Guidance for Industry
 

Dosage Delivery Devices for
 

Orally Ingested OTe Liquid
 

Drug Products
 

U.S. Department of Health and Human Services
 

Food and Drug Administration
 

Center for Drug Evaluation and Research (CDER)
 

May20n
 

Compliance
 
Guidance for Industry
 

Dosage Delivery Devices for
 

Orally Ingested OTe Liquid
 

Drug Products
 

Additional copies are available from: 

Offce of 
 Communications 

Division of 
 Drug Information, W051, Room 2210 

Food and Drug Administration 

10903 New Hampshire Ave. 

Silver Spring, MD 20993-0002 

Phone: 301-796-3400; Fax: 301-847-8714
 

http://www.fda.gov/cder/guidance/inde.Y.htm 

Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

U.S. Department of 


May 2011
 

Compliance
 
TABLE OF CONTENTS
 

I. INTRODUCTION .............................................................................................................1
 

II. BACKGROUND ................................................................................................................2
 

III. REGULATORY/POLICY DISCUSSION.......................................................................2
 

A. Statutory Requirements and Regulatory History .......................................................................2
 

B. Recommendations ..........................................................................................................................3
 

APPENDIX A: EXAMPLES OF DOSAGE CUPS THAT DO NOT CORRSPOND TO 

DOSAGE DIRECTIONS ..............................................................................................................7
 

APPENDIX B: EXAMPLE OF DOSAGE CUP THAT CORRSPONDS TO DOSAGE
 

DIRECTIONS ..............................................................................................................................11
 
Contains Nonbinding Recommendations 

Guidance for Industryl 

Dosage Delivery Devices for Orally Ingested OTe Liquid
 

Drug Products
 

This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It 

does not create or confer any rights for or on any person and does not operate to bind FDA or the public. 

You may use an alternative approach if it satisfies the requirements of 
 the applicable statutes and 

regulations. If you want to discuss an alternative approach, contact the FDA staff 
 responsible for 

implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate 

number listed on the title page of this guidance. 

I. INTRODUCTION
 

This document is intended to provide guidance to firms that are manufacturing, marketing, or 

distributing orally ingested over-the-counter (OTC) liquid drug products (e.g., elixirs, 

suspensions, solutions, syrups) that are packaged with dosage delivery devices (e.g., calibrated 

cups, droppers, syringes, spoons)? Because written, printed, or graphic matter appearing on 

dosage delivery devices packaged with aTC liquid drug products is considered labeling, such 

markings on these devices must not be false or misleading and must be clear and consistent with 

the drug product's directions for use. (See sections 201 the Federal (m), 502(a) and 502(£)(1) of 


Food, Drug, and Cosmetic Act.) 

FDA's guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidance documents describe the Agency's 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. 

i This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) at the Food and Drug 

Administration.

2 This guidance is not intended to address the adequacy of dosage delivery devices to deliver the labeled dosage. It 

is the responsibility of the manufacturers, packers, and distributors of 
 these liquid drug products packaged with 

dosage delivery devices to ensure that the accompanying dosage delivery devices accurately deliver the doses 

identified by the measurements. FDA may issue additional guidance regarding the adequacy of dosage delivery 

devices to deliver the labeled dosage and to ensure that consumers can properly use dosage delivery devices that 

accompany aTC liquid drg products. 
Contains Nonbinding Recommendations 

II. BACKGROUND
 

Many orally ingested aTC liquid drug products are packaged with dosage delivery devices 

intended to facilitate proper dispensing of the product by the patient, parent, or caregiver. In 

most cases, these devices have calibrated units of measure marked on the device (e.g., teaspoon,

tablespoon, or mililiter) that are intended to ensure proper measurement of the appropriate dose.
 

However, many orally ingested aTC liquid drug products in the marketplace are packaged with 

dosage delivery devices that bear markings that are inconsistent with the labeled dosage 

directions. For example: 

. A provided dosage device may contain superfluous liquid measure markings that are not 

referred to in the product's labeled dosage directions. 

. A provided dosage device may be missing necessary liquid measure markings that are
 

referred to in the product's labeled dosage directions. 

. There may be inconsistencies in the language used (e.g., "teaspoon" versus "tsp") in a 

product's labeled dosage directions and the provided dosage device. 

