Guidance for Industry on Nonclinical Evaluation of Late Radiation Toxicity of Therapeutic Radiopharmaceuticals; Availability, 72952-72953 [2011-30474]
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Federal Register / Vol. 76, No. 228 / Monday, November 28, 2011 / Notices
pmangrum on DSK3VPTVN1PROD with NOTICES
detection, or detection and
differentiation, of human
papillomaviruses.
DATES: Submit either electronic or
written comments on this guidance at
any time. General comments on Agency
guidance documents are welcome at any
time.
ADDRESSES: Submit written requests for
single copies of the guidance document
entitled ‘‘Establishing the Performance
Characteristics of In Vitro Diagnostic
Devices for the Detection or Detection
and Differentiation of Human
Papillomaviruses’’ to the Division of
Small Manufacturers, International, and
Consumer Assistance, Center for
Devices and Radiological Health, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 4613,
Silver Spring, MD 20993–0002. Send
one self-addressed adhesive label to
assist that office in processing your
request, or fax your request to (301)
847–8149. See the SUPPLEMENTARY
INFORMATION section for information on
electronic access to the guidance.
Submit electronic comments on the
guidance to https://www.regulations.gov.
Submit written comments to the
Division of Dockets Management (HFA–
305), Food and Drug Administration,
5630 Fishers Lane, Rm. 1061, Rockville,
MD 20852. Identify comments with the
docket number found in brackets in the
heading of this document.
FOR FURTHER INFORMATION CONTACT: Kate
Simon, Center for Devices and
Radiological Health, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 5552, Silver Spring,
MD 20993–0002, (301) 796–6210.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is issuing this guidance to
provide industry and Agency staff with
recommendations for studies to
establish the performance
characteristics of IVDs intended for the
detection, or detection and
differentiation, of human
papillomaviruses. These devices are
used in conjunction with cervical
cytology to aid in screening for cervical
cancer. They include devices that detect
a group of human papillomavirus (HPV)
genotypes, particularly high risk human
papillomaviruses, as well as devices
that detect more than one genotype of
HPV and further differentiate among
them to indicate which genotype(s) of
HPV is (are) present.
In the Federal Register of September
9, 2009 (74 FR 46433), FDA announced
the availability of the draft guidance.
Comments on the draft guidance were
due by December 8, 2009. Five
VerDate Mar<15>2010
15:34 Nov 25, 2011
Jkt 226001
comments were received on the
guidance document. We reviewed the
comments and took their suggestions
into consideration in revising this
guidance.
II. Significance of Guidance
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 establishing the
performance characteristics of in vitro
diagnostic devices for the detection or
detection and differentiation of human
papillomaviruses. 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 statute
and regulations.
III. Electronic Access
Persons interested in obtaining a copy
of the guidance may do so by using the
Internet. A search capability for all
CDRH guidance documents is available
at https://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/
GuidanceDocuments/default.htm.
Guidance documents are also available
at https://www.regulations.gov. To
receive ‘‘Establishing the Performance
Characteristics of In Vitro Diagnostic
Devices for the Detection or Detection
and Differentiation of Human
Papillomaviruses,’’ you may either send
an email request to dsmica@fda.hhs.gov
to receive an electronic copy of the
document or send a fax request to (301)
847–8149 to receive a hard copy. Please
use the document number 1740 to
identify the guidance you are
requesting.
IV. Paperwork Reduction Act of 1995
This 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 814 have been approved
under OMB control number. 0910–0231;
the collections of information in 21 CFR
part 812 have been approved under
OMB control number 0910–0078; the
collections of information in 21 CFR
part 801 and 21 CFR 809.10 have been
approved under OMB control number
0910–0485.
V. Comments
Interested persons may submit to the
Division of Dockets Management (see
ADDRESSES), either electronic or written
PO 00000
Frm 00056
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comments regarding this document. It is
only necessary to send one set of
comments. It is no longer necessary to
send two copies of mailed comments.
Identify comments 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.
Dated: November 22, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011–30552 Filed 11–25–11; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2005–D–0086 (formerly
Docket No. 2005D–0223)]
Guidance for Industry on Nonclinical
Evaluation of Late Radiation Toxicity
of Therapeutic Radiopharmaceuticals;
Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing the
availability of a guidance for industry
entitled ‘‘Nonclinical Evaluation of Late
Radiation Toxicity of Therapeutic
Radiopharmaceuticals.’’ The purpose of
this guidance is to provide
recommendations to industry for
designing nonclinical toxicity studies to
determine potential late radiation effects
(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 trials of therapeutic
radiopharmaceuticals. This guidance
finalizes the draft guidance of the same
name issued in June 2005.
DATES: Submit either electronic or
written comments on Agency guidances
at any time.
ADDRESSES: Submit written requests for
single copies of this 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. See the SUPPLEMENTARY
SUMMARY:
E:\FR\FM\28NON1.SGM
28NON1
Federal Register / Vol. 76, No. 228 / Monday, November 28, 2011 / Notices
section for electronic
access to the guidance document.
