WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 2.786

Volume 4, Issue 3, 799-810.

Research Article

ISSN 2278 4357

REGULATORY LABELLING REQUIREMENTS AND ITS

COMPARISON IN USA AND CANADA
Krupa C. Thula*1, Harita K. Odedra2 and Dr. Dilip G. Maheshwari3
1

Assistant Professor, Department of Quality Assurance, L. J. Institute of Pharmacy, Between

Kataria Motor and Sanand-Sarkhej Circle, S. G. Highway, Ahmedabad, Gujarat- 382210,
India.

Department of Quality Assurance, L. J. Institute of Pharmacy, Between Kataria Motor and

Sanand-Sarkhej Circle, S. G. Highway, Ahmedabad, Gujarat- 382210, India.
3

Head of Department of Quality Assurance, L. J. Institute of Pharmacy, Between Kataria

Motor and Sanand-Sarkhej Circle, S. G. Highway, Ahmedabad, Gujarat- 382210, India.

Article Received on
13 Dec 2014,
Revised on 07 Jan 2015,
Accepted on 02 Feb 2015
Nov 2014

ABSTRACT
Labels are beneficial description of the products which is very useful
for the consumers to distinguish the goods from others. Consequently,
these are the unique identity of the product. Now a day, it becomes a
habit of most of the population to see the product label before they go

*Correspondence for
Author
Krupa C. Thula

for purchase. An excellent design, description and posture also

influence the buyers and consumers. This article describe about various

Assistant Professor,

regulatory requirements for different dosage forms with precautions in

Department of Quality

USA and Canada according to their code of regulations and

Assurance, L. J. Institute of

comparison of labelling requirement in both countries. In the USA,

Pharmacy, Between Kataria

The content & format requirements of labelling for human prescription

Motor and Sanand-Sarkhej

Circle, S. G. Highway,

drug & biological products comes under 21 CFR 201.56(d) & 201.57.

Ahmedabad, Gujarat-

In the Canada, Labelling of Pharmaceutical Drugs for Human Use

382210, India.

replaces the Health Canada guidance document labelling of Drugs for

Human Use. In 1989, this guidance document came into effect, was

revised in 1991, Health Canada had remove it from circulation because most of its content
was deemed to be out-of-date. The inner label affixed to an immediate container of the drug.
The outer label includes any label affixed to the drug packaging, including a pouch, card,
accordion label, or other construct.
KEYWORDS: Study, Labelling, Requirements, USA, Canada and Comparison.

www.wjpps.com

Vol 4, Issue 3, 2015.

799

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

INTRODUCTION
Label
1. Labels are definite part of pharmaceutical products which manufacturers affix to their
products to indicate their customers that the product meet certain standards. Labels are
most probably printed papers which entitle information like weight, bar code, service time
and many other things. The term labeling designates all labels and other written, printed
or graphic matter upon or in package or wrapper in which it is enclosed.
2. Also label must indicate the name of manufacturer or distributer and carry an identifying
lot number.
Types of label[1]
A variety of materials are used for labeling such as paper, fabric and foil. The choice mainly
depends on the need and economics.
The various types are as follows:1. Paper label
Most labels are printed on paper, since this is the most economical and sensible method for
any quantities i.e. either large or small. There is no label to the colors and techniques that can
be used for paper label.
2. Foil labels
It is nearly always necessary to laminate with paper so that label will work properly in the
labeling machines. The foil and paper together should measure 0.0025 to 0.003 inch for ideal
results.
3. Transfer labels
There are several processes for transferring inks from a pre-printed strip so that the container
that is to be decorated.
Out of these the electrical system is more economical but it is limited to lines and solids.
Tools costs are nominal and the equipment are relatively inexpensive.
The operating temperature of the die is around 350f with pressure around 100 to 200 psi,
depending on the size of the label.

www.wjpps.com

Vol 4, Issue 3, 2015.

800

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

4. Sieve labels
There are two types of labels
Stretch band
Shrink band
Two-mil low density polythene films are used for stretch band labels. Heat shrinkable labels
are made up of 3-mil polyvinyl chloride film.
Functions of label[2]
1. Physical Protection
2. Barrier protection
3. Containment or agglomeration Information transmission
4. Marketing
A. General labeling requirements according to usfda (united states food and drug
administration)
The content and format requirements of labelling for human prescription drug and biological
products comes under 21 CFR 201.56(d) and 201.57. This guidance provides
recommendation on developing Highlights of prescribing Information (Highlights),
procedural information and formatting of labelling. On January 24, 2006, FDA published a
final rule that amended the requirements for the content and format of labelling for human
prescription drug and biological products.
Code of federal Regulations 201.56(d)[3]
A. Prescription drug labeling described must meet the following general requirements:
1) It must contain a succinct summary of essential scientific information.
2) The labeling must be descriptive and accurate.
3) The labeling must be based whenever possible on data derived from human experience.
B. Categories of prescription drugs subject to the labeling content and format requirements:
1) The hereunder categories of prescription drug products are subject to the labeling
requirements:
i. Prescription drug products for which a new drug application (NDA), biologics license
application (BLA), or efficacy supplement was approved by the Food and Drug
Administration (FDA).
ii. Prescription drug products for which an NDA, BLA, or efficacy supplement is unresolved

www.wjpps.com

Vol 4, Issue 3, 2015.

