Essentials of Healthcare Product Labeling
45
warnings, contraindications, warnings and
precautions, drug interactions, and adverse
reactions (but not adverse reactions alone)
are most common, but other sections may
also be affected to ensure that all labeling for
the product is consistent. Patient labeling
also may be updated to include patient-
oriented information about the new safety
information. In addition, the FDA has the
authority to require implementation of a
Medication Guide if one does not currently
exist.
Sponsors may respond to a safety
change notification from the FDA by
submitting a supplement with proposed
labeling changes based on the new safety
information. If the sponsor proposes revi-
sions identical to those required in the safety
change notification letter, the mechanism for
submission should be a CBE-0. If not, the
sponsor must submit a PAS with the pro-
posed alternate labeling revisions. A sponsor
also may disagree with the agency and
respond by explaining why the change to the
labeling is not warranted. Any supplement
or rebuttal letter must be submitted to the
FDA within 30 calendar days of receiving a
safety change notification letter. For a PAS
or rebuttal, the FDA may initiate a discus-
sion period of no more than 30 calendar
days, to be followed within 15 calendar days
by approval of the supplement or a mandate
to make the FDA-required changes.
• Annual report – Minor changes made
to labeling over the previous period are
described by the sponsor in an annual report.
Examples of such changes may be in the
description of the drug product, how it
is supplied (unless it involves a change in
the dosage strength or form), or editorial
revisions.60,69,70 The labeling may be imple-
mented with these changes immediately.
FDA approval is not given to annual report
changes.
Final printed labeling components are
included with the annual report for the
product, along with a description of the
change(s).
Labeling for Generic Drugs
Generic drug products are the same as innovator
products (listed drugs) if they are identical in their
active ingredient(s), dosage form, strength, route
of administration, and conditions of use (other
than those indications under patent exclusivity).71
Marketing authorization for these products will
be based on the assurance of bioequivalence72
through clinical data submitted in an abbreviated
new drug application (ANDA), information about
CMC,73 and labeling that is identical to that of
the listed drug information.74 According to the
FD&C Act, the ANDA must show:
“…that the labeling proposed for the new
drug is the same as the labeling approved for
the listed drug…except for changes required
because of differences approved under a
petition…or because the new drug and the
listed drug are produced or distributed by
different manufacturers.”75
The ANDA will include annotated draft versions
of the prescribing information and any patient
labeling for use with the generic product, as well
as carton and container labels depicting con-
tent, format, and layout. It also will include the
approved reference listed drug (RLD) labeling
and side-by-side comparisons between the RLD
labeling and that proposed for the generic, high-
lighting and explaining all differences.74
The generic labeling will be submitted
electronically, with prescribing information and
patient labeling in PDF, Word, and SPL formats.
(It is no longer necessary to submit final printed
labeling components with the ANDA.)76
Biosimilar Product Labeling
Biosimilar77products are derived from biologi-
cal sources established as “highly similar” to the
reference biologic by demonstrating there are
no clinically meaningful differences in terms of
product safety, purity, and potency.
As with generic drug products, biosimilar
labeling is based on the prescribing information
and any FDA-approved patient labeling for the
reference product. However, biosimilar labeling
will reflect relevant information from the reference
45
warnings, contraindications, warnings and
precautions, drug interactions, and adverse
reactions (but not adverse reactions alone)
are most common, but other sections may
also be affected to ensure that all labeling for
the product is consistent. Patient labeling
also may be updated to include patient-
oriented information about the new safety
information. In addition, the FDA has the
authority to require implementation of a
Medication Guide if one does not currently
exist.
Sponsors may respond to a safety
change notification from the FDA by
submitting a supplement with proposed
labeling changes based on the new safety
information. If the sponsor proposes revi-
sions identical to those required in the safety
change notification letter, the mechanism for
submission should be a CBE-0. If not, the
sponsor must submit a PAS with the pro-
posed alternate labeling revisions. A sponsor
also may disagree with the agency and
respond by explaining why the change to the
labeling is not warranted. Any supplement
or rebuttal letter must be submitted to the
FDA within 30 calendar days of receiving a
safety change notification letter. For a PAS
or rebuttal, the FDA may initiate a discus-
sion period of no more than 30 calendar
days, to be followed within 15 calendar days
by approval of the supplement or a mandate
to make the FDA-required changes.
• Annual report – Minor changes made
to labeling over the previous period are
described by the sponsor in an annual report.
Examples of such changes may be in the
description of the drug product, how it
is supplied (unless it involves a change in
the dosage strength or form), or editorial
revisions.60,69,70 The labeling may be imple-
mented with these changes immediately.
FDA approval is not given to annual report
changes.
Final printed labeling components are
included with the annual report for the
product, along with a description of the
change(s).
Labeling for Generic Drugs
Generic drug products are the same as innovator
products (listed drugs) if they are identical in their
active ingredient(s), dosage form, strength, route
of administration, and conditions of use (other
than those indications under patent exclusivity).71
Marketing authorization for these products will
be based on the assurance of bioequivalence72
through clinical data submitted in an abbreviated
new drug application (ANDA), information about
CMC,73 and labeling that is identical to that of
the listed drug information.74 According to the
FD&C Act, the ANDA must show:
“…that the labeling proposed for the new
drug is the same as the labeling approved for
the listed drug…except for changes required
because of differences approved under a
petition…or because the new drug and the
listed drug are produced or distributed by
different manufacturers.”75
The ANDA will include annotated draft versions
of the prescribing information and any patient
labeling for use with the generic product, as well
as carton and container labels depicting con-
tent, format, and layout. It also will include the
approved reference listed drug (RLD) labeling
and side-by-side comparisons between the RLD
labeling and that proposed for the generic, high-
lighting and explaining all differences.74
The generic labeling will be submitted
electronically, with prescribing information and
patient labeling in PDF, Word, and SPL formats.
(It is no longer necessary to submit final printed
labeling components with the ANDA.)76
Biosimilar Product Labeling
Biosimilar77products are derived from biologi-
cal sources established as “highly similar” to the
reference biologic by demonstrating there are
no clinically meaningful differences in terms of
product safety, purity, and potency.
As with generic drug products, biosimilar
labeling is based on the prescribing information
and any FDA-approved patient labeling for the
reference product. However, biosimilar labeling
will reflect relevant information from the reference