Selection of the Appropriate 
Package Type Terms and 
Recommendations for 
Labeling Injectable Medical 
Products Packaged in 
Multiple-Dose, Single-Dose, 
and Single-Patient-Use 
Containers for Human Use  
Guidance for Industry 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER)  
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
Office of Combination Products 
October 2018
Pharmaceutical Quality/CMC 
1816211 FNL  Selection of the Appropriate Package Type Terms and 
Recommendations for Labeling Injectable Medical 
Products Packaged in Multiple-Dose, Single-Dose, 
and Single-Patient-Use Containers for Human Use  
Guidance for Industry 
Additional copies are available from: 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor 
Silver Spring, MD 20993-0002 
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
and/or 
Office of Communication, Outreach and Development 
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
and/or 
Office of the Center Director 
Center for Devices and Radiological Health 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 66, Room 5431 
Silver Spring, MD 20993-0002 
Email: CDRH-Guidance@fda.hhs.gov 
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm 
and/or 
Office of Combination Products 
Office of Special Medical Programs 
Office of the Commissioner 
Food and Drug Administration 
10903 New Hampshire Avenue, WO-32 Hub 5129 
Silver Spring, MD 20993-0002 
(Tel) 301-796-8930 (Fax) 301-796-8619 
http://www.fda.gov/CombinationProducts/default.htm 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
Office of Combination Products 
October 2018
Pharmaceutical Quality/CMC    Contains Nonbinding Recommendations     
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  DISCUSSION .................................................................................................................... 3 
Definitions ............................................................................................................................................... 3 
1. Single-Dose Container. .................................................................................................................... 3 
2. Multiple-Dose Container. ................................................................................................................ 3 
3. Single-Patient-Use Container. ......................................................................................................... 5 
IV.  LABELING REQUIREMENTS AND RECOMMENDATIONS ................................ 6 
A.    Change from single-use to single-dose package type term ................................................. 7 
B.    All other changes to a package type term .................................................................................... 7 
C.    Changes made to add a package type term to the container/carton labeling (and, in some 
cases, the prescribing information) when no package type is included (or listed) ................... 7 
D.    Any other proposed changes in package type terminology ........................................................ 8 
E.    Addition of a discard statement or changes to an existing discard statement .......................... 8 
i  Contains Nonbinding Recommendations 
 
Selection of the Appropriate Package Type Terms and 
Recommendations for Labeling Injectable Medical Products 
Packaged in Multiple-Dose, Single-Dose, and Single-Patient-Use 
1
Containers  for Human Use 
2
Guidance for Industry  
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
I.  INTRODUCTION  
 
This guidance provides industry with the Food and Drug Administrations (FDAs) 
recommendations on the selection of appropriate package type terms and selection of appropriate 
discard statements3 for injectable medical products for human use, packaged in multiple-dose, 
 
single-dose, and single-patient-use containers.  Specifically, this guidance provides FDAs 
revised definitions for single-dose and multiple-dose containers as well as for the new package 
type term single-patient-use container.4  These containers may be part of a drug, a biological 
product, or a combination product assigned to CDER, CBER, or certain combination products 
assigned to CDRH.5 Marketing applications for such products include:  New Drug Applications 
(NDAs), Abbreviated New Drug Applications (ANDAs), Biologics License Applications 
(BLAs), Premarket Approval Applications (PMAs), Premarket Notifications under section 
510(k) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), and requests for classification 
submitted under section 513(f)(2) of the FD&C Act (De Novo request). 
 
                                                 
1 The term container in this guidance refers to all package types used for injectable medical products for human use. 
This guidance does not discuss all package type terms (e.g., Pharmacy Bulk Package).  Please refer to United States 
Pharmacopeia (USP) General Chapter <659> Packaging and Storage Requirements for other package type terms. 
2 This guidance has been prepared by the Office of Pharmaceutical Quality in the Center for Drug Evaluation and 
Research (CDER) in cooperation with the Center for Biologics Evaluation and Research (CBER), the Center for 
Devices and Radiological Health (CDRH), and the Office of Combination Products in the Office of the 
Commissioner at the Food and Drug Administration. 
3 This guidance is intended to provide recommendations on the selection of discard information for containers.  It 
does not provide information on disposal instructions.  Discard information is a statement supported by appropriate 
data on when to stop using an injectable medical product.  Disposal information is a statement on how to safely and 
appropriately destroy any unused injectable medical product. 
4 For the purpose of this guidance, such products are referred to as medical products. Diluents used to reconstitute or 
dilute human drug and biological products are also considered to be medical products. 
5 See 21 CFR 3.2. Combination products are composed of a drug, device, and/or a biological product.  For 
information on center assignment, see 21 CFR 3.4. 
  1 
  Contains Nonbinding Recommendations 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required.  
 