801

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

on June 30, 2006; or

iii. Prescription drug products for which an NDA, BLA, or efficacy supplement is given to
submit anytime on or after June 30, 2006.
C. Schedule for implementing the labeling content and format requirements.
D. Recently approved prescription drug products.
1) Prescription drug labeling described in 201.100(d) contain the specific information in the
following order:
Highlights of Prescribing Information
1. Product Names, Other Required Information
2. Boxed Warning
3. Recent Major Changes
4. Contraindications
5. Indications and Usage
6. Dosage and Administration
7. Dosage Forms and Strengths
8. Warnings and Precautions
9. Drug Interactions
10. Use in Specific Populations
11. Adverse Reactions
12. Full Prescribing Information: Contents
13. Full Prescribing Information
Boxed Warning
1. Warnings and Precautions
2. Indications and Usage
3. Dosage and Administration
4. ms and Strengths
5. Adverse Reactions
6. Contraindications
7. Drug Interactions
8. Use in Specific Populations
a) Pregnancy
b) Labor and delivery

www.wjpps.com

Vol 4, Issue 3, 2015.

802

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

c) Nursing mothers
d) Pediatric use
e) Geriatric use
9. Drug Abuse and Dependence
a) Controlled substance
b) Dependence
c) Abuse
10. Over dosage
11. Clinical Pharmacology
a) Mechanism of action
b) Pharmacodynamics
c) Pharmacokinetics
12. Nonclinical Toxicology
a) Carcinogenesis, mutagenesis, impairment of fertility
b) Animal toxicology
13. Description
14. Clinical Studies
15. References
16. How Supplied/Storage and Handling
17. Patient Counseling Information
E. Labeling requirements for older prescription drug products.
1) Prescription drug labeling description must contain the particular information required
under the following section headings and with the following order:
a) Description
b) Clinical Pharmacology
c) Indications and Usage
2) Contraindications
3) Precautions
4) Warnings
5) Adverse Reactions

www.wjpps.com

Vol 4, Issue 3, 2015.

803

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

6) Drug Abuse and Dependence

7) Over dosage
8) Dosage and Administration
2) The labeling may contain the following section headings:
a. Animal Pharmacology and/or Animal Toxicology
b. Clinical Studies
c. References
3) Remove clearly inapplicable sections, subsections, or specific information.
4) The labeling may contain a "Product Title" section preceding the "Description" section.
Code of federal regulation 201.57[4]
(a) Highlights of prescribing information
The following information must appear in all prescription drug labeling
(1) Highlights limitation statement.
(2) Drug names
(3) Initial U.S. approval.
(4) Boxed warning.
(5) Recent major changes.
(6) Indications and usage.
(7) Dosage and administration.
(8) Dosage forms and strengths.
(9) Contraindications.
(10) Warnings and precautions.
(11) Drug interactions.
(12) Use in specific populations.
(13) Revision date.
(b) Full prescribing information contents: Contents must contain a list of heading and
subheading required in the full prescribing information. Contents must also contain any
additional subheading(s).

www.wjpps.com

Vol 4, Issue 3, 2015.

804

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

(b) Full prescribing information: The full prescribing information must contain the
information in the order together with the headings, subheadings, and identifying
numbers.
Format Requirements
All labelling information must be printed in accordance with the following specification: All
headings and sub headings required must be highlighted by bold type that distinguishes the
headings and subheadings from other labelling information. Reverse type is not permitted as
a form of highlighting.
1. A horizontal line must separate the information.
2. The heading must be in the center of a horizontal line.
3. If there are multiple subheadings, each subheadings must be indicated by a bullet point.
4. The labelling information must be in bold print.
5. The letter height or type size for all labelling information, headings, and subheadings
must be a minimum of 8 points.
6. The identifying numbers must be presented in bold print and must precede the heading or
subheading by at least two square cm.
7. Section or sub section of labelling that are identified as containing recent major changes
must be highlighted in the full prescribing information by the inclusion of a vertical line
on the left edge of the new or modified text.
8. For the information each section heading must be in bold print. Each subheading within a
section must be intended and not bolded.
9. The information must be limited in length to an amount that, if printed in 2 columns on a
standard sized piece of typing paper (81/2 by 11 inches), single spaced, in 8 point type
with 12 inch margins on all sides and between columns, would fit on one half of the page.
B. Labelling requirements according to canada[5]
Labelling of Pharmaceutical Drugs for Human Use has replaced the Health Canada guidance
document labelling of Drugs for Human Use. This guidance document came into effect in
1989, was afterwards revised in 1991, and has since been removed from dissemination by
Health Canada because much of its content was supposed to be out-of-date. The inner label is
the label stick to an immediate container of the drug. The outer label includes any label
affixed to the drug packaging, including a pouch, card, accordion label, or other construct.
Manufacturer should note that shipping cartons must be labelled in such a manner as to

