pet_mail Revision of 21 CFR 361.1 Regulations

[fegallag@uci.edu (Frank E. Gallagher, III)]

Radsafers,
The following two notices of potential new FDA regs emerging from regulatory
never-never-land recently appeared on the pet-mail electronic bulletin
board.  I sent comments to Dr. Toohey regarding how the proposal would
negatively impact our PET imaging research program for brain research in our
Department of Psychiatry.  Others may want to send him comments about such
impacts on their PET studies and/or more traditional muclear medicine studies.  

Frank E. Gallagher, III, CHP
RSO, Univ. of California, Irvine 92717-2725
Voice: (714) 824-6904, Fax: (714) 824-8539
E-mail: fegallag@uci.edu

ORIGINAL NOTICE FROM DENNIS SWANSON:

Letters of correspondence between Eugene Saenger, M.D. (University 
of Cincinnati) and Richard Toohey, Ph.D. (Oak Ridge Institute for 
Science and Education, ORISE) were recently brought to my attention 
by the SNM/ACNP Government Affairs Office.

Dr. Toohey is currently reviewing the regulations for radioactive 
drugs used in research (21 CFR 361.1) under contract with the FDA's 
Center for Drug Evaluation and Research.   Based on statements 
contained in his letter, it appears that Dr. Toohey will recommend to 
the FDA that an annual limit (to include all administrations in a year) 
of 10 mSv (1 rem) EDE be established for subjects participating in 
research studies conducted under this regulation.   (Note that the 
current limits are 1) for a single study, 3 rems to the whole body, 
blood-forming organs, lens of eye, and gonads, and 5 rems to other 
organs; and 2) for annual and total dose commitment, 5 rems to the 
whole body, blood-forming organs, lens of eye, and gonads, and 15 
rems to other organs.)   Dr. Toohey is apparently basing his recommendations
on ICRP 62 and NCRP guidelines.

It is my impression that such a modification in the 21 CFR 361.1 regulations
could have a significant impact on the ability to conduct 
meaningful research studies using PET radiopharmaceuticals.  For 
example, based on ORISE dosimetry estimates, the revised 
dosimetry limit would preclude the administration of in excess of 9.0 
mCi of [F-18] FDG per year.   Thus, it may not be possible to perform
studies pre- and post-interventions , or combination cerebral blood 
flow/glucose metabolism studies (especially if the PET facility does 
not have 3-D capability).   Also, I am not convinced that the level of 
risk associated with the current dosimetry limits is out of line with the 
level of risk associated with research subject participation in Phase 
I-II trials of traditional (non-radioactive) drugs. 

Apparently, Dr. Toohey presented his recommendations in poster format at the
recent meeting of the Health Physics Society.   He requested comments to his
recommendations; however as might be anticipated by the limited attendance
of the PET community at this meeting, there has been virtually no response
(with the exception of Dr. Saenger). 

I urge you to send your comments re. this proposed change in the 
21 CFR 361.1 radiation dosimetry limits to Dr. Toohey at the 
addresses listed below.  Please also copy me so I can obtain a 
consensus of opinion in writing a SNM/ACNP response to this issue 
if and when  the revised limits appear in Federal Register format.
Spread the word to those not on PET mail.

Dennis P. Swanson
1111 Salk Hall
School of Pharmacy
University of Pittsburgh
Pittsburgh, PA 15261
email: dswanson@druginfonet.pharm-epid.pitt.edu
fax: 412-648-1086

REPLY FROM DICK TOOHEY RE NOTICE FROM DENNIS SWANSON:

Thank you for publicizing the proposed change to regulatory dose limits
for radioactive drugs used in research.  I really do want to hear from
affected parties on this matter before making any recommendation to
FDA.  I would especially like to know what people think about a limit for
any one study, as opposed to all administrations in a year--are there
many subjects who actually do participate in more than one study per
year?  Examples of current research programs that could not meet a reg
of 10 mSv EDE are especially welcome.  Finally, remember that the regs
affect only research use of radiolabelled compounds, not clinical trials or
medical applications where there is some benefit expected for the
subject.  Looking forward to more input.

Dr. R.E. Toohey
RIDIC/MSD
ORISE
P.O. Box 117
Oak Ridge, TN 37831-0117
email: TooheyR@ORAU.GOV
fax: 423-576-8673