Transcript Advisory Committee Mtgs. Sample PPT

PROGRAM UPDATE Radioactive Drug
Research Committee
CAPT Richard Fejka, USPHS, RPh, MS, BCNP
Senior Manager - Radioactive Drug Research Committee program
Division of Medical Imaging and Hematology Products
Office Of Oncology Drug Products
Center for Drug Evaluation and Research
U.S. Public Health Service
Greater New York City
RDRC Meeting, December 2007
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Outline
• History
• Regulation
• Research Under an RDRC
• Monitoring
• Reporting Forms
• Current Status of Committees, Study Summaries
and Regulatory Initiatives
• Annual Report Reviews - Observations
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A Little History
• Prior to 1975 AEC
(Atomic Energy
Commission) regulated
reactor produced
radioactive drugs
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• January 8, 1963
Federal Register notice
temporarily exempted
radioactive new drugs
for investigational use
from requirements of
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part 312
A Little History (continued)
• The purpose of the
exemption was to allow
Federal agencies to
explore ways to avoid
unnecessary duplication
of regulatory control
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• AEC and FDA concluded
ALL radioactive drugs
should now be subject
to the same clearance
procedures as other
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drugs
A Little History (continued)
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FDA established regulations on
August 25, 1975 to regulate
ALL radioactive drugs
•
Determined that all radioactive
drugs are either New Drugs or
GRAS/E (Generally Recognized
As Safe and Effective)
•
ALL radioactive drugs now
subject to an IND, NDA or
biological product license
•
EXCEPT radioactive drugs
used for certain research uses
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The Regulation
• 21 CFR 361 Prescription Drugs for Human
Use Generally Recognized as Safe
and Effective and Not
Misbranded: Drugs Used In
Research
§ 361.1 Radioactive drugs for
certain research uses.
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The Regulation
• (a) Radioactive drugs (…) are generally recognized as safe
and effective when administered, under the conditions set
forth in paragraph (b) of this section, to human research
subjects during the course of a research project intended
to obtain basic information regarding the metabolism
(including kinetics, distribution, and localization) of a
radioactively labeled drug or regarding human physiology,
pathophysiology, or biochemistry, but not intended for
immediate therapeutic, diagnostic, or similar purposes or
to determine the safety and effectiveness of the drug in
humans for such purposes (i.e., to carry out a clinical trial).
Certain basic research studies, e.g., studies to determine
whether a drug localizes in a particular organ or fluid space
and to describe the kinetics of that localization, may have
eventual therapeutic or diagnostic implications, but the
initial studies are considered to be basic research within
the meaning of this section.
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Research Under an RDRC
•
Four conditions set in § 361.1
1. Basic Science Research
2. Pharmacological dose limit
3. Radiation dose limits
4. Radioactive Drug Research
Committee
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Monitoring
FDA conducts periodic reviews of approved
committees by:
• Review of their annual report,
• Review of meeting minutes,
• Review of full protocols for certain
studies,
• On-site inspections.
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Monitoring
• Submit Annual Report by January 31
for past calendar year’s activities
consists of
• FDA FORM 2914 Membership Summary
and
• FDA Form 2915 Study Summary
for EACH study overseen by RDRC
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Reporting Forms
Membership (2914) and Study Summary (2915)
available through FDA RDRC website at
http://www.fda.gov/cder/regulatory/RDRC/default.htm
or
1. Go to www.fda.gov
2. Search on “RDRC”
3. Click on Radioactive Drug Research Committee (RDRC)
Program
4. Click on RDRC Forms and Checklist
or go to FDA’s Electronic Forms Numerical Listing page at:
http://www.fda.gov/opacom/morechoices/fdaforms/default.html
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Reporting Forms
Old Forms
New Forms
•
No instructions
•
Provide Instructions
•
Dates for submission of past
qualifications statements lacking
•
Requires a Study ID number
•
Requires a study approval and
termination date
•
Dose terms clarified, e.g.
•
Use of “dose” confusing
“Maximum amount (i.e. mg) of
nonradioactive moiety
administered per subject, per
single dose and/or the minimum
specific activity (i.e. mCi/mg) of
drug at the time of
administration.”
•
Terms not only confusing, but
incorrect:
“mR/whole body”
Greater New York City
RDRC Meeting, December 2007
- Pharmacological and NOEL*
dose (*No Observed Effect
Level )
- Activity administered
MBq - uCi, mCi
- Radiation absorbed dose
mSv - Rem
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Current Status on Committees and
Study Summary Reports
• 201 RDRCs approved
Calendar Year
# of RDRCs expected
to report
# of Study Summaries
submitted for review
2003
84
397
2004
81
487
2005
78
602
2006
73
671
2007
75
-
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Status of RDRC
Regulatory Initiatives
• Draft Guidance – being reviewed
• Reinstituted Inspection Program
• Impact of Exploratory IND
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Some Observations
Annual Report Reviews
• RDRC not associated with a medical institution.
• Medical institution did not know they had an RDRC.
• An RDRC chair who tried to convince their administration
that RDRC members were surrogate FDA employees and
therefore operate independently of the medical institution.
• An RDRC which believed that one of their roles was to
review their institution’s IRB actions.
• Inappropriate approval of First-In-Human studies under
RDRC authority.
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Some Observations
Annual Report Reviews
• Failure of RDRC to meet quarterly.
• Meeting minutes which do not show RDRC members
recusing themselves from voting on studies which they
are associated with.
• Failure to convert RDRC study into IND.
• Special Summary Reports not filed, or not filed in timely
manner.
• Reluctance to use human biodistribution data to verify
animal radiation dosimetry estimates.
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Some Observations
Annual Report Reviews
Membership
• Lack of timely notification of membership changes.
• Incomplete qualification documentation for membership
category, especially when switching from one category to
another.
Radiation Dose
• Failure to report associated x-ray doses.
• Incomplete or lack of reference for dosimetry calculations.
• Inconsistency in dosimetry among investigators within an
RDRC – obvious failure of RDRC to standardize.
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If you need assistance:
CAPT Richard Fejka USPHS, RPh, MS, BCNP
Senior Manager, RDRC Program
[email protected]
(301) 796-1353
Susan Lange, ARRT (R)(N), MPH
Project Manager, RDRC Program
[email protected]
(301) 796-4117
Orhan Suleiman MS, PhD, FAAPM,
Senior Science Policy Advisor
[email protected]
(301) 796-1471
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