Draft Guidance for Industry on Nonclinical Evaluation of Late Radiation Toxicity of Therapeutic Radiopharmaceuticals; Availability, 35448-35449 [05-12040]
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Federal Register / Vol. 70, No. 117 / Monday, June 20, 2005 / Notices
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 https://www.fda.gov/ohrms/dockets/
default.htm.
Dated: June 9, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05–12039 Filed 6–17–05; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. 2005D–0223]
Draft Guidance for Industry on
Nonclinical Evaluation of Late
Radiation Toxicity of Therapeutic
Radiopharmaceuticals; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is announcing the
availability of a draft guidance for
industry entitled ‘‘Nonclinical
Evaluation of Late Radiation Toxicity of
Therapeutic Radiopharmaceuticals.’’
The purpose of this draft guidance is to
provide recommendations to industry
for designing nonclinical toxicity
studies to determine potential late
radiation toxicities (radiation-induced
injuries occurring after a latency period
of several months to years) of
therapeutic radiopharmaceuticals
administered systemically. The purpose
of such studies is to help minimize the
risk of late-occurring irreversible
VerDate jul<14>2003
17:24 Jun 17, 2005
Jkt 205001
radiation toxicities in clinical studies of
therapeutic radiopharmaceuticals.
DATES: Submit written or electronic
comments on the draft guidance by
September 19, 2005. General comments
on agency guidance documents are
welcome at any time.
ADDRESSES: Submit written requests for
single copies of the 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 selfaddressed 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 https://
www.fda.gov/dockets/ecomments. See
the SUPPLEMENTARY INFORMATION section
for electronic access to the draft
guidance document.
FOR FURTHER INFORMATION CONTACT:
Adebayo Laniyonu or Renee Tyson,
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
‘‘Nonclinical Evaluation of Late
Radiation Toxicity of Therapeutic
Radiopharmaceuticals.’’ The objective of
this guidance is to provide
recommendations to industry for
designing nonclinical toxicity studies to
determine potential late radiation
toxicities of therapeutic
radiopharmaceutical agents. This
guidance is not intended for diagnostic
radiopharmaceuticals or for
radiobiologicals (e.g., radiolabeled
monoclonal antibodies).
Late radiation toxicity differs from
early or acute radiation toxicity. Acute
radiation toxicity (e.g., bone marrow
failure, nausea, vomiting, diarrhea, and
oral mucositis) occurs within days to
weeks of an acute dose of radiation and
is often self-limiting and reversible. In
contrast, late radiation toxicity (e.g.,
renal failure, pulmonary fibrosis, and
chord transection) occurs after a latency
period of several months to years,
during which relatively normal organ
function continues. Late radiation
toxicity is usually progressive and
irreversible.
Therapeutic radiopharmaceuticals are
typically administered systemically to
treat cancer. The radiation absorbed
PO 00000
Frm 00056
Fmt 4703
Sfmt 4703
doses delivered by therapeutic
radiopharmaceuticals may be
comparable to those delivered with
external beam radiotherapy (XRT). At
therapeutic doses of radiation, the late
radiation toxicities commonly
associated with XRT (e.g., brain
necrosis, paralysis, pulmonary fibrosis,
liver or kidney failure, and hemorrhagic
cystitis) can also be seen with
therapeutic radiopharmaceuticals. With
XRT, if the total dose given to an organ
is less than its tolerance dose, the
probability of symptomatic late
radiation toxicity to that organ will be
minimal. The tolerance doses of most
human organs for conventional
fractionated XRT are known, and are
routinely used to direct the safe
administration of XRT. In FDA’s
experience, however, there are few
clinical data from which to estimate
organ tolerance doses for therapeutic
radiopharmaceuticals. Furthermore, late
radiation toxicity has been observed
when Medical Internal Radiation Dose
(MIRDOSE) estimates of radiation
absorbed doses delivered by therapeutic
radiopharmaceuticals to target organs
were substantially below the published
XRT organ tolerance doses.
Therefore, there is a need to gain
additional knowledge in this area to
support the safe administration of
therapeutic radiopharmaceuticals to
humans. Because studies in humans
would be unethical, the best means to
gain insight into this issue is by
conducting nonclinical late radiation
toxicity studies. These studies will aid
in identifying organs at risk and
establish a margin of safety for late
radiation toxicity. As a result, these
studies will help to minimize the risk of
late-occurring radiation toxicities in
clinical studies of therapeutic
radiopharmaceuticals.
This draft guidance focuses solely on
late radiation safety concerns that are
unique to therapeutic
radiopharmaceuticals, and provides
recommendations for late radiation
toxicity nonclinical study designs
including issues regarding good
laboratory practices, species selection,
dose selection, timing of study, and
study parameters.
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 nonclinical evaluation of late
radiation toxicity of therapeutic
radiopharmaceuticals. 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
E:\FR\FM\20JNN1.SGM
20JNN1
Federal Register / Vol. 70, No. 117 / Monday, June 20, 2005 / Notices
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. The draft
guidance and 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 https://www.fda.gov/ohrms/dockets/
default.htm.