www.wjpps.com

Vol 4, Issue 3, 2015.

805

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

ensure compliance with the good manufacturing practices (GMP) requirements. Health
Canada recommends that manufacturers label the shipping carton with sufficient information
to enable product identification (e.g., brand name, common or proper name, strength, and
manufacturers name).
General labelling requirements
The main panel or principal display panel is the main product display surface visible to the
user under normal or customary conditions of display or use.
The main panel of an inner or outer label should carry the following information:
1. The brand name or if brand name does not exists, then the proper or common name is
applied,
2. The proper or common name of the finished product is applied.
3. The standard for the drug, if any,
4. The scheduling symbol, if required;
5. The drug identification number
6. The name and address of the manufacturer, and of the distributor if the manufacturer is
not Canadian;
7. The lot number;
8. The expiration date;
9. Directions for use of the drug.
10. Medicinal ingredients are also quantitatively enlisted.
11. The following information is to be disclosed on outer label of any panel:
12. The net amount of drug
13. In parenteral preparations, quantitative list of all preservatives and of all mercurial
preservatives in any drug containing mercury.
Label to be included
1. Brand Name
2. Common name
3. Proper name
4. Pharmaceutical Form
5. Standard of manufacture
6. Drug identification number
7. Lot number

www.wjpps.com

Vol 4, Issue 3, 2015.

806

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

8. Expiration date
9. Name and Address of Manufacturer
10. Adequate Directions for Use
11. Storage Conditions
12. Limit Dose Drug Products
13. Warnings and Precautions
14. Declaration of Medicinal Ingredient
Comparison of Labelling Requirement In Usa And Canada
Table 1: Comparison of labelling requirement in USA and Canada
Parameter

USA

Rule

It mainly comes under section

21 CFR 201.56 (d) & 201.57.
It became final rule in 2006.

Section

Language

Order of Label display

www.wjpps.com

Mainly labelling requirements

divided into 3 section:
Highlights of prescribing
information (highlights)
A table of contents (contents)
The full prescribing
information (FPI)
English

Canada
It mainly comes under guidance
document labelling of
pharmaceutical drugs for human
use.
It came into action into 1989 and
amended in 1991. Previously it
was amended in 2014.
Mainly label is called display
label or principal label & it is
divided into 2 panel:
Inner panel
Outer panel

English or French
The brand name or if no brand
Highlights of Prescribing
name exists, then the proper name
Information
The proper or common name of
Product names, other required
the finished product
information
The standard for the drug, if any;
Boxed Warning
The notation sterile,
Recent Major Changes
The Drug Identification Number
Indication and Usage
(DIN)
Dosage and Administration
The scheduling symbol, if
Dosage forms and Strengths
required;
Contraindications
The name and address of the
Warning and Precautions
manufacturer, and of the
Adverse Reactions
distributor if the manufacturer is
Drug Interactions
not Canadian;
Use in Specific Populations
The lot number
Full Prescribing Information
The expiration date
contents
Adequate directions for use of the
Full Prescribing Information
drug; and
Medicinal ingredients are also

Vol 4, Issue 3, 2015.

807

Krupa et al.

Product name and

Strength
Initial approval process
Barcode no.

World Journal of Pharmacy and Pharmaceutical Sciences

Proprietary name and

established name of drug is
given.
Statement of initial approval
process should be displayed
with year
NDC (National drug Code)
number

Batch number &

Expiration date

It should be included.

Dosage &
Administration

A summary of information
with subheadings including
dose range, dosage regimen,
starting dose, critical
differences among population
subsets.

Warning & precautions

A summary of the most

clinically significant
information is needed with any
Appropriate subheadings.

