of drug shortages reported

Year

Source: GAO analysis of University of Utah Drug Information Service data.

196

153

138

114

64 71

54

71 80

103

146

Shortages

reported

through

June 20

FDA responds to drug shortages by taking actions to address the underlying 

causes and to enhance product availability, for example by providing assistance 

to manufacturers to resolve manufacturing or quality problems that can result in a 

shortage. When informed of the possibility of a shortage in advance, FDA has 

increasingly been able to prevent potential drug shortages from occurring. FDA 

prevented 50 potential shortages during the first half of 2011. As part of its 

response, FDA provides general information about drug shortages to the public 

via its website. 

FDA is constrained in its ability to protect public health from drug shortages due 

to its lack of authority to require manufacturers to report actual or potential 

shortages to the agency or the public, or to require manufacturers to take certain 

actions to prevent, alleviate, or resolve shortages. As a result, the agency’s 

approach to managing drug shortages is predominately reactive. FDA’s ability to 

protect public health is also constrained by management challenges that weaken 

its ability to respond to drug shortages. For example, FDA does not 

systematically maintain data on drug shortages, without which it is unable to 

monitor trends and enhance its ability to address the causes of drug shortages. 

In addition, FDA has provided limited resources to manage its response to drug 

shortages and lacks related performance measures and priorities. View GAO-12-116 or key components. 

For more information, contact Marcia Crosse 

at (202) 512-7114 or crossem@gao.gov. 
Page i GAO-12-116 Drug Shortages

Letter 1 

Background 5

The Number of Drug Shortages Has Grown Substantially Since 

2006, and Many Involved Generic Injectable Drugs 15

Drug Shortages We Reviewed Were Generally Caused by 

Manufacturing Problems and Exacerbated by Multiple 

Difficulties 22

Actions Taken by FDA to Respond to Drug Shortages Are Intended 

to Resolve Shortages’ Underlying Causes and Enhance Product 

Availability 27

FDA Is Constrained in Its Ability to Protect Public Health from 

Drug Shortages 35

Conclusions 42

Matter for Congressional Consideration 43

Recommendations for Executive Action 43

Agency and Third-Party Comments and Our Evaluation 44

Appendix I FDA Criteria for Determining Whether a Drug Is Medically 

Necessary 47

Appendix II Summary of FDA’s Response to 15 Selected Drug Shortages 49

Appendix III Comments from the Department of Health and Human Services 51

Appendix IV GAO Contact and Staff Acknowledgments 56

Related GAO Products 57

Tables

Table 1: Summary of the Duration of Drug Shortages, January 1, 

2001, through June 20, 2011, by Shortage Status 18

Table 2: Summary of 269 Critical Drug Shortages Reported 

January 1, 2009, through June 20, 2011, by Product Type 20

Contents
Page ii GAO-12-116 Drug Shortages

Table 3: Summary of 269 Critical Drug Shortages Reported 

January 1, 2009, through June 20, 2011, by Route of 

Administration 20

Table 4: Summary of 269 Critical Drug Shortages Reported 

January 1, 2009, through June 20, 2011, by Therapeutic 

Class 21

Table 5: Summary of Difficulties That Subsequently Exacerbated 

15 Sterile Injectable Drug Shortages That Occurred 

Between January 2009 and June 2011 26

Table 6: Summary of Actions Taken by FDA in Response to 15 

Shortages of Sterile Injectable Drugs That Occurred 

Between January 2009 and June 2011 32

Table 7: Actions Taken by FDA to Prevent Potential Drug 

Shortages, 2010 and 2011, through June 34

Figures

Figure 1: Number of Drug Shortages Reported January 1, 2001, 

through June 20, 2011, by Year 16

Figure 2: Distribution of the Duration of Reported Drug Shortages, 

January 1, 2001, through June 20, 2011 17

Figure 3: Distribution of 269 Critical Drug Shortages Reported 

January 1, 2009, through June 20, 2011, by Product Type 

and Route of Administration 19

Figure 4: Summary of Primary Causes of 15 Sterile Injectable Drug 

Shortages That Occurred Between January 2009 and June 

2011 23

Figure 5: Questions Included on FDA’s Medical Necessity 

Determination Form 48

Figure 6: Actions Taken by FDA in Response to Sterile Injectable 

Drug Shortages That Were Reported Between January 

2009 and June 2011, by Drug Class and Name 50
Page iii GAO-12-116 Drug Shortages

Abbreviations

ANDA abbreviated new drug application

API active pharmaceutical ingredient

ASA American Society of Anesthesiologists

ASCO American Society of Clinical Oncology

ASHP American Society of Health-System Pharmacists

CDER Center for Drug Evaluation and Research

CNS central nervous system

FDA Food and Drug Administration

HHS Department of Health and Human Services

IDSA Infectious Diseases Society of America

NDA new drug application

NDC national drug code

OGD Office of Generic Drugs

OND Office of New Drugs

UUDIS University of Utah Drug Information Service

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Page 1 GAO-12-116 Drug Shortages

United States Government Accountability Office

Washington, DC 20548

November 21, 2011

The Honorable Tom Harkin

Chairman

Committee on Health, Education, Labor, and Pensions

United States Senate

The Honorable Richard Blumenthal

United States Senate

The Honorable Robert P. Casey, Jr.

United States Senate

In recent years, hospitals and health care professionals have increasingly 

reported nationwide shortages of prescription drugs, including those that 

are life-saving and life-sustaining. Drug shortages directly threaten public 

health by preventing patients from accessing medications that are 

essential to their care. For example, recent shortages of oncology drugs 

have sparked concerns from health care professionals about how to care 

for cancer patients that need such medications in order to survive. During 

shortages, physicians may have to ration their supplies, delay treatments, 

or use alternative medications that may be less effective for the condition, 

carry unwanted side effects, or are more costly.

The Food and Drug Administration (FDA)—an agency within the 

Department of Health and Human Services (HHS) that is responsible for 

overseeing the safety and effectiveness of drugs marketed in the United 

States—has recognized the significant public health consequences that 

can result from drug shortages. According to FDA, a record number of 

drugs were in short supply in 2010, and the number of drug shortages 

continued to grow during 2011. Consistent with its mission of protecting 

the public health, FDA established its Drug Shortage Program in 1999 out 

of growing concern over the increasing number of drug shortages. The 

purpose of this program is to help prevent, alleviate, and resolve shortage 

situations. To do this, FDA must identify and monitor potential and actual 

drug shortages, which may be reported to the agency by manufacturers, 

health professionals, and the public. To develop more comprehensive 

information on drug shortages, FDA also obtains information from the 

American Society of Health-System Pharmacists (ASHP). ASHP began 

tracking data on drug shortages—in partnership with the University of 

Utah Drug Information Service (UUDIS)—in 2001 to inform its members, 

 
 

Page 2 GAO-12-116 Drug Shortages

such as hospital pharmacists, and the public about the status of new, 

ongoing, and resolved shortages.1

You asked us to examine issues related to the causes of prescription 

drug shortages and FDA’s response to these shortages. This report 

(1) reviews trends in prescription drug shortages that occurred from 

January 2001 through June 2011, (2) identifies the reported causes of 

selected drug shortages that occurred from January 2009 through June 

2011, (3) describes FDA’s response to drug shortages, and (4) evaluates 

the extent to which FDA is able to protect the public health through its 

response to drug shortages.

To review trends in prescription drug shortages that occurred from 

January 2001 through June 2011, we analyzed UUDIS data on the 

number of shortages reported to ASHP during that time period, through 

June 20, 2011. We examined these data because FDA did not have a 

database containing information on drug shortages for the time period we 

reviewed, and UUDIS is generally regarded as the most comprehensive 

and reliable source of such information. We reviewed UUDIS data to 

determine the number of shortages of prescription drugs that were 

identified each year and the duration of these shortages.2 To identify the 

number of drugs that had been in short supply on multiple occasions and 

the collective duration of these shortages, we grouped together shortages 

that involved clinically interchangeable versions of a drug that is 

administered through the same route—for example, by injection. We 

confirmed our identification of clinically interchangeable versions of a drug 

with a knowledgeable UUDIS pharmacist. We also examined the 

characteristics of 269 critical drug shortages that were identified during a 

shorter time period, January 1, 2009, through June 20, 2011.3

 

1

ASHP posts information about drug shortages on its website. See 

UUDIS 

recognized these shortages as critical because alternative medications 

were unavailable, the shortages affected multiple manufacturers, or the 

http://www.ashp.org/menu/PracticePolicy/ResourceCenters/DrugShortages.aspx. 

2

Because our analysis focused on shortages of prescription drugs, we excluded from our 

analysis shortages of over-the-counter drugs, biologics (including vaccines), medical 

devices, and orally-administered vitamins, which UUDIS also tracks and includes in its 

data. 

3

These 269 shortages represent 54 percent of the 495 shortages reported during that time 

period.
 

Page 3 GAO-12-116 Drug Shortages

shortages were widely reported, and because the shortages were

determined to be critical, they were posted to ASHP’s website. We 

obtained from UUDIS the national drug codes (NDC) that were 

associated with each of these critical shortages; UUDIS does not 

consistently track the NDCs associated with shortages that it determines 

are not critical.4 Using these NDCs, we analyzed Red Book data to 

determine the routes of administration, therapeutic classes, and number 

of manufacturers associated with each shortage.5

To identify the reported causes of selected drug shortages that occurred 

from January 2009 through June 2011, we focused our analysis on a 

nongeneralizable sample of 15 drug shortages that have had a significant 

impact on public health. The drugs involved in these shortages—all sterile 

injectables—are from three therapeutic classes: anesthesia, oncology, 

and anti-infective drugs. To assist in the selection of shortages for our 

detailed review, we asked representatives from the American Society of 

Anesthesiologists (ASA), the American Society of Clinical Oncology 

(ASCO), and the Infectious Diseases Society of America (IDSA) to each 

identify 5 shortages of sterile injectable drugs that were specific to their 

members’ practice areas, that occurred from January 2009 through June 

2011, and that had a significant impact on patient care or public health. 

Our analysis reflects the 15 drug shortages suggested by these 

associations.

To obtain context for 

the trends we identified, we interviewed officials at FDA, UUDIS, and 

ASHP. We also discussed the data with knowledgeable officials at 

UUDIS, and we reviewed all data for reasonableness, outliers, and 

consistency; we determined that the data were sufficiently reliable for our 

purposes.

6

 

4

NDCs identify a drug’s manufacturer, product name, route of administration, dosage 

form, and package size, among other information. One drug can have multiple NDCs 

associated with it. For example, a drug made by one manufacturer in one strength but in 

three package sizes would have three NDCs. 

We asked FDA officials to provide information on the 

causes of these 15 drug shortages, as reported by manufacturers. Using 

5

Red Book is a compendium published by Thomson Reuters that includes information 

about the characteristics of drug products.

6

Specifically, the associations suggested, and we reviewed, information about shortages 

for five anesthesia drugs (epinephrine, neostigmine, propofol, thiopental, and 

succinylcholine), five oncology drugs (cisplatin, cytarabine, doxorubicin, etoposide, and 

vincristine) and five anti-infective drugs (acyclovir, amikacin, cefotetan, clindamycin, and

sulfamethoxazole-trimethoprim). 
 

Page 4 GAO-12-116 Drug Shortages

the information FDA provided, we determined the first event that resulted 

in the shortage. We also captured information on other events that 

affected the availability of the drug before the shortage was resolved. For 

additional information on the causes of shortages, we obtained 

information from four manufacturers of sterile injectable drugs—APP 

Pharmaceuticals, Bedford Laboratories, Hospira, and Teva 

Pharmaceuticals. All of these manufacturers produce drugs that recently 

were in short supply, and all of the 15 drug shortages we selected for 

review involved drugs that were manufactured by one or more of these 

manufacturers. The results of our review of the 15 drug shortages are not 

generalizable to other drug shortages.

To describe FDA’s response to drug shortages, we interviewed FDA 

officials and reviewed agency documents, including policies and 

procedures.7

To evaluate the extent to which FDA is able to protect public health 

through its response to drug shortages, we analyzed FDA’s authority 

under the Federal Food, Drug, and Cosmetic Act. We also examined 

relevant FDA regulations, policies, and procedures, and reviewed FDA’s 

strategic priorities regarding drug availability. We evaluated FDA’s 

approach to managing its response to drug shortages using standards for 

internal control—including those for information and communications, 

monitoring, and risk assessment.

To describe how FDA responded to the 15 selected drug 

shortages we reviewed in detail, we examined information the agency

provided about its response to these shortages. We also analyzed FDA 

information on potential drug shortages the agency prevented from 

January 2010 through June 2011. To determine the number of shortages 

prevented, we grouped together shortages that involved multiple versions 

of a drug that had the same route of administration.