There have been numerous reports of accidental overdose that were attributed, in part, to liquid 

measure markings on dosage cups provided with orally ingested aTC liquid drug products that 

were misleading or incompatible with the labeled dosage directions for use. In addition, these 

diffculties may lead consumers to use less accurate means (e.g., household spoons) to give 

children medication, leading to underdosing or overdosing. FDA is especially concerned 

because orally ingested aTC liquid drug products are frequently intended to be used in pediatric 

patients. 

FDA is issuing this guidance because of ongoing safety concerns about the serious potential for 

drug overdoses of orally ingested aTC liquid drug products that can result from the use of 

dosage delivery devices with markings that are inconsistent or incompatible with the labeled 

dosage directions for aTC drug products. 

III. REGULATORY/POLICY DISCUSSION
 

A. Statutory Requirements and Regulatory History
 

Section 502 of 
 the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C 352) states that 

a drug is considered to be misbranded: 

its labeling is false or misleading in any particular (or) . . . (a) if 


adequate directions for use. . . . (f) unless its labeling bears (1) 


the FD&C Act further defines labeling as "all labels and other written, 

printed, Or graphic matter (l) upon any article or any of its containers or wrappers, or (2) 

accompanying such article" (21 U.S.C 321(m)). The Agency considers any written, printed, or 

graphic matter, including measurements on dosage delivery devices, packaged with aTC liquid 

drug products to be labeling. FDA has issued notices and Warning Letters that cite misbranding 

Section 201(m) of 


violations under section 502(a) of 
 the FD&C Act (21 U.S.C. 352(a)) when markings on dosage

2 
Contains Nonbinding Recommendations 

delivery devices are inconsistent with the labeled dosage directions. Examples include the 

following: 

. On December 9, 1991, FDA issued a Compliance Notice to alert all drugestablishrents that 

were registered with the Agency to review the labeling of all drug products marketed with an 

the product's labeling was compatible 

with the markings on the dosage device, and make corrections where necessary. 

accompanying dosage delivery device to determine if 


In this notice, FDA said that dosage delivery devices that had markings inconsistent with the 

product's labeling rendered the drug product misbranded under 21 u.s.e. 352(a). 

. On January 21, 1992, FDA issued a Public Health Announcement warning parents against
 

the inadvertent overdosing of children with liquid OTe medications for colds and flu. 

. Between November 1991 and January 1992, FDA issued Warning Letters to five firms that 

were marketing OTe liquid drug products with dosage delivery devices that were not 

compatible with the products' labeled dosage directions. Those letters cited violations of 

the FD&e Act (21 u.s.e. 352(a)) because the markings on the dosage cups 

packaged with the products were misleading within the context of the labeled directions for 

use. Eight firms initiated recalls of over 980,000 retail units nationwide of OTe oral liquid 

drug products that had misleading or incompatible dosage delivery devices during the same 

time period. Since January 1992, several other firms have conducted large-scale recalls of 

section 502(a) of 


OTe oral 
 liquid drug products with misleading or incompatible dosage delivery devices.

. On January 17,2008, FDA issued a Public Health Advisory recommending that when giving 

OTe cough and cold medicines to children ages 2 years and older, parents and caregivers use 

only the measuring spoons or cups that corne with the medicine or those made specially for 

measuring drugs. 

Despite these efforts, through routine monitoring and surveilance programs, FDA is aware that 

an increasing number of orally ingested OTe liquid drug products are packaged with dosage 

delivery devices that are incompatible with labeled product dosage directions. 

the FD&e Act (21 u.s.e. 352(a)), when 

dosage delivery devices packaged with OTe liquid drug products fail to bear a liquid measure 

mark or markings consistent with the labeled dosage directions, the products also lack adequate 

In addition to misbranding under section 502(a) of 


directions for use and are misbranded under section 502(f)(1) of 
 the FD&e Act (21 u.s.e.

352(f)(1)). 

B. Recommendations
 

The Agency makes the following recommendations for orally ingested OTe liquid drug 

products: 

. Dosage delivery devices should be included for all orally ingested OTe drug products that 

are liquid formulations. 