II.  BACKGROUND 
 
Unsafe injection practices, including the use of needles or syringes for more than one patient or 
the improper use of medication vials for more than one patient, threaten patient safety and have 
resulted in multiple blood borne bacterial and viral infection outbreaks.  Bacterial and viral 
infections have been transmitted to patients when single-dose containers were used improperly, 
the contents became contaminated and these contents were then administered to multiple 
patients.  Failure to follow standard precautions and aseptic techniques has also been associated 
with several outbreaks of infections involving multiple-dose vials.  Examples of such incidents 
with single-dose and multiple-dose vials are: 
 
  From 1998 through 2008, patient to patient transmission of blood borne pathogens due to 
unsafe injection practices resulted in 33 outbreaks of viral hepatitis in nonhospital health 
care settings in the United States.6 
 
  According to the Centers for Disease Control and Prevention (CDC), at least 26 incidents 
involving the improper use of single-dose medications in outpatient settings have 
occurred over a five year period resulting in the potential exposure of more than 95,000 
patients to infectious diseases.7 
 
  In 2002, 71 cases of hepatitis C virus (HCV) infection and 31 cases of hepatitis B virus 
  infection were attributed to unsafe needle/syringe practices in an Oklahoma pain clinic.8 
 
  In 2008, an investigation of an HCV outbreak in Nevada revealed that reuse of syringes 
in multiple patients and use of single-use medication vials for multiple patients were the 
likely mechanisms by which HCV infections were transmitted.9 
 
It is evident from the examples described above that single-dose containers, which are intended 
for use for a single patient, have been used for more than one patient in the past, and that this 
practice has contributed to many of these bacterial and viral infection outbreaks.  Additionally, 
there is a concern that existing package type terms do not adequately convey that some 
                                                 
6 Thompson, ND, et al. 2009, Nonhospital Health Care-Associated Hepatitis B and C Virus Transmission: United 
States, 1998-2008. Ann Int Med; 150:33-39. 
7 CDC: Injection Safety, 2012, CDCs position-protect patients against preventable harm from improper use of 
single-dose/single-use vials. Atlanta, GA: US Department of Health and Human Services. Available at: 
http://www.cdc.gov/injectionsafety/cdcposition-singleusevial.html. 
8 Comstock RD, et al. 2004, A Large Nosocomial Outbreak of Hepatitis C and Hepatitis B Among Patients 
Receiving Pain Remediation Treatments. ICHE; 25:576-583. 
9 CDC: 2007, Acute hepatitis C virus infections attributed to unsafe injection practices at an endoscopy clinic- 
Nevada. MMWR 2008; 57:513-7. Available at:  http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5719a2.htm. 
  2 
  Contains Nonbinding Recommendations 
 
containers (e.g., insulin pens) that provide multiple doses are intended for use for only a single 
patient.10 
 
III.  DISCUSSION     
 
As part of its review of medical products, FDA clears or approves package type terms and 
discard statements as part of the labeling of injectable medical products.  FDA believes that 
consistent use of correct package type terms and discard statements for injectable medical 
products for human use will promote their proper use and provide a foundation for educational 
efforts to reduce the transmission of blood borne pathogens.  The following sections describe the 
appropriate package type terms for multiple-dose, single-dose, and single-patient-use containers 
that may be part of injectable drug and biological products for human use, CDER-led, CBER-led, 
or certain CDRH-led combination products for injection, and diluents used to reconstitute or 
dilute human drug and biological products. 
 
Definitions 
 
The package type terms single-dose container and multiple-dose container have been in use 
for a long time.  To provide clarity on the intended use of these terms, the definitions are being 
revised as follows: 
 
1.  Single-Dose Container:  A single-dose container is a container of a sterile 
medication11 for parenteral administration (injection or infusion) that is not 
required to meet the antimicrobial effectiveness testing requirements.  A single-
dose container is designed for use with a single patient as a single injection/ 
infusion.  When space permits, a single-dose container is labeled as such and 
should include on the label appropriate discard statements.  Examples of single-
dose containers are vials, ampules, and prefilled syringes. 
 
