p"o....,,._ Ii f U.S. FOOD & DRUG \.:!/­ ADMINISTRATION 

Report on Drug Shortages 

for Calendar Year 2016 

Required by 

Section 1002 ofthe 


Food and Drug Administration Safety and 


Innovation Act 


Food and Drug Administration 


Department ofHealth and Human Services 


Date 5 •

/\0tiI/ \'7 

Scott Gottlieb, M.D. 

Commissioner of Food and Drugs 
Table of Contents 


EXECUTI-VE SUMMARY .......................................................................................................... 1 


INTRODUCTION......................................................................................................................... 2 


BACKGROUND ........................................................................................................................... 2 


1. Executive Order 13588 - Reducing Prescription Drug Shortages ................................ 4 


2. FDA Safety and Innovation Act ....................................................................................... 5 


3. FDA Strategic Plan to Prevent and Mitigate Shortages ................................................. 5 


4. Final Rule - Permanent Discontinuance or Interruption in Manufacturing of 

Certain Drug or Biological Products ....................................................................................... 5 


DAT A SOU.RCES USED IN THIS REPORT ............................................................................ 6 


ANNUAL REPORT REQUIREMENTS PER 506C-1 .............................................................. 6 


CONTINUED DRUG SHORTAGES EFFORTS IN 2016 ...................................................... 11 


1. DSS Shortage Tracker..................................................................................................... 11 


2. FDA Public Communications Regarding Drug Shortages........................................... 12 


3. FDA Drug Shortage Assistance Award.......................................................................... 12 


4. FDA Internal Efforts Regarding Drug Shortages ......................................................... 13 


CONCLUSION ........................................................................................................................... 13 


DEFINITIONS ............................................................................................................................ 14 


APPENDIX 1 ............................................................................................................................... 15 


APPENDIX 2 ............................................................................................................................... 16 


APPENDIX 3 ............................................................................................................................... 17 


2 

EXECUTIVE SUMMARY 


This fourth annual report to Congress summarizes the major actions taken by the Food 

and Drug Administration (FDA) during the first three quarters of 2016 to prevent or 

mitigate drug shortages 1 in the United States. Because drug shortages can pose a 

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

needed care for patients, shortages remain a top priority for FDA. As a result of actions 

by the President, Congress, and FDA, manufacturers are notifying FDA about potential 

shortages earlier than in the past. Early notification of potential shortages gives FDA 

additional time to work with sponsors and other stakeholders to identify ways to maintain 

treatment options and prevent a shortage. Using a range of available tools, including 

regulatory flexibility and discretion when appropriate, FDA's Center for Biologics 

Evaluation and Research (CBER) and FDA's Center for Drug Evaluation and Research 

(CDER) worked with manufacturers to successfully prevent 63 shortages from January 1 

to September 30, 2016. In addition, the number of new shortages tracked by CBER and 

CDER for this same time period is 21, compared to a peak of 251 new shortages during 

the full calendar year o/2011.2 

Based on our experience to date and the data on drug shortages presented in this report, 

FDA believes that the requirements related to early notification of potential shortages and 

FDA's own actions are helping to reduce the threat and impact ofdrug shortages. FDA 

will continue to prioritize this important public health issue, working to ensure the 

availability of necessary drugs and biological products for the American public. 

1 For purposes of this report, the term "drug shortage" includes shortages of human drug and biological 

products. The report may individually refer to shortages tracked by FDA 's Center for Drug Evaluation and 

Research or FDA 's Center for Biologics Evaluation and Research, if the context requires distinguishing 

between these. 

