ML20151E799

Advises of Agreement W/Stated Recommendations Noted in Draft Commission Paper Submitted w/871231 Memo Re Naturally Occurring & Accelerator Produced Radioactive Matls.Resource Estimates & Recommendations Reasonable.Related Info Encl

ML20151E799
Person / Time
Issue date:	01/21/1988
From:	Loach R NRC OFFICE OF ADMINISTRATION & RESOURCES MANAGEMENT (ARM)
To:	Joseph Austin NRC OFFICE OF NUCLEAR MATERIAL SAFETY & SAFEGUARDS (NMSS)
Shared Package
ML20151B338	List: ML20151B335 ML20151E799 PNO-III-87-123, on 870909,Region III Notified by State of Mo That Scrap Dealer in Sikeston,Mo Detected Radioactive Contamination in Two Rail Car Loads of Aluminum Matl Received from United Technology,Inc.Related Info Encl
References
RTR-NUREG-1310 NUDOCS 8804150383
Download: ML20151E799 (29)

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[ g NUCLEAR REGULATORY COMMISSION 5 l WASHINGTON, D. C. 20!iS5 3-  %, * * . * / JAN 211988 MEMORANDUM JOR: John H. Aus'in, Special Assistant, N!-!SS FROM: Robert E. L ach, Chief Program Analysis Branch Division of Budget and Analysis Office of Administration and Resources Management

SUBJECT:

DRAFT COMMISSION PAPER ON NARM I have reviewed the draft commission Paper submitted with your December 31, 1987 memorandum to me and agree with the following -

i recommendations:

1. In the first paragraph on p. 45 dealing with resource implications, it states that the resource implications for the regulation of the disposal of discrete source of radium would likely amount to no more than a few FTE's per year.

In all probability, if this is handled like other low level j waste issues, the FTE usage will be less than 5 FTE for NRC but the paper should add a reference to the potential that there may te a cost to the Agreement States.

! 2. The resource estimates in the second paragraph on p. 45 '

appear to be quite reasonable, but again, I suggest that a reference be made to the potential that there may be additional costs incurred by the Agreement Statess '

I It might be helpful for the reader to know that the entire materials licensing and inspection resources are approximately 85-90 FTE per year and $1-2 million.

Considering the resource constraints that NRC is currently experiencing and the probability that they will continua in the near future, the resource estimates and recommendations from a resource perspective are very reasonable.

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R bert E. Loach, dhief 1 Program Analysis Branch

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Office of Administration and 8804150303 880331 PDR NUREG 1310 R PDR v v- .

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t CL4 SCllOOL OF 41LDICINE H ARBOR - rCL4 4tEDIC AL CENTER 1RO C AR50N STREET Robert Temple, M.D. TORR ANCE. CAUFoRN!4 XW4 Director, Office of Drug July 20, 1987 Research and Review U.S. icod and Drug Administration 5600 Fishers Lane Parklawn Bldg., B-45 Pockville, MD 20852

Dear Dr. Temple:

The purpose of this letter is to bring three categories of radiopharmaceu-tical problems to your attention and to obtain written clarification of the Agency's policies and plans with respect to these issues.

Aspects of these radiopharmaceutical problems have been previously brought to your attention during meetings with members of the Society of Nuclear Medicine (SNM) and the American College of Nuclear Physicians (ACNP). How-ever, apparent changee in Agency policy and continued delays with some issues have continued to cause confusion and frustration in the nuclear medicine /radiopharmaceutical community.

I am therefore requesting a written connit (nt of the Agency's policy and plans regarding the issues itemized below. I am certain that you understand that these issuas are critical to the practice of nuclear medicine.

I. Radiochemicals and Chemicals vs. Radiopharmaceuticals and Pharmaceuticals.

For many years it has been the practice in radiopharmacy to obtain radio-chemicals and chemicals and from them prepare radiopharmaceuticals and pharmaceuticals. These drugs are used in the practice of nuclear medi-cine. The preparation of these drugs has been the responsibility of licensed radiopharmacists/ pharmacists or licensed nuclear cedicine physicians or their supervised designees. The responsibility for the qua)ity of the drug belongs to the pharmacist and the physician. This is entirely within the boundc of laws set out by the various States re-gardint' the practice of pharmacy and the practice of medicine. In addition, radioactive materials licenses are required, but'this aspect is not the responsibility of FDA.

Within the past year or so, the FDA has stepped in and prevented radis-pharmacists and nuclear medicine physicians f rom receiving -adio-chemicals which may or may not become incorpcrated into radiopharmaceu-ticals. Such.radiochemicals may be simple radionuclides (e.g. I-123.

In-llD ,or radiolabeled compounds. In addition, certain companies (e.g. Sigma) will not sell certain chemicals to pharmacists / physicians if these materials will eventually be incorporated into a drug pre-paration fur human use. This firm refuses to do this because of FDA pressure.

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2 This new behavior of FDA is confusing and, I believe, inappropriate.