2.  Multiple-Dose Container:12 A multiple-dose container is a container of a 
sterile medication13 for parenteral administration (injection or infusion) that has 
met antimicrobial effectiveness testing requirements, or is excluded from such 
testing requirements by FDA regulation.14  A multiple-dose container is intended 
                                                 
10 In March 2009, in response to reports of improper use of insulin pens in hospitals, FDA issued a Safety Alert for 
health care professionals reminding them that insulin pens are meant for use on a single patient only and are not to be 
shared between patients. Available at: 
https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInfor
mationforHeathcareProfessionals/ucm133352.htm. 
11 The term sterile medication applies to both active drug products and diluents. 
12 The term multi-dose may be used instead of multiple-dose. 
13 See footnote 11. 
14 Antimicrobial effectiveness testing determines whether the product prevents microbial growth if contamination of 
the container occurs during patient use conditions.  Some injectable chemical formulations may possess sufficient 
inherent antimicrobial effectiveness characteristics without the addition of a preservative, while other products rely 
on the addition of a preservative to meet this requirement.  However, certain specially designed packaging and 
delivery systems or certain radiopharmaceuticals with short expiration dates permit the use of preservative-free injectable 
 
  3 
  Contains Nonbinding Recommendations 
 
to contain more than one dose of the drug product.  When space permits, a 
multiple-dose container is labeled as such.  Multiple-dose containers are generally 
expected to contain 30 mL or less of medication.15  The beyond-use date16 for an 
opened or entered (e.g., needle-punctured) multiple-dose container is 28 days, 
unless otherwise specified by the manufacturer on the label.17, 18  An example of a 
multiple-dose container is a vial. 
 
In the vast majority of cases, the package type terms single-dose and multiple-dose are 
properly used.  However, in some unique situations, a package contains multiple doses of a 
medical product that is intended to be for use in a single patient.  The medical product in this 
package type may not contain a preservative or be able to pass antimicrobial effectiveness if 
tested, yet this package type contains multiple doses for use in a single patient.  An example of 
this package type is a drug intended for intrathecal administration that is packaged in a patient-
controlled analgesia cartridge.  Because the package type is designed to administer multiple 
doses, the package type term single-dose is not appropriate.  However, the package type term 
multiple-dose is also inappropriate because the package contents are not able to meet 
antimicrobial effectiveness testing requirements. 
 
In other cases, the medical products in this package type do contain a preservative and are 
expected to pass antimicrobial effectiveness if tested, yet the intent is that the package is to be 
restricted to use by a single patient.  In this scenario, referring to the package type as multiple- 
dose does not adequately convey the intent to restrict the use to a single patient.  An example 
of such a product is an insulin pen that contains multiple doses of insulin for individual patient 
use. 
 
In the past, the term single-use container has been used by FDA to describe a package type 
that contained multiple doses but was intended to be used in a single patient.  Unfortunately, the 
term single-use was also inappropriately used as if it were interchangeable with the term 
single-dose which was not the Agencys original intent.  To address this confusion regarding 
the terminology, the Agency is retiring the term single-use and a new package type term 
single-patient-use container, has been created to address the need for describing a package that 
contains multiple doses of an injectable medical product that is intended to be used in a single 
patient. 
 
                                                                                                                                                             
products for multiple patient uses.  While most multiple dose biological products require a preservative, 21 CFR 
610.15 provides for a few exceptions. 
15 United States Pharmacopeia-National Formulary (USP-NF-) <659> PACKAGING AND STORAGE 
REQUIREMENTS, Injection Packaging. 
16 Beyond-use date (BUD) is the date or time beyond which a product should not be used. See USP-NF <7> 
LABELING, Expiration Date and Beyond-Use Date. 
17 See 
https://www.jointcommission.org/standards_information/jcfaqdetails.aspx?StandardsFaqId=1091&ProgramId=46. 
18 Vaccines in multiple-dose vials should be used and disposed of according to their FDA approved product labeling. 
Unless a multiple-dose vial is labeled otherwise, vaccines supplied in multiple-dose vials may be used up to the date 
of expiry of the product.  See also  http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm. 
  4 
  Contains Nonbinding Recommendations 
 
3.  Single-Patient-Use Container: A single-patient-use container is a 
container of a sterile medication19 for parenteral administration (injection or 
infusion) that is intended to be used multiple times for a single patient.  When 
space permits, a single-patient-use container is labeled as such and should include 
on the label appropriate discard statements.  Examples of single-patient-use 
containers are patient controlled analgesia cartridges and certain pens for 
injection. 
 