2 This fourth annual report to Congress addresses all covered drug and biological products. This includes 

all drugs within the meaning of section 506C(h)(l) ofthe Federal Food, Drug, and Cosmetic Act (FD&C 

Act), as well as other products tracked by CDER's Drug Shortage Staff, such as biological products 

approved under section 505 ofthe FD&C Act. This also includes biological products licensed under 

section 351 of the Public Health Service Act and tracked by CBER's Office of Compliance and Biologics 

Quality, such as vaccines and blood products. See Appendix 2 for a breakdown of 20 I 6 CBER and CDER 

numbers. 
INTRODUCTION 

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

July 9, 2012. Title X ofFDASIA, which addresses drug shortages, took effect on the 

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

Cosmetic Act (FD&C Act) (21 U.S.C. 301 et seq.) by updating section 506C. Section 

506C sets forth the requirement that manufacturers notify FDA of a permanent 

discontinuance or interruption in the production of certain prescription drugs that are lifesaving, life-sustaining, or intended for use in the prevention or treatment of a debilitating 

disease or condition. In addition, section 1002 ofTitle X ofFDASIA added section 

506C-l to the FD&C Act, requiring FDA to file a report to Congress at the end of each 

calendar year on drug shortages. FDA is submitting this ammal report to fulfill its 

obligations under section 506C-l. The report provides background about drug shortages 

and FDA efforts to address them to date. FDA also responds to the specific issues listed 

under section 506C-1. The analyses reflect data collected and evaluated by FDA's 

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

Evaluation and Research (CDER) from January 1, 2016, through September 30, 2016. 

This report also summarizes some important ongoing activities FDA believes will help to 

address drug shortages in the future. A list of definitions and three appendices, which 

includes the statutory language regarding annual reporting on drug shortages and the 

breakdown ofdata supplied by CBER and CDER, are included at the end ofthis report. 

BACKGROUND 

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

patients, and preventing shortages is a priority for FDA. At the height ofthe drug 

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

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

The following figure shows the number of new drug shortages identified by year from 

2010 through September 30, 2016. 

2 

I 250 ------- .,, 

QI 

tlO 

~ "' 200 +------

~ 

VI 

~ 

~ 150 

-0 

.... 

~ 100 

• CBER 

• CDER

E 

:::J 

I 


z 

0 L-1-.-• ···-·--------, 2010 2011 2012 2013 2014 2015 2016 Q1-Q3 

Calendar Year 


L _______________________ 

20163 

Figure 1. Number of New Drug Shortages Per Year, 2010 Through September 30, 

13~0______ 

­

Although the number of new drug shortages has declined since 2011 as a result ofwork 

by many groups including the FDA, shortages continue to pose a real challenge to public 

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

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

the shortage of intravenous saline solution. These shortages can delay or deny needed 

care for patients, creating a potential lapse in medical care. Shortages can also lead 

prescribers to use second-line alternatives, which may be less effective or pose additional 

risks. To prevent these situations from occurring, FDA has used a variety of methods to 

prevent shortages, working within the confines of the statutory and regulatory framework 

in place and in partnership with manufacturers and other stakeholders. As tracked by 

CDER, FDA helped prevent 282 drug shortages in 2012, 170 shortages in 2013, 10I 

shortages in 2014, and 142 shortages in 2015. In the first three quarters of2016, FDA 

helped to prevent 63 shortages as tracked by CBER and CDER.4 

The following figure shows the number of prevented drug shortages identified by 

year from 2010 through September 30, 2016. 

3 This fourth annual report to Congress is the first year to include both reporting for those covered drug and 

biologic products. See Appendix 2 for a breakdown of2016 CBER and CDER numbers. 

4 See supra n. 2. 

3 

300 

~ 250 QI) 

~ 

~ 

0 

~ 200 

"tJ 

!!! 

c 

QI 150 ~ -+- -----

---·-------------

... • CBER Cl.

-0 • CDER ... 100 QI 

.D 

E 

:I 

z so

0 

2010 2011 2012 2013 2014 2015 2016 Ql-Q3 

Calendar Year 

Figure 2. Number of Prevented Drug Shortages Per Year, 2010 Through 

September 30, 20165 

Several actions have been taken in recent years that helped FDA address drug shortages. 