8

 

7

Our work did not include a review of FDA’s response to shortages of biological products, 

such as vaccines. 

In addition, we considered information 

in our previous reports on strategic planning, workforce planning, and the 

establishment of results-oriented performance measures. We also 

obtained the health care community’s perspective on FDA’s response to, 

and communication about, drug shortages by interviewing officials from 

ASA, ASCO, ASHP, IDSA, and the Institute for Safe Medication 

8

See GAO, Standards for Internal Control in the Federal Government, 

GAO/AIMD-00-21.3.1 (Washington, D.C.: November 1999).
 

Page 5 GAO-12-116 Drug Shortages

Practices. To obtain drug manufacturers’ perspective on FDA’s response 

to shortages, we interviewed officials from the four manufacturers of 

generic drugs noted above, as well as officials from the Generic 

Pharmaceutical Association, the Pharmaceutical Research and 

Manufacturers of America, and the Biotechnology Industry Organization. 

We also interviewed officials from Premier Healthcare Alliance, a group 

purchasing organization, the Healthcare Distribution Management 

Association, and the United States Pharmacopoeia to obtain the 

perspective of other stakeholders involved in drug production and the 

drug supply chain.

We conducted this performance audit from June 2011 to October 2011 in 

accordance with generally accepted government auditing standards. 

Those standards require that we plan and perform the audit to obtain 

sufficient, appropriate evidence to provide a reasonable basis for our 

findings and conclusions based on our audit objectives. We believe that 

the evidence obtained provides a reasonable basis for our findings and 

conclusions based on our audit objectives.

The unavailability of drugs can result in problems that directly affect the 

public health and increase costs for providers and patients. FDA’s role in 

overseeing the safety and effectiveness of drugs provides the agency an 

opportunity to take actions to prevent, alleviate, and resolve drug 

shortages.

A variety of factors can trigger drug availability problems. These factors 

can involve any segment of the supply chain, from problems related to the 

growth or harvest of ingredients required to manufacture a drug, to 

increased demand for products by consumers or providers.9

•

They include 

the following:

Disruption in the supply of raw materials

 

9

The causes of drug shortages have been widely reported. See for example, American 

Society of Health-System Pharmacists, ASHP Guidelines on Managing Drug Product 

Shortages, American Journal of Health-System Pharmacists, vol. 58, no. 1445-50 (2001): 

26-30.

. Manufacturers are 

sometimes unable to obtain the raw materials used in producing a 

drug, including the active pharmaceutical ingredients (API) and 

Background 

Factors Affecting Drug 

Availability
 

Page 6 GAO-12-116 Drug Shortages

inactive ingredients.10 APIs may become in short supply as a result of 

climactic or environmental changes that depress the growth of plants 

from which the materials are extracted, or the APIs could be 

contaminated or degraded during harvesting, storage, or transport. 

API manufacturers may encounter problems synthesizing the 

chemical components of an API or face shortages of their ingredients. 

Finally, firms involved in the harvest, manufacture, storage, or 

transport of these materials could decide to exit the market, which 

could affect the availability of these materials for the manufacture of 

finished drug products. According to FDA, the majority of APIs used in 

FDA-approved drugs are imported from foreign countries, which may 

add to challenges related to their availability. For example, regulations 

issued by foreign countries regarding the use or export of these 

materials could affect their availability. In addition, APIs may be held 

for examination during the importation process, delaying their 

availability.

• Manufacturing problems. Manufacturers may have problems 

producing a finished drug that is safe, pure, and of high quality. 

Manufacturers may identify these problems themselves, or FDA may 

identify them during an inspection. Regardless of how the problems 

are identified, a manufacturer may voluntarily decide to stop 

producing a drug until the problem can be resolved. In addition, the 

manufacturer may decide to recall a drug in order to remove it from 

the market.11

• Manufacturers’ business decisions. Manufacturers’ business 

decisions may affect the production and supply of a drug. For 

example, a manufacturer may decide to discontinue its production of a 

drug as a result of decreased profitability. Or, a manufacturer may 

decide to renovate a facility, requiring a temporary shutdown of 

production.

 

10An API is any component that is intended to provide pharmacological activity or other 

direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease. FDA 

defines inactive ingredients as any component of a drug product other than the API, such 

as materials that improve the appearance, stability, and palatability of the product. See 

21 C.F.R. § 210.3(b)(7), (8) (2011).

11See 21 C.F.R. § 7.40 (2011). Manufacturers may also decide to recall a product for 

other reasons, such as errors in the product’s labeling. 
 

Page 7 GAO-12-116 Drug Shortages

• Industry consolidations. Recent mergers and acquisitions within the 

drug industry have reduced the number of manufacturers making 

drugs. Many drugs that have recently been in short supply are only 

produced by a few manufacturers. As the number of manufacturers of 

a product decreases, there is an increased likelihood that a problem 

with one manufacturer will lead to a shortage of all versions of that 

drug. For example, if only three manufacturers make a drug and one 

manufacturer halts production, it is often difficult—if not impossible—

for the remaining two manufacturers to increase their production 

enough to meet consumer demand.

• Unexpected increase in demand. A shortage may occur due to 

unexpected shifts in demand caused, for example, by a change in the 

clinical use of a product or due to a shortage of a similar drug. 

Shortages may also occur when hospitals or other health care 

providers stockpile particular drugs to take advantage of low prices, 

by placing orders that exceed normal demand.12

• Natural disasters. Natural disasters can create drug shortages when 

they affect the supply of raw materials or manufacturing facilities.

• Unstable supply chain. An increasingly unstable supply chain for 

drugs also contributes to drug shortages. Recent changes in supply 

chain management have increased the cost-effectiveness of individual 

participants in the supply chain, but have also resulted in a reduction 

in individual participants’ capacity to respond to supply disruptions. 

Factors that impact the availability of drugs in the supply chain include 

the complex nature of the global supply chain, reduced manufacturing 

capacity, and lean inventory systems.

• Complex, global supply chain. The supply chain for drugs is highly 

complex, increasingly global, and involves a large number of 

organizations that are highly dependent on each other. 

 

12For example, we recently found evidence of drug shortages related to stockpiling within 

the 340B Drug Pricing Program—a program through which participating drug

manufacturers give certain entities, such as federally funded health centers and other 

federal grantees, access to discounted prices on outpatient drugs. In some cases when 

the price of a 340B drug dropped, providers with access to 340B’s discounted prices 

stockpiled a drug, resulting in shortages in the supply of that drug for other providers. See 

GAO, Drug Pricing: Manufacturer Discounts in the 340B Program Offer Benefits, but 

Federal Oversight Needs Improvement, GAO-11-836 (Washington, D.C.: Sept. 23, 2011).
 

Page 8 GAO-12-116 Drug Shortages

Manufacturers of finished drug products rely on an increasingly 

global supply chain in which each manufacturing step may be 

outsourced to foreign establishments.13 For example, 

manufacturers of finished drug products are dependent on 

manufacturers of active and inactive ingredients as well as the 

distribution of those products to the manufacturing site where the 

finished drug is produced. As a result of the large numbers of 

entities involved in the supply chain, every individual member of 

the chain has less control, and is less able to respond to problems 

experienced by those on which it is dependent.

• Manufacturing capacity constraints. Some companies may have 

reduced manufacturing redundancies to save on costs—for 

example, by cutting back on the number of their manufacturing 

facilities, or the number of manufacturing lines available to 

produce certain drugs. These changes reduce the manufacturer’s 

capacity to respond to its own manufacturing problems. In 

addition, some companies produce multiple drugs using the same 

manufacturing line. If a problem occurs with the manufacturing 

line, it can affect the production of all drugs made on that line.

• Lean inventory systems. Manufacturers, distributors, hospitals, 

and other health care providers have been increasingly using 

leaner “just-in-time” inventory systems that allow them to maintain 

smaller inventories of drugs at any given time. Many providers 

have reduced on-hand inventories to the extent that they are 

dependent on daily replenishments from suppliers. As a result, all 

parts of the supply chain are more likely to feel the effects of a 

shortage more quickly.

Shortages of drugs can result in a variety of problems, ranging from those 

that directly affect patient care to those that increase costs for providers 

and patients. These include the following:

 

13We have previously reported on the challenges FDA faces in overseeing an increasingly 

complex foreign drug manufacturing supply chain. For example, see GAO, Drug Safety: 

FDA Faces Challenges Overseeing the Foreign Drug Manufacturing Supply Chain, 

GAO-11-936T (Washington, D.C.: Sept. 14, 2011).

Potential Effects of Drug 

Shortages 
 

Page 9 GAO-12-116 Drug Shortages

• Delays in patient care. Some shortages result in situations where a 

viable alternative drug is not available, and a patient may be unable to 

receive treatment. Some hospitals and ambulatory surgery centers 

have been forced to postpone surgeries due to a shortage of 

anesthetic drugs.14 A lack of treatment can have serious 

consequences. For example, a recent shortage of anti-infective drugs 

contributed to patient deaths from infections that were only treatable 

by drugs that were in short supply.

• Ethical dilemmas. When drugs are in short supply, providers may be 

unable to obtain needed drugs to treat all of their patients. They may 

therefore have to make difficult choices, such as deciding which 

cancer patients should start or complete a round of chemotherapy.

• Treatment with less effective alternative drugs. Alternative drugs may 

be able to treat some patients. However, some alternative treatments 

may provide a lower rate of effectiveness and a higher likelihood of 

adverse events.

• Medication errors. Drug shortages can result in the need to treat 

patients with unfamiliar drugs, for example, different drugs, or the 

same drug that is available in a different strength. Administering such 

products can result in medication errors.15

• Increased costs for providers and patients

 

14According to a 2011 American Hospital Association survey, over 80 percent of the 820 

responding hospitals reported that patient treatment had been delayed as a result of drug 

shortages. American Hospital Association, AHA Survey on Drug Shortages (Washington, 

D.C.: July 12, 2011).

. Shortages require time 

and resources to manage. Health care providers need to determine 

how to obtain the drug in short supply, or staff must spend time 

searching for available treatment options. In addition, the use of 

alternative medications can result in the need for additional training. In 

order to learn how to avoid medication errors, health care providers 

need to learn how to accurately prescribe and administer the 

alternative products, with which they may lack familiarity. Finally, the 

15According to a report issued by the Institute for Safe Medication Practices, about

25 percent of the 1,800 health care practitioners that responded to its 2010 survey 

reported medication errors which occurred as a result of a drug shortage. Institute for Safe 

Medication Practices, Drug Shortages: National Survey Reveals High Level of Frustration, 

Low Level of Safety (Horsham, Pa.: Sept. 23, 2010).
 

Page 10 GAO-12-116 Drug Shortages

cost of the drug in short supply—or available alternative—may be 

higher than usual.16

• Use of the gray market. Providers who are unable to obtain drugs 

from their regular distributors may resort to purchasing drugs from 

distribution channels that were not authorized by the manufacturer, 

referred to as the gray market.17 Gray market suppliers typically 

obtain small quantities of a drug that is in short supply and offer it for 

purchase to others at an inflated price.18 Because the origin of gray 

market drugs may be unknown, there is no guarantee of the drug’s 

pedigree or assurance that it was stored and transported 

appropriately. As a result, patients who receive treatment with such 

drugs may experience adverse events or receive inadequate or 

inappropriate treatment.19

• Unauthorized use of compounding pharmacies. In some cases, those 

unable to purchase drugs from their regular distribution channels have 

turned to compounding pharmacies.20

 

16According to AHA Survey on Drug Shortages, over 90 percent of 820 responding 

hospitals reported an increase in drug costs as a result of drug shortages.

While compounding 

pharmacies play a vital role in health care by tailoring drugs to better 

meet patients’ needs (such as removing a dye from a drug to prevent 

an allergic reaction) they are not authorized to prepare drugs that are 

copies of commercially available products.

17A report issued by the Institute for Safe Medication Practices noted that over half of the 

549 hospitals that participated in its 2011 survey reported receiving daily solicitations from 

gray market vendors for drugs that were in short supply. Institute for Safe Medication 

Practices, Gray Market, Black Heart: Pharmaceutical Gray Market Finds a Disturbing 

Niche During the Drug Shortage Crisis (Horsham, Pa.: Aug. 25, 2011).

18Premier healthcare alliance, a group purchasing organization, recently reported that 42 

of its member hospitals recorded 1,745 offers to purchase drugs that were in short supply 

from the gray market during a 2-week period at the beginning of 2011. Prices for these 

products were, on average, 650 percent greater than Premier’s contract price, and ranged 

up to 4,533 percent greater than their contract price. Premier healthcare alliance, Buyer 

Beware: Drug Shortages and the Gray Market (Charlotte, N.C.: Aug. 16, 2011).

