Essentials of Healthcare Product Labeling
43
Expedited Programs for Serious
Conditions – Labeling Implications
The initial PDUFA in 1992 established the
user fee model of review and performance goals
for drug and biologic applications, including a
category for priority reviews. Since then, other
mechanisms have been introduced by legisla-
tive actions (Food and Drug Administration
Modernization Act [FDAMA], Food and
Drug Administration Safety and Innovation
Act [FDASIA]) to facilitate patient access by
expediting the development and review of new
therapies: fast-track designation, breakthrough
therapy designation, accelerated approval, and
priority review designation.57
The standard practices of labeling develop-
ment and review prevails under each program.
However, the importance of reaching agreement
over prescribing information and any patient
labeling in the compressed timeframe associated
with these programs underscores the advan-
tage of developing target labeling early in the
process (see Target Labeling chapter for more
information).
Because the FDA may approve a product
for a serious or life-threatening illness based
on surrogate or intermediate endpoints using
the accelerated approval pathway,58 the agency
issued a guidance to ensure that the prescribing
information indications and usage section offers
clear and complete information about the under-
lying clinical evidence, including limitations of
usefulness and clinical benefit uncertainty. The
guidance directs any confirmatory research to
be highlighted in the indications section when a
postmarketing study is required for approval. It
also describes how the labeling is to be revised
when clinical benefit has been verified or when
an accelerated indication must be withdrawn.
Postapproval Labeling Revisions
Labeling is arguably the most dynamic regula-
tory document associated with drug development
and maintenance, with hundreds of labeling
changes made in the US each year.59 A product’s
labeling will need frequent revision following
the product’s initial introduction, as it is used by
a broader variety of patients than were exposed
to it in controlled clinical settings, and when
postapproval commitments include requirements
for additional clinical research. The labeling also
will reflect continuing sponsor development,
such as research into additional indications and
improved understanding about benefit-risk
and usage revealed through continued safety
monitoring. Further, it may be necessary to
revise a product’s labeling to comply with new
regulations impacting product information or
packaging. Revision frequency tends to diminish
as products mature, shifting focus from enhanced
usage to one of maintaining up-to-date safety
information, pharmaceutical particulars, and
regulatory compliance (see Table 5-4).
Revisions to FDA-approved drug and
biologic labeling are submitted to the agency as
supplements to the NDA or BLA. The type of
submission depends on the nature of the changes.
Refer to 21 CFR 314.70 (NDA) or 21 CFR
601.12 (BLA).60-62
Table 5-4. Some Reasons for Labeling
Revision
New or expanded indications
Additional or modified dosing regimens
Changes to or addition of safety information
Addition or discontinuation of product strength,
formulation, or packaging configuration
Change in the name or address of the manufacturer
Inclusion of class labeling statements
Compliance with new labeling requirements
Changes in international sourcing
• Prior Approval Supplement (PAS) is used
for major changes that require submission
and approval of a supplement before the
product may be distributed with the revised
labeling. This includes revisions to the
Medication Guide or to any information
required by regulations for the prescribing
information (other than minor changes
submitted in annual reports). For biologics,
examples of this supplement type include
labeling changes requiring completion of a
study to demonstrate equivalence or changes
in a cell line.60,63,64
43
Expedited Programs for Serious
Conditions – Labeling Implications
The initial PDUFA in 1992 established the
user fee model of review and performance goals
for drug and biologic applications, including a
category for priority reviews. Since then, other
mechanisms have been introduced by legisla-
tive actions (Food and Drug Administration
Modernization Act [FDAMA], Food and
Drug Administration Safety and Innovation
Act [FDASIA]) to facilitate patient access by
expediting the development and review of new
therapies: fast-track designation, breakthrough
therapy designation, accelerated approval, and
priority review designation.57
The standard practices of labeling develop-
ment and review prevails under each program.
However, the importance of reaching agreement
over prescribing information and any patient
labeling in the compressed timeframe associated
with these programs underscores the advan-
tage of developing target labeling early in the
process (see Target Labeling chapter for more
information).
Because the FDA may approve a product
for a serious or life-threatening illness based
on surrogate or intermediate endpoints using
the accelerated approval pathway,58 the agency
issued a guidance to ensure that the prescribing
information indications and usage section offers
clear and complete information about the under-
lying clinical evidence, including limitations of
usefulness and clinical benefit uncertainty. The
guidance directs any confirmatory research to
be highlighted in the indications section when a
postmarketing study is required for approval. It
also describes how the labeling is to be revised
when clinical benefit has been verified or when
an accelerated indication must be withdrawn.
Postapproval Labeling Revisions
Labeling is arguably the most dynamic regula-
tory document associated with drug development
and maintenance, with hundreds of labeling
changes made in the US each year.59 A product’s
labeling will need frequent revision following
the product’s initial introduction, as it is used by
a broader variety of patients than were exposed
to it in controlled clinical settings, and when
postapproval commitments include requirements
for additional clinical research. The labeling also
will reflect continuing sponsor development,
such as research into additional indications and
improved understanding about benefit-risk
and usage revealed through continued safety
monitoring. Further, it may be necessary to
revise a product’s labeling to comply with new
regulations impacting product information or
packaging. Revision frequency tends to diminish
as products mature, shifting focus from enhanced
usage to one of maintaining up-to-date safety
information, pharmaceutical particulars, and
regulatory compliance (see Table 5-4).
Revisions to FDA-approved drug and
biologic labeling are submitted to the agency as
supplements to the NDA or BLA. The type of
submission depends on the nature of the changes.
Refer to 21 CFR 314.70 (NDA) or 21 CFR
601.12 (BLA).60-62
Table 5-4. Some Reasons for Labeling
Revision
New or expanded indications
Additional or modified dosing regimens
Changes to or addition of safety information
Addition or discontinuation of product strength,
formulation, or packaging configuration
Change in the name or address of the manufacturer
Inclusion of class labeling statements
Compliance with new labeling requirements
Changes in international sourcing
• Prior Approval Supplement (PAS) is used
for major changes that require submission
and approval of a supplement before the
product may be distributed with the revised
labeling. This includes revisions to the
Medication Guide or to any information
required by regulations for the prescribing
information (other than minor changes
submitted in annual reports). For biologics,
examples of this supplement type include
labeling changes requiring completion of a
study to demonstrate equivalence or changes
in a cell line.60,63,64