Office of Establishment Licensing and Product Surveillance
Advertising and Promotional Labeling Staff
[PDF version of this document]
Procedural Guidance Document
Draft
August 1994
This document has been revised to address comments received subsequent to the announcement of availability in the Federal Register dated August 9, 1993. This document replaces the previous edition dated July 1993.
The Advertising and Promotional Labeling Staff Procedural Guide
Introduction
This guidance document was developed to assist manufacturers in understanding
the current procedures to be followed for the submission of promotional
labeling and advertising materials to the Center for Biologics Evaluation and
Research. FDA is currently reviewing its regulation on guidelines in 21 CFR
10.90(b), and therefore, this document is not issued under this regulation.
As with other guidance documents, FDA does not view this document as all
inclusive, and recognizes that alternative approaches may be suitable in
specific situations. This document does not bind FDA and does not create or
confer any rights, privileges, or benefits on or for any person, and is
intended merely for guidance.
Procedure
In an effort to reduce the burden of reporting, the Center for Biologics
Evaluation and Research (CBER) is providing guidance on its current
interpretation of the regulation for reporting important proposed changes in
the labeling of biologic products, as applicable to promotional labeling [see
21 CFR 601.12]. This document does not change the procedures to be followed
for the submission of changes to container or package labels, and circulars
(package inserts). Labeling (which includes promotional labeling) is defined
in section 201(m) of the Act, promotional labeling is described in 21 CFR
202.1(l)(2) and is subject to various provisions in the Act including sections
502(a) and (f). Examples of advertisements subject to section 502(n) of the
Federal Food, Drug and Cosmetic Act are described in 21 CFR 202.1(l)(1) of the
regulations.
For promotional labeling, CBER has determined that preapproval is required only
for any biological product for which a license is pending, for "newly approved"
products (the first 120 days following approval), and any licensed biological
products for which a supplement has been filed that requests or would require a
labeling change. Supplements requiring a change in the labeling include new
indications for use, new dosage forms or dosing regimens, expanded patient
population and additional safety or effectiveness information.
Manufacturers of biological products reviewed under the Accelerated Approval
regulations [Reference 21 CFR 601 Subpart E] must continue to submit, after the
120 days following approval, all promotional materials, including promotional
labeling and advertising, at least 30 days prior to the intended time of
distribution and/or dissemination, until otherwise notified by this Center.
For introductory advertising materials, it is requested that manufacturers
continue to submit before publication/dissemination, for review only, proposed
drafts of introductory advertising materials including "Coming Soon"
advertisements, launch advertisements and those advertisements intended to be
used in the first 120 days following approval.
CBER will review all advertising and promotional labeling for products that
have been licensed for more than 120 days on a surveillance basis (except as
noted above for products reviewed under the Accelerated Approval regulations).
The FDA form 2567 is to be used for all introductory advertising and
promotional labeling, all materials following approval, as well as any
submission for a request for review and comment. Applicants should submit all
proposed drafts of introductory advertising and promotional labeling, including
all "Coming Soon" pieces and "launch" materials in duplicate with Part I of the
form FDA-2567, to the Advertising and Promotional Labeling Staff (APLS) prior
to the issuance of a biological product license and/or receipt of an approval
letter.
Applicants may request the APLS to review and comment on a proposed promotional
labeling piece or an advertising campaign at any time. This request should be
in writing, accompanied by Part I of the form FDA-2567 and sent directly to
APLS.
Applicants should continue to submit to APLS final copies of all advertising
and promotional labeling with Part II of the form FDA-2567, at the time of
initial publication of the advertisement or distribution of the promotional
labeling, for inclusion in their product files.
Part II of the completed form FDA-2567 should accompany all final printed,
published or produced material and all media.
Please follow the instructions provided below in completing the form FDA-2567:
- The form should be typed.
- Include the license number and name of the firm in the space provided for
the manufacturer's name.
If a license is pending and has not been issued, or if the submission
reflects information contained in a supplement to an existing Product
License Application, include the reference number of the pending
submission.
- The form should be signed by the responsible head with the typed name also
appearing (signatures are often difficult to read).
- List the in-house control number and revision date for each piece.
- To minimize delays, we suggest using one completed form per piece to be
reviewed. This will enable APLS to process through ("clear") the material
found to have no objection for use. However, similar and closely related
materials may be submitted on one form.