19The Institute for Safe Medication Practices reported in Gray Market, Black Heart, that 

over 10 percent of the 549 hospitals that participated in its 2011 survey were aware of 

product authenticity issues, medication errors, or adverse drug reactions that were 

associated with the use of products purchased from the gray market during the last 

2 years.

20Compounding pharmacies, like other pharmacies, are primarily regulated by the states.
 

Page 11 GAO-12-116 Drug Shortages

• Disruption of the development of new drugs. Ongoing shortages of 

drugs have affected clinical trials (studies in humans) that are used to 

gauge the safety and effectiveness of a newly developed drug to that 

of a drug known to be effective. The inability to obtain adequate 

supplies of drugs, such as oncology drugs, has resulted in clinical 

trials being suspended indefinitely. Without such trials, new drugs 

cannot move forward through the development process.

FDA is responsible for overseeing the safety and effectiveness of drugs. 

Within FDA, the Center for Drug Evaluation and Research (CDER) 

manages these responsibilities. FDA’s approval is required before new 

drugs and generic drugs—drugs that are copies of approved drugs—can 

be marketed for sale in the United States.21 To obtain FDA’s approval for 

a new drug, sponsors must submit a new drug application (NDA) 

containing data on the safety and effectiveness of the drug as determined 

through clinical trials and other research for review by CDER’s Office of 

New Drugs (OND). Sponsors of generic drugs may obtain FDA approval 

by submitting an abbreviated new drug application (ANDA) to the agency 

for review by CDER’s Office of Generic Drugs (OGD). The ANDA 

contains data showing, among other things, that the generic drug is 

bioequivalent to, or performs in the same manner as, a drug approved 

through the NDA process.22

Once the agency receives an NDA, it is reviewed by one of OND’s 

medical review divisions, depending on the indication the drug has been 

proposed to treat. ANDA applications are reviewed by OGD to determine 

bioequivalence to approved drugs. In reviewing each application, FDA 

considers whether the proposed product labeling clearly states the 

condition and population the product is intended to treat. If the agency 

determines that a new drug is safe and effective for its intended use (that 

its clinical benefits outweigh its potential health risks) or that a generic 

drug is bioequivalent to a previously approved drug, and that other 

requirements are met, it will approve the application. After obtaining 

FDA’s approval, drug companies that want to change any part of their 

original application—such as changes to product manufacturing location 

 

2121 U.S.C. § 355.

2221 U.S.C. § 355(j). The application for generic drugs is abbreviated because FDA does 

not require sponsors to conduct, or provide evidence from, clinical trials that are required 

of sponsors of new drugs. 

FDA Oversight of Drugs
 

Page 12 GAO-12-116 Drug Shortages

or process, type or source of active ingredients, or the product’s 

labeling—must generally submit an application supplement to obtain 

FDA’s review and, if the change has a substantial potential to have an 

adverse effect on the product, approval.23

After approving new and generic drugs for marketing, FDA’s 

responsibilities continue as it is charged with monitoring the safety, 

effectiveness, quality, and promotion of approved drugs, and the agency 

may take enforcement actions in response to violations of laws and 

regulations. However, FDA may exercise regulatory discretion in deciding 

what actions to take or when to take them. For example, as part of its 

efforts to ensure the safety of approved drugs, FDA periodically inspects 

drug manufacturing establishments to assess their ongoing compliance 

with quality standards.24 If FDA finds manufacturing deficiencies, it may 

request that the manufacturer take corrective actions, or it may take 

enforcement action to require the manufacturer to take corrective actions. 

FDA may also take steps to ensure that manufacturers do not 

disseminate false or misleading information about a drug. Drugs whose 

labeling includes information not consistent with the labeling approved by 

FDA are considered misbranded and may be subject to regulatory action. 

FDA could seek civil monetary penalties from manufacturers that have 

misbranded their drugs.

FDA’s response to drug shortages is managed by CDER’s Drug Shortage 

Program. The agency maintains a website that includes information about 

how drug shortages can be reported to the Drug Shortage Program, and 

encourages manufacturers and the public to report shortages. Once the 

Drug Shortage Program becomes aware of a potential or actual shortage, 

agency officials attempt to determine whether the total supply of the drug 

and any pharmaceutical equivalents is inadequate to meet demand—

FDA’s definition of a shortage.25

 

2321 C.F.R. §§ 314.70, 314.97 (2011).

To make this determination, Drug 

24These standards, referred to as current good manufacturing practice regulations, 

provide a framework for a manufacturer to follow to produce safe, pure, and high-quality 

drugs. See 21 C.F.R. parts 210-211.

25A pharmaceutical equivalent is a drug product that is identical in dosage form, API, and 

strength, and delivers an identical amount of API over an identical dosing period. See 

21 C.F.R. § 320.1(c) (2011).

FDA Oversight of Drug 

Shortages 
 

Page 13 GAO-12-116 Drug Shortages

Shortage Program officials contact manufacturers of the drug to confirm 

how much inventory remains and how much of the drug they are currently 

producing. Drug Shortage Program officials compile this information and 

compare it to pharmaceutical industry sales data, including that which is 

available from IMS Health, in order to determine historical demand for the 

product. If the amount of the drug—or pharmaceutical equivalents—is 

insufficient to meet market demand, the agency considers the drug to be 

in shortage, and the Drug Shortage Program takes actions intended to 

alleviate and resolve the shortage.

FDA’s Drug Shortage Program also collaborates with ASHP to identify 

new drug shortages; however, ASHP also tracks shortages that do not 

meet FDA’s definition of a shortage. Once the Drug Shortage Program 

determines that a shortage is in effect, it may coordinate its response with 

several CDER offices, including OGD, OND, and the Office of 

Compliance. If a drug in shortage is manufactured by a company involved 

in a regulatory action, the Office of Compliance may also work with FDA’s 

Office of Regulatory Affairs and the company to mitigate and remediate 

the underlying problem.

The use of strategic planning can help federal agencies manage their 

programs more effectively by developing strategies to address current 

and future management challenges. To be successful, strategic plans 

should include clearly established goals and objectives and a description 

of how program activities can serve those goals. We have previously 

reported on a variety of leading practices for successful strategic 

planning.26 One such practice is the development of a set of resultsoriented performance measures, which provide an important way of 

helping to evaluate program performance, demonstrate progress in 

achieving results, balance competing priorities, and inform decision 

making. When possible, such measures should demonstrate a program’s 

contributions toward the long-term outcomes, or the results the agency 

expects a program to achieve. Given FDA’s mission of ensuring the 

public health, we have previously noted that the agency’s long-term 

outcomes should be focused on this mission.27

 

26See, for example, GAO, Managing for Results: Critical Issues for Improving Federal 

Agencies’ Strategic Plans, 

When long-term outcomes 

GAO/GGD-97-180 (Washington, D.C.: Sept. 16, 1997). 

27GAO, Food and Drug Administration: Opportunities Exist to Better Address Management 

Challenges, GAO-10-279 (Washington, D.C.: Feb. 19, 2010). 

Federal Strategic and 

Workforce Planning
 

Page 14 GAO-12-116 Drug Shortages

may be influenced by multiple agency programs and external factors, 

short-term and intermediate measures can also demonstrate a program’s 

specific contribution to a long-term outcome.28

Another important management tool is workforce planning, which helps 

agencies to align their workforce with current and future program needs 

and develop long-term strategies for recruiting, training, and retaining 

staff.29

We have previously reported on the need for FDA to improve its strategic 

planning and performance metrics. In 2010, we reported that FDA was 

not fully utilizing practices for effective strategic and workforce planning.

Workforce planning assists agencies in thinking strategically about 

how to put the right people in the right jobs at the right time. Although 

approaches to such planning can vary by agency, depending on an 

agency’s unique needs and mission, workforce plans should share certain 

principles, such as the identification of skills and competencies to fill 

critical workforce gaps and the strategies needed to recruit them.

30

 

28GAO, Agency Performance Plans: Examples of Practices That Can Improve Usefulness 

to Decisionmakers, 

We found that most of FDA’s established performance measures were 

not results-oriented as they did not focus on actual public health 

outcomes. In addition, we reported that FDA lacked clear linkages 

between its resources and goals, generally did not track workload by 

strategic goals, and that only about one-third to one-half of FDA 

managers used performance information to a great extent in making 

management decisions, such as setting program priorities. We also noted 

that FDA’s internal coordination was one of the major management 

challenges facing the agency. We recommended, and FDA agreed, that 

the agency issue an up-to-date strategic workforce plan, make its 

performance measures more results-oriented, and more clearly align 

center and office program activities to FDA’s strategic goals. In January 

2009 we added FDA’s oversight of medical products to our High-Risk List 

because FDA continued to face multiple challenges that threatened to 

compromise its ability to protect the public health. In 2011, in an update to 

our High-Risk Series, we noted that although FDA had begun taking 

steps to improve its oversight, the agency needs to do more to resolve 

GAO/GGD/AIMD-99-69 (Washington, D.C.: Feb. 26, 1999).

29GAO, Human Capital: Key Principles for Effective Strategic Workforce Planning, 

GAO-04-39 (Washington, D.C.: Dec. 11, 2003). 

30GAO-10-279.
 

Page 15 GAO-12-116 Drug Shortages

concerns, such as by improving resource management and strategic 

planning, responding to globalization, and overseeing postmarket 

safety.31

Our analysis of the trends in drug shortages that were reported from 

January 2001 through June 2011 showed that the number of drug 

shortages reported has grown substantially since 2006, and many 

shortages since 2009 have involved generic injectable drugs.

Since 2006, the number of drug shortages reported each year has grown 

substantially. In total, 1,190 drug shortages were reported to ASHP from 

January 2001 through June 20, 2011, according to our analysis of UUDIS 

data.32

 

31GAO, High-Risk Series: An Update, 

The number of drug shortages reported varied from year to year, 

and from 2001 through 2006, generally declined. However, from 2006 

through 2010, the number of drug shortages increased each year, and 

grew by more than 200 percent over this period. A record number of 

shortages (196) were reported in 2010, and 2011 is on pace to surpass 

2010’s record, with 146 shortages reported through June 20, 2011. (See 

fig. 1.)

GAO-11-278 (Washington, D.C.: February 2011). 

32When tracking shortages, UUDIS groups together shortages of multiple versions—for 

example, multiple concentrations—of the same drug; the count of shortages reported 

therefore reflects this grouping. The total number of shortages includes those that have 

been resolved as well as active shortages. As of June 20, 2011, there were 230 active 

shortages, including some that were reported in prior years.

The Number of Drug 

Shortages Has Grown 

Substantially Since 

2006, and Many 

Involved Generic 

Injectable Drugs

The Number of Drug 

Shortages Has Grown 

Substantially Since 2006
 

Page 16 GAO-12-116 Drug Shortages

Figure 1: Number of Drug Shortages Reported January 1, 2001, through June 20, 

2011, by Year

Over half (64 percent, or 766) of the 1,190 shortages represent drugs that 

were in shortage more than once. Specifically, 283 drugs were in 

shortage on multiple occasions during this time frame, representing 766 

individual shortages. These 283 drugs were each in short supply between 

two and eight times during this period, with an average of 2.7 times per 

drug. Over the entire time period, the 283 drugs were in short supply for 

an average of nearly 2 years.

While the duration of the reported shortages varied considerably, most—

74 percent—of the shortages lasted 1 year or less.33

 

33We excluded 92 shortages from this analysis because UUDIS listed these shortages as 

lasting zero days; the majority of these represented manufacturers’ decisions to 

discontinue their production of a drug.

However, an 

additional 16 percent, or 178, lasted between 1 and 2 years, and 

10 percent (110) lasted more than 2 years. (See fig. 2.) The duration of 

these shortages varied greatly, ranging from 1 day to over 7 years.
 

Page 17 GAO-12-116 Drug Shortages

Figure 2: Distribution of the Duration of Reported Drug Shortages, January 1, 2001, 

through June 20, 2011

Note: Our analysis on the duration of the shortages includes 1,098 of the 1,190 total shortages 

reported from January 1, 2001, through June 20, 2011; we excluded 92 shortages from this analysis 

because the University of Utah Drug Information Service listed these shortages as lasting zero days; 

the majority of these represented manufacturers’ decisions to discontinue their production of a drug.

Overall, the average duration of the drug shortages over this period was 

286 days—or over 9 months. The average duration of shortages was 

longer for shortages that were active as of June 20, 2011 (360 days, or 

nearly 12 months) in comparison to those that were resolved by that time 

(266 days, or nearly 9 months). (See table 1.)
 

