0338 21cfr601 34 2007

§ 601.30

21 CFR Ch. I (4–1–05 Edition)

the CBER list from the Office of Communication, Training, and Manufacturers Assistance (HFM–40), Center for
Biologics Evaluation and Research,
Food and Drug Administration (see
mailing addresses in § 600.2 of this chapter).

carrier or ligand component of the diagnostic radiopharmaceutical); and
(c) The estimated absorbed radiation
dose of the diagnostic radiopharmaceutical.

[65 FR 56480, Sept. 19, 2000, as amended at 70
FR 14984, Mar. 24, 2005]

(a) For diagnostic radiopharmaceuticals, the categories of proposed
indications for use include, but are not
limited to, the following:
(1) Structure delineation;
(2) Functional, physiological, or biochemical assessment;
(3) Disease or pathology detection or
assessment; and
(4) Diagnostic or therapeutic patient
management.
(b) Where a diagnostic radiopharmaceutical is not intended to provide disease-specific information, the proposed
indications for use may refer to a biochemical, physiological, anatomical, or
pathological process or to more than
one disease or condition.

§ 601.33

Subpart D—Diagnostic
Radiopharmaceuticals
SOURCE: 64 FR 26668, May 17, 1999, unless
otherwise noted.

§ 601.30

Scope.

This subpart applies to radiopharmaceuticals intended for in vivo administration for diagnostic and monitoring
use. It does not apply to radiopharmaceuticals intended for therapeutic purposes. In situations where a particular
radiopharmaceutical is proposed for
both diagnostic and therapeutic uses,
the radiopharmaceutical must be evaluated taking into account each intended use.
§ 601.31

§ 601.34

Evaluation of effectiveness.

(a) The effectiveness of a diagnostic
radiopharmaceutical is assessed by
evaluating its ability to provide useful
clinical information related to its proposed indications for use. The method
of this evaluation varies depending
upon the proposed indication(s) and
may use one or more of the following
criteria:
(1) The claim of structure delineation
is established by demonstrating in a
defined clinical setting the ability to
locate anatomical structures and to
characterize their anatomy.
(2) The claim of functional, physiological, or biochemical assessment is
established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological,
biochemical, or molecular process(es).
(3) The claim of disease or pathology
detection or assessment is established
by demonstrating in a defined clinical
setting that the diagnostic radiopharmaceutical has sufficient accuracy
in identifying or characterizing the disease or pathology.
(4) The claim of diagnostic or therapeutic patient management is established by demonstrating in a defined
clinical setting that the test is useful

Definition.

For purposes of this part, diagnostic
radiopharmaceutical means:
(a) An article that is intended for use
in the diagnosis or monitoring of a disease or a manifestation of a disease in
humans and that exhibits spontaneous
disintegration of unstable nuclei with
the emission of nuclear particles or
photons; or
(b) Any nonradioactive reagent kit or
nuclide generator that is intended to
be used in the preparation of such article as defined in paragraph (a) of this
section.
§ 601.32 General factors relevant
safety and effectiveness.

Indications.

to

FDA’s determination of the safety
and effectiveness of a diagnostic radiopharmaceutical includes consideration
of the following:
(a) The proposed use of the diagnostic
radiopharmaceutical in the practice of
medicine;
(b) The pharmacological and toxicological activity of the diagnostic
radiopharmaceutical (including any

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Food and Drug Administration, HHS

§ 601.40

in diagnostic or therapeutic patient
management.
(5) For a claim that does not fall
within the indication categories identified in § 601.33, the applicant or sponsor
should consult FDA on how to establish the effectiveness of the diagnostic
radiopharmaceutical for the claim.
(b) The accuracy and usefulness of
the diagnostic information is determined by comparison with a reliable
assessment of actual clinical status. A
reliable assessment of actual clinical
status may be provided by a diagnostic
standard or standards of demonstrated
accuracy. In the absence of such diagnostic standard(s), the actual clinical
status must be established in another
manner, e.g., patient followup.
§ 601.35

may require, among other information,
the following types of data:
(A) Pharmacology data,
(B) Toxicology data,
(C) Clinical adverse event data, and
(D) Radiation safety assessment.
(2) The amount of new safety data required will depend on the characteristics of the product and available information regarding the safety of the diagnostic radiopharmaceutical, and its
carrier or ligand, obtained from other
studies and uses. Such information
may include, but is not limited to, the
dose, route of administration, frequency of use, half-life of the ligand or
carrier, half-life of the radionuclide,
and results of clinical and preclinical
studies. FDA will establish categories
of diagnostic radiopharmaceuticals
based on defined characteristics relevant to risk and will specify the
amount and type of safety data that
are appropriate for each category (e.g.,
required safety data may be limited for
diagnostic radiopharmaceuticals with
a well established, low-risk profile).
Upon reviewing the relevant product
characteristics and safety information,
FDA will place each diagnostic radiopharmaceutical into the appropriate
safety risk category.
(d) Radiation safety assessment. The
radiation safety assessment must establish the radiation dose of a diagnostic radiopharmaceutical by radiation dosimetry evaluations in humans
and appropriate animal models. The
maximum tolerated dose need not be
established.

Evaluation of safety.

(a) Factors considered in the safety
assessment of a diagnostic radiopharmaceutical include, among others,
the following:
(1) The radiation dose;
(2) The pharmacology and toxicology
of the radiopharmaceutical, including
any radionuclide, carrier, or ligand;
(3) The risks of an incorrect diagnostic determination;
(4) The adverse reaction profile of the
drug;
(5) Results of human experience with
the radiopharmaceutical for other uses;
and
(6) Results of any previous human experience with the carrier or ligand of
the radiopharmaceutical when the
same chemical entity as the carrier or
ligand has been used in a previously
studied product.
(b) The assessment of the adverse reaction profile includes, but is not limited to, an evaluation of the potential
of the diagnostic radiopharmaceutical,
including the carrier or ligand, to elicit the following:
(1) Allergic or hypersensitivity responses,
(2) Immunologic responses,
(3) Changes in the physiologic or biochemical function of the target and
nontarget tissues, and
(4) Clinically detectable signs or
symptoms.
(c)(1) To establish the safety of a diagnostic radiopharmaceutical, FDA

Subpart E—Accelerated Approval
of Biological Products for Serious or Life-Threatening Illnesses
SOURCE: 57 FR 58959, Dec. 11, 1992, unless
otherwise noted.

§ 601.40

Scope.

This subpart applies to certain biological products that have been studied
for their safety and effectiveness in
treating serious or life-threatening illnesses and that provide meaningful
therapeutic benefit to patients over existing treatments (e.g., ability to treat
patients unresponsive to, or intolerant

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