3 
Contains Nonbinding Recommendations 

. These devices should have calibrated units of liquid measure marked on the device (e.g., 

teaspoon, tablespoon, or mililiter) that are the same as the units of liquid measure specified 

in the labeled dosage directions on any outside packaging (carton labeling), bottle, and any 

accompanying written instructions. 

. If units of liquid measure are abbreviated on the dosage delivery device, the abbreviation
 

used on the device should be the 
 same abbreviation used in the labeled dosage directions, 

outside packaging (carton labeling), bottle, and any accompanying written instructions. 

- International or national standards for abbreviations should be used. For example,
 

mililiters should be abbreviated as "mL" and teaspoons abbreviated as "tsp," and less 

common or nonstandard used abbreviations should be avoided. 

- Avoid the use of 
 trailing zeros after decimal points ("4" not "4.0") to avoid IO-fold 

dosing errors. 

- Abbreviations should be defined on the dosage device (e.g., tsp = teaspoon) and, if 

they are not, should be defined in the labeled dosage directions, outside packaging 

(carton labeling), bottle, and any accompanying written instructions. 

. Any decimals or fractions included on dosage delivery devices should be listed as clearly as 

possible. 

- Use leading zeroes before decimal points ("0.4" not ".4") to help avoid IO-fold
 

dosing errors. 

- Use smaller font size for numerals in fractions ("W' not "1/2") to help avoid 

interpreting "1/2" as "lor 2."
 

. Dosage delivery devices should not bear extraneous or unnecessary liquid measure markings
 

that may be confusing. 

. Manufacturers should try to ensure that the dosage delivery devices are used only with the 

products with which they are included. Possible ways of accomplishing this are to either 

- Include a statement on the drug product's bottle andlor carton labeling and, if
 

possible, on the dosage delivery device that only the provided dosage delivery device 

is to be used with the particular aTe drug product with which it is included. This 

information can also be included under the Directions section of the product's Drug 

Facts paneL.
 

or 

- Devise a mechanism to secure the dosage delivery device to the drug product, such as 

creating an integrated dosage device. 

. Dosage delivery devices should not be significantly larger than the largest dose described in 

the labeled dosage directions and should permit clear measurement and delivery of the

smallest labeled dosage.3 . 

3 As an example, for concentrated acetaminophen infant drops, the Agency recommends that dosage delivery 

devices should also permit clear measurement and delivery of 
 the smallest intended dosage consistent with

professional labeling for infants under 2 years of age. 

4 
Contains Nonbinding Recommendations 

. The liquid measure markings on dosage delivery devices should be clearly visible and not be 

obscured when the liquid product is added to the device. 

The Agency also recommends that firms conduct usability studies to ensure that dosage delivery 

devices are easily understood and accurately used by consumers.4 

Because the Agency regards the markings on these delivery devices as labeling, FDA considers 

their failure to bear liquid measure markings consistent with the labeled dosage directions to 

the bottle and/or carton labeling for a 

drug product contains dosage directions that are written exclusively in terms of a specific unit of 

measure, the accompanying dosage delivery device should contain liquid measure markings in 

the same unit of measure. The following examples ilustrate situations that would render the 

cause the drug product to be misbranded. For example, if 


products misbranded: 

Example 1: The directions for use on the bottle and/or carton specify teaspoon measures 

to describe the dosage amount; the dosage cup that is supplied with the product bears 

three different graduated scales (one is a combined scale of 

teaspoonfuls/dessertspoonfuls/tablespoonfuls; the second provides metric measurements 

fluid ounces and drams) (see Appendix A, (cc/ml); and, the third is a combined scale of 


Ilustration #2).
 

Example 2: The directions for use on the bottle and/or caron specify teaspoon measures 

to describe the dosage amount; the dosage cup provided with the product bears two 

different graduated scales (one is a combined scale of teaspoonfuls/tablespoonfuls with 

juxtaposed conversions to mililiters (Note: the ilustration also has a dessertspoon 

marking); the second is a combined scale of 
 mililiters and fluid ounces) (see Appendix

A, Ilustration #3).
 

