Pediatric Studies of Sodium Nitroprusside Conducted in Accordance With the Public Health Service Act; Availability of Summary Report and Requested Labeling Changes, 4167-4168 [2014-01390]
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Federal Register / Vol. 79, No. 16 / Friday, January 24, 2014 / Notices
approximately 45 days after the public
workshop on the Internet at https://
www.fda.gov/MedicalDevices/
NewsEvents/WorkshopsConferences/
default.htm. (Select this public
workshop from the posted events list).
I. Background
Biofilms play a key role in the
development of device-related and other
healthcare associated infections.
Published literature indicates that
biofilms are a major culprit in the
development of resistant infections.
However, the biochemical and
physiochemical characteristics of
biofilms are not widely understood.
With the increasing use of implanted
and indwelling devices, understanding
biofilm development on these devices
and factors that impact biofilm
formation is critical. Research on the
basic science of biofilms may provide
insight on device-associated biofilms,
ultimately advancing research on
technologies that are intended to
prevent biofilm formation.
This public workshop seeks to share
scientific information between
academia, industries interested in
developing products to address biofilm
contamination, and U.S. Government
scientists.
II. Topics for Discussion at the Public
Workshop
TKELLEY on DSK3SPTVN1PROD with NOTICES
FDA seeks to address and receive
comments on the following topics:
1. Research on biofilms and their
public health impact.
2. Challenges faced by the scientific
community, government, and industry
on addressing biofilm contamination of
medical devices.
3. Critical areas of research that will
address the scientific and clinical
challenges faced by the stakeholders
when developing technologies that are
intended to prevent biofilm formation.
This public workshop may also form
the basis for future discussions related
to novel biofilm prevention technologies
that could benefit U.S. public health.
Dated: January 17, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014–01412 Filed 1–23–14; 8:45 am]
BILLING CODE 4160–01–P
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16:22 Jan 23, 2014
Jkt 232001
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2012–N–0284]
Pediatric Studies of Sodium
Nitroprusside Conducted in
Accordance With the Public Health
Service Act; Availability of Summary
Report and Requested Labeling
Changes
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is publishing a
summary report of the pediatric studies
of sodium nitroprusside conducted in
accordance with the Public Health
Service Act (the PHS Act) and is making
available requested labeling changes for
sodium nitroprusside. The Agency is
making this information available
consistent with the PHS Act.
FOR FURTHER INFORMATION CONTACT: Lori
Gorski, Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 22, rm. 6415, Silver Spring,
MD 20993–0002, 301–796–2200, Fax:
301–796–9855, email: lori.gorski@
fda.hhs.gov.
SUMMARY:
SUPPLEMENTARY INFORMATION:
I. Sodium Nitroprusside Summary
Review
In the Federal Register of January 21,
2003 (68 FR 2789), sodium
nitroprusside (SNP) was identified as a
drug that needed further study in
pediatrics. The approved labeling
lacked adequate information on dosing,
pharmacokinetics, tolerability, and
safety information in pediatric patients
from birth to 18 years of age who receive
SNP for controlled reduction of blood
pressure.
A written request (WR) for pediatric
studies of sodium nitroprusside was
issued on July 8, 2002, to Abbott
Laboratories, the holder of the new drug
application for sodium nitroprusside.
FDA did not receive a response to the
written request. Accordingly, the
National Institutes of Health (NIH)
issued a request for proposals to
conduct the pediatric studies described
in the written request in July 2004 and
awarded funds to Duke University and
Stanford University in September 2004
to complete the studies described in the
written request.
The Eunice Kennedy Shriver National
Institute of Child Health and Human
Development (NICHD) submitted
PO 00000
Frm 00018
Fmt 4703
Sfmt 4703
4167
clinical study reports for SNP. The two
studies are:
• NICHD–2003–09–DR–SNP1: A
randomized double-blind, parallel
group, dose-ranging, effect-controlled,
multicenter study of intravenous
infusions of SNP in pediatric patients
who require deliberate, controlled
relative-induced hypotension for at least
2 hours.
• NICHD–2003–09–LT–SNP2: A
multicenter, randomized, double-blind,
placebo-controlled, parallel group study
to determine the pharmacodynamics of
sodium nitroprusside during the
prolonged infusion in pediatric subjects.
This study was a withdrawal to placebo
study.
