[Federal Register Volume 73, Number 60 (Thursday, March 27, 2008)]
[Notices]
[Pages 16311-16312]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-6210]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0180]


Draft Guidance for Industry on Coronary Drug Eluting Stents-
Nonclinical and Clinical Studies; Availability

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice.

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SUMMARY:  The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Coronary Drug 
Eluting Stents--Nonclinical and Clinical Studies.'' This draft guidance 
is intended to provide recommendations to sponsors or applicants 
planning to develop, or to submit to FDA, a marketing application for a 
coronary drug eluting stent (DES). The draft guidance discusses the 
clinical studies that should be performed and the data that should be 
submitted to support such an application. The draft guidance is being 
issued in two parts. The companion document provides additional and 
more detailed guidance on some of the recommendations included in this 
document. The companion document is intended to be used together with 
this draft guidance.

DATES:  Although you can comment on any guidance at any time (see 21 
CFR 10.115(g)(5)), to ensure that the agency considers your comment on 
this draft guidance before it begins work on the final version of the 
guidance, submit written or electronic comments on the draft guidance 
by July 25, 2008.

ADDRESSES:  Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. Submit written comments on the draft guidance to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic 
comments to

[[Page 16312]]

http://www.regulations.gov. See the SUPPLEMENTARY INFORMATION section 
for electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:
    Ashley Boam, Center for Devices and Radiological Health (HFZ-450), 
Food and Drug Administration, 9200 Corporate Blvd., Rockville, MD 
20850, 240-276-4222, or
    Devi Kozeli, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 4183, Silver 
Spring, MD 20903-0002, 301-796-1128.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Coronary Drug Eluting Stents--Nonclinical and Clinical 
Studies.'' Coronary stents are implantable devices that are placed 
percutaneously in one or more coronary arteries to maintain patency. As 
defined by section 503(g) of the Federal Food, Drug, and Cosmetic Act 
(21 U.S.C. 353(g)), DESs are considered combination products because 
they are a combination of two different types of regulated components 
(a device and a drug) that are physically and/or chemically combined 
and produced as a single entity (21 CFR 3.2(e)(1)). A combination 
product is assigned to an agency component, such as the Center for 
Devices and Radiological Health (CDRH) or the Center for Drug 
Evaluation and Research (CDER) for premarket review and regulation 
based on a determination of the product's primary mode of action. In 
response to several requests for designation under 21 CFR 3.7, the 
agency determined that the primary mode of action for current DESs is 
that of the device component in maintaining coronary artery patency; 
the drug component plays a secondary role in preventing restenosis, 
augmenting the safety and/or effectiveness of the uncoated (bare) 
stent.\1\ Therefore, the premarket review and regulatory responsibility 
has been assigned to CDRH. Nevertheless, careful consideration should 
be given to characterizing the drug component of DESs. This draft 
guidance is intended to provide recommendations on meeting the 
regulatory requirements for both the drug and device components of a 
DES.
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    \1\ See ``Jurisdictional Update: Drug-Eluting Cardiovascular 
Stents,'' http://www.fda.gov/oc/combination/stents.html. This 
Jurisdictional Update is applicable to DESs for which the primary 
mode of action is the device component in maintaining vessel 
patency. However, a DES for which the primary mode of action is 
attributable to the drug component would be assigned to CDER.
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    DESs incorporate a pharmacologically active agent (drug) that is 
delivered at the site of stent deployment to reduce the incidence of 
restenosis due to neointimal hyperplasia associated with bare metal 
stenting. In many cases, the drug is incorporated into and released 
from a polymeric coating of sufficient capacity to accommodate the 
selected dose and to modulate its delivery at the intended site of 
action and for the intended duration. The chemical, physical, and 
mechanical attributes of the polymer coating system are important for 
stent deployment, biocompatibility, and stability. To perform a 
regulatory assessment of a DES, FDA must review data from a 
comprehensive evaluation of individual components (drug, polymer, and 
stent), as well as from a comprehensive evaluation of the finished 
drug-device combination product.
    This draft guidance clarifies a number of issues related to the 
development DESs including the following.
     How to characterize the drug substance, including 
chemistry, nonclinical systemic and local tissue pharmacology and 
toxicology, and how to evaluate potential for and consequences of 
systemic clinical exposure.
     How to characterize the drug-device combination product, 
including the chemical/physical/mechanical properties of the DES, the 
nonclinical local vascular and regional myocardial toxicology, and the 
clinical performance of the drug-stent combination.
     Regulatory considerations that are unique to DES 
combination products.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the agency's current thinking on this topic. 
It does not create or confer any rights for or on any person and does 
not operate to bind FDA or the public. An alternative approach may be 
used if such approach satisfies the requirements of the applicable 
statutes and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document. Received comments may be seen in the 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.
    Please note that on January 15, 2008, the FDA Division of Dockets 
Management Web site transitioned to the Federal Dockets Management 
System (FDMS). FDMS is a Government-wide, electronic docket management 
system. Electronic comments or submissions will be accepted by FDA 
through FDMS only.

III. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collections of information in 21 CFR part 211 (current good 
manufacturing practice for finished pharmaceuticals) have been approved 
under OMB control number 0910-0139. The collections of information in 
21 CFR parts 312 (investigational new drug application) and 314 
(applications for FDA approval to market a new drug) have been approved 
under OMB control numbers 0910-0014 and 0910-0001. The collections of 
information in FDA's medical devices regulations in 21 CFR parts 801 
(labeling), 803 (medical device reporting), 812 (investigational device 
exemptions), 814 (premarket approval of medical devices), and 820 
(quality system regulation) have been approved under OMB control 
numbers 0910-0485, 0910-0437, 0910-0078, 0910-0231, and 0910-0073.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/ohrms/dockets/default.htm.

    Dated: March 21, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-6210 Filed 3-26-08; 8:45 am]
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