- If the material was previously reviewed by us, include the label review
number previously assigned to the piece in the appropriate space on the
form.
Prior to dissemination of introductory or launch promotional labeling,
manufacturers need to obtain APLS review and approval. Advertisements for use
in launch campaigns will be reviewed for consistency against other launch
materials to be used in the first 120 day period.
All advertising materials and promotional labeling for all biologic products
will be monitored to determine that they:
- are not false or misleading in any particular manner;
For example, a sponsor cannot make claims of greater safety and or
efficacy than what was demonstrated in clinical trials used to support
licensure or make "global" claims of efficacy or safety on the basis of
results obtained in one trial with a limited scope.
- are consistent with the current approved labeling (package insert) or
applicable sections of the FD&C; Act and regulations concerning advertising
and labeling, clinical trial data used to support licensure, relevant
information contained in the Summary Basis of Approval (SBA) and when
applicable, previously approved promotional labeling;
- present a "fair balance" of information about the product;
Applicants should balance claims of safety or efficacy with related
information regarding any safety concerns or side effects, etc.
- include proper prescribing information (a minimum of a "brief summary" for
advertisements and full prescribing information for all promotional
labeling).
[Reference FD&C; 502(a)&(f); 502(n)1,2,&3; 21 CFR 201.100(d) and 21 CFR
202.1]
The review time for introductory or launch campaigns depends directly on the
scope, completeness of the submission, and the depth and expanse of the initial
campaigns. APLS anticipates the average review time to be approximately four
weeks from the date the material is received by the staff.
After APLS completes its review of the new promotional material , APLS will
notify the manufacturer of the completion of the review by a previously agreed
upon form of electronic communication and followed up with hard copy by mail.
The hard copy constitutes the official acknowledgement.
If problems are discovered in the course of the review, the APLS staff may
contact the Responsible Head or approved alternate Responsible Head in the
event of an unavoidable absence. APLS will provide comments and requests for
modifications or revisions will be in writing and noted on Part I of the form
FDA 2567 unless otherwise discussed and noted. APLS will arrange meetings
between the manufacturer, the CBER review division, and any other parties or
disciplines involved, to resolve outstanding issues as needed.
Upon resolution of any problems encountered during the review, manufacturers
should send the corrected material as final copy, in duplicate with Part II of
form FDA-2567, along with a copy of the package insert to the APLS as a routine
submission for record purposes.
Following the 120 day period after approval, manufacturers are requested to
submit final printed copies of all advertising and promotional labeling at the
time of initial publication or dissemination to allow the APLS to review the
materials on a surveillance basis. As stated earlier in this document,
manufacturers of those products reviewed under the Accelerated Approval
regulations are required after the 120 day period following approval, to submit
promotional materials at least 30 days prior to their intended distribution
and/or dissemination until otherwise notified by this Center.
When manufacturers make changes to the approved package insert that affect the
message in their promotional materials, manufacturers should submit proposed
copies of all affected advertising and promotional labeling identifying the
changes in the comment section of Part I of the form FDA 2567. Manufacturers
should submit the revised package insert with the revised promotional
materials. In those cases where the printing or inclusion of the full
prescribing information is integrated into the promotional labeling piece, as
in file cards or brochures, the material should be resubmitted as a "new"
piece.
If the information or message in the promotional materials is not affected by
the labeling change and the full prescribing information is included in a
separate pocket or sleeve, then it is not necessary to resubmit the product
promotional materials. However, it is the responsibility of the manufacturer
to ensure that the previous version of the package insert (full prescribing
information) has been replaced with the most recent, approved package insert
prior to distribution or dissemination.
The staff may initiate regulatory action if the advertising and promotional
labeling are not consistent with the approved labeling (package insert),
clinical data used to approve the product, or applicable sections of the FD&C;
Act and regulations for labeling and advertising by notifying the manufacturer
in writing of the violations. If significant problems in the advertising or
promotional labeling are discovered that could pose a potential health hazard,
or if violations as cited in previous correspondence persist, a "Warning"
letter may be issued. These letters will request that corrective actions be
taken, including the material in question be discontinued or canceled promptly.
If further regulatory action is warranted (e.g., because of past history or if
dissemination of the material poses a potential health hazard), APLS will work
with the Office of Compliance to implement appropriate compliance actions as
necessary.
The effective date for implementation of this revised procedure by the
Advertising and Promotional Labeling Staff is July, 1994.
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