ML19282A823
| ML19282A823 | |
| Person / Time | |
|---|---|
| Issue date: | 02/13/1979 |
| From: | Chilk S NRC OFFICE OF THE SECRETARY (SECY) |
| To: | |
| References | |
| RULE-PR-35 NUDOCS 7903070139 | |
| Download: ML19282A823 (9) | |
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Title 10 - Energy CHAPTER I - NUCLEAR REGULATORY COMMISSION PART 35 - HUMAN USES OF BYPRODUCT MATERIAL Change in License Conditions for Certain Medical Licenses AGENCY:
U.S. Nuclear Regulatory Commission (NRC)
ACTION:
Final rule.
SUMMARY
The Nuclear Regulatory Commission is amending its regula-tions (a) to permit physicians greater latitude, when they use certain low risk diagnostic radiopharmaceuticals, by no longer designating authorized clinical procedures and (b) by deleting from several licens-ing groups certain chemical forms not approved by FDA.
EFFECTIVE DATE: The amendment becomes effective on March 22, 1979.
FOR FURTHER INFORMATION CONTACT:
Edward Podolak, Office of Standards Development, U.S. Nuclear Regulatory Commission, Washington, D.C. 20555 (Phone:
301-443-5860).
SUPPLEMENTARY INFORMATION: On March 17, 1978, the NRC published for a 60-day comment period a proposed rule (43 FR 11206) to amend its regula-tions to delete the specification of the diagnostic clinical procedures from the lists of radiopharmaceuticals in Groups
- I, II, and III of 7 9 0 3 0 7 0 l'3fl
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5 35.100.
In the same proposal an amendment to I 35.14 would require physicians to follow the product labeling for the chemical and physical form, route of administration and recommended dosage range when they use Groups I, II and III radiopharmaceuticals for clinical procedures not specified in the product labeling. -In the same proposal the Commission also proposed to update the lists in Groups I, II and III by deleting certain chemical forms not approved by the Food and Drug Administration (FDA).
Copies of the proposed rule were sent to all NRC medical licensees, the States and 25 professional societies and individuals.
Eighteen comment letters were received.
Seven commenters fa.vored the proposal without qualification. Seven-commenters favored the proposal but suggested a change.
Three comme.n.t.er.s. objected to the proposal.
One
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comenter discussed a point that wa.s beyond the scope of the proposal but will be considered by NRC separately.
DISCUSSION OF MAJOR COMMENTS.
. The comments favoring the proposal.but-suggesting a change suggested that NRC should. not restrict physicians to follow the product The most common types of NRC specific licenses for the cedical uses of byproduct material are the Group medical licenses under 5 35.14 that I
apply to those radioactive materials listed in 5 35.100.
The radio-
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active materials listed in s 35.100 are divided into six groups, each group having similar requirements for user training and experience facilities and equipment, and radiation safety procedures.
Groups I, II and III are lists of radiopharmaceuticals for diagnostic procedures; y
Groups IV and V are lists of radiopharmaceuticals for therapeutic procedures; and Group VI is a list of radioactive medical devices for both diagnostic and therapeutic procedures.
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labeling for the chemical and physical form, route of administration and recomended dosage range when using radiopharmaceuticals for clinical procedures not specified in the product labeling.
Most of these conmenters felt that the route of administration should b to the physician.
The example cited most often was the administration of Tc-99m pertechnetate orally or rectally when it has been approved by FDA only for intravenous administration.
These commenters state that the oral or rectal route might, in some instances, be safer than intravenous administration, for example, in an emergency situation or when a vein is not available for injection.
One commenter suggested that agents approved by FDA for intravenous injections should be allowed to be injected into the venous side of the circulation through an in-dwelling heart catheter or even into the pulmonary arterial cir-culation through a Swan-Ganz ~ catheter.
Two commenters pointed out that FDA does not restrict the physician to the chemical and physical form route of administration or recommended dosage range in the product label-ing.