Page 18 GAO-12-116 Drug Shortages

Table 1: Summary of the Duration of Drug Shortages, January 1, 2001, through 

June 20, 2011, by Shortage Status

Summary of shortage duration

Total number 

of shortages 

Average 

duration

(in days)

Median 

duration 

(in days)

Resolved shortages 868 266 148

Active shortages (as of June 20, 2011) 230 360 256

All active and resolved shortages 1098 286 159

Source: GAO analysis of University of Utah Drug Information Service data.

Note: Our analysis on the duration of the shortages includes 1,098 of the 1,190 total shortages 

reported from January 1, 2001, through June 20, 2011; we excluded 92 shortages from this analysis 

because the University of Utah Drug Information Service listed these shortages as lasting zero days; 

the majority of these represented manufacturers’ decisions to discontinue their production of a drug.

Based on our review of the characteristics of a smaller group of critical 

drug shortages reported between January 1, 2009, and June 20, 2011, 

we found that over half involved generic injectable drugs. Specifically, 

53 percent of the 269 drug shortages reported during this time period 

involved generic injectable drugs.34

 

34We reviewed 269, or 54 percent, of the 495 total shortages reported January 1, 2009, 

through June 20, 2011. These drug shortages were those that UUDIS determined were 

critical. 

About 39 percent of shortages 

involved injectable drugs that were available only in generic form, and 

about 14 percent involved injectable drugs available in both brand-name 

and generic form. An additional 15 percent of shortages involved 

injectable drugs that were available in brand-name form only. The 

remaining portion of shortages—about 32 percent—involved either brandname or generic drugs that were administered through other routes. (See 

fig. 3.)

Generic Injectable Drugs 

Comprised Over Half of 

Critical Shortages Since 

2009
 

Page 19 GAO-12-116 Drug Shortages

Figure 3: Distribution of 269 Critical Drug Shortages Reported January 1, 2009, 

through June 20, 2011, by Product Type and Route of Administration

Note: This figure reflects 269, or 54 percent, of the 495 total shortages reported January 1, 2009, 

through June 20, 2011. Our analysis was limited to the shortages the University of Utah Drug 

Information Service identified as critical.

a

Other drugs include those administered via nasal, inhalation, rectal, topical, ophthalmic, and 

transdermal methods, as well as those that are available for administration through multiple routes 

and one drug whose route of administration was unavailable from Red Book.

The share of critical drug shortages involving generic injectable drugs has 

increased. Specifically, from 2009 through 2010, the share of reported 

shortages involving generic injectable drugs grew from 37 percent to 

64 percent. Forty-six critical shortages reported in 2011 through June 20 

involved generic injectable drugs; this represents 56 percent of all such 

shortages.

Generic drugs were more often in shortage than brand-name drugs. 

Overall, about three-fourths (76 percent) of the 269 drug shortages 

involved drugs that were available in generic form, with nearly half of all 

shortages involving drugs that were available only in generic form. 

Twenty-four percent of these drug shortages involved only brand-name 
 

Page 20 GAO-12-116 Drug Shortages

drugs. (See table 2.) The share of reported drug shortages involving 

generic drugs—including those with a brand-name counterpart—

remained relatively stable from January 1, 2009, through June 20, 2011.

Table 2: Summary of 269 Critical Drug Shortages Reported January 1, 2009, 

through June 20, 2011, by Product Type 

Product type Number of shortages Percent

Brand-name only 64 24

Generic only 133 49

Brand-name and generic drugs 72 27

Total 269 100

Source: GAO analysis of University of Utah Drug Information Service and Red Book data.

Note: This table reflects 269, or 54 percent, of the 495 total shortages reported January 1, 2009, 

through June 20, 2011. Our analysis was limited to the shortages the University of Utah Drug 

Information Service identified as critical.

Among the 269 critical drug shortages, those administered by injection 

were the most commonly in shortage. In total, 68 percent of drug 

shortages involved drugs administered by injection. (See table 3.) 

Additionally, the share of shortages involving injectable drugs grew from 

51 percent to 77 percent between 2009 and 2010. Fifty-nine critical 

shortages reported in 2011 (through June 20) involved injectable drugs; 

this represents 72 percent of the shortages.

Table 3: Summary of 269 Critical Drug Shortages Reported January 1, 2009, 

through June 20, 2011, by Route of Administration

Route of administration Number of shortages Percent

Injection 182 68

Oral 56 21

Other 28 a 10

Multiple routes 3 1 

Total 269 100

Source: GAO analysis of University of Utah Drug Information Service and Red Book data.

Note: This table reflects 269, or 54 percent, of the 495 total shortages reported January 1, 2009, 

through June 20, 2011. Our analysis was limited to the shortages the University of Utah Drug 

Information Service identified as critical.

a

Other routes of administration included nasal, inhalation, rectal, topical, ophthalmic, and transdermal, 

as well as one drug whose route of administration was unavailable from Red Book.
 

Page 21 GAO-12-116 Drug Shortages

Certain therapeutic classes were more likely than others to be affected by 

a shortage. Specifically, five therapeutic classes—anesthetic and central 

nervous system (CNS), anti-infective, cardiovascular, nutritive, and 

oncology drugs—represented 68 percent of critical drug shortages. 

Anesthetic and CNS drugs were the most represented therapeutic class, 

with 23 percent of shortages reported. (See table 4.)

Table 4: Summary of 269 Critical Drug Shortages Reported January 1, 2009, 

through June 20, 2011, by Therapeutic Class

Therapeutic class Number of shortages Percent

Anesthetic and central nervous system drugs 61 23

Anti-infective drugs 37 14

Nutritive agents 30 11

Oncology drugs 28 10

Cardiovascular drugs 26 10

Endocrine and metabolic drugs 14 5 

Toxicology antidote drugs 10 4 

Dermatological drugs 9 3 

Musculoskeletal drugs 9 3 

Other 41 a 15

Multiple therapeutic classes 4 1 

Total 269 b 99

Source: GAO analysis of University of Utah Drug Information Service and Red Book data.

Note: This table reflects 269, or 54 percent, of the 495 total shortages reported January 1, 2009, 

through June 20, 2011. Our analysis was limited to the shortages the University of Utah Drug 

Information Service identified as critical.

a

Includes other therapeutic classes such as gastrointestinal drugs and ophthalmologic drugs, as well 

as one drug whose therapeutic class was unavailable from Red Book.

b

Percentages do not sum to 100 due to rounding.

Although the numbers are small, shortages of oncology drugs rose 

significantly between 2009 and 2010. Specifically, the number of reported 

shortages for oncology drugs increased by 600 percent, from 2 shortages 

in 2009 to 14 shortages in 2010. Additionally, the number of reported 

oncology drug shortages in 2011 (12 shortages as of June 20, 2011) is on 

pace to surpass the total number of such shortages in 2010. Other 

therapeutic classes saw increases in the number of shortages reported 

from 2009 to 2010: endocrine and metabolic drugs (3 to 7, or 

133 percent); nutritive agents (5 to 13, or 160 percent); and toxicology 

antidote drugs (1 to 4, or 300 percent).
 

Page 22 GAO-12-116 Drug Shortages

Anesthetic and CNS drugs and anti-infective drugs saw decreases in the 

number of shortages reported between 2009 and 2010, at 16 and 

25 percent, respectively. However, shortages for these therapeutic 

classes reported through June 20, 2011, are on pace to surpass the total 

number of such shortages reported in 2010, and remain among the most 

commonly reported shortages.

We noted several other characteristics among these drug shortages. 

Specifically, 59 percent of drug shortages involved more than one 

manufacturer—meaning that most shortages reflected disruptions in the 

supply of more than one manufacturer’s drugs. Additionally, 35 percent of 

these drug shortages involved at least one discontinued product—such 

as one strength or package size of a drug that was in short supply. In 

such cases, a manufacturer’s decision to discontinue a product may have 

caused the shortage, or may have occurred during an ongoing shortage.

Our analysis of the causes of 15 sterile injectable drug shortages 

(involving 5 anesthesia drugs, 5 anti-infective drugs, and 5 oncology 

drugs) showed that manufacturing problems were the primary cause of 

most shortages, and over half were exacerbated by multiple difficulties 

after the drug initially went into short supply.

Most (12 of the 15) drug shortages we reviewed in detail were reportedly 

caused by manufacturing problems, including those that resulted in 

manufacturing shutdowns, according to information provided by FDA and

manufacturers. The remaining 3 shortages were reportedly caused by 

disruptions in the supply of APIs. (See fig. 4.) These problems were the 

primary cause of the shortages reviewed—that is, the first event that 

triggered the drug shortage.

Drug Shortages We 

Reviewed Were 

Generally Caused by 

Manufacturing 

Problems and 

Exacerbated by 

Multiple Difficulties

Manufacturing Problems 

Reportedly Caused Most of 

the 15 Shortages of Sterile 

Injectable Drugs
 

Page 23 GAO-12-116 Drug Shortages

Figure 4: Summary of Primary Causes of 15 Sterile Injectable Drug Shortages That Occurred Between January 2009 and June 

2011

Of the 12 shortages caused by manufacturing problems, 6 resulted from 

manufacturers’ temporary shutdowns of entire facilities so they could be 

upgraded. Four of these six shortages were caused by one 

manufacturer’s shutdown of a single facility. Representatives from this 

manufacturer told us that it shut down the facility in order to improve its 

manufacturing capabilities. The manufacturer had anticipated that the 

upgrade would take 3 months, but it took 1 year to complete. Prior to the 

shortage, the manufacturer built up its inventory to ensure that it could 

meet the market’s demand for its products during the expected 3-month 

shutdown. However, because the manufacturer had not planned for an 

extended shutdown, 4 of the 15 drug shortages we reviewed, as well as 

other sterile injectable drugs produced at that facility, went into short 

supply.

Another four shortages we reviewed were caused when manufacturers 

temporarily suspended production of a particular drug in order to 

investigate or resolve a specific manufacturing problem—for example, a 

quality problem. The remaining two shortages were caused by 

unspecified manufacturing delays.
 

Page 24 GAO-12-116 Drug Shortages

Officials from FDA and manufacturers explained that sterile injectable 

drugs are complex to make, and as such, can be prone to manufacturing 

and quality problems. These products require a sterile environment, 

which is difficult to maintain. FDA officials told us that the most common 

manufacturing problems experienced for sterile injectable drugs are lack 

of assurance of sterility and particulate matter included in the drug. 

According to FDA officials, sterile injectable drugs can take weeks to 

produce; in comparison, oral tablets may only take up to a few days to 

produce. The complexity and duration of the manufacturing process for 

sterile injectable drugs makes these drugs more susceptible to 

manufacturing problems. In addition, according to FDA, such drugs are 

being made by a decreasing number of aging facilities, which may 

contribute to the recent increase in manufacturing problems.

Certain types of sterile injectable drugs, such as anti-infective and 

oncology drugs, can be particularly challenging to manufacture. Officials 

from FDA and other organizations we interviewed explained that 

manufacturers of sterile injectable anti-infective and oncology drugs face 

unique challenges because of the nature of the drugs’ ingredients. 

Specifically, some anti-infective drugs, such as penicillin, are highly 

sensitizing and can trigger serious allergic reactions at very low levels. As 

a result, FDA requires manufacturers to produce penicillin in isolation 

from other drugs.35

Most of the drugs involved in the shortages we reviewed have been 

available in generic form for over 15 years. When asked how the prices 

and profits for their generic sterile injectable drugs have affected 

manufacturers’ interest in maintaining, upgrading, or increasing 

redundancy within their manufacturing lines, or in continuing to 

In addition, some oncology drugs are toxic and can 

present serious risks to people who come into contact with these 

compounds, even at low concentrations. As a result, FDA suggests that 

manufacturers of oncology drugs consider using dedicated production 

lines in order to ensure that other products are not contaminated.

According to FDA officials, the special containment controls necessary for 

some oncology and anti-infective drugs can limit manufacturers’ transfer 

of production of these drugs to other lines. As a result, manufacturers 

may have increased difficulty keeping up with demand for such products 

when they are in short supply.

 

35See 21 C.F.R. § 211.42(d) (2011).
 

Page 25 GAO-12-116 Drug Shortages

manufacture these drugs, three of the four manufacturers we contacted 

stated that such factors had no effect on decisions they make for their 

current product portfolio. These manufacturers indicated that they are 

committed to the sterile injectable drug market or to appropriately 

supporting the manufacture of their current portfolio of drugs. However, 

one of these three manufacturers told us that such factors may affect 

future decisions it makes about the products it manufactures. In contrast, 

the fourth manufacturer told us that it carefully weighs factors, including 

market demand and product price erosion for generic drugs, when 

making capital investment decisions. This manufacturer added that in its 

opinion, lower profits available for the manufacture of generic drugs have 

led to much lower levels of redundancy in manufacturing generic drugs 

than for brand-name drugs. Despite this, officials from three of the four 

manufacturers we contacted told us that they continue to produce drugs 

that garner low or no profits. Rather than assessing the profitability of any 

single drug product, they instead make business decisions based of their 

overall portfolio of drugs or concerns for patients.