For multiple-dose and single-patient-use containers, the antimicrobial effectiveness testing 
results, if performed, will be used to support the labeled beyond-use date or discard statements. 
 
The following diagram illustrates how the appropriate package type term for an 
injectable medical product can be determined: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Use of the term single-dose container does not imply the entire contents of the container constitute a single dose. 
In some instances, a single-dose container may contain more drug than is required for a single dose or multiple vials 
may be needed to obtain a single dose. For example, for a medical drug product that is dosed based on body weight, 
or due to the required overfill in vials and ampules, there may be excess amount constituting more than one dose in 
the container, which should be discarded. Please refer to FDAs guidance for industry on Allowable Excess Volume 
and Labeled Vial Fill Size in Injectable Drug and Biological Products.20  Furthermore, although dosed over an 
extended time period, infusion containers (large or small volume) are considered single-dose containers because 
they are designed for use with a single patient as a single infusion. 
 
 
                                                 
19 See footnote 11. 
20 This guidance is available on the Internet at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm under Guidances 
(Drugs). 
  5 
  Contains Nonbinding Recommendations 
 
IV.  LABELING REQUIREMENTS AND RECOMMENDATIONS 
 
Applicants should determine the proper package type term (single-dose, multiple-dose, or 
single-patient-use) for injectable medical products for human use and use only the correct 
term for the package type throughout the labeling.  FDA recommends that the appropriate 
package type term appear on all components of the labeling of injectable medical products for 
human use so the user will be able to easily identify the package type.  This includes the 
container label and carton labeling, prescribing information, and where applicable, labeling 
intended for the patient.21 
 
The package type term single-dose is required to appear on the container labels of single-dose 
injectable medical products that have a United States Pharmacopeia (USP) monograph, when 
space permits (FD&C Act section 502(g) (21 U.S.C. 352(g)).22  When space does not permit the 
single-dose term to appear on such products container labels, then according to 21 CFR 
201.10(i)(2), it must appear on the carton or other outer container or wrapper, if space permits, 
or in the prescribing information.  In FDAs experience, there has always been sufficient space 
to include this information on the carton labeling. 
 
When space permits, the appropriate package type term should appear on the container label of 
multiple-dose and single-patient-use injectable medical products, as well as single-dose 
injectable medical products that do not have a USP monograph.  If there is insufficient space to 
include this information on the container label, the package type term should appear on the 
carton labeling where it will be easily visible. 
 
When appropriate, the prescribing information for single-patient-use and single-dose 
injectable medical products should include a discard statement.23  The discard statement 
should also be included on the container label and carton labeling, when space permits.  For 
example, single-dose container labeling should typically include the statement Discard 
unused portion. 
 
Multiple-dose containers do not normally have a discard statement because the beyond-use date 
is assumed to be 28 days for an opened or entered (e.g., needle-punctured) multiple-dose 
container, unless otherwise indicated.24  If the beyond-use date is other than 28 days for a 
product in a multiple-dose container, an appropriate discard statement (supported by 
appropriate data) should be included on the container label, carton labeling, and in the 
                                                 
21 Examples of sections within the prescribing information for drug products where the package type term may 
appear include, but are not limited to: DOSAGE AND ADMINISTRATION, DOSAGE FORMS AND 
STRENGTHS, DESCRIPTION, and HOW SUPPLIED/STORAGE AND HANDLING (21 CFR 201.56 and 
201.57). 
22 21 U.S.C. section 352(g); The following statement A single-dose container shall be labeled as such.... appears in 
United States Pharmacopeia-National Formulary (USP-NF), <7> Labeling, and a similar phrase ...a single-dose 
container is labeled as such.... appears in <659> Packaging and Storage Requirements. 
23 This statement should be placed in the DOSAGE AND ADMINISTRATION, Preparation Instructions section of 
the prescribing information and, when applicable, in patient labeling such as the INSTRUCTIONS FOR USE. (21 
CFR 201.56, and 201.57). 
24 See footnotes 17, 18. 
  6 
  Contains Nonbinding Recommendations 
 
prescribing information.  Examples of statements that might appear on multiple-dose containers 
include: 
 
  Discard within XX hours after opening or after assembly or 
 
  After first use, refrigerate or keep at a temperature not greater than XX for XX days. 
 
