Presented by: Edward Basile
THE FDC ACT’S DEFINITION OF
LABELING
• Labeling (21 U.S.C. § 321(m))
– All written, printed, or graphic matter upon an article
or container or accompanying such article.
• Generally, anything written which supplements or
explains the product, is disseminated by the
manufacturer and reaches the customer, doctor,
or patient, before, with, or after the product does,
is labeling.
THE FDC ACT’S DEFINITION OF
LABELING (con’t)
• Labeling is also defined by regulation as
brochures, booklets, mailing pieces, detailing
pieces, file cards, bulletins, calendars, price lists,
catalogs, house organs, letters, motion picture
films, film strips, etc. for use by medical
practitioners, pharmacists or nurses supplied by
the manufacturer, packer or distributor. 21
C.F.R. § 202.1(1)(2).
DEFINITION OF ADVERTISING
• Advertisements regulated under Section 502(n)
are defined by regulation to include
advertisements in published journals, magazines,
other periodicals, and newspapers, and
advertisements broadcast through media such as
radio, television, and telephone communications
systems. 21 C.F.R. §202.1(1)(1).
FDA AUTHORITY OVER LABELING AND
ADVERTISING (con’t)
• Misbranding
– A drug, device, or biologic is considered misbranded
and subject to FDA enforcement action if its labeling is
false or misleading in any particular. (21 U.S.C. §
352(a)).
• Includes failure to reveal material facts (21 U.S.C. § 321
(n)). (321(n) refers to labeling or advertising.)
FDA AUTHORITY OVER LABELING AND
ADVERTISING (con’t)
• Prescription drug is misbranded if all advertisements and other descriptive printed matter does
not contain a true statement of information or
brief summary relating to side effects,
contraindications, and effectiveness as required by
FDA regulations. (21 U.S.C. § 352(n)).
FDA AUTHORITY OVER LABELING AND
ADVERTISING (con’t)
• Restricted device (includes all Class III PMA
devices) is misbranded if all advertisements and
other descriptive printed matter do not contain a
brief statement of the intended uses of the device
and relevant warnings, precautions, side effects
and contraindications. (21 U.S.C. § 352(r)).
PRE-APPROVAL PROMOTION
• FDA prohibits pre-approval promotion of an
investigational biologic or drug. 21 C.F.R. §
312.7(a).
• Failure to adhere to § 312.7(a) is a violation of the
IND regulations and can result in termination of
the IND or other FDA enforcement action. 21
C.F.R. § 312.44(b)(1)(v) and (2)(1).
• Promotion of an investigational device is
prohibited, and subjects the violator to FDA
enforcement action. 21 C.F.R. § 812.7
PRE-APPROVAL PROMOTION (con’t)
Drugs and Biologics
• FDA does permit limited preapproval advertising
for drugs and biologics
– “Institutional” advertising that states a named drug
company is conducting research in a certain therapeutic
area to develop new and important drugs. (May not
mention drug name.)
– “Coming Soon” advertisements announce the
impending availability of a named drug product. (May
not include information on intended use, safety, or
effectiveness.)
PRE-APPROVAL PROMOTION (con’t)
Drugs and Biologics
• Once a sponsor uses either an “Institutional” or
“Coming Soon” advertisement for a drug or
biologic, the sponsor may use only that type.
• Usually permitted within six (6) months of
introduction of product.
PRE-APPROVAL PROMOTION
(con’t)
Devices
• For Class III PMA devices, CDRH does not
permit “Coming Soon” advertising.
• A firm may advertise or display a device that is
the subject of a pending 510(k), but a firm may
not take orders or be prepared to take orders, that
might result in contracts for its sale (Compliance
Policy Guide 7124.19; September 24, 1987).
– Where investigation is ongoing, include statement like:
“Caution-Investigational Device Limited by Federal (or
U.S.) Law to Investigational Use.”
PRE-APPROVAL PROMOTION
(con’t)
Methods of Promotion
• Scientific journal articles distributed by a
manufacturer’s representatives are labeling and
can misbrand a product
• A manufacturer can be responsible for
unapproved claims made by a physician or other
third party, if:
– there is a financial relationship between the physician
and the manufacturer, or
– the statements are made at the request of the
manufacturer
OTHER PRE-APPROVAL ACTIVITIES
(con’t)
Recruiting Clinical Investigators
• For unapproved PMA devices, drugs or biologics,
FDA permits manufacturers to distribute “Notices
of Availability of an Investigational Drug/Device/
Biologic” to recruit investigators for clinical
studies.