Three of the 15 shortages of sterile injectable drugs we reviewed in detail 

were caused by disruptions in the supply of APIs. For 2 of these 

shortages, manufacturers were not receiving their normal shipments of 

API because of problems related to the manufacturing of these 

ingredients. For 1 shortage, the manufacturer’s supplier of API 

discontinued its production of the ingredient, which led to the shortage.

In addition to the initial problems that caused the shortages, over half of 

the shortages we reviewed (8 of 15) were subsequently exacerbated by 

multiple other difficulties that arose after the shortages began. These 

8 shortages were each affected by an average of four distinct difficulties 

that occurred in addition to the primary cause of the shortage and 

generally affected multiple manufacturers. Four of these shortages were 

exacerbated by five or more difficulties—including 1 shortage that was 

exacerbated by seven distinct difficulties. In addition to the 8 shortages 

that were exacerbated by multiple issues, 4 were exacerbated by one 

issue after the drug initially went into short supply. The factors that 

impacted drug shortages did not vary substantially by the drugs’ 

therapeutic class.

The two most common difficulties that exacerbated shortages after the 

drugs went into short supply were other manufacturers’ inability to keep 

up with an increased demand for their products once a competitor’s drug 

went into short supply, and manufacturing problems, including those that 

Over Half of the 15 

Shortages Were 

Subsequently Exacerbated 

by Multiple Difficulties
 

Page 26 GAO-12-116 Drug Shortages

involved manufacturing shutdowns. Each of these difficulties affected 

9 shortages. The drugs involved in the 15 shortages we reviewed were 

produced by an average of three manufacturers at the time the drug went 

into short supply. According to officials from FDA and manufacturers, 

when only a few make a drug and one manufacturer’s drug is in short 

supply, it can be difficult for the others to substantially increase production 

of a drug to ensure that demand for a drug is met—even in the absence 

of any other problems.

Some of the 15 shortages we reviewed were subsequently exacerbated 

by other difficulties in addition to their primary causes. For example, 

5 shortages were exacerbated by manufacturers’ decisions to discontinue 

a drug. In addition, 3 drug shortages were exacerbated by manufacturers’ 

decisions to recall products for product quality reasons, including 

1 shortage that was exacerbated by two drug recalls. Finally, 2 shortages 

were exacerbated by disruptions in the supply of API, and 1 was 

exacerbated by a delay related to the importation of a finished drug 

product. (See table 5.)

Table 5: Summary of Difficulties That Subsequently Exacerbated 15 Sterile 

Injectable Drug Shortages That Occurred Between January 2009 and June 2011

Difficulties affecting drug supply

Number of 

shortages 

affected

Manufacturers’ inability to keep up with demand 9 

Manufacturing problems 9 a

Temporary manufacturing shutdown in order to upgrade an entire 

facility 2 

Temporary manufacturing suspension of a particular drug in order to 

investigate or resolve a manufacturing problem 5 

Temporary manufacturing shutdown for unspecified reasons 1 

Manufacturing delays 3 

Other manufacturing problems 1 

Product discontinuations 5 

Disruption in the supply of active pharmaceutical ingredients 2 

Delays associated with the importation of finished drug products 1 

Source: GAO analysis of information provided by FDA and manufacturers.

Note: The number of shortages affected by these difficulties is greater than the number of shortages 

reviewed because most of the shortages we reviewed were affected by multiple difficulties, such as 

multiple types of manufacturing problems.

a

As a result of manufacturing problems, three drug shortages were affected by recalls and one of 

these shortages experienced two product recalls.
 

Page 27 GAO-12-116 Drug Shortages

During these shortages, multiple manufacturers sometimes experienced 

the same exacerbating issues, once a shortage was already ongoing. For 

example, 9 of the 15 shortages we reviewed were extended as a result of 

manufacturing problems that occurred in addition to the shortages’ 

primary causes, as displayed in table 5 above. During 2 of these 

shortages, three manufacturers of the drugs in shortage each 

experienced manufacturing problems; during another shortage, two 

manufacturers each experienced such problems, and during the 

remaining 6 shortages, one manufacturer experienced manufacturing 

problems. Officials from one manufacturer described recent shortage 

situations as a perfect storm of several manufacturers coincidentally 

experiencing manufacturing problems all at the same time.

Three shortages we reviewed were not affected by issues beyond the 

primary cause of the shortage. One of these shortages involved a drug 

that was produced by only one manufacturer at the time of the shortage. 

The other two shortages were not exacerbated by other issues because, 

according to FDA, other manufacturers were able to produce enough of 

the drug to meet the market’s demand.

FDA responds to drug shortages by taking various actions to address the 

shortages’ underlying causes and enhance product availability. Our 

analysis of FDA’s response to 15 shortages of sterile injectable drugs 

showed that FDA took a variety of actions to respond to each shortage. In 

addition, FDA has increasingly prevented drug shortages from occurring. 

FDA primarily communicates information about drug shortages and 

product availability to the public through its website.

FDA attempts to address the underlying cause of shortages as well as to 

provide ways to enhance the drug’s availability until the underlying cause 

of the shortage has been addressed and the shortage is resolved, 

according to FDA officials we interviewed. FDA officials explained that 

they respond to all of the shortages the agency becomes aware of, and 

they determine how to address each shortage based on its cause and the 

public health risk associated with the shortage. Along with this 

determination, FDA officials told us that the agency places the highest 

priority on responding to shortages of those drugs that it considers 

medically necessary—that is, those that have the greatest potential to 

Actions Taken by FDA 

to Respond to Drug 

Shortages Are 

Intended to Resolve 

Shortages’ Underlying 

Causes and Enhance 

Product Availability

FDA’s Goal Is to Resolve 

the Underlying Causes of 

Shortages 
 

Page 28 GAO-12-116 Drug Shortages

affect public health.36 FDA defines a medically necessary drug as any 

drug that is used to treat or prevent a serious disease or medical 

condition for which there is no other adequately available drug that is 

judged by medical staff to be an appropriate substitute.37

FDA may take a variety of actions to respond to the shortages of 

medically necessary and non-medically necessary drugs by providing 

assistance directly to the manufacturer. If a manufacturer is experiencing 

technical problems with its manufacturing processes, FDA may be able to 

assist in the resolution of those problems—for example, by providing 

advice on how to address quality issues and ensure compliance with 

current good manufacturing practice regulations. If the manufacturer is 

facing difficulties obtaining raw materials, FDA may be able to assist in 

identifying an alternative supplier. Similarly, if a manufacturer is unable to 

obtain APIs or a finished drug as a result of importation delays, FDA may 

be able to coordinate with other entities, such as other federal agencies, 

to enable these materials to be imported more quickly.

FDA’s goal in 

identifying such drugs is to assist in the prioritization of their response to 

drug shortages. As such, FDA’s determination of whether a drug is 

medically necessary may differ from a health care provider’s assessment 

that a certain drug is needed to treat a particular patient. FDA officials told 

us that they sometimes consult with health professional organizations 

such as ASHP when making a determination regarding the medical 

necessity of a particular drug. During shortages, FDA officials told us that 

if a drug is determined to be medically necessary, they will inform the 

manufacturer of their decision. Appendix I summarizes the criteria FDA 

uses to determine whether a drug is medically necessary.

 

36For example, FDA officials told us that if they were informed of a shortage of a medically 

necessary and a non-medically necessary drug on the same day, they would first respond 

to the medically necessary drug shortage.

37As part of making this determination, FDA considers whether the drug is being 

administered to patients for off-label uses—that is, among other things, for conditions or 

patient populations for which the drug was not approved or in a manner that is 

inconsistent with the drug’s FDA-approved label. Although FDA may not have approved a 

drug to treat a particular condition or patient population, the agency is aware that 

physicians may determine that prescribing a drug off label constitutes good care for an 

individual patient, and therefore factors off-label usage into its determination that a drug is 

medically necessary for the purpose of prioritizing drug shortages. FDA also considers 

drugs being studied in clinical trials in making its determination. However, FDA does not 

consider patient inconvenience, such as needing to take two tablets instead of one, as a 

reason to classify a drug as medically necessary. 
 

Page 29 GAO-12-116 Drug Shortages

During a shortage, FDA may encourage manufacturers to increase 

production of the drug or to seek approval to begin production of a drug in 

short supply. If more than one manufacturer produces the drug that is in 

short supply, FDA may contact the other manufacturers to alert them to 

the potential of increased demand and may encourage them to increase 

their production of the drug. During shortages involving generic drugs, 

FDA may also encourage other manufacturers to submit ANDAs for 

review, so that additional manufacturers can gain FDA approval to 

produce the drug that is in short supply.

FDA may also expedite its review of ANDAs, ANDA supplements, and 

NDA supplements during a shortage, but this is largely dependent on the 

manufacturers’ request for an expedited review. Some shortages may be 

resolved with changes to a manufacturing process or site, or the use of 

an alternative supplier for an API. FDA reviews manufacturers’ requests 

for such changes, as documented in an application supplement, and any 

changes that have substantial potential to have an adverse effect on the 

product must be approved prior to their implementation. To assist in 

resolving a shortage, FDA may expedite its review of these supplements, 

or may expedite its review of ANDAs, which can substantially decrease 

the agency’s review time.38

 

38According to FDA, the agency expedited its review of 375 ANDAs, and 289 ANDA 

supplements from 2008 through July 2011 as a result of potential or current drug 

shortages; the number of expedited reviews exceeds the number of shortages reported 

during this period because multiple applications or supplements may be expedited to 

alleviate a shortage. FDA was unable to provide data regarding the length of time it took 

for them to expedite their review of these applications, including whether the reviews were 

completed prior to the resolution of related shortages. The expedited reviews comprise a 

small portion of the total number of applications pending FDA review as of July 30, 2011, 

which included 2,485 ANDAs, 6,235 ANDA supplements (which includes 5,040 

supplements requesting approval for manufacturing changes and 1,195 supplements 

requesting approval for labeling changes), and 894 NDA supplements requesting approval 

for manufacturing changes.

FDA officials told us that an expedited review 

involves the same amount of analysis as a review that is not expedited, 

but can take significantly less time since the agency prioritizes its review 

of such applications. For example, FDA officials noted that certain 

expedited ANDA supplements have been approved in as quickly as a few 

days to a week, in contrast to the year or more it may take for such 

supplements to be reviewed under the typical process. FDA’s review of 

NDA supplements in 2009 took the agency an average of 5 months, while 
 

Page 30 GAO-12-116 Drug Shortages

those that were expedited took an average of 2.5 months.39

FDA may also apply its regulatory discretion to enhance drug availability 

during shortages of medically necessary drugs.

FDA has 

encouraged manufacturers to note their request for an expedited review 

due to a shortage in their cover letter to an application supplement or 

ANDA, or to inform FDA officials working in the Drug Shortage Program, 

OND, or OGD directly.

40

If FDA is unable to resolve or alleviate a shortage of a medically 

necessary drug within the United States, the agency may use its 

regulatory discretion with regard to the importation into the United States 

of “unapproved drugs.” These drugs are approved for use in foreign 

countries, but not the United States. For example, FDA officials told us 

When considering 

whether to apply its regulatory discretion, the agency weighs the risks and 

benefits of taking such an approach. For example, FDA may exercise its 

regulatory discretion for manufacturers to continue marketing a medically 

necessary drug despite labeling or quality issues that would typically 

result in regulatory action. While FDA considers a drug with labeling 

errors to be misbranded, to alleviate or resolve a shortage of a medically 

necessary drug, agency officials told us that FDA may exercise its 

regulatory discretion with regard to a manufacturer’s continued marketing 

of a drug with labeling errors. In this scenario, the manufacturer would 

issue an FDA-reviewed letter to health care professionals informing them 

of the error, or provide the corrected label text. FDA may also apply its 

regulatory discretion with regard to manufacturers’ continued marketing of 

medically necessary drugs that have quality problems, if the manufacturer 

can develop a method to resolve the problem prior to the drug’s 

administration. For example, if a manufacturer finds particulate in a drug

and determines that a filter can be used to remove the particulate prior to 

administration of the drug, at FDA’s discretion, the manufacturer may 

continue to market the drug with the filter. In such cases, FDA would 

review evidence of the filter’s effectiveness provided by the manufacturer, 

to ensure that it removes the particulate from the drug.

 

39FDA officials were unable to provide data regarding the length of time it took to review 

ANDAs and ANDA supplements that were expedited as a result of a shortage. 

40FDA officials told us that they do not typically consider exercising regulatory discretion to 

respond to shortages of non-medically necessary drugs because these drugs are, by 

definition, not used to treat serious diseases or medical conditions, or other clinically 

interchangeable versions of the drug are available.
 