Upon completion of these pediatric
studies, a report of the pediatric studies
of sodium nitroprusside was submitted
to NIH and FDA. In the Federal Register
of October 3, 2012 (77 FR 60441), FDA
announced the opening on August 31,
2012, of docket FDA–2012–N–0284 for
submission of data from pediatric
studies of sodium nitroprusside. The
data submitted to the docket were
submitted in accordance with section
409I of the PHS Act (42 U.S.C. 284m)
and were the same data submitted to
investigational new drug application
71,979, with the exception that personal
privacy information had been redacted
from the data submitted to the docket.
The sodium nitroprusside docket
remained opened for public comment
from October 3, 2012, through
November 2, 2012. There were no
comments submitted to the docket
during that time, and a memorandum
for the record stating such was posted
to the docket on November 5, 2012.
During the review of the submission,
the Division of Cardiovascular and
Renal Products identified
inconsistencies in subject numbers
between the pharmacokinetic/
pharmacodynamic (PK/PD) analysis set
and the ITT–E (intent to treat-efficacy)
population in the study report NICHD–
2003–09–DR–SNP1 and notified NIH. In
a meeting with FDA on November 29,
2012, NIH indicated that that they
identified treatment assignment
inconsistencies between the two
datasets and provided a strategy for
addressing the concern and performing
reanalysis. The need for reanalysis
resulted in suspension of the review as
of November 29, 2012. The corrected
datasets and reanalysis were provided to
the Agency and submitted to the docket
on September 26, 2013.
The key findings of this submission
are:
• The blood pressure lowering effect
of SNP was demonstrated in both of the
trials.
E:\FR\FM\24JAN1.SGM
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TKELLEY on DSK3SPTVN1PROD with NOTICES
4168
Federal Register / Vol. 79, No. 16 / Friday, January 24, 2014 / Notices
• A higher proportion of patients in
the high-dose group achieved target
mean arterial pressure (MAP) compared
to the lowest dose of 0.3 microgram/
kilogram/minute (mg/kg/min). The timeto-target MAP was also significantly
shorter for the high-dose groups.
• With a starting dose of 0.3 mg/kg/
min, ∼25 percent of patients achieved
target MAP in 5 minutes. Maintaining
on a stable dose of 0.3 mg/kg/min for 10
minutes resulted in ∼50 percent of
patients reaching target MAP. Hence, a
starting dose of 0.3 mg/kg/min is
reasonable. It should also be noted that
it may be prudent to maintain the
infusion rate for an additional 5 to 10
minutes before titrating.
• The proportion of patients with
MAP reductions of >20 percent below
target increased in a dose-dependent
manner.
• The safety profile of SNP in both
the trials was largely consistent with the
expected events as a result of the
underlying disease and preoperative
setting. Only blood pressure reduction
events were clearly drug- and doserelated.
• Even though only four neonates
were studied in the trial, there is no
expectation that the PK/PD relationship
and the safety profile would be any
different in this age group.
• The FDA Adverse Event Reporting
System (FAERS) search (up to October
25, 2012) retrieved only 26 pediatric
cases with SNP use. Of these, four cases
of elevated carboxyhemoglobin
associated with SNP treatment were
reported. The Office of Surveillance and
Epidemiology review outlines several
reasons why these data cannot be used
to calculate incidence of adverse events
in the population.
• For this submission, one large site
(N = 36 enrolled in Protocol NICHD–
2003–09–LT–SNP2; Investigator: Dr.
David Rosen) was inspected. The Office
of Scientific Investigations recommends
the data be accepted.
• As a part of the WR, long-term
safety data and a 1-year followup period
for patients enrolled in the trial were
sought. Information from followup was
not available in the submission.
However, the value of such information
is limited and is not expected to have
an impact on the ability to overcome the
labeling gap. The complete report can be
found at docket number FDA–2012–N–
0284.
II. Recommendation
The submission provides a reasonable
algorithm for administration of sodium
nitroprusside to allow its use in
perioperative settings to achieve
controlled hypotension for pediatric
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patients from birth to 18 years. FDA’s
requested labeling changes are available
on the FDA Web site at https://
www.fda.gov/Drugs/
DevelopmentApprovalProcess/
DevelopmentResources/ucm379088.htm
and in the docket (Ref. 1).