1. Executive Order 13588 - Reducing Prescription Drug Shortages 

In response to a dramatic increase in shortages, on October 31, 2011, the President issued 

Executive Order 13588, recognizing that "shortages ofpharmaceutical drugs pose a 

serious and growing threat to public health ...endanger patient safety ...burden doctors, 

hospitals, pharmacists, and patients ...and increase health care costs." 6 The Executive 

Order acknowledged the need for a "multifaceted approach" to address the many 

different factors that contribute to drug shortages. The Executive Order directed FDA to 

take steps to help prevent and reduce current and future disruptions in the supply oflifesaving medicines, including notifications and expedited reviews, as appropriate. 

5 This fourth annual report to Congress is the first year to include both reporting for those covered drug and 

biologic products. See Appendix 2 for a breakdown of 2016 CBER and CDER numbers. 

6 Executive Order 13588, available at http://www. whitehouse.govlthe-press-offi ce/20 I Ii I 0/31 /executiveorder-reducing-prescription-drug-shortages. 

4 

2. 	 FDA Safety and Innovation Act 

With the passage of FD ASIA on July 9, 2012, FDA was given important new authorities 

related to drug shortages. For example, section 1001 ofFDASIA broadened the scope of 

the early notification provisions by requiring manufacturers of all prescription drugs 

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

of a debilitating disease or condition (whether approved or unapproved) to notify FDA of 

a pennanent discontinuance or temporary interruption in manufacturing. FDASIA also 

allowed FDA to require, by regulation, early notification of discontinuances or 

interruptions in manufacturing of biologics. FD ASIA requires FDA to send a noncompliance letter to firms that fail to notify FDA in accordance with section 506C, as 

amended by FDASIA. FDA sent the first two letters in 2014, and posted the letters and 

the responses from the manufacturers on its website. As described in more detail below, 

two additional non-compliance letters were sent during the first three quarters of 2016. 

Section 506C also authorizes FDA to expedite reviews of drug applications and 

supplemental applications and to expedite inspections that could help mitigate a shortage. 

Other FDASIA requirements with respect to prescription drug shortages include 

improving FDA's internal and external communications about shortages, improving 

communication between FDA and the Drug Enforcement Administration (DEA) 

regarding shortages of controlled substances, and developing a strategic plan to enhance 

FDA's response to preventing and mitigating drug shortages. 

3. 	 FDA Strategic Plan to Prevent and Mitigate Shortages 

On October 31, 2013, FDA issued its Strategic Plan for Preventing and Mitigating Drug 

Shortages. 7 The plan contains details on the origin of drug shortages, FDA' s processes 

and procedures for helping to prevent or mitigate shortages, and FDA's strategy for 

strengthening those processes and procedures. The plan also recommends actions that 

other stakeholders can consider to help prevent shortages. 

4. 	 Final Rule - Permanent Discontinuance or Interruption in Manufacturing of 

Certain Drug or Biological Products 

On July 8, 2015, FDA published a final rule to implement certain drug shortages 

provisions of section 506C, as amended by FD ASIA. 8 Among other requirements, the 

rule requires all applicants of covered approved drug or biological products, including 

certain applicants of blood or blood components for transfusion, and all manufacturers of 

covered drug products marketed without an approved application to notify FDA 

electronically of a permanent discontinuance or an interruption in manufacturing ofthe 

product that is likely to lead to a meaningful disruption in supply (or a significant 

disruption in supply for blood or blood components) ofthe product in the United States. 

7 To view the Strategic Plan and related information, visit 


http: 1I www.fda. gov IdownloadsiDrugs'DrugSa fety/Orn gS hona ges/U CM3 7 2 5 66. pd f. 


8 80 FR 38915 (July 8, 2015). See also 21CFR310.306, 314.81 , and 600.82. 

5 

The rule became effective on September 8, 2015. As noted above, this fourth annual 

report to Congress includes reporting for all covered drug and biological products. 

