ML19241B061
| ML19241B061 | |
| Person / Time | |
|---|---|
| Issue date: | 05/31/1979 |
| From: | Chilk S NRC OFFICE OF THE SECRETARY (SECY) |
| To: | |
| References | |
| RULE-PR-30, RULE-PR-35 NUDOCS 7907110613 | |
| Download: ML19241B061 (7) | |
Text
MRC PUBLIC DOCUMENT ROOM NUCLEAR REGULATORY COMMISSION
[10 CFR Parts 30 and 35]
TESTING OF RADIGIS0 TOPE GENERATORS AGENCY:
U.S. Nuclear Regulatory Commission (NRC)
ACTION:
Proposed rule.
SUMMARY
Certain NRC medical licensees are authorized to prepare radiopharmaceuticals from radioisotope generators.
NRC is considering requiring licensees to test these radiopharmaceuticals for a contaminant called molybdenum-99.
The proposed rule also includes maximum limits for molybdenum-99 in these radiopharmaceuticals.
DATES:
Comment period expires August 6,1979 AL ESSES:
Written comments or suggestions for consiceration in connection with the proposed amendment should be submitted to the Secretary of the Commission, U.S. Nuclear Regulatory Cammission, Washington, D.C.
20555, Attention:
Docketirc and Service Branch.
Copies of comments receiveu be e'.amined at tne Commission's Public Document Room at 1717 H Street, N.W., Washington, D.C.
FOR FURTHEP INFORMATION CONTACT:
Edward Podolak, Off e of Standards Development, U.S. Nuclear Regulatory Commission, Washington, D.C.
20555 (Phone:
301-443-5860).
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SUPPIIMEf!TARY Ilu0RMATION:
In diagnostic nuclear mecicine, the most widely used radiopharmaceutical is technetium-95m (Tc-99m) which has a radioactive half-life of 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br />.
Many hospitals and nuclear phar-macies obtain their Tc-99m by purchasing a radionuclide generator from a raciopharmaceutical manufacturer and eluting the generator.
The radioisotope generator is a shieiC'd device that is often called a molybdenum ger.erator or molybdenum " cow" because molybdenum-99 (Mo-99), the parent of Tc-99m, is contained within the generator.
The Mo-99 is adsorbed on an alumina eclumn which is arranged so that sterile saline can be fed through the column to wash out, or elute, only the Jaughter radioisotope, Tc-99m.
The parent, Mo-99, has a longer half-life than the daughter, Tc-99m, and the parent continuously decays to form the daughter radioisotope, which is eluted when needed. The generator is usually eluted, or " milked", every 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> and replaced with a new generator once a week because the parent, Mo-99, has decayed below useful levels.
The United States Pharmacopeia (USP) XIX, which is recognized the Food and Drug Administration (FDA) and the pharmaceutical industry as the basic standard for drug strength, quality and purity, has upper limits for the presance of Mo-99 in Tc-99m radiopharmaceuticals.
These limits apply to molybdenum generator manufactt rers and the generator's labeling includes methods or references methods for quantifying the amount of Mo-99 in Tc-99m.
This is usually called a molybdenum break-through test.
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Molybdenum breakthrough testing by the gererator :ser has always been considered a good laboratory practice or a good cuality control measure.
In a section describing molyboenum breakthrough testing, the Bureau of Radiological Health (FDA) " Workshop Manual on Radiophar-maceutical Quality Assurance" (July 1978) states: "Thus, it is impor-tant that testing for Mo-99 be performed routinely."
Until 1S75, all NRC medical licenses authorizing generators included a license condition requiring molybdenum breakthrough testing.
In 1975 this condition was dropped be:ause of a provision in the new 9 35.14 group medical licensing regulations.
Section 35.14(b)(4) requires licensees ta follow the generator labeling or package inser+s which at that time included methods for molybdenum breakthrough testing.
Over the intervening years, gene.rator labeling has become equivocal on molybdenum breakthrough testing.
Some package inserts imply that you should do it, others imply that you are doing it, and still others recommend that you do it.
Thus, there are no niform requirements in NRC licenses, regulations, or manufacturer's laaeling for the perform-ance of tests to determine the amount of Mo-99 in Tc-99m radiophar-maceut'cals prior to administration to patients.
A recent joint NRC/FDA investigation revealed the possibility of greater than normal cuantities of Mo-99 in ic-99m generator eluate.
