PROGRAM UPDATE - Radioactive Drug Research Committee
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Transcript of PROGRAM UPDATE - Radioactive Drug Research Committee
1Greater New York City Greater New York City RDRC Meeting, December 2007RDRC Meeting, December 2007
PROGRAM UPDATE -PROGRAM UPDATE -Radioactive DrugRadioactive Drug
Research CommitteeResearch Committee
CAPT Richard Fejka, USPHS, RPh, MS, BCNPSenior Manager - Radioactive Drug Research Committee program
Division of Medical Imaging and Hematology ProductsOffice Of Oncology Drug Products
Center for Drug Evaluation and ResearchU.S. Public Health Service
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OutlineOutline• 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 HistoryA Little History• Prior to 1975 AEC (Atomic
Energy Commission) regulated reactor produced radioactive drugs
• January 8, 1963 Federal Register notice temporarily exempted radioactive new drugs for investigational use from requirements of part 312
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A Little History A Little History (continued)(continued)
• The purpose of the exemption was to allow Federal agencies to explore ways to avoid unnecessary duplication of regulatory control
• AEC and FDA concluded ALL radioactive drugs should now be subject to the same clearance procedures as other drugs
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A Little History A Little History (continued)(continued)
• 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 RegulationThe 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 RegulationThe 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 RDRCResearch 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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MonitoringMonitoringFDA 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 Monitoring
• Submit Annual Report by January 31 for past calendar year’s activitiesconsists of
• FDA FORM 2914 Membership Summaryand
• FDA Form 2915 Study Summary for EACHEACH study overseen by RDRC
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Reporting FormsReporting FormsMembership (2914) and Study Summary (2915)
available through FDA RDRC website at
http://www.fda.gov/cder/regulatory/RDRC/default.htmor1. Go to www.fda.gov2. Search on “RDRC”3. Click on Radioactive Drug Research Committee (RDRC)
Program4. 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 FormsReporting Forms
Old Forms New FormsOld Forms New Forms • No instructions
• Dates for submission of past qualifications statements lacking
• 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”
• Provide Instructions
• Requires a Study ID number
• Requires a study approval and termination date
• Dose terms clarified, e.g.
- Pharmacological and NOEL*dose (*No Observed Effect Level )
- Activity administeredMBq - uCi, mCi
- Radiation absorbed dose mSv - Rem
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Current Status on Committees and Current Status on Committees and Study Summary ReportsStudy 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 Status of RDRC Regulatory InitiativesRegulatory Initiatives
• Draft Guidance – being reviewed
• Reinstituted Inspection Program
• Impact of Exploratory IND
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Some ObservationsSome ObservationsAnnual Report ReviewsAnnual 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 ObservationsSome ObservationsAnnual Report ReviewsAnnual 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 ObservationsSome ObservationsAnnual Report ReviewsAnnual 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:If you need assistance:CAPT Richard Fejka USPHS, RPh, MS, BCNPSenior Manager, RDRC Program [email protected](301) 796-1353
Susan Lange, ARRT (R)(N), MPHProject Manager, RDRC Program [email protected](301) 796-4117
Orhan Suleiman MS, PhD, FAAPM,Senior Science Policy Advisor [email protected](301) 796-1471