The Agency also recommends that the dosage delivery device for a drug product provide 

markings that can readily measure the dosage indicated by the directions on the bottle and/or 

carton labeling. Again, the following examples ilustrate situations that would render the 

products misbranded: 

Example 3: The directions for use on the drug product's bottle and/or carton specify a 2­

teaspoonful dose (see Appendix A, Ilustration #1); the dosage cup does not bear a 

corresponding 2-teaspoonful graduation (See Appendix A, Ilustration #2). 

Example 4: The directions for use on the drug product's bottle and/or carton specify Yiteaspoonful dose (see Appendix A, Ilustration #3); the dosage cup does not bear a 

corresponding Yi-teaspoonful graduation (see Appendix A, Ilustration #4). 

Appendix B provides an example of a dosage cup that corresponds to the dosage directions on 

the drug product's bottle and/or carton labeling. 

4 Although this guidance is not intended to address the adequacy of dosage delivery devices to deliver the labeled 

dosage, the Agency may consider issuing future guidance to industry that addresses topics such as age, weight, 

solubilty, viscosity, patient populations, and instrctions for cleaning, reuse, and storage. 

5 
Contains Nonbinding Recommendations 

In addition to the scenarios described above, FDA is concerned about products that include a 

dosage delivery device and provide directions for use that state: 

Under 2 ¡or 6, etc.) years of age: consult a 
 physician

The Agency recommends that firms educate pharmacists and health care providers about the 

need for consumers to obtain appropriate measuring devices when a physician recommends a 

dose that does not correspond to the dosing directions on the product labeling. 

6 
Contains Nonbinding Recommendations 

APPENDIX A: EXAMPLES OF DOSAGE CUPS THAT DO NOT CORRSPOND TO
 

DOSAGE DIRECTIONS
 

BOTTLE AND/OR CARTON LABELING
 

ILLUSTRATION # 1
 

DrUfl Facts (continued) 

Directions . do not take more than 6 doses in any 24 hour period 

. use only with enclosed measuring cup 

. dose as follows 

adults and children 12 years of age and 2 teaspoons every 4 hours 

older 

children 6 to 12 years of age 1 teaspoon every 4 hours 

children 2 years to 6 years of age 1/2 teaspoon every 4 hours. 

children under 2 years of age Do not use 

Other information 

. store at 20 - 25°C (68 - nOp) 

. alcohol free 

Inactive ingredients: (established names of each inactive ingredient listed in 

alphabetic order) 

Questions? call weekdays 9 AM to 5 PM EST at 1-800-XX- XX 

7 
Contal14S Nonbinding Rcommendations 

DOSAGE CUP 

ILLUS.TRATION # 2 ( 

-: 11BS. -. IA

- 10SSP.
 

- 1 TSP.
 -..SP. 

. 2
 

SIDE A 

OOSO-30M L 

26-25 20-20 

.115 -15 10-10 

5 - 5
 

SIDES SIDE.C 

8 
'j-; 

. Contains Nonbinding Rcommendations 

DOSAGE CUp; 

ILLUSTRATION # 3 

SIDE A . SIDEB 

9 
Contains Nonbinding Recommendations 

DOSAGE CUP
 

IllUSTRATION # 4
 

- 2 TSP. 

-1 TSP.
 

SIDE A SIDE B 

10 
Contains Nonbinding Recommendations 

APPENDIX B: EXAMPLE OF DOSAGE CUP THAT CORRSPONDS TO DOSAGE 

DIRECTIONS 

The example below ilustrates a dosage cup that corresponds to the dosage directions described 

in the drug facts panel below. 

BOTTLE AND/OR CARTON LABELING
 

DrUfl Facts (continued) 

Directions . do not take more than 6 doses in any 24 hour period 

. use only with enclosed measuring cup. 

. dose as follows 

adults and children 12 years of age and 2 teaspoons (tsp) every 4 hours 

older 

children 6 to 12 years of age 1 teaspoon (tsp) every 4 hours 

children 2 years to 6 years of age 'l teaspoon (tsp) every 4 hours. 

children under 2 years of age Do not use 

Other information 

. store at 20 - 25°C (68 - 77°P) 

. alcohol free 

Inactive ingredients: (established names of each inactive ingredient listed in 

alphabetic order)
 

Questions? call weekdays 9 AM to 5 PM EST at 1-800-XX- XX 

-2 tsp
 

-1 tsp
 

- 'h tsp
 

11