[Federal Register Volume 71, Number 41 (Thursday, March 2, 2006)]
[Notices]
[Pages 10693-10694]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-2942]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005D-0033]


Guidance for Industry on Internal Radioactive Contamination--
Development of Decorporation Agents; 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 guidance for industry entitled ``Internal Radioactive 
Contamination--Development of Decorporation Agents.'' This document 
provides guidance to industry on the development of decorporation 
agents for the treatment of internal radioactive contamination when 
evidence is needed to demonstrate the effectiveness of the agents, but 
human efficacy studies are unethical or infeasible. In such instances, 
the animal efficacy rule may be invoked to approve new decorporation 
agents not previously

[[Page 10694]]

marketed or new indications for previously marketed drug products. 
Specifically, this guidance addresses chemistry, manufacturing, and 
controls (CMC) information; animal efficacy, safety pharmacology, and 
toxicology studies; clinical pharmacology, biopharmaceutics, and human 
safety studies; and postapproval commitments.

DATES: Submit written or electronic comments on agency guidances at any 
time.

ADDRESSES: Submit written requests for single copies of this guidance 
to the Division of Drug Information (HFD-240), Center for Drug 
Evaluation and Research, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857. Send one self-addressed adhesive label to 
assist that office in processing your requests. Submit written comments 
on the 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 http://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Patricia A. Stewart, Center for Drug 
Evaluation and Research (HFD-160), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-7510.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Internal Radioactive Contamination--Development of 
Decorporation Agents.'' This guidance is being issued to facilitate the 
development of new decorporation agents or new uses of previously 
marketed drug products for the treatment of internal radioactive 
contamination.
    In the Federal Register of February 15, 2005 (70 FR 7747), FDA 
announced the availability of a draft version of the guidance document 
entitled ``Internal Radioactive Contamination--Development of 
Decorporation Agents.'' No comments were received and, with one 
exception, only minor editorial changes have been made. The references 
to biological products have been removed from the guidance because FDA 
does not expect many products developed for use as decorporation agents 
to be biologics.
    Internal radioactive contamination can arise from accidents 
involving nuclear reactors, industrial sources, or medical sources. The 
potential for these accidents has been present for many years. Recent 
events also have highlighted the potential for nonaccidental 
radioactive contamination as a result of criminal or terrorist actions. 
Internal contamination occurs when radioactive material is ingested, 
inhaled, or absorbed from a contaminated wound. As long as these 
radioactive contaminants remain in the body, they may pose significant 
health risks. Long-term health concerns include the potential for the 
development of cancers of the lung, liver, thyroid, stomach, and bone 
and, when a radioactive contaminant is inhaled, for the development of 
fibrotic changes in the lung that may lead to restrictive lung disease. 
The only effective method of reducing these risks is removal of the 
radioactive contaminants from the body.
    ``Decorporation agents'' refer to medical products that increase 
the rate of elimination or excretion of inhaled, ingested, or absorbed 
radioactive contaminants. The effectiveness of most decorporation 
agents for the treatment of internal radioactive contamination cannot 
be tested in humans because the occurrence of accidental or 
nonaccidental radioactive contamination is rare, and it would be 
unethical to deliberately contaminate human volunteers with potentially 
harmful amounts of radioactive materials for investigational purposes.
    FDA is issuing this guidance to industry to facilitate the 
development of new decorporation agents or new indications for 
previously marketed drug products that may be eligible for approval 
under the animal efficacy rule (21 CFR 314.600-314.650). As set forth 
in this rule, under certain circumstances animal studies can be relied 
on to provide substantial evidence of effectiveness of a product. 
Evaluation of the product for safety in humans is still required, and 
cannot be addressed by animal studies alone. The adequacy of human 
safety data will need to be assessed based on clinical pharmacology and 
safety studies conducted in humans. This guidance addresses the design 
and conduct of the requisite CMC, animal efficacy, safety pharmacology, 
toxicology, clinical pharmacology, biopharmaceutics, and human safety 
studies needed to support approval of new decorporation agents or new 
uses of previously marketed drug products for the treatment of internal 
radioactive contamination.
    In addition, approval under the animal efficacy rule is subject to 
certain postapproval commitments, including submission of a plan for 
conducting postmarketing studies that would be feasible should an 
accidental or intentional release of radiation occur; postmarketing 
restrictions to ensure safe use, if deemed necessary; and product 
labeling information intended for the patient advising that, among 
other things, the product's approval was based on effectiveness studies 
conducted in animals alone. This guidance addresses the postapproval 
commitments that would be needed for approval of a new decorporation 
agent or for a new indication for a previously approved drug product 
under the animal efficacy rule.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
agency's current thinking on the development of decorporation agents 
for the treatment of internal radioactive contamination. 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.

III. 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: February 23, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-2942 Filed 3-1-06; 8:45 am]
BILLING CODE 4160-01-S