• Notices must be limited to sponsor’s
name/address; how to apply as an investigator;
how to obtain investigational product; a list of
investigator responsibilities; objective statements
about product; and description of protocol.
CONTINUING MEDICAL
EDUCATION
MANUFACTURER INVOLVEMENT
IN CONTINUING MEDICAL
EDUCATION
• Under 1997 Final Guidance, a manufacturer may
have an independent third party conduct a
scientific/educational activity so long as the
activity does not promote the company’s
investigational products or promote
cleared/approved products for
unapproved/uncleared uses.
• If the activity does not qualify as “independent” of
manufacturer’s influence, it will be regulated as
promotion/advertising for the product.
CONTINUING MEDICAL
EDUCATION (con’t)
• Independence of industry-supported activities is
determined in accordance with the following
criteria (criteria are considered in total; none is
dispositive by itself):
– Control of content and selection of presenters and
moderators
• Whether provider maintains full control over program
content;
CONTINUING MEDICAL
EDUCATION (con’t)
• Whether, in response to provider request, company
suggests speakers who have actively promoted company
products or been subject to complaints about biased
presentations favoring company products;
• Whether Company engages in scripting, targeting points
for emphasis, or other actions influencing program
content;
CONTINUING MEDICAL
EDUCATION (con’t)
–
–
–
–
–
Disclosures
Program focus
Relationship Between Provider and Company
Provider Involvement in Sales or Marketing
Provider’s Demonstrated Failure to Meet
Standards
– Opportunities for Discussion
– Audience Selection
PRESS RELEASES
• Product-specific press releases, including those
targeted to investors and regulated by the SEC,
may be subject to FDA scrutiny (e.g., as
“labeling,” “advertising”, and/or material that
demonstrates a manufacturer’s “intended use”).
• Press releases must be accurate and consistent
with approved labeling or indications that have
been cleared for a product.
FDA REGULATION OF THE
INTERNET
INFORMATION ON THE
INTERNET
• Information on the Internet is treated as
labeling and subject to all of the laws and
regulations governing labeling
• FDA has been very active in reviewing
websites and citing companies for violations.
INFORMATION ON THE
INTERNET (con’t)
• Links. “What you link, becomes yours.”
– Links between web sites that discuss approved
products and approved uses do not create regulatory
issues.
– Links to third-party web sites that have a major focus
on unapproved uses is prohibited.
– FDA’s unwritten policy is that it is permissible to link
a corporate home page to another corporate home
page that does provide specific information about
approved uses in a foreign country, even though those
are not approved in the U.S.
INFORMATION ON THE
INTERNET (con’t)
• Disclaimers. In certain circumstances (the financial
section that targets potential investors) FDA seems
comfortable with disclaimers to indicate that the
product is not yet approved in the U.S.
• Interactive sites.
– Manufacturers may sponsor interactive site where
consumers can communicate on-line, including about offlabel uses.
INFORMATION ON THE
INTERNET (con’t)
• Risk Disclosure. FDA has informally stated that
Web page information should include prominent
discussion of side effects and risks associated with
products, and that manufacturers should adhere
strictly to agency-approved labeling when
discussing risks and instructions for use.
ENFORCEMENT OF PROMOTION
AND ADVERTISING REGULATIONS
WHAT ARE THE CONSEQUENCES
OF ILLEGAL PROMOTION
• Illegal promotion is a violation of the
FFDCA and subjects the responsible
company and individuals to certain
sanctions:
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–
–
–
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Criminal Prosecution
Criminal Fines
Injunction
Warning Letter
Untitled Letter
WARNING LETTERS FOR ILLEGAL
PROMOTION DURING “FOCUS GROUPS”
• Hemispherx Biopharma received a warning letter
for promoting an investigational new drug at a
teleconference.
• Schering Corporation received a warning letter for
illegal promotional presentations given at
“interactive scientific teleconferences” or “market
research” (i.e., focus groups).
• FDA required Schering to send corrective “Dear
Doctor” letters to all persons who participated in
the programs or otherwise received the violative
message.