III. Reference
Room 749, 6707 Democracy Boulevard,
Bethesda, MD 20892–5452, (301) 594–8894,
begumn@niddk.nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.847, Diabetes,
Endocrinology and Metabolic Research;
93.848, Digestive Diseases and Nutrition
Research; 93.849, Kidney Diseases, Urology
and Hematology Research, National Institutes
of Health, HHS)
The following reference has been
placed on display in the Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, rm. 1061, Rockville, MD 20852,
and may be seen by interested person
between 9 a.m. and 4 p.m., Monday
through Friday, and is available
electronically at https://
www.regulations.gov.
1. FDA Requested Labeling Changes.
[FR Doc. 2014–01386 Filed 1–23–14; 8:45 am]
Dated: January 10, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
U.S. Citizenship and Immigration
Services
[FR Doc. 2014–01390 Filed 1–23–14; 8:45 am]
[OMB Control Number 1615–0099]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institute of Diabetes and
Digestive and Kidney and Diseases;
Notice of Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. App.), notice is
hereby given of the following meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Institute of
Diabetes and Digestive and Kidney Diseases
Special Emphasis Panel PAR12–265: NIDDK
Ancillary Studies to Major Ongoing Clinical
Research: Epidemiology of Gut Microbiome
in Diabetes.
Date: February 28, 2014.
Time: 2:00 p.m. to 4:00 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health, Two
Democracy Plaza, 6707 Democracy
Boulevard, Bethesda, MD 20892, (Telephone
Conference Call).
Contact Person: Najma Begum, Ph.D.,
Scientific Review Officer, Review Branch,
DEA, NIDDK, National Institutes of Health,
PO 00000
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Dated: January 17, 2014.
David Clary,
Program Analyst, Office of Federal Advisory
Committee Policy.
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SECURITY
Agency Information Collection
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Nonimmigrant Status; Application for
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Recipient; and Declaration of Law
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Supplements A and B. Extension,
Without Change, of a Currently
Approved Collection
ACTION:
60-day notice.
The Department of Homeland
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Immigration Services (USCIS) invites
the general public and other Federal
agencies to comment upon this
proposed extension of a currently
approved collection of information or
new collection of information]. In
accordance with the Paperwork
Reduction Act (PRA) of 1995, the
information collection notice is
published in the Federal Register to
obtain comments regarding the nature of
the information collection, the
categories of respondents, the estimated
burden (i.e. the time, effort, and
resources used by the respondents to
respond), the estimated cost to the
respondent, and the actual information
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submissions, please use only one of the
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SUMMARY:
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]]>Agencies
[Federal Register Volume 79, Number 16 (Friday, January 24, 2014)]
[Notices]
[Pages 4167-4168]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-01390]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2012-N-0284]
Pediatric Studies of Sodium Nitroprusside Conducted in Accordance
With the Public Health Service Act; Availability of Summary Report and
Requested Labeling Changes
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is publishing a summary
report of the pediatric studies of sodium nitroprusside conducted in
accordance with the Public Health Service Act (the PHS Act) and is
making available requested labeling changes for sodium nitroprusside.
The Agency is making this information available consistent with the PHS
Act.
FOR FURTHER INFORMATION CONTACT: Lori Gorski, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, rm. 6415, Silver Spring, MD 20993-0002, 301-
796-2200, Fax: 301-796-9855, email: lori.gorski@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Sodium Nitroprusside Summary Review
In the Federal Register of January 21, 2003 (68 FR 2789), sodium
nitroprusside (SNP) was identified as a drug that needed further study
in pediatrics. The approved labeling lacked adequate information on
dosing, pharmacokinetics, tolerability, and safety information in
pediatric patients from birth to 18 years of age who receive SNP for
controlled reduction of blood pressure.
A written request (WR) for pediatric studies of sodium
nitroprusside was issued on July 8, 2002, to Abbott Laboratories, the
holder of the new drug application for sodium nitroprusside. FDA did
not receive a response to the written request. Accordingly, the
National Institutes of Health (NIH) issued a request for proposals to
conduct the pediatric studies described in the written request in July
2004 and awarded funds to Duke University and Stanford University in
September 2004 to complete the studies described in the written
request.
The Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD) submitted clinical study reports for SNP. The
two studies are:
NICHD-2003-09-DR-SNP1: A randomized double-blind, parallel
group, dose-ranging, effect-controlled, multicenter study of
intravenous infusions of SNP in pediatric patients who require
deliberate, controlled relative-induced hypotension for at least 2
hours.
NICHD-2003-09-LT-SNP2: A multicenter, randomized, double-
blind, placebo-controlled, parallel group study to determine the
pharmacodynamics of sodium nitroprusside during the prolonged infusion
in pediatric subjects. This study was a withdrawal to placebo study.