DAT A SOURCES USED IN THIS REPORT 

The data used to fulfill the reporting requirements of section 506C-l are collected by 

several program areas within FDA,. Tracking the data for reporting requirements related 

to drugs and biological products (the number ofproducts in shortage) is within the 

purview of CBER's Office ofCompliance and Biologics Quality (CBER/OCBQ) and the 

Drug Shortage Staff (DSS). Similarly, CBER/OCBQ and DSS track information about 

notifications and their source (and, therefore, the number ofreporting manufacturers). In 

contrast, reporting requirements related to expedited review are tied to specific 

submissions by manufacturers that are experiencing production disruptions or 

manufacturers that are adding or expanding their production capabilities to address a 

specific shortage. CBER and CDER offices reviewing these submissions track which 

reviews and related inspections they expedite as a part of a larger set of activities related 

to their review of submissions. Other reporting requirements for this report relate to 

instances ofregulatory flexibility and discretion. These specific cases, all requiring 

separate regulatory and scientific evaluation and justification, are tracked by 

CBER/OCBQ and CDER's Office ofCompliance (CDER/OC). 

ANNUAL REPORT REQUIREMENTS PER 506C-1 

Section 1002 ofTitle X ofFDASIA added section 506C-1 to the FD&C Act, requiring 

FDA to file a report to Congress on drug shortages at the end of each calendar year. 

The statutory requirements for the report are as follows. 

Requirement 1: Specify the number of manufacturers that submitted a 

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

year. 

For the first three quarters of calendar year 2016, FDA was notified of 186 potential drug 

and biological product shortage situations by 67 different manufacturers. 

Requirement 2: Describe the communication between FDA field investigators 

and CDER/OC and DSS, including FDA's procedures for enabling and 

ensuring such communication. 

CDER/OC and the FDA field investigators in the Office ofRegulatory Affairs (ORA) are 

crucial to FDA's prompt response to a drug shortage. These two groups have separate 

functions with respect to drug shortages. Consistent with sections 506D(b) and (c) ofthe 

FD&C Act, CDER/OC communicates with DSS on warning letter and enforcement 

action recommendations being reviewed within CDER/OC. FDA field investigators in 

ORA typically conduct inspections at manufacturing facilities and report on their 

findings. Ifthe investigators identify actions or activities during an inspection that 

6 

warrant a warning letter or enforcement action that could reasonably be anticipated to 

lead to a meaningful disruption in the supply of a drug, information regarding the 

observations and the products manufactured can be relayed to CDER/OC immediately so 

that DSS can begin to assess the supply situation for those products. These procedures 

are critical to FDA's efforts to prevent and mitigate a potential drug shortage. 

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

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

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

district has a District Drug Shortage Coordinator who serves as the point of contact 

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

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

potential to lead to a product shortage (e.g., information obtained during an inspection or 

other field activities). FMD #15 clarified communication roles, responsibilities, and 

expectations related to potential and current product shortage situations between ORA 

and the centers. 

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

mitigate drug shortages. 

Mitigation efforts begin once FDA has confinned that a shortage exists or could occur. 

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

• 	 Identify the extent ofthe shortfall and determine if other manufacturers are 

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

• 	 Expedite FDA inspections and reviews of submissions from manufacturers 

attempting to restore production; 

• 	 Expedite FDA inspections and reviews ofsubmissions from competing 

manufacturers who are interested in starting new production or increasing existing 

production of products in shortage; 

• 	 Exercise temporary regulatory flexibility for new sources ofmedically necessary 

drugs; 

• 	 Work with the affected manufacturers to ensure adequate investigation into the 

root cause ofthe shortage; and 

• 	 Develop risk mitigation measures, such as the use of sterile filters, to allow 

individual batches of a drug product initially not meeting established standards to 

be released. 

FDA can use one or more ofthese mitigation tools, or seek to develop other options, 

depending on the severity ofthe potential shortage and the surrounding circumstances. 