Page 31 GAO-12-116 Drug Shortages

that from January 2011 through September 2011, at the agency’s 

discretion, manufacturers imported seven unapproved drugs into the 

United States to address drug shortages. Four of these importations were 

ongoing as of October 3, 2011. FDA officials we interviewed explained 

that they only consider using this option for severe shortages of medically 

necessary drugs. To explore whether the importation of drugs not 

approved in the United States is an option for agency discretion during a 

shortage, agency officials told us that FDA collaborates with foreign 

regulatory agencies to identify whether a similar drug is manufactured in a 

country that requires adherence to manufacturing practice standards that 

are similar to those required by FDA. Once any such manufacturers are 

identified, FDA asks the firm whether they would be willing to provide the 

drug for the U.S. market. When possible, FDA selects a firm that has a 

subsidiary in the United States and an existing distribution network in 

order to expedite the process and the agency’s access to information 

about the foreign manufacturing facility and drug. To help ensure the 

quality of the drug, FDA officials told us that they examine information 

about the manufacturer, its manufacturing facility, the chemical 

formulation of the drug, and information about the manufacturer’s quality 

control processes. FDA also reviews the firm’s compliance history and 

inspection reports that foreign regulatory agencies make available. 

Agency officials told us that, depending on the amount and currency of 

available information about the manufacturing facility, they may conduct 

an inspection prior to the importation of the unapproved drug into the 

United States. After a manufacturer has been identified and FDA has 

completed its quality review, FDA works with the company to reach an 

agreement on the conditions of the agency’s enforcement discretion and 

monitors the supply and distribution of the drug that comes into the United 

States. FDA also encourages manufacturers to communicate with health 

care professionals and the public about potential differences between the 

imported drug and the drug in shortage through the use of letters to 

health care professionals. These letters detail any differences in chemical 

composition, strength, or formulation between the imported drug and the 

drug in short supply. FDA officials told us that, at their discretion, 

importation of such drugs may continue until the manufacturers of the 

FDA-approved drug are able to meet demand.

FDA considers a shortage to be resolved when the supply of the drug 

meets demand, which FDA calculates using market data that it obtains 

from IMS Health. FDA officials told us that they continue to monitor 

recently resolved shortages until any ongoing issues that could affect the 

supply of the drug are resolved.
 

Page 32 GAO-12-116 Drug Shortages

Our review of FDA’s response to 15 shortages of sterile injectable drugs 

showed that FDA typically used two or more types of actions to respond 

to each shortage, and for 8 shortages, the agency responded with four or 

more types of actions. At the time of these shortages, FDA determined 

that all 15 drugs involved with shortages we reviewed in detail were 

medically necessary. To respond to these shortages, FDA most 

frequently offered assistance to manufacturers to prevent, alleviate, or 

resolve the shortage, or notified other manufacturers to expect increased 

demand or encouraged other manufacturers to increase production, as 

shown in table 6. (See app. II for information on FDA’s response to each 

of the 15 shortages.)

Table 6: Summary of Actions Taken by FDA in Response to 15 Shortages of Sterile 

Injectable Drugs That Occurred Between January 2009 and June 2011 

Types of actions taken by FDA 

Number of 

shortages

FDA offered assistance to manufacturers to prevent, alleviate, or resolve 

the shortage 15

FDA notified other manufacturers to expect increased demand or 

encouraged other manufacturers to increase production 13

FDA provided assistance to address manufacturing problems related to 

drug quality issues 8 

FDA searched for a firm willing and able to import a version of the drug in 

shortage not approved in the United States 7 

At FDA’s discretion, a manufacturer imported a version of the drug in 

shortage not approved in the United States 1 

FDA expedited its review of an application supplement or abbreviated new 

drug application 5 

At FDA’s discretion, a manufacturer continued to market a drug despite 

labeling or quality issues 5 

FDA provided assistance to address importation delays for active 

pharmaceutical ingredients or finished products 5 

Source: GAO analysis of information provided by FDA.

Note: The total number of types of actions taken by FDA is greater than the number of shortages 

reviewed because FDA used more than one action to respond to most of the shortages we reviewed.

FDA Responded to 

Selected Shortages with a 

Variety of Actions
 

Page 33 GAO-12-116 Drug Shortages

While FDA responded to all of the 15 shortages of sterile injectable drugs 

we reviewed, agency officials told us that 3 of these supply disruptions did 

not meet the agency’s criteria for a shortage.41 Specifically, FDA officials 

told us that while it was aware of disruptions in the supply of these three 

drugs, the overall market supply of each drug was able to meet demand, 

based on the agency’s knowledge of manufacturers’ production. Even 

though FDA did not recognize these 3 cases as drug shortages, agency

officials nonetheless notified other manufacturers to expect increased 

demand for their products or encouraged them to increase production, 

and also offered assistance to the affected manufacturers.

FDA has increasingly prevented potential drug shortages from occurring 

when it has been informed of the potential for a shortage in advance. 

According to our analysis of information provided by FDA, the agency 

prevented 50 potential drug shortages during the first 6 months of 2011—

about 1.5 times the number of potential drug shortages (35) prevented 

during all of 2010.42

To prevent these potential shortages, FDA took some of the same types 

of actions it uses to alleviate and resolve shortages. During 2010 and the 

first half of 2011, FDA most frequently prevented potential drug shortages 

by expediting its review of application supplements. FDA also took a 

FDA officials partially attributed the increase in 

potential shortages prevented to manufacturers’ willingness to report 

information that could impact the supply of their drugs in advance of a 

shortage. The recent increase in the number of shortages presented 

additional opportunities for manufacturers to report potential supply 

disruptions to the agency. According to our analysis of information 

provided by FDA, during the first half of 2011, the agency was able to 

prevent about 90 percent of potential shortages that it learned about in 

advance.

 

41While these three shortages did not meet FDA’s criteria, all of the shortages we 

reviewed in detail were identified by representatives from ASA, ASCO, and IDSA as 

recent shortages that had a significant impact on patient care or public health. 

42We grouped together shortages of multiple versions of the same drug to identify the total 

number of shortages prevented. FDA officials told us that the agency prevented 38 drug 

shortages in 2010 and 99 shortages in 2011, through June. However, these data 

represented the number of individual drug products for which a shortage had been 

averted, and did not group together multiple versions—for example, multiple 

concentrations—of the same drug. 

FDA Has Increasingly 

Prevented Potential Drug 

Shortages from Occurring
 

Page 34 GAO-12-116 Drug Shortages

variety of other actions to prevent drug shortages during this period. (See 

table 7.)

Table 7: Actions Taken by FDA to Prevent Potential Drug Shortages, 2010 and 2011, 

through June

Number of actions 

taken to prevent 

potential shortages

Actions taken by FDA 2010 2011

FDA expedited review of application supplements

a

12 37

At FDA’s discretion, a manufacturer continued to market a drug 

despite labeling or quality issues 2 9 

FDA helped to ensure timely importation of an active 

pharmaceutical ingredient or finished products 8 2 

FDA either notified firms that they would experience increased 

demand or encouraged manufacturers to increase production 9 1 

FDA provided assistance to address manufacturing problems 6 8 

At FDA’s discretion, a manufacturer imported a version of the 

drug in shortage not approved in the United States 0 1 

Other 1 b 2 

Source: GAO analysis of information provided by FDA.

Note: The total number of actions taken by FDA exceeds the number of shortages prevented 

because in some instances, FDA took multiple actions to prevent shortages.

a

Data presented for 2011 reflect potential shortages prevented through June 2011.

b

Other actions included FDA applying its regulatory discretion with regard to a manufacturer 

continuing its production of a drug while using laboratory testing equipment that the agency had not 

yet reviewed.

FDA’s primary means of communicating information to the public about 

drug shortages is its website, which lists both current and resolved 

shortages.43

 

43See 

FDA officials told us that they post information on their 

website about shortages of medically necessary drugs, as well as some 

shortages of non-medically necessary drugs for which it has received 

multiple requests for information. However, FDA may not post any 

information about shortages if the agency anticipates that the shortage 

will be brief in duration. FDA may not immediately post information about 

current shortages if the agency is concerned that such information could 

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

FDA Communicates 

Information about 

Shortages to the Public via 

Its Website
 

Page 35 GAO-12-116 Drug Shortages

make the shortage worse—for example, by inducing hoarding. Once FDA 

decides to post information about a shortage, it lists the manufacturers of 

the drug as well as a broad explanation of the cause for the shortage—for 

example, “manufacturing issues.” FDA may post more detailed 

information about the cause and expected duration of the shortage, as 

well as information about other versions of the drug that are available, if 

manufacturers provide them with text to post on its website, or if the 

manufacturer makes such information publicly available.

Once the shortage is resolved—that is, once the supply of the drug is 

sufficient to meet the market’s demand for it—FDA officials told us that 

they may move information about the shortage from its current shortages 

web page to its resolved shortages web page. However, FDA officials told 

us that they may keep listings of resolved shortages on its current 

shortages web page to inform the public about the availability of the 

product. In addition, they may keep a shortage listed as current until they 

are confident that any underlying causes of the shortage are addressed. 

FDA officials told us that they post information about resolved shortages 

for 6 months before removing such information from their website.

FDA is constrained in its ability to protect the public health from drug 

shortages due to its lack of authority to require manufacturers to take 

certain actions. In addition, management challenges, such as a lack of 

systematic data and performance measures, weaken the agency’s 

response to drug shortages and inhibit its ability to protect public health.

FDA is constrained by its lack of authority to require manufacturers to 

provide the agency and the public with information about shortages, or 

require that manufacturers take certain actions to prevent, alleviate, or 

resolve shortages. FDA’s sole authority related to manufacturers’ 

reporting of drug shortages pertains to the discontinuation of approved 

drugs that are life-supporting, life-sustaining, or for use in the prevention 

of a debilitating disease or condition, when such drugs are produced by 

one manufacturer.44

 

44See 21 U.S.C § 356c; 21 C.F.R. § 314.81(b)(3)(iii) (2011). To the maximum extent 

possible, FDA is to distribute information on the discontinuance of these products to 

appropriate physician and patient organizations. FDA does not have the authority to 

enforce this requirement, for example, by seeking civil monetary penalties.

In such instances, companies are required to provide 

FDA Is Constrained in 

Its Ability to Protect 

Public Health from 

Drug Shortages

FDA Lacks Authority to 

Require Manufacturers to 

Report Potential and 

Actual Shortages
 

Page 36 GAO-12-116 Drug Shortages

FDA with at least 6 months notice of discontinuations.45

FDA does not have the authority to require manufacturers to report actual 

or potential shortages—including information about their causes and 

expected duration—to the agency or the public. FDA has encouraged 

manufacturers to report potential supply disruptions to the agency. While 

our draft report was at HHS for comment, the President directed FDA to 

use all appropriate administrative tools to require drug manufacturers to 

provide adequate advance notice of situations that could lead to drug 

shortages, to the extent permitted by law.

However, such 

discontinuations have not been the primary cause of most recent drug 

shortages. As a result of the constraints on its authority, the agency’s 

approach to managing drug shortages is predominately reactive, which 

limits its ability to prevent, alleviate, and resolve shortages to protect the 

public health.

46

Without information on current or potential shortages, other 

manufacturers’ ability to increase production of the drug may also be 

compromised. For example, one manufacturer told us that FDA did not 

notify it soon enough to enable it to increase production to alleviate or 

resolve two of the seven shortages that it was involved in and that were 

included in our review. In both instances, by the time FDA informed the 

manufacturer of the shortage, demand for its products was already at 

levels the firm could not support.

In addition, on the same day, 

FDA sent a letter to all drug manufacturers urging them to report potential 

supply disruptions to the agency. According to FDA officials, while the 

agency could have been notified in advance of most shortages, less than 

half of all shortages are reported to the agency by manufacturers. 

Instead, FDA is most often notified by ASHP, or health care providers or 

consumers when they are unable to purchase a drug—a point at which 

the shortage is already impacting public health. As a result, FDA’s 

response to shortages may be delayed.

 

45On October 31, 2011, the Commissioner of FDA sent a letter to all drug manufacturers, 

reminding them of this requirement. See 

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm277675.htm. 

46Exec. Order No. 13,588, 76 Fed. Reg. 68,295 (Nov. 3, 2011).
 

Page 37 GAO-12-116 Drug Shortages

Officials from several manufacturers told us that they would like other 

manufacturers to openly share information with FDA about shortages of 

their drugs because doing so can speed FDA’s response, and can 

enhance other manufacturers’ ability to increase production of the drug in 

short supply. These officials told us that they support efforts to improve 

communication between FDA and industry through early notification of 

potential drug shortages. However, some of these officials also noted that 

a requirement to report potential drug shortages within a specific time 

frame would be difficult for manufacturers to observe. They explained that 

drug shortages can be unpredictable and are often the unexpected result 

of several factors or causes. As a result, they were concerned that 

manufacturers may not foresee the impending shortage soon enough to 

be able to comply with a lengthy advance notification requirement.