Dated: June 9, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05–12040 Filed 6–17–05; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HOUSING AND
URBAN DEVELOPMENT
[Docket No. FR–4975–N–18]
Notice of Proposed Information
Collection: Comment Request;
Request for Credit Approval of
Substitute Mortgagor
Office of the Assistant
Secretary for Housing-Federal Housing
Commissioner, HUD.
ACTION: Notice.
AGENCY:
SUMMARY: The proposed information
collection requirement described below
will be submitted to the Office of
Management and Budget (OMB) for
review, as required by the Paperwork
Reduction Act. The Department is
soliciting public comments on the
subject proposal.
DATES: Comments Due Date: August 19,
2005.
ADDRESSES: Interested persons are
invited to submit comments regarding
this proposal. Comments should refer to
the proposal by name and/or OMB
Control Number and should be sent to:
Wayne Eddins, Reports Management
Officer, Department of Housing and
Urban Development, 451 7th Street,
SW., L’Enfant Plaza Building, Room
8001, Washington, DC 20410 or
Wayne_Eddins@hud.gov.
VerDate jul<14>2003
17:24 Jun 17, 2005
Jkt 205001
FOR FURTHER INFORMATION CONTACT:
Joseph McCloskey, Director, Office of
Single Family Asset Management, 451
7th Street SW., Washington, DC 20410,
telephone (202) 708–1672 (this is not a
toll free number) for copies of the
proposed forms and other available
information.
The
Department is submitting the proposed
information collection to OMB for
review, as required by the Paperwork
Reduction Act of 1995 (44 U.S.C.
Chapter 35, as amended).
This Notice is soliciting comments
from members of the public and affected
agencies concerning the proposed
collection of information to: (1) Evaluate
whether the proposed collection is
necessary for the proper performance of
the functions of the agency, including
whether the information will have
practical utility; (2) Evaluate the
accuracy of the agency’s estimate of the
burden of the proposed collection of
information; (3) Enhance the quality,
utility, and clarity of the information to
be collected; and (4) Minimize the
burden of the collection of information
on those who are to respond; including
the use of appropriate automated
collection techniques or other forms of
information technology, e.g., permitting
electronic submission of responses.
This Notice also lists the following
information:
Title of Proposal: Request for Credit
Approval of Substitute Mortgagor.
OMB Control Number, if applicable:
2502–0036.
Description of the need for the
information and proposed use: This
information collection is used by HUD
to approve the credit of a substitute
mortgagor who desires to assume an
FHA-insured mortgage. The information
is also needed to document the financial
stability of the mortgagor.
Agency form numbers, if applicable:
HUD–92210 and HUD–92210.1.
Estimation of the total numbers of
hours needed to prepare the information
collection including number of
respondents, frequency of response, and
hours of response: The estimated total
number of hours needed to prepare the
information collection is 2,400. The
number of respondents is 600 generating
approximately 2,400 annual responses,
the frequency of response is on
occasion, and the number of hours per
response is one.
Status of the proposed information
collection: Currently approved.
SUPPLEMENTARY INFORMATION:
Authority: The Paperwork Reduction Act
of 1995, 44 U.S.C., Chapter 35, as amended.
PO 00000
Frm 00057
Fmt 4703
Sfmt 4703
35449
Dated: June 3, 2005.
Frank L. Davis,
General Deputy Assistant Secretary for
Housing-Deputy Federal Housing
Commissioner.
[FR Doc. 05–12027 Filed 6–17–05; 8:45 am]
BILLING CODE 4210–27–P
DEPARTMENT OF THE INTERIOR
Fish and Wildlife Service
Notice of Availability of the Draft
Comprehensive Conservation Plan and
Environmental Assessment for Sand
Lake National Wildlife Refuge,
Columbia, SD
Fish and Wildlife Service,
Interior.
ACTION: Notice of Availability.
AGENCY:
SUMMARY: The U.S. Fish and Wildlife
Service (Service) announces that the
Draft Comprehensive Conservation Plan
and Environmental Assessment (CCP/
EA) for the Sand Lake National Wildlife
Refuge (Refuge) is available for public
review and comment. This Draft CCP/
EA was prepared pursuant to the
National Wildlife Refuge System
Administration Act, as amended, and
the National Environmental Policy Act
(NEPA). The Draft CCP/EA describes the
Service’s proposal for management of
the Refuge for 15 years.
DATES: Written comments must be
received at the postal or electronic
addresses listed below by July 20, 2005.
Comments may also be submitted VIA
electronic mail to:
kathleen_linder@fws.gov.
To provide written
comments or to obtain a copy of the
Draft CCP/EA, please write to Linda
Kelly, Planning Team Leader, U.S. Fish
and Wildlife Service, P.O. Box 25486,
Denver Federal Center, Denver, CO
80225–0486; (303) 236–8132; fax
(303)236–4792, or Gene Williams,
Refuge Manager, Sand Lake National
Wildlife Refuge, 39650 Sand Lake Drive,
Columbia, South Dakota 57433; (605)
885–6320; fax (605) 885–6401. The Draft
CCP/EA will also be available for
viewing and downloading online at
https://mountain-prairie.fws.gov/
planning.