When selecting specific tools, FDA continues to work with the manufacturer to tailor its 

7 

response to the specific situation. As a part of these actions, FDA also frequently 

communicates available information about a potential shortage or existing shortage to 

affected stakeholders and monitors the shortage until it has been resolved. 

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

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

FDA expedited the review of 102 submissions in the first three quarters of 2016.9 

• 	 List the number of establishment inspections or reinspections related to 

mitigation or prevention of a shortage that the Secretary expedited under 

section 506C(g)(2) during such calendar year.10 

Ten FDA inspections were prioritized to address a drug shortage in the first three 

quarters of 2016. 11 

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

alleviate drug shortages. 

If a drug at risk of shortage is a controlled substance, FDA works closely with DEA in 

efforts to prevent or mitigate its shortage. Among other issues, DEA is responsible for 

setting aggregate limits on the amount of each controlled substance that may be 

manufactured and for allocating to each manufacturer a specific percentage ofthe 

aggregate limit (a quota). This tight control over controlled-substance products requires 

FDA and DEA to coordinate when a shortage of a controlled substance is looming. For 

example, FDA may work with DEA to enable a manufacturer to increase its allotted 

quota if this step would help avoid a shortage ofthe product. 

Recognizing this need, FDASIA included provisions on improved coordination and 

communication between FDA and DEA regarding a potential shortage of a controlled 

substance. To help streamline and improve communications, FDA and DEA developed a 

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

including identifying contacts, for efficiently tracking and exchanging relevant 

infonnation. 12 

9 See Appendix 3 for a breakdown of submission types. 

10 Includes prioritized inspections or site reviews for new applications or supplements, which were granted 

expedited review due to drug shortage. 

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

sites that require multiple inspections. 

12 The MOU can be found at 

http:I/www.fda.govIAbout FDAiPartners hi psCoIla bora tions/M emorandao tundersta ndingM 0 UsIDomestic 

M0Us1ucm44009 I.htm. 

8 

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

FDA exercised regulatory flexibility and discretion to prevent or alleviate a 

drug shortage. 

FDA' s standards of safety, efficacy, and quality do not change in a shortage situation. 

FDA' s preferred solution to a shortage is to help ensure that there is a supply of approved 

drugs and biological products sufficient to meet patient demand, as well as meet the 

appropriate quality, safety, and efficacy standards. However, FDA recognizes that there 

can also be risks to patients if treatment options are not available for critical conditions 

and understands the importance of using appropriate tools for a given situation to prevent 

or mitigate a shortage. In appropriate cases, the temporary exercise ofregulatory 

flexibility and discretion has proven to be an important tool in ensuring access to 

treatment options for patients in critical need. 

During the first three quarters of calendar year 2016, FDA has exercised regulatory 

flexibility and discretion in 25 instances, affecting 15 products. 13 Examples ofsituations 

in which FDA has exercised regulatory flexibility and discretion to prevent or mitigate a 

shortage are listed below: 

• 	 FDA has used temporary regulatory flexibility and discretion for medically 

necessary products that present quality issues through the use ofmeasures to 

mitigate the risks associated with those products when weighed against the 

risk to patients of not receiving the drug, as follows: 

Filters are supplied with a product to remove particulate matter, 


Extra testing for product quality or identity is done at the manufacturing 


facility before releasing the product into the marketplace, 


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


and 


Special instructions are provided to health care professionals/patients. 


• 	 FDA has used temporary regulatory flexibility and discretion with regard to 

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

while FDA reviews a supplement/proposed change to address a problem with 

the drug product. 

• 	 FDA has used temporary regulatory flexibility and discretion with regard to 

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

sources, in rare instances when all alternative approaches have been 

exhausted. 

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

product may involve multiple instances of regulatory flexibility. 