Adverse reaction

Drug interaction

Specific issues:

www.wjpps.com

It should be included but not

repeated if it is already in
warning & precaution section.
A concise summary of the
information required with any
appropriate subheadings.

quantitatively enlisted.
Common name assigned by
manufacturer and approved by
Health Canada.
NA
DIN (Drug identification number)
The lot number may be any
combination of letters, figures, or
both by which a drug can be
traced to the manufacturer and if
applicable, to the distributor or
importer. The expiration date
must be on the inner and outer
labels of all drug products.
Examples: 2008 April 30,
08AL30, or 08AL.
The pharmacological
classification may substitute
specific indications on the labels,
in cases where indications are
specified, the dosage directions
applicable to each indication or a
dosage range encompassing all
the indications should appear
where possible.
Caution shown within quotation
marks & should be printed
exactly. If the caution or warning
does not appear within quotation
marks, the wording may be
altered but the meaning must be
retained.
It should be included in all
panels.
NA
The inner and outer labels show
adequate directions for use of
the drug.
This is interpreted to include:
Indications for use or
pharmacological classification;
Recommended single and daily
dose;

NA

Vol 4, Issue 3, 2015.

808

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Table 2: Labelling requirements for specific dosage form

Dosage form

USA

Solid oral

The established name of the

drug and the quantity of the
active ingredient per dosage unit
The expiration date
The lot number
The name and place of business
of the manufacturer
Special storage conditions.

Liquid dosage form

Topical

Injectable products

Biological products

www.wjpps.com

These products are non-sterile

but may be monitored for
changes in bio burden.
If co solvents are present in
dosage form then extractable
information should be given.
If it is sterile then microbial
limit should be included.
The total amount of active
ingredient (medicine name)
must be identified, including
units (e.g., mg).
The total volume of fluid
contained in the syringe must be
identified in milliliters (mL).
The concentration (units/mL)
must be identified.
Labelling of product name,
batch number and expiry date.
The proper name of the product;
The name, address, and license
number of manufacturer;
The lot number
The expiration date;
The preservative used and its
concentration,
The amount of product in the
container
The recommended storage
temperature;
The adjuvant, if present;
Minimum potency of product
The statement:
Rx only for prescription
biological.

Vol 4, Issue 3, 2015.

Canada
The brand name
The proper or common name of
the finished product.
The standard for the drug.
The scheduling symbol.
The Drug Identification Number
The name and address of the
distributor.
The lot number;
The expiration date
Medical ingredient
Pharmaceutical forms
Indication
Dosage directions
There should be antimicrobial
preservative included.
Common name
Product concentration
Declaration of medical ingredient
A if liquid preparation SVP then it
should be declared per milliliter.
B. if liquid preparation LVP then
it should be declared in
percentage.
c. Parenteral salt must be declared
in mill equivalents per unit final
volume.

Scientific name
Trade name
Expiry date
Serial number
Route of administration
Dosage recommendation for use
Precautions
The establishment number of the
firm

809

Krupa et al.

World Journal of Pharmacy and Pharmaceutical Sciences

CONCLUSION
Labelling is one of the crucial documents for filling any drug product. Comparison of
labelling requirements in different countries make easier for person to make & prepare
simple, accurate & precise label from country requirements when they are filling their
product in different countries. Labelling reduces medication error. Labelling should be
readable and it should be easily accessible to the consumer. Omission and inaccuracy of drug
labeling information on pharmaceutical excipients may expose susceptible individuals to
adverse reactions caused by preservatives and dyes. Out-of-date or incomplete drug product
labeling information may increase the risk of otherwise preventable adverse drug events.
Proper label design attracts the consumers which may lead to the increase in demand of the
product. Package labels are proficient to steer the product differentiation and to gain the trust
and attractiveness of the consumers by product labels and can also attain communication with
different consumer segment by regularly maintaining their quality.
ACKNOWLEDGEMENT
The authors are thankful to Dr. Pundarikakshudu, Director of L. J. Institute of Pharmacy,
Ahmedabad, India for providing facilities and encouragements to carry out the research work.
REFERENCES
1. Walter L. Pharmaceutical Codex: Principal and Practice of Pharmaceutics. 12th ed.,
Pharmaceutical press, 1994; 115-67: 401-2.
2. Drug Labelling URL:http://www.faqs.org/health/topics/89/Drug-labeling.html.
3. Code of federal regulation 21 Labelling Requirements for Prescription Drugs and/or
Insulin
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSeaarch.cfm?fr=201.56.
4. Code of federal regulation 21 Labelling Requirements for Prescription Drugs and/or
Insulin
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSeaarch.cfm?fr=201.57.
5. Guidance

document

labelling

of

pharmaceutical

drugs

for

human

use

http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/label_guide_ldeng.php.

www.wjpps.com

Vol 4, Issue 3, 2015.

810