[Federal Register: February 15, 2005 (Volume 70, Number 30)]
[Notices]               
[Page 7747-7748]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15fe05-77]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005D-0033]

 
Draft Guidance for Industry on Internal Radioactive 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availability of a draft guidance for industry entitled ``Internal 
Radioactive Contamination--Development of Decorporation Agents.'' This 
draft 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 medical products not previously marketed or new indications for 
previously marketed products. Specifically, this draft guidance 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DATES: Submit written or electronic comments on the draft guidance by 
May

[[Page 7748]]

16, 2005. General comments on agency guidance documents are welcome at 
any time.

ADDRESSES:  Submit written requests for single copies of this draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 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on the draft guidance to the Division of Dockets Management (HFA-305), 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 http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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 draft guidance for industry 
entitled ``Internal Radioactive Contamination--Development of 
Decorporation Agents.'' This draft guidance is being issued to 
facilitate the development of new decorporation agents or new uses of 
previously marketed medical products for the treatment of internal 
radioactive contamination.
    Internal radioactive contamination can arise from accidents 
involving nuclear reactors, industrial sources, or medical sources. The 
potential for such accidents has been present for many years. Recent 
events also have highlighted the potential for nonaccidental 
radioactive contamination as a result of malicious, 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 draft guidance to facilitate the development of 
new decorporation agents or new indications for previously marketed 
medical products that may be eligible for approval under the Animal 
Efficacy Rule (21 CFR part 314, subpart I and 21 CFR part 601, subpart 
H). 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 from 
clinical pharmacology and safety studies conducted in humans. This 
draft 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 medical 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 draft 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 
agent under the Animal Efficacy Rule.
    This draft 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 on the guidance at any 
time. Two copies of mailed comments are to be submitted, except that 
individuals may submit one copy. Comments are to be identified with the 
docket number found in brackets in the heading of this document. The 
draft guidance and received comments are available for public 
examination 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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm or http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm.
    Dated: February 4, 2005.

Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-2821 Filed 2-14-05; 8:45 am]

BILLING CODE 4160-01-S