The Agency recommends that applicants make the necessary labeling changes to follow these 
recommendations within two years of the publication of this guidance.  All submissions (annual 
reports and supplements) should clearly identify the change(s) being made.  In addition, a 
supplement submission to follow the recommendations in the guidance should be identified as 
Labeling Changes to Follow the Package Type Term Guidance.  For approved applications, 
changes made to labeling to follow the recommendations in this guidance should be submitted to 
the FDA as described below:25 
 
A.  Change from single-use to single-dose package type term 
 
For a drug product that was designed and otherwise labeled for use with a single patient as a 
single injection/infusion, a change from the package type term single-use to single-dose 
to accurately reflect the package type should be submitted in an annual report.  See 21 CFR 
314.70(d)(2)(x); 21 CFR 314.94(a)(8)(iv) and 21 CFR 601.12(f)(3)(i)(A).26 
 
B.  All other changes to a package type term 
 
ALL other changes to a package type term, including a change from the package type term 
single-use to single-patient-use, as well as a change from multiple-dose to single-
patient-use should be submitted as a Prior Approval Supplement (PAS) for NDAs and BLAs 
only.  See 21 CFR 314.70(b)(2)(v)(A); and 21 CFR 601.12(f)(1). 
 
After FDA approval of a PAS for an NDA, the holders of any ANDAs that relied upon the  
NDA as the reference listed drug (RLD) are required to submit conforming labeling revisions.  
See 21 CFR 314.94(a)(8)(iv) and 21 CFR 314.150(b)(10).  FDA is specifically requesting that 
these conforming ANDA labeling revisions be submitted in a Changes Being Effected (CBE-
0) supplement.  See 21 CFR 314.70(c)(6)(iii)(E).  If approval of the NDA for the RLD has 
been withdrawn, the corresponding ANDA holders should submit a PAS to propose changes to 
a package type term. 
 
C.  Changes made to add a package type term to the container/carton labeling (and, 
in some cases, the prescribing information) when no package type is included (or 
listed) 
 
                                                 
25 This information is specific for NDAs, ANDAs, and BLAs.  For information on other cleared or approved 
medical products regulated by CBER or CDRH, contact the appropriate Center. 
26 This discussion of potential regulatory pathways for submission assumes that the change in package type term 
from single-use to single-dose is the only change being made to the labeling.  Other changes may require 
submission of a supplement. 
  7 
  Contains Nonbinding Recommendations 
 
1.   If the prescribing information already includes the appropriate assigned package 
type but the container/carton labeling lacks the designation for some reason other 
than lack of space, NDA, BLA, and ANDA holders may submit the addition of the 
package type term to the container/carton labeling in an annual report under 21 CFR 
314.70(d)(2)(x), and 21 CFR 601.12(f)(3)(i)(A), as long as the package type term 
being added to the container/carton labeling is the same correct term that has 
already been included in the approved prescribing information.  The same 
procedure applies if the container/carton labeling includes the appropriate assigned 
package type but the prescribing information lacks the designation. 
 
2.   If neither the container/carton labeling nor the prescribing information has a 
package type term listed, NDA and BLA holders should submit a PAS to add the 
appropriate term to the container/carton labeling and prescribing information, see 21 
CFR 314.70(b)(2)(v)(A) and 21 CFR 601.12(f)(1).  After FDA approval of the PAS 
for the NDA RLD, corresponding ANDA holders are required to submit conforming 
labeling revisions.  See 21 CFR 314.94(a)(8)(iv) and 21 CFR 314.150(b)(10).  FDA 
is specifically requesting that these conforming ANDA labeling revisions be 
submitted in a CBE-0 supplement.  See 21 CFR 314.70(c)(6)(iii)(E).  If approval of 
the NDA for the RLD has been withdrawn, the corresponding ANDA holders should 
submit a PAS to propose a package type term.  
 
D.  Any other proposed changes in package type terminology 
 
For any other proposed changes regarding package type terms, please contact the Agency.27 
 
  E.  Addition of a discard statement or changes to an existing discard statement 
 
1.  Discard unused portion   
The addition of or change to the phrase Discard unused portion in the labeling 
of a single-dose container should be submitted in an annual report.  See 21 CFR 
314.70(d)(2)(x); 21 CFR 314.94(a)(8)(iv) and 21 CFR 601.12(f)(3)(i)(A).28 
 
2.  Any other proposed change in a discard statement 
For any other proposed change regarding a discard statement, please contact the 
Agency.29 
 
                                                 
27 See footnote 25. 
28 See footnote 25. 
29 When the submission is for an NDA or BLA, contact the specific drug products review division with questions.  
When the submission is for an ANDA, submit questions as a General Correspondence to the application. 
  8