Chapter 5: Pharmaceutical Labeling in the US
36 Regulatory Affairs Professionals Society (RAPS)
pharmacology, chemistry, manufacturing, and
controls [CMC]) or in one or more marathon
review sessions of the entire draft. It cannot
be overemphasized that any delay in finalizing
source documents is likely to impact completion
of labeling work. Reviewer comments on labeling
documents, such as table format, may influence
final source document versions. As prescribing
information and any patient labeling are the last
dossier items to be completed, such a delay may
ultimately affect submission timing.
Quality checks of labeling documents,
including format verification, should be con-
ducted prior to senior management review to
ensure the FDA’s template requirements are met
and all statements mandated by regulation are
included. Given the ultimate, practical purpose of
the prescribing information, text readability also
should be assessed. Following internal approval
by senior management, a final content quality
review should be conducted and all annotations
verified to ensure the appropriate source doc-
ument sections are referenced to support each
label statement.
Prescribing Information
General Requirements
Prescription medicine labeling requirements
reflect attention to healthcare professionals’ needs
for product information, including adequate
directions for use. The FDA has imple-
mented and continues to update regulations
and guidances for labeling development and
maintenance, so a search of the agency website
is recommended to verify current prevailing
requirements before beginning work on labeling.
Current and comprehensive information is avail-
able on the FDA’s website, including guidance
documents and presentations on prescribing
information, patient labeling, carton and con-
tainer labeling, and more.21
Regulations (21 CFR 201.56) specify that
prescription drug labeling must:
• “…contain a summary of the essential sci-
entific information needed for the safe and
effective use of the drug.
• “…be informative and accurate and neither
promotional in tone nor false or mislead-
ing in any particular…the labeling must be
updated when new information becomes
available that causes the labeling to become
inaccurate, false, or misleading.
• “…be based whenever possible on data
derived from human experience. No implied
claims or suggestions of drug use may be
made if there is inadequate evidence of
safety or a lack of substantial evidence of
effectiveness.”17
Specific Requirements
Non-promotional labeling components required
for FDA submission as the basis of a new drug
or biologic product’s marketing approval include:
• Prescribing information, submitted as
Structured Product Labeling
• Any required patient labeling and
• Trade and sample packaging, including the
immediate container label.
Requirements for each of these components are
detailed in 21 CFR.22
The Immediate Container Label
Table 5-21,13,23-30 specifies the required elements
for the label on the immediate container of pre-
scription drug and biological products.
Content and Format of the Prescribing
Information
In January 2006, the FDA introduced the
Physician’s Labeling Rule, or PLR, which
substantially changed requirements for prescrip-
tion drug labeling content and format in the
US. These changes included the introduction of
new features, such as a Highlights section and
table of contents, and the reordering of informa-
tion to ensure the most important information
for prescribers appears at the beginning. As
described in the PLR Final Rule, these revisions
were intended to “…make it easier for healthcare
professionals to access, read, and use information
in prescription drug labeling. The revisions will
36 Regulatory Affairs Professionals Society (RAPS)
pharmacology, chemistry, manufacturing, and
controls [CMC]) or in one or more marathon
review sessions of the entire draft. It cannot
be overemphasized that any delay in finalizing
source documents is likely to impact completion
of labeling work. Reviewer comments on labeling
documents, such as table format, may influence
final source document versions. As prescribing
information and any patient labeling are the last
dossier items to be completed, such a delay may
ultimately affect submission timing.
Quality checks of labeling documents,
including format verification, should be con-
ducted prior to senior management review to
ensure the FDA’s template requirements are met
and all statements mandated by regulation are
included. Given the ultimate, practical purpose of
the prescribing information, text readability also
should be assessed. Following internal approval
by senior management, a final content quality
review should be conducted and all annotations
verified to ensure the appropriate source doc-
ument sections are referenced to support each
label statement.
Prescribing Information
General Requirements
Prescription medicine labeling requirements
reflect attention to healthcare professionals’ needs
for product information, including adequate
directions for use. The FDA has imple-
mented and continues to update regulations
and guidances for labeling development and
maintenance, so a search of the agency website
is recommended to verify current prevailing
requirements before beginning work on labeling.
Current and comprehensive information is avail-
able on the FDA’s website, including guidance
documents and presentations on prescribing
information, patient labeling, carton and con-
tainer labeling, and more.21
Regulations (21 CFR 201.56) specify that
prescription drug labeling must:
• “…contain a summary of the essential sci-
entific information needed for the safe and
effective use of the drug.
• “…be informative and accurate and neither
promotional in tone nor false or mislead-
ing in any particular…the labeling must be
updated when new information becomes
available that causes the labeling to become
inaccurate, false, or misleading.
• “…be based whenever possible on data
derived from human experience. No implied
claims or suggestions of drug use may be
made if there is inadequate evidence of
safety or a lack of substantial evidence of
effectiveness.”17
Specific Requirements
Non-promotional labeling components required
for FDA submission as the basis of a new drug
or biologic product’s marketing approval include:
• Prescribing information, submitted as
Structured Product Labeling
• Any required patient labeling and
• Trade and sample packaging, including the
immediate container label.
Requirements for each of these components are
detailed in 21 CFR.22
The Immediate Container Label
Table 5-21,13,23-30 specifies the required elements
for the label on the immediate container of pre-
scription drug and biological products.
Content and Format of the Prescribing
Information
In January 2006, the FDA introduced the
Physician’s Labeling Rule, or PLR, which
substantially changed requirements for prescrip-
tion drug labeling content and format in the
US. These changes included the introduction of
new features, such as a Highlights section and
table of contents, and the reordering of informa-
tion to ensure the most important information
for prescribers appears at the beginning. As
described in the PLR Final Rule, these revisions
were intended to “…make it easier for healthcare
professionals to access, read, and use information
in prescription drug labeling. The revisions will