Robert J. Berlin, JD, MPH
The primary mission of the US Food and Drug
Administration (FDA) is to ensure the safety
and efficacy of drugs, medical devices, and
biological products.1The FDA’s Center for Drug
Evaluation and Research (CDER) is responsible
for the safety and efficacy of drugs, including
certain therapeutic biological drugs.2Although
CDER must exercise stringent control to ensure
drugs’efficacy and safety,itmustalsoensure that
vitally needed products receive timely approval.
Four major legislative and regulatory tools aid in
that process: accelerated approvals, priority re-
views, orphan drug designations, and fast-track
Accelerated approval, which was established
through a notice in the Federal Register on De-
products that treat serious unmet clinical needs
have been gathered. These approvals are based
on an FDA finding that a surrogate marker of
efficacy (or surrogate endpoint) has been satis-
fied.4For example, the FDA usually wants to
know if a new chemotherapeutic agent increases
patient survival time compared with the current
standard of care or placebo. Because gathering
such data can take manyyears, a delay in time to
instead of survival time. Generally, the FDA
requires that surrogate endpoint evidence be
compelling. In addition, such approvals are often
made with the promise that the manufacturer
to ensure that the surrogate endpoint findings
truly reflect the product’s safety and efficacy.4
Priority review, which was established as a
result of the Prescription Drug User Fee Act
of 1992,5is the process by which products
submitted to the FDA receive faster review.
This designation is typically given to products
that, if approved, will represent a substantial
improvement over current treatment options.6
The targeted review time for these products
is 6 months rather than the standard 12
The Orphan Drug Act of 19838established
the orphan drug designation, which is given to
products that treat rare conditions or diseases.9
Theorphan drug system is administered through
interactions between the Office of Orphan Pro-
duct Development and the relevant FDA center,
usually CDER. Orphan drug designations can be
made at or prior to FDA approval. Orphan
fees10and extended patent exclusivity.1 1
Fast-track designation, which was added to
the FDA’s regulatory arsenal in 1997 under
the Food and Drug Administration Moderni-
zation Act of1997,12isasupplementaryprocess
to such existing programs as accelerated ap-
proval and priority review. Using the fast-track
process, manufacturers seeking approval for
drugs that treat serious or life-threatening con-
ditions and show the potential to address cur-
rently unmet medical needs receive additional
regulatory assistance. For example, the manu-
facturer seeking approval may have more fre-
quent interactions with the FDA to discuss
product issues or regulatory concerns.
The FDA undoubtedly strives to accurately
categorize the products it examines and to use
consistent procedures for reviewing products.
However, current review processes are not
necessarily ideal. One way to measure the
program’s success would be to observe what
happens once these products enter the market.
A recent US Government Accountability Office
report on the FDA’s postmarket surveillance
provides insight into the efficacy of the FDA’s
postmarket regulation.13I focused on labeling
changes to examine how FDA decisions made
during the approval process related to product
A product’s label describes the risks and
benefits associated with its use.14Under a vari-
ety of circumstances, a manufacturer either must
revise or chooses to revise its product’s label.
Objectives. I examined the relationship between the Food and Drug Admin-
istration’s (FDA’s) use of special regulatory designations and the frequency with
which labels of oncology drugs are revised to explore how the FDA’s designation
of products relates to product development and refinement.
Methods. One hundred oncology drugs, designated by the FDA as accelerated
approval, priority review, orphan drug, or traditional review, were identified
from publicly available information. Drug information for each product was
evaluated to assess the rate at which manufacturers revised product labeling.
Rates were compared between specially categorized products and traditional
review products (e.g., orphan vs nonorphan drugs) to produce revision rate
ratios for each special category.
Results. Labeling for accelerated approval and priority review products are
revised significantly more frequently than are labels for traditional products.
Conclusions. Accelerated approval products are approved based on surrogate
endpoints; this approval process anticipates subsequent labeling refinement.
Priority review products, however, are approved through a process that is
ostensibly as rigorous as traditional review. Their higher than expected label
revision rate may suggest deficiencies in the FDA’s current priority review
evaluation processes. (Am J Public Health. 2009;99:1693–1698. doi:10.2105/
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Berlin | Peer Reviewed | Research and Practice | 1693
first step toward understanding a complex and
difficult topic. j
About the Author
At the time of the study, the author was a student at the
University of Minnesota, Minneapolis.
Requests for reprints should be sent to Robert J. Berlin,
JD, MPH, Hogan & Hartson LLP, 555 13th St NW,
Washington, DC 20004 (e-mail: firstname.lastname@example.org).
This article was accepted October 7, 2008.
I thank Sue Duval and Eileen Harwood of the University
of Minnesota School of Public Health and Ralph Hall
of the University of Minnesota Law School for their
thoughtful review of this article and their vital comments
on the methods and conclusions involved in its devel-
Human Participant Protection
No human participants were involved in the research.
1. US Food and Drug Administration. FDA’s mission
statement. Available at: http://www.fda.gov/opacom/
morechoices/mission.html. Accessed November 21,
Evaluation and Research (CDER). CDER home page.
Available at: http://www.fda.gov/cder/index.html.
Accessed November 21, 2008.
US Food and Drug Administration, Center for Drug
57 Federal Register 58942 (1992).
4. 21 CFR x314.510 (2000).
Prescription Drug User Fee Act of 1992, Pub L No.
management: priority review policy. August 10, 2007.
Available at: http://www.fda.gov/cder/mapp/
6020.3R.pdf. Accessed November 21, 2008.
Center for Drug Evaluation and Research. Review
celerated approval and priority review. Available at:
http://www.fda.gov/oashi/fast.html. Accessed Novem-
ber 21, 2008.
US Food and Drug Administration. Fast track, ac-
8.The Orphan Drug Act, Pub L No. 97-414 (1983).
9.21 USC 360bb (1997).
10. US Food and Drug Administration, Office of Orphan
Products Development (OOPD). OOPD frequently asked
questions. Available at: http://www.fda.gov/orphan/
faq/index.htm. Accessed November 21, 2008.
11. 21 CFR x316.31 (2007).
12. Food and Drug Administration Modernization Act
of 1997, Pub L No. 105-115 (1997).
13. US General Accounting Office. FDA drug review:
postapproval risks 1976–85 (1990). Available at: http://
22.214.171.124/d24t8/141456.pdf. Accessed November
14. 21 CFR pt 201 (2007).
15. US Food and Drug Administration, Center for Drug
Evaluation and Research. List of approved oncology
drugs with approved indications. Available at: http://
November 21, 2008.
16. US Food and Drug Administration, Center for Drug
Evaluation and Research. Fast track, priority review
and accelerated approval. Available at: http://www.
Accessed November 21, 2008.
17. US Food and Drug Administration, Center for Drug
Evaluation and Research. Orphan Drug Designation.
Available at: http://www.accessdata.fda.gov/scripts/
cder/onctools/orphan.cfm. Accessed November 21,
18. US Food and Drug Administration, Center for Drug
Evaluation and Research. Drugs@FDA: FDA approved
drug products. Available at: http://www.accessdata.fda.
November 21, 2008.
19. US Food and Drug Administration, Center for Drug
Evaluation and Research. Cumulative list of all products
that have received orphan designation. Available at:
March 17, 2009.
20. US Food and Drug Administration, Center for Drug
Evaluation and Research (CDER). CDER Drug and Bio-
logic Approval Reports. Available at: http://www.fda.gov/
cder/rdmt/default.htm. Accessed March 17, 2009.
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