Chapter 5: Pharmaceutical Labeling in the US
34 Regulatory Affairs Professionals Society (RAPS)
accompanying such article.”1This term’s scope
has been extended through legal interpretation
of the condition “accompanying such article”
to include information not physically packaged
with the product.14 The familiarly termed package
insert includes the product’s prescribing infor-
mation as well as any FDA-approved patient
labeling. (See chapter on Patient Labeling in the
US.) The PI is packaged with the product and
also is disseminated electronically via the compa-
ny’s website(s) and through the National Library
of Medicine’s DailyMed website.15
As articulated by the FDA:
“A prescription drug product’s FDA-
approved labeling (also known as
‘professional labeling,’ ‘package insert,’
‘direction circular,’ or ‘package circular’) is a
compilation of information about the prod-
uct, approved by FDA, based on the agency’s
thorough analysis of the new drug applica-
tion (NDA) or biologics license application
(BLA) submitted by the applicant. This
labeling contains information necessary for
safe and effective use. It is written for the
healthcare practitioner audience, because
prescription drugs require ‘professional
supervision of a practitioner licensed by law
to administer such drug’” – Section 503(b) of
the act (21 U.S.C. 353(b)).16
Prescribing information must be an informative
and accurate summary of essential information to
support healthcare professionals in the product’s
Table 5-1. Laws and Amendments Relating to Pharmaceutical Labeling in the US
Laws and Amendments Labeling Implications
Federal Food, Drug, and Cosmetic
Act (FD&C Act, 1938)
Set standards for safety and efficacy for marketed drug products defined label
and labeling established qualifications that labeling must:
• Not be false or misleading [§502(a)]
• Include adequate directions for use [§502(f)]
• Be supported by substantial evidence [§505(d)]1
Durham-Humphrey Amendment to
FD&C Act (1951)
Distinguished prescription from nonprescription products, with labeling differ-
entiated by the information needs of healthcare professionals and consumers.2
Kefauver-Harris Amendment to
FD&C Act (1962)
Set standards for safety and efficacy for marketed drug products, through evi-
dence reflected in labeling.
Controlled Substances Act (1970) Places all substances regulated under existing federal law into a labeled
“schedule” based on medical use, potential for abuse, and safety or dependence
liability.3
Fair Packaging and Labeling Act
(1966)
Requires labeling of consumer products, including pharmaceuticals, to disclose
identity, net contents, and name and address of the manufacturer, packer, or
distributor. It further authorized regulations to prevent consumer deception.4
Federal Anti-Tampering Act (1983) Prohibits tampering with consumer products that affects the labeling or renders
it materially false or misleading with intent to cause harm.5
Food and Drug Administration
Modernization Act (FDAMA, 1997)
Section 126 eliminated legend for prescription medicines (“Caution: Federal Law
Prohibits Dispensing without a Prescription”) introduced “Rx only.”6,7
Best Pharmaceuticals for Children
Act (BPCA, 2002)
Incentivized pediatric research and expanded labeling on the use of pharmaceu-
tical products in children.8
Food and Drug Administration
Safety and Innovation Act
(FDASIA, 2012)
Section 904 addressed best practices for accessibility of prescription container
labels by the visually impaired and blind Section 1140 required the Comptroller
General to conduct a study on the use of electronic prescription drug labeling.9
Food and Drug Administration
Amendments Act (FDAAA, 2007)
Section 901(a) added a new Section 505(o)(4) to the FD&C Act, giving FDA
authority to require sponsors to amend approved labeling in response to new
safety information.10
34 Regulatory Affairs Professionals Society (RAPS)
accompanying such article.”1This term’s scope
has been extended through legal interpretation
of the condition “accompanying such article”
to include information not physically packaged
with the product.14 The familiarly termed package
insert includes the product’s prescribing infor-
mation as well as any FDA-approved patient
labeling. (See chapter on Patient Labeling in the
US.) The PI is packaged with the product and
also is disseminated electronically via the compa-
ny’s website(s) and through the National Library
of Medicine’s DailyMed website.15
As articulated by the FDA:
“A prescription drug product’s FDA-
approved labeling (also known as
‘professional labeling,’ ‘package insert,’
‘direction circular,’ or ‘package circular’) is a
compilation of information about the prod-
uct, approved by FDA, based on the agency’s
thorough analysis of the new drug applica-
tion (NDA) or biologics license application
(BLA) submitted by the applicant. This
labeling contains information necessary for
safe and effective use. It is written for the
healthcare practitioner audience, because
prescription drugs require ‘professional
supervision of a practitioner licensed by law
to administer such drug’” – Section 503(b) of
the act (21 U.S.C. 353(b)).16
Prescribing information must be an informative
and accurate summary of essential information to
support healthcare professionals in the product’s
Table 5-1. Laws and Amendments Relating to Pharmaceutical Labeling in the US
Laws and Amendments Labeling Implications
Federal Food, Drug, and Cosmetic
Act (FD&C Act, 1938)
Set standards for safety and efficacy for marketed drug products defined label
and labeling established qualifications that labeling must:
• Not be false or misleading [§502(a)]
• Include adequate directions for use [§502(f)]
• Be supported by substantial evidence [§505(d)]1
Durham-Humphrey Amendment to
FD&C Act (1951)
Distinguished prescription from nonprescription products, with labeling differ-
entiated by the information needs of healthcare professionals and consumers.2
Kefauver-Harris Amendment to
FD&C Act (1962)
Set standards for safety and efficacy for marketed drug products, through evi-
dence reflected in labeling.
Controlled Substances Act (1970) Places all substances regulated under existing federal law into a labeled
“schedule” based on medical use, potential for abuse, and safety or dependence
liability.3
Fair Packaging and Labeling Act
(1966)
Requires labeling of consumer products, including pharmaceuticals, to disclose
identity, net contents, and name and address of the manufacturer, packer, or
distributor. It further authorized regulations to prevent consumer deception.4
Federal Anti-Tampering Act (1983) Prohibits tampering with consumer products that affects the labeling or renders
it materially false or misleading with intent to cause harm.5
Food and Drug Administration
Modernization Act (FDAMA, 1997)
Section 126 eliminated legend for prescription medicines (“Caution: Federal Law
Prohibits Dispensing without a Prescription”) introduced “Rx only.”6,7
Best Pharmaceuticals for Children
Act (BPCA, 2002)
Incentivized pediatric research and expanded labeling on the use of pharmaceu-
tical products in children.8
Food and Drug Administration
Safety and Innovation Act
(FDASIA, 2012)
Section 904 addressed best practices for accessibility of prescription container
labels by the visually impaired and blind Section 1140 required the Comptroller
General to conduct a study on the use of electronic prescription drug labeling.9
Food and Drug Administration
Amendments Act (FDAAA, 2007)
Section 901(a) added a new Section 505(o)(4) to the FD&C Act, giving FDA
authority to require sponsors to amend approved labeling in response to new
safety information.10