One commenter expressed Wncern that the NRC restrictions would
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hinder research into new uses and dosage forms.
Some of these commenters who suggested that NRC should not restrict the route of administration and dosage range erroneously assumed that these restrictions also applied when using drugs for clinical procedures specified in the product labeling. With the exception of the restric-tion on the chemical and physical form of the radiopharmaceutical, which will still be specified in the 5 35.100 Groups, the NRC restric-tions on route of administration and dosage range apply only when 1...
physicians use a radiopharmaceutical for clinical procedures not spec'ified in the product labeling.
n Stated alternatively, physicians t=
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may depart from the product labeling regarding dosage range and route of administration when they follow that labeling regarding the FDA-approved clinical procedure.
This policy is consistent with FDA's recognition that good medical practice re ires physicians to be free to use drugs according their best knowledge and judgment in the interest of the patient.
The compatibility between NRC and FDA policy in this matter is discussed in detail in the preamble to the proposed regulation (43 FR 11206).
The Commission recognizes that holding physicians to the labeled chemical and physical form, labeled route of administration, and labeled dosage range (when they use a radiopharmaceutical for clinical procedures not specified in the product labeling) is'more restrictive than FDA.
The Commission believes that these restrictions minimize the risk to patients from diagnostic clinical procedures that have not been approved by FDA.
Regarding the comment about hindering research, each of the Groups I, II, and III includes a provision authorizing the use of products for which a " Notice of Claimed Investigational Exemption for a New Drug" (IND) has been accepted by the FDA.
Research may also be con-ducted under NRC licenses of broad scope provided the studies are i
performed in accordance with FDA regulations and are approved by the licensee's Medical Isotopes Committee.
One commenter who disapproved of the proposed rule believes that the existing rule provides adequate control and should not be changed. Another commenter challenged the assumption that physicians always use their best knowledge and judgment when using drugs for unapproved uses.
This commenter noted that the patient is generally totally incompetent to judge whether the benefit of a procedure exceeds the risk and that the proof of damage generally rests with 4
the patient.
The third connenter who disapproved of the proposed rule questioned how the benefit-risk decision would be made by the physician.
This commenter wanted to know if the procedure is automatically war-ranted when there is an expectation that the procedure will yield some useful diagnostic infomation.
In answer, the Comission believes that the use of diagnostic radiophamaceuticals listed in Groups I, II and III for clinical procedures not yet approved by FDA entails low risk to the patient, provided the chemical and physical form, route of administration and the dosage range remain the same as specified in the radiopharmaceutical labeling. Advances in medical knowledge and practice inevitably precede labeling revision by the manufacturer and formal label approval by the FDA. Good medical practice and patient interests are best served when the physicians are free to use radiopharmaceuticals to their best knowledge and judgment, notwithstanding the opportunity for abuse of this freedom by some physicians.
The text of the final rule has not changed from the text of the proposed rule except for:
(1) the additions of some chemical forms that have been added to the 5 35.100 groups through previous Federal Reaister notices; and (2) the names of some chemical forms have been changed to conform with FDA guidelines (e.g., "diethylenetriaminepenta-acetic acid" is now called "pentatate sodium").
Under the Atomic Energy Act of 1954, as amended, the Energy Reorgar.ization Act of 1974, as amended, and Sections 552 and 553 of Title 5 of the United States Code, the following amendments to Title 10, Chapter I, Code of Federal Regulations, Part 35 are pub-lished as a document subject to codification.
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1.
In 5 35.14(b), a new paragraph (6) is added which reads as follows:
5 35.14 Specific licenses for certain grouos of medical uses of byvproduct material.
(b) * * *
(6) For Groups I, II and III any licensee using byproduct material for clinical procedures other than those specified in the product labeling (package insert) shall comply with the product labeling regarding:
(i) chemical and physical form; (ii) route of administration; and (iii) dosage range.
2.