The presence of molybdenum-99 serves no diagnostic purpose.
It could result in a radiation dose to a critical organ of one or more rems and 3
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if such doses occur in large populationc patients, tr.ey would be unacceptable from a public health and safety standpoint.
There are several thousand generators shipped weekly with each generator account-ing for up to 50 patient dosages per day.
If a problem develops in the manufacture, shipping, handling or elution of these generators and this results in molybdenum breakthrough in excess of the USP XIX limits, there is a potential for the exposure of a large number of persons.
In view of this, on March 12, 1979, NRC issued an order requiring medical licensecs t; perform molybdenum breakthrough testing on each elution of Tc-99m from a generator and also prohibiting licensees from administering any Tc-99m radiopharmaceuticals that exceed the USP XIX limits for Mo-99 contamination.
The following proposed rule contains the essentials of that order.
This proposed rule does not change or modify the March 12, 1979 order to licensees requiring molybdenum break-through testing.
Howe
, the order will be rescinded upon publication of an effective tule.
The proposed rule (and the NPC order) covers three types of NRC medical licenses:
(1) the nuclear pharmacy license, (2) the broad medical license and (3) the group medical license.
The proposed rule (and the NRC order) applies only to medical licensees who actually elute the radioisotope generators and does not apply to those medical licensees who purchase prepared Tc-9Cn radiopharmaceuticals frem a radiopharmaceutical manufacturer or nuclear pharmacy.
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Basically, the proposed s 35.14(b)(4) requires the group medi:11 licensees to perform molybdenum breakthrough tests if they use gener-ators.
The proposed 6 30.34(f) requires nuclear pharmacy licensees and broad medical licensees to perform the same molybdenum breakthrough tests if they ase generators.
Copies of th2 value/ impact analysis supporting the proposed rule are available for public inspection at the Commission's Public Document Room at 1717 H Street, N.W., Washington, D.C.
Single copies of the value/ impact analysis may be obtained on request from Edward Podolak at the above address.
Under the Atomic Energy Act of 1954, as amended, the Energy Reorganization Act of 1974, as amended, and section 553 of title 5 of the United States Ccde, notice is hereby given that adoption of the following amendments to 10 CFR Parts 30 and 35 are contemplated.
1.
A new paragraph (f) is added to S 30.34 to read as fci tows:
e 30.34 Terms and conditions of licenses.
(f)
Each licensee who prepares technetium-99m radiopharmaceuticals from molybdenum-99/ technetium-99m generators shall test the generator eluates for molybdenum-99 breakthrough in accordance with S 35.14(b)
(4)(i) thru (iv).
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2.
In 35.14, paragraph (b)(4) is revised to read as follows:
9 35.14 Specific licenses for certain aroups of medical uses of byproduct material.
A A
A (b) Any licensee wha is authorized to use byproduct material pur-suant to one or more groups in SS 35.14(a) and 35.100 is subject to the following conditions:
a a
a a
x (4) For Group III, any licensee who uses generators or reagent kits shall:
(i) Elute the generator or process radioactive caterial with the reagent kit in accordance with instructions which are approved by the Nuclear Regulatory Commission or an Agree-ment State and are furnished by the manufacturer on the label attached to or in the leaflet or brochure that accompanies the generator or reagent kit; (ii) Cause each elution or extraction from the ganerator to be tested to determine either the total molybdenum-99 activity, or the concentration of molybdenum-99, before administration to patients.
This testing shall be con-ducted according to written prccedures and by personnel who have been specifically trained to perform the test; 6
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(iii) Prohibi' the administration to patients of technetium-93m containing more than one microcurie of molybdenum-99 per millicurie of technetium-99m, or more than 5 microcuries of molybdenum-99 per administered dose, at the time of administration; and (iv) Maintain for 3 years for Commission inspection records of tne molybdenum-99 test conducted on each elution from the generator.
a (Secs. 81, 161, Pub. Law 83-703, 68 Stat. 935, 948 (42 U.S.C. 2111, 220~); Sec. 201. Pub. Law 93-438, 88 Stat. 1242 (42 U. S. C. 5841))
Dated at Washir.gton,D.[tiis 31st day of May
, 1979.
For the Nuclear Regulatory Co:nmissicn.
a f
ist4 k trN
_jf' 5ariiuel J. C'hi f Secretary c f the Commissior i
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