Upon completion of these pediatric studies, a report of the
pediatric studies of sodium nitroprusside was submitted to NIH and FDA.
In the Federal Register of October 3, 2012 (77 FR 60441), FDA announced
the opening on August 31, 2012, of docket FDA-2012-N-0284 for
submission of data from pediatric studies of sodium nitroprusside. The
data submitted to the docket were submitted in accordance with section
409I of the PHS Act (42 U.S.C. 284m) and were the same data submitted
to investigational new drug application 71,979, with the exception that
personal privacy information had been redacted from the data submitted
to the docket.
The sodium nitroprusside docket remained opened for public comment
from October 3, 2012, through November 2, 2012. There were no comments
submitted to the docket during that time, and a memorandum for the
record stating such was posted to the docket on November 5, 2012.
During the review of the submission, the Division of Cardiovascular
and Renal Products identified inconsistencies in subject numbers
between the pharmacokinetic/pharmacodynamic (PK/PD) analysis set and
the ITT-E (intent to treat-efficacy) population in the study report
NICHD-2003-09-DR-SNP1 and notified NIH. In a meeting with FDA on
November 29, 2012, NIH indicated that that they identified treatment
assignment inconsistencies between the two datasets and provided a
strategy for addressing the concern and performing reanalysis. The need
for reanalysis resulted in suspension of the review as of November 29,
2012. The corrected datasets and reanalysis were provided to the Agency
and submitted to the docket on September 26, 2013.
The key findings of this submission are:
The blood pressure lowering effect of SNP was demonstrated
in both of the trials.
[[Page 4168]]
A higher proportion of patients in the high-dose group
achieved target mean arterial pressure (MAP) compared to the lowest
dose of 0.3 microgram/kilogram/minute ([micro]g/kg/min). The time-to-
target MAP was also significantly shorter for the high-dose groups.
With a starting dose of 0.3 [micro]g/kg/min, ~25 percent
of patients achieved target MAP in 5 minutes. Maintaining on a stable
dose of 0.3 [micro]g/kg/min for 10 minutes resulted in ~50 percent of
patients reaching target MAP. Hence, a starting dose of 0.3 [micro]g/
kg/min is reasonable. It should also be noted that it may be prudent to
maintain the infusion rate for an additional 5 to 10 minutes before
titrating.
The proportion of patients with MAP reductions of >20
percent below target increased in a dose-dependent manner.
The safety profile of SNP in both the trials was largely
consistent with the expected events as a result of the underlying
disease and preoperative setting. Only blood pressure reduction events
were clearly drug- and dose-related.
Even though only four neonates were studied in the trial,
there is no expectation that the PK/PD relationship and the safety
profile would be any different in this age group.
The FDA Adverse Event Reporting System (FAERS) search (up
to October 25, 2012) retrieved only 26 pediatric cases with SNP use. Of
these, four cases of elevated carboxyhemoglobin associated with SNP
treatment were reported. The Office of Surveillance and Epidemiology
review outlines several reasons why these data cannot be used to
calculate incidence of adverse events in the population.
For this submission, one large site (N = 36 enrolled in
Protocol NICHD-2003-09-LT-SNP2; Investigator: Dr. David Rosen) was
inspected. The Office of Scientific Investigations recommends the data
be accepted.
As a part of the WR, long-term safety data and a 1-year
followup period for patients enrolled in the trial were sought.
Information from followup was not available in the submission. However,
the value of such information is limited and is not expected to have an
impact on the ability to overcome the labeling gap. The complete report
can be found at docket number FDA-2012-N-0284.
II. Recommendation
The submission provides a reasonable algorithm for administration
of sodium nitroprusside to allow its use in perioperative settings to
achieve controlled hypotension for pediatric patients from birth to 18
years. FDA's requested labeling changes are available on the FDA Web
site at https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm379088.htm and in the docket (Ref. 1).
III. Reference
The following reference has been placed on display in the Division
of Dockets Management (HFA-305), Food and Drug Administration, 5630
Fishers Lane, rm. 1061, Rockville, MD 20852, and may be seen by
interested person between 9 a.m. and 4 p.m., Monday through Friday, and
is available electronically at https://www.regulations.gov.
1. FDA Requested Labeling Changes.
Dated: January 10, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-01390 Filed 1-23-14; 8:45 am]
BILLING CODE 4160-01-P
