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Food and Drug Administration, HHS.
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 Start Printed Page 10694marketed 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.
Submit written or electronic comments on agency guidances at any time.
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.Start Further Info
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.End Further Info End Preamble Start Supplemental Information
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.
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 AccessStart Signature
Dated: February 23, 2006.
Assistant Commissioner for Policy.
[FR Doc. E6-2942 Filed 3-1-06; 8:45 am]
BILLING CODE 4160-01-S