Why has FDA decided to regulate intermediates? Why is FDA attempt-ing to negate State laws regulating _the practice of. pharmacy _and_,

medicine? fWh5Eproblem is .beingisolved?p What need;is -being:filledf I regard this action as trespassing on the territory of other regula-tory agencies, and would be most grateful for an explanation.

I Let us examine a few of the ramifications of this new policy which is being implemented without discussion, consultation, or impact con-siderations.  ;

First, patients are being deprived of optimal care because suppliers are being prevented from shipping intermediates to physicians for drug preparation for their own patients.

Second, the-National; Laboratories'are'beingtshut outqas suppliers ofg

, radionuclides for.the; practice of nuclear medicine.. .Then do not have'm 3 NDA'efon any of the'iri radioactive materials :or non-radioactive kits',' '"

.and furthermore,"the Federal-Government.will not permit'them to'obtain lan NDA.;either. Therefore, everything-theyl sell is a radiochemical ord a' chemical,~and the sale'of:these(materials to radiopharmacists/ nuclear:

medicinc phy icifr.641s prohibited. Does DOE know they have been fund-

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ing the National Laooratories for cooperation with nuclear medicine for i nothing? Does FDA realize it is doing this? I i

Third, does FDA plan to stop all use of chemicals by pharmacists in '

general for compounding non-radioactive drugs as well? Is it the I agency's intent to remodel the entire practice of pharmacy in this country?

Please reconsider your actions. Albert Lavender stated in a telephone conversation with me in December, 1986 that pharmacists should not com-pound any drugs which use any components that are not NDA approved. I do not think this statement accurately reflects existing law.

II. Radiopharmaceuticals for PET Imaging. ,

i PET imaging is not a new modality. In 1974 it was described in the l plenary session of the Annual Meeting of the Society of Nuclear Medicine.

It is a technique of unique capability and proven value. It is being crippled by bureaucracy and unwillingness to act. At issue is a form of approval for PET radiopharmaceuticals, all of which are made on site and none of which have NDA's. Many never will have NDA's because they will never be supplied by a manufacturer; their half-lives are too short. Yet calling many of these drugs "investigational" (e.g., i F-18-FDG) is a mistake. The title "investigational" also means "non- I reimbursable", and this sort of economics is not practical. The i preparation of these drugs in-house is simply the practice of pharma?y and cedicine, and an approval mechanism must be found to make these 1

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1 drugs easily available and legitimate. Last year I proposed such a  !

mechanism. Quite simply, I suggested using the old drug monograph mechanism. No "perpetual" IND or NDA would be needed if this were done. We do not really care if the Agency chooses to use this mechanism or not. We do wish that the Agency finds some mechanism, however, and establishes an approval basis fer these drugs. This technology was supported by taxes from the people of the United States, and they deserve to reap its benefits.

In addition to the above problem, there are related regulatory night-mares afoot involving cyclotrons, automated drug synthesis devices, and the purchasing of F-18 as a radiochemical from a central supplier for in-house F FDG preparation. Again we have the problem of regulating intermediates rather than the final product, and the pur-chase of a radiochemical from which to prepare a radiopharmaceutical.

1 We urge you to_stop this regulatory eeddling now. 1The'rpspon-

,sibility'for the finalTdrug product quality rests,on.the shoulders of the_ pharmacists-and physicians who put:theirl professional; competence on.the linelwhen they prepare-these; compounds for human'use. 11t d doesn't' matter whether they~use a cyclotron, an automated., synthesis;

' machine,;a centrifuge,;or chromatography _ equipment.' These are_not drugs or devices. They are intermediates in drug preparation. The  :

1 final drug must be adequately tested for quality, and the pharmacist, physician, and institution _ determine what is, appropriate. . The. con- -

' sequences ~ of Ecarele's sness are ' lawsuits against the institution and mal,-

practice charges;against the pharmacist and physician. 1These,are;4 strong deterrents'to-sloppiness. They are'all.that is needed. dIdeally, the drug monographs rhnuld coatain or refer to appropriate quality con-'

trol procedures for the .cugs, and these would become the "standard of practice".

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1 l Please consider this approach to PET radiopharmaceuticals. It is clean. I appropriate, and adequate. The drug monographs can be provided by experts in radiopharmasy, and the FDA can simply stop there. The State laws regarding the practice of pharmacy and medicine and the use of radioactive material are adequate regulatory mechanisms from then on.

III. Thysician Sponsored IND's and Outside Review of IND's.

The FDA has been re'using to accept certain physician sponsored IND's, and has even asked radiopharmaceutical companies not to allow physicians to refer to the appropria te drug master files. This effectively thwarts submission. On the one hand, I understand that FDA is short staffed and cannot handle a large number of IND reviews efficiently.

The decision to stop certain physician sponsored IND's in order to i concentrate available manpower on a commercial IND or NDA for the same j product is an appropriate approach given the circumstances. Howsver,  ;

it is by no means a good solution. I would like to propose an idea i i

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that NIH has used successfully for many years.---- peer review.