Submit electronic comments on the
guidance to https://www.regulations.gov.
Submit written comments to the
Division of Dockets Management (HFA–
305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville,
MD 20852.
FOR FURTHER INFORMATION CONTACT:
Adebayo Laniyonu, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, rm. 2350,
Silver Spring, MD 20993–0002, (301)
796–2050; or Siham Biade, Center for
Drug Evaluation and Research, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, rm. 2311,
Silver Spring, MD 20993–0002, (301)
796–2050.
SUPPLEMENTARY INFORMATION:
INFORMATION
pmangrum on DSK3VPTVN1PROD with NOTICES
I. Background
FDA is announcing the availability of
a 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 effects
of therapeutic radiopharmaceutical
agents. This guidance is not intended to
address late radiation toxicity of
radiobiologicals (e.g., radiolabeled
monoclonal antibodies) or to apply to
diagnostic radiopharmaceuticals whose
low doses are not expected to elicit late
radiation toxic effects.
This 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.
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
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20:00 Nov 25, 2011
Jkt 226001
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
(exclusive of estimated risks of
secondary malignancy) 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 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 trials of therapeutic
radiopharmaceuticals.
This guidance finalizes the draft
guidance of the same name issued in
June 2005 and includes edits based on
public comments to improve clarity.
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 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
requirements of the applicable statutes
and regulations.
II. Comments
Interested persons may submit to the
Division of Dockets Management (see
PO 00000
Frm 00057
Fmt 4703
Sfmt 4703
72953
ADDRESSES)
either electronic or written
comments regarding this document. It is
only necessary to send one set of
comments. It is no longer necessary to
send two copies of mailed comments.
Identify comments 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
https://www.fda.gov/Drugs/
GuidanceComplianceRegulatory
Information/Guidances/default.htm or
https://www.regulations.gov.
Dated: November 22, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011–30474 Filed 11–25–11; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No: FDA–2011–N–0002]
Science Board to the Food and Drug
Administration; Notice of Meeting
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
This notice announces a forthcoming
meeting of a public advisory committee
of the Food and Drug Administration
(FDA). The meeting will be open to the
public.
Name of Committee: Science Board to
the Food and Drug Administration
(Science Board).
General Function of the Committee:
The Science Board provides advice
primarily to the Commissioner of Food
and Drugs and other appropriate
officials on specific complex and
technical issues, as well as emerging
issues within the scientific community
in industry and academia. Additionally,
the Science Board provides advice to
the Agency on keeping pace with
technical and scientific evolutions in
the fields of regulatory science, on
formulating an appropriate research
agenda, and on upgrading its scientific
and research facilities to keep pace with
these changes. It will also provide the
means for critical review of Agency
sponsored intramural and extramural
scientific research programs.
E:\FR\FM\28NON1.SGM
28NON1
]]>Agencies
[Federal Register Volume 76, Number 228 (Monday, November 28, 2011)]
[Notices]
[Pages 72952-72953]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-30474]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2005-D-0086 (formerly Docket No. 2005D-0223)]
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 guidance for industry entitled ``Nonclinical
Evaluation of Late Radiation Toxicity of Therapeutic
Radiopharmaceuticals.'' The purpose of this guidance is to provide
recommendations to industry for designing nonclinical toxicity studies
to determine potential late radiation effects (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 trials of therapeutic
radiopharmaceuticals. This guidance finalizes the draft guidance of the
same name issued in June 2005.
DATES: Submit either electronic or written comments on Agency guidances
at any time.
ADDRESSES: Submit written requests for single copies of this 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. See
the SUPPLEMENTARY
[[Page 72953]]
INFORMATION section for electronic access to the guidance document.
Submit electronic comments on the guidance to https://www.regulations.gov. Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Adebayo Laniyonu, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, rm. 2350, Silver Spring, MD 20993-0002, (301)
796-2050; or Siham Biade, Center for Drug Evaluation and Research, Food
and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 2311,
Silver Spring, MD 20993-0002, (301) 796-2050.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a 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 effects of
therapeutic radiopharmaceutical agents. This guidance is not intended
to address late radiation toxicity of radiobiologicals (e.g.,
radiolabeled monoclonal antibodies) or to apply to diagnostic
radiopharmaceuticals whose low doses are not expected to elicit late
radiation toxic effects.
This 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.
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 (exclusive of estimated risks of
secondary malignancy) 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 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
trials of therapeutic radiopharmaceuticals.
This guidance finalizes the draft guidance of the same name issued
in June 2005 and includes edits based on public comments to improve
clarity.
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 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 requirements of the applicable statutes and regulations.
II. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. It is only necessary to send one set of comments. It is no
longer necessary to send two copies of mailed comments. Identify
comments 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 https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or https://www.regulations.gov.
Dated: November 22, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-30474 Filed 11-25-11; 8:45 am]
BILLING CODE 4160-01-P
