Essentials of Healthcare Product Labeling
47
companies’ and brand sponsors’ obligations to
ensure that their products’ labeling does not
become false, inaccurate, or misleading, stating,
“If a generic drug maker becomes aware of new
safety information that’s not already in the drug
label, they must also report it to the agency. This
action, in turn, can result in safety changes that
are directed by the FDA and would apply to all
versions of the drug.” Related initiatives and the
FDA’s commitment to play a proactive role in
updating the labeling of older generic drugs were
cited as the new approach for keeping labeling
current throughout the product lifecycle.81
Labeling updates also are needed to reflect
accruing information about biological prod-
ucts during their lifecycle. Biosimilar sponsors
are responsible for pharmacovigilance of their
products and updating labeling with new infor-
mation to prevent it from becoming inaccurate,
false, or misleading. Updates to the biosimilar
labeling also could be prompted by expanded
indications, either to catch up with the Reference
Listed Biologic’s (RLB’s) original set of approved
indications or to include a newly approved RLB
indication. Changes in a biologic product’s label-
ing during its lifecycle will create the need for
updates to any biosimilar product’s labeling for
which it serves as a reference.77
Approval and Dissemination
Following negotiations for agreed labeling
content, whether after initial NDA or BLA sub-
mission or as the result of revisions submitted in
a supplement, the FDA will provide the sponsor
with an approval letter (marked, for example,
“NDA Approval” or “Supplement Approval”)
along with the final, approved version of label-
ing. (Examples of such letters can be found at
Drugs@FDA.78) Sponsors should employ quality
checks at each stage in the negotiation process,
including carefully proofreading the final version
delivered by the FDA.
The approval letter also will include
instructions to submit the “content of label-
ing” (prescribing information) in SPL format.
In December 2003, the FDA amended its
regulations to require submission of all drug
and biologic labeling in an electronic format.
Following approval, the FDA requires the
submission of the new prescribing informa-
tion in SPL format to the drug establishment
registration and labeling system, which then will
transmit it to the National Library of Medicine
for posting on the DailyMed website.54,55
The approved new or revised labeling should
be expediently distributed within the sponsoring
company to departments for which it serves as
a critical reference, including pharmacovigilance
for determining labeled and unlabeled adverse
events, medical affairs for responding to prod-
uct inquiries, and marketing departments for
support of promotional activities. Company
websites also should be updated with new or
revised labeling when such websites display
current product information. While there are
no regulations regarding timelines for company
website postings, it should be done in a timely
manner. Company management should estab-
lish implementation timelines for its product
labeling, including website posting as well as
packaging printed inserts with products. The
labeling development team must communicate
with the manufacturing site to alert graphics and
packaging engineers to an impending approval so
printed labeling inventory can be appropriately
managed.
Electronic Package Inserts (Paperless
Labeling)
In the US, prescribing information still is required
to physically accompany the product and is usu-
ally packaged with the carton or container. This
situation arises from the provisions of FD&C Act
Section 502 (f)(1), which declares82 a drug is mis-
branded unless its label bears adequate directions
for use, from which prescription medicines are
exempted as long as “[l]abeling on or within the
package from which the drug is to be dispensed
bears adequate information for its use.”83
In other words, in the US, the product
received by pharmacists for dispensing must
be accompanied by (packaged with) approved
prescribing information. This situation persists,
despite advances in information technology that
support reliable electronic access to information,
including drug information.
47
companies’ and brand sponsors’ obligations to
ensure that their products’ labeling does not
become false, inaccurate, or misleading, stating,
“If a generic drug maker becomes aware of new
safety information that’s not already in the drug
label, they must also report it to the agency. This
action, in turn, can result in safety changes that
are directed by the FDA and would apply to all
versions of the drug.” Related initiatives and the
FDA’s commitment to play a proactive role in
updating the labeling of older generic drugs were
cited as the new approach for keeping labeling
current throughout the product lifecycle.81
Labeling updates also are needed to reflect
accruing information about biological prod-
ucts during their lifecycle. Biosimilar sponsors
are responsible for pharmacovigilance of their
products and updating labeling with new infor-
mation to prevent it from becoming inaccurate,
false, or misleading. Updates to the biosimilar
labeling also could be prompted by expanded
indications, either to catch up with the Reference
Listed Biologic’s (RLB’s) original set of approved
indications or to include a newly approved RLB
indication. Changes in a biologic product’s label-
ing during its lifecycle will create the need for
updates to any biosimilar product’s labeling for
which it serves as a reference.77
Approval and Dissemination
Following negotiations for agreed labeling
content, whether after initial NDA or BLA sub-
mission or as the result of revisions submitted in
a supplement, the FDA will provide the sponsor
with an approval letter (marked, for example,
“NDA Approval” or “Supplement Approval”)
along with the final, approved version of label-
ing. (Examples of such letters can be found at
Drugs@FDA.78) Sponsors should employ quality
checks at each stage in the negotiation process,
including carefully proofreading the final version
delivered by the FDA.
The approval letter also will include
instructions to submit the “content of label-
ing” (prescribing information) in SPL format.
In December 2003, the FDA amended its
regulations to require submission of all drug
and biologic labeling in an electronic format.
Following approval, the FDA requires the
submission of the new prescribing informa-
tion in SPL format to the drug establishment
registration and labeling system, which then will
transmit it to the National Library of Medicine
for posting on the DailyMed website.54,55
The approved new or revised labeling should
be expediently distributed within the sponsoring
company to departments for which it serves as
a critical reference, including pharmacovigilance
for determining labeled and unlabeled adverse
events, medical affairs for responding to prod-
uct inquiries, and marketing departments for
support of promotional activities. Company
websites also should be updated with new or
revised labeling when such websites display
current product information. While there are
no regulations regarding timelines for company
website postings, it should be done in a timely
manner. Company management should estab-
lish implementation timelines for its product
labeling, including website posting as well as
packaging printed inserts with products. The
labeling development team must communicate
with the manufacturing site to alert graphics and
packaging engineers to an impending approval so
printed labeling inventory can be appropriately
managed.
Electronic Package Inserts (Paperless
Labeling)
In the US, prescribing information still is required
to physically accompany the product and is usu-
ally packaged with the carton or container. This
situation arises from the provisions of FD&C Act
Section 502 (f)(1), which declares82 a drug is mis-
branded unless its label bears adequate directions
for use, from which prescription medicines are
exempted as long as “[l]abeling on or within the
package from which the drug is to be dispensed
bears adequate information for its use.”83
In other words, in the US, the product
received by pharmacists for dispensing must
be accompanied by (packaged with) approved
prescribing information. This situation persists,
despite advances in information technology that
support reliable electronic access to information,
including drug information.