9 
• 	 FDA has permitted expanded access to investigational drugs for treatment use 

under an investigational new drug application (IND) (21 CFR 

312.315(a)(3)(ii)) to mitigate a shortage of an approved drug product. 

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

506C(t). 

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

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

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

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

providing the reason for noncompliance and the required information on the 

discontinuance or interruption. Within 45 calendar days ofits original letter to the 

manufacturer, FDA is required to post that letter and any response received on FDA's 

website, 

14 with appropriate redactions to protect trade secrets or confidential commercial 

infonnation, unless FDA determines that the original notification was issued in error or, 

after review ofthe manufacturer' s response, that the manufacturer had a reasonable basis 

for not notifying FDA as required. 

To date, FDA has issued four non-compliance letters under section 506C(f). In 2016, 

two letters were sent on April 19, 2016, to Par Pharmaceutical and Teva Pharmaceuticals. 

The letters sent by FDA and the responses received from the manufacturers are available 

on FDA's website. 

Requirement 7: Specify the number of drug shortages occurring during 2016 

(the first three quarters of 2016). 

The data from CDER' s drug shortage database 15 shows that the number of new shortages 

has significantly decreased in recent years, from 117 in 2012 to 44 in 2013, 44 in 2014, 

and 26 in 2015. Data indicate that this trend continued into 2016. As ofSeptember 30, 

2016, there were a total of 21 new drug and biological product shortages identified.

16 In 

the first three quarters of 2016, FDA prevented 63 drug and biological product shortages. 

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

previous years. FDA identified 97 ongoing CD ER-tracked shortages at the end ofCY 

2013, 74 ongoing CDER-tracked shortages at the end ofCY 2014, and 64 ongoing 

CDER-tracked shortages at the end of CY 2015. As of September 30, 2016, there were 

48 ongoing sh01tages, the lowest number since FDA started collecting such data. 

14 Links to letters of non-compliance with notification requirement can be found at 

http: I/ www. f da. gov /Drugs/ Drug Safety/ DrugSho1iageslucm403 90 2. ht m. 

15 CDER's drug shortage statistics can be found at 

http:/1 www.fda.gov/Drugs. DrugSafety/DrugS hortages/ucm050796.htm. 

16 See Appendix 2 for a breakdown of 2016 CBER and CDER numbers. 

10 

120 

11'1 

QI 

QI) 100 

2013 2014 2015 2016Q1-Q3 

Calendar Year 

l'CI 

+' (5 

..t: 80 "" QI) 

c 

·cs 

QI) 60 

c 

0 

'O 40 _; - ... I QI I .c 

• CBER 

• CDER 

E 

:J 20 i z 

0 ~ ----, 

Figure 3. Number of Ongoing Drug Shortages Per Year, 2013 Through September 30, 

201617 

CONTINUED DRUG SHORT AGES EFFORTS IN 2016 

1. DSS Shortage Tracker 

FDA continues to improve its system for data tracking and analysis for drug shortages 

and last year put into place a system called the CDER Shortage Tracker, which is housed 

within Panorama, a CDER Platform. This system addressed certain recommendations in 

the 2014 Government Accountability Office (GAO) report on drug shortages for further 

enhancing the tracking ofdrug shortage data. 18 The primary function ofthe CDER 

Shortage Tracker is to streamline day-to-day work to identify and mitigate shortages, 

including research, data entry, and data management for DSS. The CDER Shortage 

Tracker is not designed to predict whether a manufacturer or product is at risk of 

shortage. 

While we have been able to link Shortage Tracker to the CDER Informatics Platform, 

certain processes, such as receiving notifications under section 506C ofthe FD&C Act 

and updating the FDA Drug Shortage website, still require manual input spanning 

multiple platforms. The next goal for DSS is to launch an external collaboration portal 

for industry. The CDER Direct NextGen Collaboration Portal will enable sponsors to 

17 This fourth annual report to Congress is the first year to include both reporting for those covered drug 

and biologic products. See Appendix 2 for a breakdown of 2016 CBER and CDER numbers. 