ADDRESSES:
FOR FURTHER INFORMATION CONTACT:
Linda Kelly, Planning Team Leader at
the above address or at (303) 236–8132.
SUPPLEMENTARY INFORMATION: The
National Wildlife System
Administration Act of 1966, as amended
by the National Wildlife Refuge
Improvement Act of 1997 (16 U.S.C.
668dd-668ee et seq), requires the
E:\FR\FM\20JNN1.SGM
20JNN1
]]>Agencies
[Federal Register Volume 70, Number 117 (Monday, June 20, 2005)]
[Notices]
[Pages 35448-35449]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-12040]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2005D-0223]
Draft Guidance for Industry on Nonclinical Evaluation of Late
Radiation Toxicity of Therapeutic Radiopharmaceuticals; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled ``Nonclinical
Evaluation of Late Radiation Toxicity of Therapeutic
Radiopharmaceuticals.'' The purpose of this draft guidance is to
provide recommendations to industry for designing nonclinical toxicity
studies to determine potential late radiation toxicities (radiation-
induced injuries occurring after a latency period of several months to
years) of therapeutic radiopharmaceuticals administered systemically.
The purpose of such studies is to help minimize the risk of late-
occurring irreversible radiation toxicities in clinical studies of
therapeutic radiopharmaceuticals.
DATES: Submit written or electronic comments on the draft guidance by
September 19, 2005. General comments on agency guidance documents are
welcome at any time.
ADDRESSES: Submit written requests for single copies of the 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 https://www.fda.gov/dockets/
ecomments. See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft guidance document.
FOR FURTHER INFORMATION CONTACT: Adebayo Laniyonu or Renee Tyson,
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 ``Nonclinical Evaluation of Late Radiation Toxicity of
Therapeutic Radiopharmaceuticals.'' The objective of this guidance is
to provide recommendations to industry for designing nonclinical
toxicity studies to determine potential late radiation toxicities of
therapeutic radiopharmaceutical agents. This guidance is not intended
for diagnostic radiopharmaceuticals or for radiobiologicals (e.g.,
radiolabeled monoclonal antibodies).
Late radiation toxicity differs from early or acute radiation
toxicity. Acute radiation toxicity (e.g., bone marrow failure, nausea,
vomiting, diarrhea, and oral mucositis) occurs within days to weeks of
an acute dose of radiation and is often self-limiting and reversible.
In contrast, late radiation toxicity (e.g., renal failure, pulmonary
fibrosis, and chord transection) occurs after a latency period of
several months to years, during which relatively normal organ function
continues. Late radiation toxicity is usually progressive and
irreversible.
Therapeutic radiopharmaceuticals are typically administered
systemically to treat cancer. The radiation absorbed doses delivered by
therapeutic radiopharmaceuticals may be comparable to those delivered
with external beam radiotherapy (XRT). At therapeutic doses of
radiation, the late radiation toxicities commonly associated with XRT
(e.g., brain necrosis, paralysis, pulmonary fibrosis, liver or kidney
failure, and hemorrhagic cystitis) can also be seen with therapeutic
radiopharmaceuticals. With XRT, if the total dose given to an organ is
less than its tolerance dose, the probability of symptomatic late
radiation toxicity to that organ will be minimal. The tolerance doses
of most human organs for conventional fractionated XRT are known, and
are routinely used to direct the safe administration of XRT. In FDA's
experience, however, there are few clinical data from which to estimate
organ tolerance doses for therapeutic radiopharmaceuticals.
Furthermore, late radiation toxicity has been observed when Medical
Internal Radiation Dose (MIRDOSE) estimates of radiation absorbed doses
delivered by therapeutic radiopharmaceuticals to target organs were
substantially below the published XRT organ tolerance doses.
Therefore, there is a need to gain additional knowledge in this
area to support the safe administration of therapeutic
radiopharmaceuticals to humans. Because studies in humans would be
unethical, the best means to gain insight into this issue is by
conducting nonclinical late radiation toxicity studies. These studies
will aid in identifying organs at risk and establish a margin of safety
for late radiation toxicity. As a result, these studies will help to
minimize the risk of late-occurring radiation toxicities in clinical
studies of therapeutic radiopharmaceuticals.
This draft guidance focuses solely on late radiation safety
concerns that are unique to therapeutic radiopharmaceuticals, and
provides recommendations for late radiation toxicity nonclinical study
designs including issues regarding good laboratory practices, species
selection, dose selection, timing of study, and study parameters.
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 nonclinical
evaluation of late radiation toxicity of therapeutic
radiopharmaceuticals. 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
[[Page 35449]]
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. The draft guidance and 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 https://www.fda.gov/cder/guidance/index.htm or https://
www.fda.gov/ohrms/dockets/default.htm.
Dated: June 9, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-12040 Filed 6-17-05; 8:45 am]
BILLING CODE 4160-01-S