FDA officials also told us that manufacturers sometimes do not provide 

the agency with information about the causes and expected duration of 

shortages as soon as it is available. As a result, the information posted on 

FDA’s website does not always reflect current information. FDA officials 

told us that they cannot communicate detailed information about the 

causes or expected duration of a shortage unless the affected 

manufacturers provide text for the agency to post on its website. FDA 

officials explained that such information is generally considered 

confidential commercial information, which cannot be disclosed by FDA 

without the manufacturer’s consent. Officials at several health care 

professional associations we interviewed noted that information on the 

cause and expected duration of a shortage is important for clinicians to 

understand so that they can determine the best method to treat their 

patients during a shortage.

FDA does not have the authority to require that manufacturers take 

certain actions to prevent, alleviate, or resolve shortages, such as by 

continuing or increasing their production of a drug, or by taking actions to 

prevent or resolve shortages. FDA does not control the distribution of 

drugs and also cannot compel manufacturers or distributors to take 

actions to prevent hoarding or diversion of drugs to the gray market. 

FDA’s ability to respond to a drug shortage may be limited by 

manufacturers’ business decisions, such as a manufacturer choosing to 

discontinue production of a drug already in shortage. While FDA can 

encourage a manufacturer not to discontinue its production of a drug, it 

cannot require the company to continue production. Also, while it may be 

in manufacturers’ interest to increase their production of a drug in short 

supply, FDA cannot compel a manufacturer to increase its production of a 

drug. In addition, FDA cannot compel manufacturers to take steps to 
 

Page 38 GAO-12-116 Drug Shortages

resolve shortages, such as by accepting the agency’s offers of 

assistance. Based on our review of FDA’s response to 15 shortages, we 

found that manufacturers do not always accept FDA’s offer of assistance. 

FDA officials also told us that they encounter challenges finding 

manufacturers that are willing to import drugs that are not approved in the 

United States in order to alleviate a shortage. Agency officials told us that 

some manufacturers had expressed hesitancy in working with FDA to 

alleviate a shortage in this manner because it would require a substantial 

financial investment accompanied with a time-limited benefit. In our 

review of FDA’s response to 15 shortages, we found that the agency tried 

to find firms that were willing to import drugs that were not approved in 

the United States during 7 shortages, but was only able to find a firm to 

import a product in order to help alleviate 1 shortage.

FDA’s ability to respond to drug shortages is also constrained by its lack 

of systematic data, limited resources, and an absence of performance 

measures and priorities. Although FDA obtains information about drug 

shortages, the agency does not maintain data related to these shortages, 

such as their causes and the agency’s response. Without such data, FDA 

is unable to systematically monitor trends and identify actions it could 

take to address the fundamental or contributing causes of drug shortages. 

Drug Shortage Program staff currently track drug shortages in individual 

electronic files, not in a database. To summarize information on drug 

shortages for other FDA offices, the Drug Shortage Program prepares email status reports, which do not present information in a consistent 

format and are not conducive to easy retrieval of information or data 

analysis. In addition, officials from FDA’s Drug Shortage Program, OND, 

OGD, Office of Compliance, and ORA told us that they routinely share 

information about drug shortages via e-mails, phone calls, or meetings—

not in any systematic format or system. FDA’s information does not lend 

itself to analysis—it is not easily retrievable, routinely recorded, or 

sufficiently reliable. As a result of FDA’s lack of systematic data, the 

agency was unable to provide us with information necessary to analyze 

trends in drug shortages and we therefore obtained these data from 

UUDIS.47

 

47FDA officials told us that the best data that they could supply us with would be copies of 

weekly e-mail messages, containing brief narratives on the status of shortages in effect for 

the week in question.

Management Challenges 

Further Constrain FDA’s 

Ability to Respond to Drug 

Shortages 
 

Page 39 GAO-12-116 Drug Shortages

Without a systematic method to store, track, and share data on drug 

shortages, the agency cannot ensure that it responds to potential and 

current shortages in a timely and coordinated manner. FDA has faced a 

growing workload in recent years associated with the increase in the 

number of drug shortages reported, but Drug Shortage Program staff lack 

a system to manage information to ensure that they are responding to 

shortages in a timely manner. The Drug Shortage Program’s work 

requires staff to maintain a large volume of complex information on drug 

shortages, communicate regularly with other agency officials in other 

parts of the agency, as well as manufacturers, and monitor significant 

shortage situations until they are resolved.48 Other CDER offices that 

coordinate with the Drug Shortage Program may be unaware of 

information about current or potential shortages and therefore miss 

opportunities to respond to shortages—for example, by neglecting to 

recognize that supplements submitted for review could help to alleviate a 

shortage. While FDA officials told us they review applications and 

supplements in the queue to determine whether any should be expedited 

in order to alleviate a shortage, representatives from organizations we 

interviewed noted concerns about the agency’s ability to review ANDA 

supplements in a timely manner to prevent, alleviate, or resolve 

shortages. Specifically, some representatives told us that they were 

aware of instances where manufacturers had submitted ANDA 

supplements, which, if approved, could have helped to alleviate or resolve 

a shortage.49

 

48For example, many shortages involve multiple manufacturers and each may face 

multiple problems related to the production of the drug before the shortage is resolved. 

During shortages, Drug Shortage Program officials may need to communicate with 

officials from each manufacturer to obtain information, as well as communicate with 

different offices within FDA to share information related to the agency’s response.

According to these representatives, FDA’s review of these 

supplements can take several years. In addition, representatives noted 

that in at least one case, FDA’s review was not expedited until months 

after the supplement was received.

49In addition, we previously reported that, in response to a potential shortage of heparin in 

2008, FDA encouraged a manufacturer to submit an ANDA, for which it had granted an 

expedited review. However, despite the expedited designation, the approval process for 

the application took 18 months, so this product was not available until well after the supply 

of heparin had stabilized. See GAO, Food and Drug Administration: Response to Heparin 

Contamination Helped Protect Public Health; Controls That Were Needed for Working 

With External Entities Were Recently Added, GAO-11-95 (Washington, D.C.: Oct. 29, 

2010), 18.
 

Page 40 GAO-12-116 Drug Shortages

FDA officials have acknowledged that a database is needed to store 

current and historic data on drug shortages, and in response to this need, 

they recently developed, and are in the process of implementing, an 

electronic spreadsheet to gather such data. Agency officials told us that 

they intend to use this spreadsheet to monitor shortages and conduct 

descriptive analyses of shortages in a more standardized format. In 

addition, they plan to use this spreadsheet to generate data to use for 

annual reporting. We reviewed an early draft of FDA’s spreadsheet and 

identified several weaknesses. For example, while the spreadsheet will 

enhance the agency’s ability to more rapidly obtain and analyze data on 

drug shortages, it was not intended to—nor will it provide—a method for 

FDA to systematically manage information about drug shortages on a 

daily basis or provide a means to share information about drug shortages 

with other FDA offices. FDA’s newly developed spreadsheet will not 

enable the agency to improve the management of its workload, such as 

its ability to organize the large volume of information about drug 

shortages that it receives in a systematic manner, safeguard institutional 

knowledge about past shortages, or help Drug Shortage Program officials 

share information with other FDA offices. In addition, because the 

spreadsheet requires additional resources for data entry, it will add to the 

workload of the Drug Shortage Program—instead of alleviating it. The 

spreadsheet is also incomplete and does not allow the agency to track a 

variety of datapoints. For example, the spreadsheet does not have a 

mechanism for the agency to group together shortages of multiple 

versions of the same drug; without this capability, it will be difficult for 

FDA to track the number of similar products affected by a shortage. 

The spreadsheet also does not include space for FDA to track the NDCs 

associated with each drug shortage. Such data are necessary in order to 

fully analyze the characteristics of drugs that have been in short supply. 

In addition, because FDA’s current spreadsheet only includes space to 

note one action FDA took to respond to each shortage, it will not be able 

to provide the agency with systematic data on multiple actions the agency 

takes in response to a shortage. For example, for shortages involving 

drugs produced by multiple manufacturers, the spreadsheet will not be 

able to systematically capture multiple types of actions FDA takes to 

address each shortage.

FDA has consistently staffed its Drug Shortage Program—which is 

responsible for the coordination of all of the agency’s activities related to 

the prevention and mitigation of drug shortages—with a small number of 

employees. Despite a dramatic increase in the number of drug shortages 

reported in recent years, the number of staff working in the Drug Shortage 
 

Page 41 GAO-12-116 Drug Shortages

Program remained constant at three full-time employees from 2009 until 

February 2011, when FDA hired a fourth staff person for the Drug 

Shortage Program. As of October 2011, FDA had hired a fifth staff 

person, but was unable to provide a time frame for when that person 

would start work.50 Because FDA has lacked detailed data on drug 

shortages, it may not have been able to develop reliable estimates of the 

current and future resource needs of the Drug Shortage Program, a topic 

on which we have previously reported.51

FDA also does not have a set of results-oriented performance metrics 

and strategic priorities related to drug shortages. As a result, FDA may be 

unable to effectively evaluate its work and improve its ability to protect the 

public health. FDA has not developed a set of results-oriented 

performance metrics to measure the success of the agency’s response to 

drug shortages in either the long term or the short term. FDA recently 

began tracking information on one results-oriented performance metric—

the number of drug shortages prevented in a year. However, FDA lacks 

other measures that could be used to measure the results of its work—

such as the effectiveness of the actions the agency takes to respond to 

shortages. Without such metrics, FDA may be unable to evaluate how it 

could most effectively improve the program’s ability to respond to drug 

shortages and protect the public health. Furthermore, while FDA has 

recognized the significant public health consequences that can result 

from drug shortages, the agency has not identified drug shortages as an 

However, representatives from 

many of the organizations we interviewed told us that they are concerned 

that the agency does not have adequate staffing to effectively respond to 

drug shortages.

 

50Agency officials estimated that, in addition to those staff working in the Drug Shortage 

Program, about 25 full-time equivalent employees provide some level of assistance in 

preventing, alleviating, and resolving shortages—for example, by conducting 

determinations of medical necessity and reviewing application supplements. However, 

these additional staff also have other primary responsibilities.

51See GAO, Food and Drug Administration: FDA Faces Challenges Meeting Its Growing 

Medical Product Responsibilities and Should Develop Complete Estimates of Its Resource 

Needs, GAO-09-581 (Washington, D.C.: June 19, 2009).
 

Page 42 GAO-12-116 Drug Shortages

area of strategic importance for the agency.52 As a result, the agency may 

be unable to coordinate an agencywide response to drug shortages, and 

make decisions on the best ways that it can employ its resources to fulfill 

its mission to protect the public health.

The number of drug shortages has substantially increased in recent 

years—including those for life-saving medications such as oncology 

drugs, which has jeopardized the public health. Health care providers and 

patients have struggled with the consequences of these shortages and 

have raised concerns about what the federal government is doing to 

prevent and resolve these shortages.

FDA may not always be able to prevent shortages from occurring, in part 

because it does not have control over private companies’ business 

decisions, for example, regarding whether to continue making a drug. 

Further, the agency’s response to drug shortages is constrained by its 

lack of authority to require manufacturers to report potential or current 

shortages to the agency. FDA has demonstrated that when it learns of 

shortages in advance, it can prevent the majority of such shortages from 

occurring. However, it does not currently have the authority to require 

manufacturers to provide it with information about potential or current 

shortages, and therefore it can only prevent the shortages that it becomes 

aware of through voluntary reporting. As a result, FDA’s response to 

shortages is most frequently reactive. Also, information communicated to 

health care providers and the public about shortages may remain 

incomplete, because FDA cannot disclose detailed information to the 

public without manufacturers’ consent.

We have been critical of FDA in the past for not paying sufficient attention 

to strategic and workforce planning and reliably estimating needed 

resources. Our prior reports have also expressed concern that the agency 

has not established result-oriented performance metrics, that agency 

managers often do not use existing performance measures to set 

 

52FDA has incorporated the concept of availability of drugs into one of its strategic 

objectives; however, this objective is focused solely on the processes FDA takes to 

ensure the availability of safe and effective new drugs for the market. As such, it does not 

encompass the availability of all drugs, including many medically necessary drugs that are 

no longer manufactured by the company that marketed the brand-name version of the 

drug and are thus available in generic form only. 

Conclusions 
 

Page 43 GAO-12-116 Drug Shortages

program priorities, and that coordination between internal FDA offices is a 

significant management challenge. These concerns are echoed in the 

agency’s current approach to managing its Drug Shortage Program. 