In 5 35.ln, paragraphs (a), (b) and (c) are revised to read as follows:
5 35.100 Schedule A - Groups of medical uses of byoroduct material.
(a) Group I.
Use of prepared radiopharmaceuticals for certain diagnostic studies involving measurements of uptake, dilution and excretions This group does not include imaging or localization studies, g
(1)
Iodine-131 as sodium iodide, fodinated human serum albumin, labeled rose bengal, triolein, or sodium iodohippurate; (2)
Iodine-125 as sodium iodide, iodinated human serum albumin, oleic acid or sodium iothalamate; (3) Cobalt-58 as labeled cyanocobalamin; 6
(4) Cobalt-60 as labeled cyanocobalamin; (5) Chromium-51 as sodium chromate or labeled human serum albumin; (6)
Iron-59 as citrate; (7) Technetium-99m as pertechnetate; and (8) Any byproduct material in a radiopharmaceutical and for a diagnostic use involving measurements of uptake, dilution or excretion for which a
" Notice of Claimed Investigational Exemption for a New Drug" (IND) has been accepted by the Food and Drug Administration (FDA).
(b) Group II.
Use of prepared radiopharmaceuticals for diagnostic imaging and localization studies.
(1)
Iodine-131 as sodium iodide, iodinated human serum albumin, macro-aggregated iodinated human serum albumin, colloidal (microaggregated) iodinated human serum albumin, rose benegal or sodium iodohippurate; (2)
Iodine-125 as sodium iodide or fibrinogen; (3) Chromium-51 as human serum albumin; (4) Gold-198 in colloidal form; (5) Mercury-197 as chlormerodrin; (6) Mercury-203 as chlonnerodrin; (7)
Selenium-75 as selenomethionine; (8) Strontium-85 as nitrate; (9) Technetium-99m as pertechnetate, sulfur colloid or macroaggregated human serum albumin; (10) Ytterbium-169 as pentatate sodium; 7
(11)
Indium-ll3m as chloride; (12) Any byproduct material in a radiopharmaceutical prepared from a reagent kit listed in paragraph (c)(4) cf this section; and (13) Any byproduct material in a radiopharmaceutical and for a diagnostic use involving imaging or localizing for which a " Notice of Claimed Investigational Exemption for a New Drug" (IND) has been accepted by the Food and Drug Administration (FDA).
(c) Group III.
Use of generators and reagent kits for the prepara-tion and use of radiopharmaceuticals containing byproduct material for certain diagnostic studies.
(1) Molybdenum-99/ technetium-99m generators for the elution of technetium-99m as pertechnetate; (2) Technetium-99m as pertechnetate for use with reagent kits for preparation and use of radiopharmaceuticals containing technetium-99m as provided in paragraphs (c)(4) and (5) of this section; (3) Tin-ll3/ indium-ll3m generators for the elution of the indium-ll3m as chloride; (4)
Reagent kits for preparation of technetium-99m labeled:
(i)
Sulfur colloid; (ii) pentatate sodium; (iii) Human serum albumin microspheres:
(iv) Polyphosphates; (v) Macroaggregated human serum albumin; 8
l./b90-utj (vi) Etidronate sodium; (vii) Stannous pyrophosphate; (viii) Human serum albumin; (ix) Medronate sodium; (x) Gluceptate sodium; and (5) Any generator or reagent kit for preparation and diagnostic use of a radiopharmaceutical containing byproduct material for which generator or reagent kit a " Notice of Claimed Investigational Exemption of a New Drug" (IND) has been accepted by the Food and Drug Administration (FDA).
(Secs. 81, 167b, Pub. Law 83-703, as amended, 68 Stat. 935, 948 (42 U.S.C. 2111, 2201); Sec. 201, Pub. Law 93-438, as amended, 88 Stat.
1242 (42 U.S.C. 5841).)
Dated at Washington, D. C.
this 13th day of February 1979.
For the Nuclear R ulatory Commission.
6 Samuel J ' Chilk Secretary of tjae Commission 9