18 GAO's report can be found at http:t/www.gao.gov assets/670/660785.pdf. 

11 

submit drug shortage notifications to FDA based on FDA-validated product information, 

such as National Drug Code (NDC), active ingredient, and product name. The Portal will 

allow industry users to log in, enter their shortage information, and submit notifications 

directly into the CDER Shortage Tracker. This online capability will help to minimize 

manual data entry and track notifications for better drug shortage monitoring and 

mitigation. FDA is currently piloting the NextGen Collaboration Portal and anticipates 

making it available for broader use in 2017. 

2. FDA Public Communications Regarding Drug Shortages 

In March 2015, FDA launched its first mobile application (app) that provided the public 

with easier and faster access to important information about drug shortages. The free 

mobile app is an innovative tool designed to identify current drug shortages, resolved 

shortages, and the discontinuations of drug products. The app provides health care 

professionals and pharmacists with real-time information about drug shortages to help 

them make treatment decisions. Users of this app can search or browse by a drug's brand 

name, generic name, active ingredient, or therapeutic category. The app can also be used 

to report a suspected drug shortage or supply issue to FDA. The mobile app was further 

enhanced in August 2016 for Android devices. Android device users are able to receive 

notifications when there is new or updated information about a shortage of a drug product 

or about a drug within selected therapeutic categories. As of September 30, 2016, there 

have been almost 32,500 installs ofthe Drug Shortage App. 

Further outreach during the first three quarters of 2016 included seven presentations 

given to professional and patient advocacy organizations, industry and trade associations, 

as well as stakeholder groups. 

3. FDA Drug Shortage Assistance Award 

In September 2014, FDA created the FDA Drug Shortage Assistance Award 19 to publicly 

recognize drug companies and manufacturers that have demonstrated a commitment to 

preventing or alleviating drug shortages ofmedically necessary drugs. This award 

recognizes efforts of drug manufacturers who, while maintaining federally mandated 

quality standards, have worked in cooperation with FDA and implemented strategies to 

help provide a steady supply ofmedically necessary drugs for patients at a time when 

c1itical drug shortages pose a challenge for health care providers and patients nationwide. 

FDA hopes that shining a spotlight on the efforts of drug manufacturers that have gone 

above and beyond in this area will encourage other manufacturers to follow suit. 

On April 14, 2016, FDA issued its third Drug Shortage Assistance Award to Eurohealth 

International Sarl, a subsidiary ofHik.ma Phannaceuticals for its efforts related to the 

shortages ofThiotepa for injection and phentolamine mesylate for injection. 

19 Link to FDA Drug Shortage Assistance Award infom1ation can be found at 

hllp: \\ W \\ . foa.go \'1Drugs1DrugSa fety DrugShortagc!'. ucm4 I 5807.htm. 

12 

4. FDA Internal Efforts Regarding Drug Shortages 

The recent establishment ofthe Office of Pharmaceutical Quality (OPQ) within CDER 

created a single unit dedicated to product quality by improving FDA's oversight of 

quality throughout the lifecycle of a drug product. DSS has important and frequent 

interactions with OPQ as well as CDER/OC to assess drug shortage risk at manufacturing 

sites as a preventative effort to address shortages. 

DSS also works closely with CDER ·s Office of Generic Drugs (OGD) on sho1tage 

mitigation and prevention efforts and, when a product quality review is involved, DSS 

and OGD work with OPQ to ensure coordination across offices. OGD works 

expeditiously to review and approve abbreviated new drug applications (ANDAs) and 

ANDA supplements for drug products that are in shortage. 

Likewise, CBER/OCBQ has procedures similar to CDER/OC and DSS, and works 

closely with all CBER product review offices concerning shortage mitigation and 

prevention efforts. CBER/OCBQ also works to facilitate and ensure coordination across 

CBER product review offices. 

