Chapter 5: Pharmaceutical Labeling in the US
48 Regulatory Affairs Professionals Society (RAPS)
The requirement to package drugs and
biologics with printed prescribing information
also persists despite the pharmaceutical indus-
try’s long-term efforts to influence regulatory
changes that would permit reliance on electronic
labeling dissemination. The economic advantages
of not having to maintain printed components
and package them physically with their prod-
ucts are clear. Of potentially greater relevance to
healthcare is eliminating outdated printed com-
ponents.84 Printed package inserts received at the
pharmacy may be many weeks out of date due to
the time required to print and package the com-
ponents and to deliver inventory to dispensing
sites. By contrast, electronic files can be updated
rapidly, including correcting any errors, which
may avoid recalls.
For more than a decade, beginning in the
late 1990s, a Pharmaceutical Research and
Manufacturers of America (PhRMA) task force
representing industry, health professionals, the
generic industry, and patients worked to assess
practitioner readiness and consider various
paperless models to support eliminating the
requirement for printed prescribing information.
(The initiative pointedly excepted patient label-
ing, which would continue to be packaged with
the product.)
In 2014, the FDA issued a proposed
rule on electronic distribution of prescribing
information.85The proposal excluded emer-
gency medicines, nonprescription drugs, and
patient labeling. The report by the Government
Accountability Office (GAO) on the study,
prompted by FDASIA, found no consensus
among stakeholders on the advantages and disad-
vantages of eliminating printed labeling. However,
it is noteworthy that some of the concerns
expressed in the report relate to the inclusion of
patient labeling in the assessment’s scope.86
In 2018, Congress – referring to the GAO
report’s “conclusions” that the proposal could
adversely impact public health – forbid the
FDA to use any funds to promulgate the rule.87
Despite current congressional reluctance to move
forward, the initiative to modernize prescrib-
ing information distribution has long-term
viability.88
Pediatric Labeling
For the purposes of this section, label or labeling
refers specifically to the prescribing informa-
tion. The FDA implemented several initiatives
to improve pediatric use information in drug
labeling. Two regulations that were made per-
manent in 2012 under FDASIA were the Best
Pharmaceuticals for Children Act (BPCA) and
the Pediatric Research Equity Act (PREA).
The BPCA contains economic incentives for
conducting pediatric studies, while PREA estab-
lishes requirements for studies of certain drugs
and biologics in pediatric patients.
The sponsor must submit all data for
inclusion in the labeling, which includes data
submitted in response to a written request (per
BPCA), a pediatric assessment in response
to a study requirement (per PREA), or data
required to fulfill an initial Pediatric Study Plan.
Regardless of whether the data is positive, neg-
ative, or inconclusive, it must still be presented
in the labeling. In addition, any safety concerns
or lack of efficacy in a specific pediatric subpop-
ulation must be included in the Pediatric Use
section of the label. The Pediatric Use section
is a subsection of Section 8 Use in Special
Populations of the prescribing information.
Information provided in this section may need
to be divided into pediatric subpopulations, such
as neonates, infants, children, and adolescents,
depending on the data available that confirms
the safety and efficacy in the pediatric popu-
lation. As with all sections of the prescribing
information, pediatric information must not be
false or misleading. Additionally, the Pediatric
Use section must include a regulatory statement,
which is referred to as a Pediatric Use statement.
This statement is required regardless of whether
the drug or biologic is approved for the same
indication in pediatric and adult patients or if
the indication is different for pediatric and adult
patients. The Pediatric Use statement should
typically be the first sentence in the Pediatric Use
subsection of the prescribing information.
Per the FDA guidance Pediatric Information
Incorporated into Human Prescription Drug
and Biological Product Labeling, dated March
2019,44 there are four scenarios describing the
48 Regulatory Affairs Professionals Society (RAPS)
The requirement to package drugs and
biologics with printed prescribing information
also persists despite the pharmaceutical indus-
try’s long-term efforts to influence regulatory
changes that would permit reliance on electronic
labeling dissemination. The economic advantages
of not having to maintain printed components
and package them physically with their prod-
ucts are clear. Of potentially greater relevance to
healthcare is eliminating outdated printed com-
ponents.84 Printed package inserts received at the
pharmacy may be many weeks out of date due to
the time required to print and package the com-
ponents and to deliver inventory to dispensing
sites. By contrast, electronic files can be updated
rapidly, including correcting any errors, which
may avoid recalls.
For more than a decade, beginning in the
late 1990s, a Pharmaceutical Research and
Manufacturers of America (PhRMA) task force
representing industry, health professionals, the
generic industry, and patients worked to assess
practitioner readiness and consider various
paperless models to support eliminating the
requirement for printed prescribing information.
(The initiative pointedly excepted patient label-
ing, which would continue to be packaged with
the product.)
In 2014, the FDA issued a proposed
rule on electronic distribution of prescribing
information.85The proposal excluded emer-
gency medicines, nonprescription drugs, and
patient labeling. The report by the Government
Accountability Office (GAO) on the study,
prompted by FDASIA, found no consensus
among stakeholders on the advantages and disad-
vantages of eliminating printed labeling. However,
it is noteworthy that some of the concerns
expressed in the report relate to the inclusion of
patient labeling in the assessment’s scope.86
In 2018, Congress – referring to the GAO
report’s “conclusions” that the proposal could
adversely impact public health – forbid the
FDA to use any funds to promulgate the rule.87
Despite current congressional reluctance to move
forward, the initiative to modernize prescrib-
ing information distribution has long-term
viability.88
Pediatric Labeling
For the purposes of this section, label or labeling
refers specifically to the prescribing informa-
tion. The FDA implemented several initiatives
to improve pediatric use information in drug
labeling. Two regulations that were made per-
manent in 2012 under FDASIA were the Best
Pharmaceuticals for Children Act (BPCA) and
the Pediatric Research Equity Act (PREA).
The BPCA contains economic incentives for
conducting pediatric studies, while PREA estab-
lishes requirements for studies of certain drugs
and biologics in pediatric patients.
The sponsor must submit all data for
inclusion in the labeling, which includes data
submitted in response to a written request (per
BPCA), a pediatric assessment in response
to a study requirement (per PREA), or data
required to fulfill an initial Pediatric Study Plan.
Regardless of whether the data is positive, neg-
ative, or inconclusive, it must still be presented
in the labeling. In addition, any safety concerns
or lack of efficacy in a specific pediatric subpop-
ulation must be included in the Pediatric Use
section of the label. The Pediatric Use section
is a subsection of Section 8 Use in Special
Populations of the prescribing information.
Information provided in this section may need
to be divided into pediatric subpopulations, such
as neonates, infants, children, and adolescents,
depending on the data available that confirms
the safety and efficacy in the pediatric popu-
lation. As with all sections of the prescribing
information, pediatric information must not be
false or misleading. Additionally, the Pediatric
Use section must include a regulatory statement,
which is referred to as a Pediatric Use statement.
This statement is required regardless of whether
the drug or biologic is approved for the same
indication in pediatric and adult patients or if
the indication is different for pediatric and adult
patients. The Pediatric Use statement should
typically be the first sentence in the Pediatric Use
subsection of the prescribing information.
Per the FDA guidance Pediatric Information
Incorporated into Human Prescription Drug
and Biological Product Labeling, dated March
2019,44 there are four scenarios describing the