Despite the recent increase in drug shortages, FDA has not substantially 

changed the resources or priority it places on its response to drug 

shortages. Although FDA recognizes the significant public health 

consequences that can result from drug shortages, it has not taken the 

important step of developing metrics that would help it manage the Drug 

Shortage Program. Indeed, the agency does not maintain data in a 

manner that would enhance its ability to understand trends in the 

shortages that are, and are not, occurring. The agency has not identified 

drug shortages as an area of strategic priority, and generally does not 

track its own performance related to preventing or mitigating the effects of 

drug shortages. Therefore, FDA cannot fully understand the extent to 

which its actions are effective. FDA lacks a systematic method to manage 

its complex workload related to drug shortages—and to share this 

information among the many offices within the agency whose efforts must 

be coordinated. Without sufficient data, prioritization, or performance 

metrics, FDA cannot ensure that it is doing all it can to protect the public 

health.

To strengthen FDA’s ability to respond to drug shortages, Congress 

should consider establishing a requirement for manufacturers to report 

potential or actual supply disruptions to FDA. Such notification 

requirements should call for manufacturers to notify FDA of any changes, 

interruptions, or adjustments that could affect the supply of their drugs. 

Congress may also wish to consider providing FDA with the authority to 

seek civil monetary penalties or use other enforcement mechanisms to 

ensure compliance with this requirement.

To strengthen FDA’s ability to protect the public health through its 

response to drug shortages, we recommend that the Commissioner of 

FDA take the following four actions:

• assess the resources allocated to the Drug Shortage Program to 

determine whether reallocation is needed to improve the agency’s 

response to drug shortages;

Matter for 

Congressional 

Consideration 

Recommendations for 

Executive Action
 

Page 44 GAO-12-116 Drug Shortages

• develop an information system that will enable the Drug Shortage 

Program to manage its daily workload in a systematic manner, track 

data about drug shortages—including their causes and FDA’s 

response—and share information across FDA offices regarding drugs 

that are in short supply;

• ensure that FDA’s strategic plan articulates goals and priorities for 

maintaining the availability of all medically necessary drugs—including 

generic drugs; and

• develop results-oriented performance metrics to assess and quantify 

the implementation of the agency’s goals and FDA’s response to drug 

shortages.

In its comments on a draft of this report, HHS acknowledged that drug 

shortages pose serious risks to public health and emphasized the 

agency’s position on addressing this challenge. HHS stated that it 

supports legislation that would require manufacturers to report potential or 

actual supply disruptions to FDA. In addition, HHS outlined its intent to 

take actions that are consistent with our recommendations. For example, 

it noted that it has plans to increase the number of staff working in the 

Drug Shortage Program, and that it has identified some potential 

performance metrics that it may use to gauge the success of FDA’s 

response to drug shortages. We believe that such plans are an important 

first step toward enhancing the agency’s response to drug shortages.

HHS’s comments also stated that FDA has developed a database to 

analyze drug shortages in real time. As noted in our report, we believe 

that the spreadsheet FDA refers to as a database will not enable the 

agency to optimally manage drug shortage information on a systematic 

basis, and we encourage the agency to implement our recommendation 

to develop a more robust information system to manage these data. In 

addition, HHS stated that FDA has prevented 137 drug shortages from 

2010 through September 2011. Our counts of prevented drug shortages 

differ from FDA’s because we consider a prevented shortage of multiple 

versions of the same drug (for example, multiple concentrations of the 

same drug) as one prevented shortage, whereas FDA counted each 

separately. Thus for example, we reported 50 potential shortages avoided 

during the first half of 2011 in contrast to FDA reporting 99.

Agency and ThirdParty Comments and 

Our Evaluation
 

Page 45 GAO-12-116 Drug Shortages

HHS’s comments also cited a number of actions that the Administration 

has taken since receiving our draft report for review. Specifically, while 

our draft report was at HHS for comment, the President issued an 

Executive Order on October 31, 2011, that directs FDA to take steps that 

are intended to support, enhance, and amplify the agency’s response to 

drug shortages.53 The order directed FDA to expand its efforts to expedite 

reviews of applications that would help to prevent or resolve shortages. 

FDA also issued a report summarizing its approach to drug shortages, 

which includes a list of actions the agency should take in order to 

strengthen its response to drug shortages.54 HHS’s Office of the Assistant 

Secretary for Planning and Evaluation also issued a report summarizing 

the economic factors that cause drug shortages.55

HHS’s comments are reprinted in appendix III. We also provided UUDIS 

with excerpts of the draft report related to the number of drug shortages.

We received technical comments from both HHS and UUDIS, which we 

incorporated as appropriate.

We are encouraged by 

the Administration’s response to this issue, and believe its expeditious 

implementation of the recommendations included in our report, as well as 

the executive order and FDA’s report, will serve to strengthen the 

agency’s ability to prevent, alleviate, and resolve drug shortages.

As agreed with your offices, unless you publicly announce the contents of 

this report earlier, we plan no further distribution until 30 days from the 

report date. At that time, we will send copies to the Commissioner of FDA 

and appropriate congressional committees. The report also will be 

available at no charge on the GAO website at http://www.gao.gov. 

 

53Exec. Order No. 13,588, 76 Fed. Reg. 68,295 (Nov. 3, 2011). 

54Food and Drug Administration, A Review of FDA’s Approach to Medical Product 

Shortages (Silver Spring, Md.: Oct. 31, 2011).

55Office of the Assistant Secretary for Planning and Evaluation, Economic Analysis of the 

Causes of Drug Shortages (Washington, D.C.: Oct. 31, 2011). 
 

Page 46 GAO-12-116 Drug Shortages

If you or your staff have any questions about this report, please contact 

me at (202) 512-7114 or crossem@gao.gov. Contact points for our 

Offices of Congressional Relations and Public Affairs may be found on 

the last page of this report. GAO staff who made key contributions to this 

report are listed in appendix IV.

Marcia Crosse

Director, Health Care
Appendix I: FDA Criteria for Determining 

Whether a Drug Is Medically Necessary

Page 47 GAO-12-116 Drug Shortages

FDA’s Drug Shortage Program places the highest priority on responding 

to shortages of medically necessary drugs, since such shortages have 

the greatest potential to impact the public health. FDA defines a medically 

necessary drug as any drug that is used to treat or prevent a serious 

disease or medical condition for which there is no other adequately 

available drug that is judged to be an appropriate substitute.1 To 

determine whether a drug is medically necessary for the purpose of 

prioritizing its response to drug shortages, FDA’s Drug Shortage Program 

requests the input of medical officers in the Office of New Drugs (OND) 

who have relevant expertise with the drug.2

The background questions listed on the form request information about 

the drug, such as its trade name or generic name and the product’s 

formulation(s). It also includes questions about the manufacturer, 

including its name, address, and phone number, and whether the drug is 

available from more than one manufacturer. In addition to requesting this 

background information about the drug, the form includes several 

questions, the responses to which are used to determine whether the 

drug meets the agency’s definition of medically necessary. (See fig. 5.)

Specifically, the Drug 

Shortage Program asks OND medical officers to complete a form that 

requests information about the drug and requests the official’s judgment 

regarding whether the drug meets the agency’s criteria for medical 

necessity. FDA officials told us that they ensure consistency in the 

process by ensuring that each completed form is reviewed by three FDA 

officials who have expertise with the drug before it is finalized and 

provided to the Drug Shortage Program. In addition, FDA officials told us 

that they sometimes consult with health professional organizations such 

as the American Society of Health-System Pharmacists when determining 

whether a drug is medically necessary.

 

1

FDA does not consider patient inconvenience alone as a sufficient reason to classify a 

product as medically necessary. 

2

FDA officials told us that if a drug is used to treat multiple therapeutic conditions, they will 

request the input of multiple medical officers, each of whom would have relevant expertise 

with the drug.

Appendix I: FDA Criteria for Determining 

Whether a Drug Is Medically Necessary
Appendix I: FDA Criteria for Determining 

Whether a Drug Is Medically Necessary

Page 48 GAO-12-116 Drug Shortages

Figure 5: Questions Included on FDA’s Medical Necessity Determination Form
Appendix II: Summary of FDA’s Response to 

15 Selected Drug Shortages

Page 49 GAO-12-116 Drug Shortages

Based on our review of FDA’s response to 15 drug shortages, we found 

that the agency took multiple actions to address the causes of shortages 

and to enhance the drugs’ availability. Specifically, we reviewed FDA’s 

response to shortages involving 5 anti-infective drugs (acyclovir, 

amikacin, cefotetan, clindamycin, and sulfamethoxazole-trimethoprim), 

5 oncology drugs (cisplatin, cytarabine, doxorubicin, etoposide, and 

vincristine), and 5 anesthesia drugs (epinephrine, neostigmine, propofol, 

thiopental, and succinylcholine). At the time of these shortages, FDA 

determined that all 15 drugs involved with the shortages we reviewed in 

detail were medically necessary.1

 

1

Twelve of these drugs are FDA-approved and 3—epinephrine, neostigmine, and 

thiopental—were not FDA-approved as of October 2011. According to FDA, the 3 

unapproved drugs have been marketed in the United States since before 1938, which is 

when the Federal Food, Drug, and Cosmetic Act was enacted. The Act required FDA to 

approve new drugs prior to their being marketed for sale. Because manufacturers of these 

3 drugs have not obtained FDA’s approval, the agency considers the drugs to be illegally 

marketed. FDA estimates that there are as many as several thousand unapproved drug 

products that are marketed illegally. While unapproved drugs are subject to enforcement 

action, FDA gives a higher priority to taking action against unapproved drugs in certain 

categories, such as drugs with potential safety risks and drugs that lack evidence of 

effectiveness. However, FDA officials told us that some unapproved drugs may have 

medically necessary uses.

 Our analysis showed that FDA typically 

used two or more types of actions to respond to each shortage, and for 

8 of these shortages, the agency responded with four or more types of 

actions. For example, during the shortage of doxorubicin, an oncology 

drug, FDA used seven types of actions to respond to the shortage, 

including providing assistance to address manufacturing problems related 

to drug quality issues and providing assistance to address importation 

delays for active pharmaceutical ingredients or finished products. Our 

analysis also showed that while FDA searched for a firm willing and able 

to import a version of the drug in shortage not approved in the United 

States during 7 of the 15 shortages we reviewed, the agency applied its 

regulatory discretion regarding the importation of a version of the drug 

that was not approved in the United States in order to alleviate 

1 shortage. Figure 6 displays FDA’s response to each of the 15 drug 

shortages we reviewed. 

Appendix II: Summary of FDA’s Response to 

15 Selected Drug Shortages
Appendix II: Summary of FDA’s Response to 

15 Selected Drug Shortages

Page 50 GAO-12-116 Drug Shortages

Figure 6: Actions Taken by FDA in Response to Sterile Injectable Drug Shortages That Were Reported Between January 2009 

and June 2011, by Drug Class and Name

Note: Not all potential FDA actions are relevant for every shortage. For example, during a shortage 

caused by a disruption in the supply of an active pharmaceutical ingredient, it would not be necessary 

for FDA to provide assistance to address manufacturing problems.

a

Agency officials told us that although all of these shortages involved medically necessary drugs, 

three did not meet the agency’s criteria for a shortage. While these three shortages did not meet 

FDA’s criteria, all shortages we reviewed in detail were identified by representatives from the 

American Society of Anesthesiologists, American Society of Clinical Oncology, and the Infectious 

Diseases Society of America as recent shortages that had significant impact on patient care or public 

health.
Appendix III: Comments from the Department 

of Health and Human Services

Page 51 GAO-12-116 Drug Shortages

Appendix III: Comments from the 

Department of Health and Human Services
Appendix III: Comments from the Department 

of Health and Human Services

Page 52 GAO-12-116 Drug Shortages
Appendix III: Comments from the Department 

of Health and Human Services

Page 53 GAO-12-116 Drug Shortages
Appendix III: Comments from the Department 

of Health and Human Services

Page 54 GAO-12-116 Drug Shortages
Appendix III: Comments from the Department 

of Health and Human Services

Page 55 GAO-12-116 Drug Shortages
Appendix IV: GAO Contact and Staff 

Acknowledgments

Page 56 GAO-12-116 Drug Shortages

Marcia Crosse, (202) 512-7114, crossem@gao.gov.

In addition to the contact named above, Geraldine Redican-Bigott, 

Assistant Director; Nick Bartine; Zhi Boon; Emily Goodman; Cathleen 

Hamann; Yesook Merrill; Lisa Motley; and Patricia Roy made key 

contributions to this report.

Appendix IV: GAO Contact and Staff 

Acknowledgments 

GAO Contact

Acknowledgments 
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Page 57 GAO-12-116 Drug Shortages

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