CONCLUSION 

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

priority for FDA. To address them, FDA is working with other partners to help prevent 

shortages from occurring and to mitigate the impact of shortages that cannot be 

prevented. As a part of this work, early and open dialogue between FDA and 

manufacturers is critical to our success. Because of important actions taken by the 

President and Congress, FDA has been able to learn of possible shortages before they 

occur and take steps to prevent or mitigate them. During the first three quarters of2016, 

FDA helped prevent 63 potential new shortages, and there were only 21 new shortages 

for the first three quarters of 2016. 

20 While important progress has been made in 

preventing drug shortages from occurring, and decreases have been seen in the total 

numbers ofshortages, FDA continues to work to ensure that patients in the United States 

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

continue our important work to prevent or mitigate drug shortages. 

20 This fourth annual report to Congress is the first year to include both reporting for those covered drug 

and biologic products. See Appendix 2 for a breakdown of 2016 CBER and CDER numbers. 

13 

DEFINITIONS 

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

demand for the drug within the United States exceeds the supply ofthe drug. 

Biological Product Shortage: A biological product shortage means a period oftime 

when the demand or projected demand for the biological product within the United States 

exceeds the supply ofthe biological product. 

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

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

manufacturer that is more than negligible and affects the ability ofthe manufacturer to fill 

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

interruption in manufacturing due to matters such as routine maintenance and does not 

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

resume operations in a short period oftime. 

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

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

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

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

interruptions in manufacturing due to matters such as routine maintenance or 

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

operations in a short period oftime. 

Life Supporting or Life Sustaining: L~fe supporting or life sustaining is used to 

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

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

continuation ofhuman life. 

14 

APPENDIX l 

SEC. 506C-l. ANNUAL REPORTING ON DRUG SHORTAGES. 

(a) ANNUAL REPORTS TO CONGRESS.- Not later than the end of calendar year 

2013, and not later than the end of each calendar year thereafter, the Secretary shall 

submit to the Committee on Energy and Commerce ofthe House of Representatives 

and the Committee on Health, Education, Labor, and Pensions of the Senate a report on 

drug shortages that­

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

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

(2) describes the conununication between the field investigators ofthe Food and Drug 

Administration and the staff ofthe Center for Drug Evaluation and Research's Office 

of Compliance and Drug Shortage Program, including the Food and Drug 

Administration's procedures for enabling and ensuring such communication; 

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

shortages described in paragraph (7); 

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

(i) the number of applications and supplements for which the Secretary 

expedited review under section 506C(g)(l) during such calendar year; and 

(ii) the number of establishment inspections or reinspections that the 

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

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

Enforcement Administration on efforts to prevent or alleviate drug shortages; 

(5) identifies the number of and describes the instances in which the Food and Drug 

Administration exercised regulatory flexibility and discretion to prevent or alleviate a 

drug shortage; 

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

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

identified by the Secretary. 

15 

APPENDIX2 

Breakdown ofCDER and CBER Shortage Numbers, Ql-Q3, 2016 

CDER CBER 

NEW SHORTAGES 20 1 

PREVENTED SHORTAGES 54 9 

ONGOING SHORTAGES 46 2 

NOTIFICATIONS 162 24 

NO. OF MANUFACTURERS 50 17 

NOTIFYING 

ACTIONS TAKEN TO MITIGATE SHORTAGES 

REGULATORY FLEXIBILITY 24 1 

AND DISCRETION 

EXPEDITED REVIEWS 96 6 

EXPEDITED INSPECTIONS 10 0 

16 
APPENDIX3 

Breakdown of Expedited Reviews by Submission Type 

CDER NDA/NDA SUPPLEMENTS 

CDER ANDA/ANDA SUPPLEMENTS 

CDER BLA/BLA SUPPLEMENTS 

CBER BLA/BLA SUPPLEMENTS 

EXPEDITED REVIEWS 

17 

78 

1 

6 

17