Peer review of physician spm.sored IND's that FDA does not wish to evaluate could neatly W1ve the problem at hand. The reviews t would probably be tough and complete, as they are for grant pro-  !

posals, and the final decision of course would still rest with FDA.--

Reviewers could receive instructions as to how the FDA wishes the- -

IND's to be evaluated, just as NIH issues instructions to reviewers as to how to evaluate graat proposals. It would not be necessary to have study sections;-this could really all be accomplished by ,

mail and telephone. ShM/ACNP could provide a list of reviewers which '

could assist FDA in choosing appropriate persons. Or, the Radio-pharmaceutical Drug Product Advisory Committee could take on some

• peer review functions or help distribute physician sponsored IND's for outside peer review.

FDA has precedence for this, of course, in the formation of Radio-  ;

active Drug Research Committees, which review research projects in-  ;

volving metabolism and kinetics. FDA has essentially delegated this  !

category of research to peer review, while maintaining ultimate ,

power. l Please consider this suggestion carefully, because it is unlikely that  !

FDA manpower will ever be increased to the point that it can efficiently i handle all requests for evaluat'.on.

Thank you for your attention and consideration. I eagerly await your reply, as does the radiopharmaceutical and nuclear medicine community.

Very truly yours, v l

, Carol S. Marcus, Ph.D., M.D.

Director, Nuclear Medicine Outpt. Clinic, Harbor-UCLA Medical Center 1000 W. Carson St., Bldg. A-13 >

Torrance, CA 90509 J

(213) 533-2845 4

and l Asst. Prof. of Radiological Sciences, UCLA

President, California Chapter, ACNP 1 Board of Trustees So. Calif. Chapter, SNM Member, Govt. Relations Committee, ShH Member, Govt. Affairs Committee ACNP Member, Radiopharmaceutical Committee ACNP Past Member, Radiopharmaceutical Drug Products Advisory Committee, FDA i

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Relations Committee, SNM B. Leonard Holman, M.D., President. SNM David H. Woodbury, Jr., M.D., President, ACNP James J. Conway, M.D., Chairman, Radiopharmaceutical Committee, ACNP Jose Martinez, M.D., Chairman, Covt. Policy Committee, ACNP Myron Pollycove, M.D., President-Elect, ACNP, Henry L. Ernstthal, CAE, Executive Director, SNM Carol A. Lively, Executive Director ACNP Michael E. Phelps, Ph.D., Professor of Radiological Sciences, UCLA Eric Jones, M.D. , Group Leader, Radiopharmaceuticals i

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s4Ntas4ns4na . 54NTacatd a el UCLA SCHOOL OF ME"'ONE H ARBOR - UCLA MEDICAL Ct.. TER IMO CAh50N STREET Robert Temple, M.D. TORRANCE, cAuroRNIA emm Director, Office of Drug Research Nov. 5, 1987 and Review U.S. Food and Drug Administration 5600 Fishers Lane Parklawn Bldg., B-45 Rockville, MD 20852

Dear Dr. Temple:

I't is now three and a half months since I wrote to you on behalf of SNM and ACNP requesting clarification of severa1' crucial issues re-garding radiopharmaceuticals. As yet, I have received _no answer.

When I wrote you on 21 Sept 87 reminding you that two months had elapsed since my letter to you, Eric Jones called to tell me that the matter had been delegated by you to John Palmer, and that Palmer was working on it. I have heard nothing from him, either.

As I have stated before, these issues are absolutely vital to the practice of Nuclear Medicine in the United States. The continued

, failure of EDA to consider these issues sericusly, and commit them-selves publicly and clearly to an appropriate policy regarding these issues, has become unconscionable.

The Nuclear Medicine community would be very grateful if you would give prompt, personal attention to these issues.

l Thank you for your attention and consideration. l

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Very truly yours, I

Carol S. Marcus, Ph.D., M.D., F.A.C.N.P. )

, Director, Nuclear Hedicine Outpt. Clinic Building A-13 Harbor-UCLA Medical Center 1000 W. Carson St.

l Torrance, CA 90509 ,

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(213) 533-2845 j 1

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cc: Capt. William H. Briner, Chair  !

Govt. Relations Committee, SNM ,

i James J. Conway, M.D., Chair Radiopharmaceutical Committee, ACNP i Josd Martinez, M.D. , Chair Govt. Policy Committee. ACNP Eric Jones, M.D., Group Leader, Radio-pharmaceuticals, FDA David Woodbury, M.D., President. ACNP Leonard Holman, M.D., President, SNM Myron Pollycove, M.D., President-Elect, ACNP Henry L. Ernstthal, CAE,  !

Executive Director, SNM Carol A. Lively, Executive Director, SNM l i

Melissa Brown, ACNP-SNM

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Michael E. Phelps, Ph.D., Professor of Radiological Sciences, UCLA i j

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