Human Use Subcommittee Radioactive Drug Research Committee

By Manuel Gibson,2014-05-19 16:38
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Routine quality control procedures: Indicate the testing procedures that will be performed on each batch of the radioactive drug to ensure that is meets the

    Instructions for Completing HUSC-RSC Form 1002,

    “Information Required in Support of the Research Use of a

    Non-Approved (F.D.A.) Radioactive Drug”

    A. General Instructions

1. Responses to the requests for information should be type-set (i.e., handwritten responses will

    not be accepted).

2. Use of supplementary pages or appendices is permitted if additional space is required.

    3. One completed HUSC-RSC Form 1002 for a given radioactive drug may serve as a “Master

    File” for multiple research projects involving the administration of that radioactive drug. Each

    new submission of a research protocol should specifically cite the current Master File for the

    applicable radioactive drug.

    B. Specific Instructions

    1. Identity of the Radioactive Drug

    a. Identify the {radionuclide}-active ingredient/carrier (e.g., [C-14] glucose)

    b. Identify the non-radioactive ingredients that appear within the final dosage form (e.g.,

    10% V/V ethanol in 0.9% Sodium Chloride for injection, U.S.P.)

    2. Route of Administration

    a. Indicate the proposed route of administration.

3. Estimated Radiation Dose to Human Subjects

    a. Absorbed dose calculation:

    ? Provide radiation absorbed dose estimates for the radioactive drug. At a minimum,

    radiation dose estimates must address the effective dose equivalent and absorbed

    doses to the total body, gonads, active blood-forming organs, critical organ, and lens

    of the eye. (The latter may be assumed to be equivalent to the total body dose unless

    specific eye uptake of the radioactive drug has been demonstrated or is expected).

    Submit a complete list, to include absorbed doses to other organs, when respective

    data is available. These dose estimates must take into account the contribution of

    any significant radionuclide contaminant(s) present in the final product.

    ? Specify the literature reference from which the biodistribution data for calculation of

    the radiation absorbed dose estimates were obtained; or, if not published, provide a

    summary of the biodistribution data and identify the laboratory and personnel involved

    in its collection.

    ? Specify the individual or entity responsible for calculation of the radiation absorbed

    estimates and the methodology (e.g., MIRD or ICRP absorbed fraction) utilized; or, if

    taken from a published source, include a copy of the respective reference.

    Instructions for HUSC-RSC Form 1002

b. Method of radioassay:

Specify the method by which the radioactive drug will be assayed prior to use so as to ensure

    that the administered radioactivity dosage and corresponding absorbed dose estimated are as

    stated in the research proposal.

c. Assay instrumentation quality control:

Indicate the procedures that will be performed to ensure accurate operation of the

    instrumentation used to assay the radioactive drug.

    4. Pharmacological Dosage of Active Ingredient

a. For an FDA-approved (i.e., NDA) radiopharmaceutical prepared using a non-approved

    method and/or used for a non-approved (i.e., off-label) indication: Provide supporting

    statements to address the requirement that deviation(s) from the approved product

    labeling will not significantly increase the risk to the research subject.

b. For a radioactive drug prepared and administered under the authority of 21 CFR

    361.1: Provide data, based on published or other valid human studies, in support of

    the requirement that the amount of active ingredient/carrier in the proposed dosage of

    the final radioactive drug will not cause any clinically detectable pharmacological

    effects. (Append copies of key referenced publications or cited human studies.)

     5. Quality of the Radioactive Drug

a. Method of preparation/dispensing:

    ? Identify the individual(s) or entity that will be responsible for the preparation,

    repackaging, and/or dispensing of the radioactive drug.

    ? Describe, in detail, the procedures that will be used in the preparation,

    repackaging, and/or dispensing of the radioactive drug. (May be appended in

    the form of a master formula card.)

b. Minimum acceptance criteria:

    Delineate minimum acceptance specifications for the final radioactive drug,

    addressing each of the criteria listed below:

    ? Visual appearance

    ? pH

    ? Radiochemical purity

    ? Chemical purity

    ? Specific activity

    ? Radionuclide purity of identification:

    ? Pyrogens or bacterial endotoxins (limited to parenteral administration)

    ? Sterility (limited to parenteral administration)

c. Preclinical validation studies:

    Summarize the outcome of any preclinical validation studies that have been

    performed to confirm that the final radioactive drug will meet the designated minimum

    acceptance criteria when prepared/repackaged according to the indicated procedures.

    Such validation studies may include procedures performed on site and/or data

    obtained from the supplier of the radioactive drug.

    Instructions for HUSC-RSC Form 1002

d. Routine quality control procedures:

    ? Indicate the testing procedures that will be performed on each batch of the

    radioactive drug to ensure that is meets the designated minimum acceptance


    ? Note that because of test complexity it may not be possible or practicable to

    address each of the designated minimum acceptance criteria on each batch

    of the radioactive drug. In such an event, compliance of the radioactive drug

    with the applicable minimum acceptance criterion should be addressed in the

    preclinical validation studies. For certain criteria (e.g., sterility,

    pyrogens/bacterial endotoxins), it may be a requirement (i.e., based on the

    physical half-life of the radionuclide) that testing be completed following

    release of the radioactive drug for human use.

    ? Indicate the individual(s) or entity that will be responsible for routine quality

    control testing of the radioactive drug.

e. Expiration dating:

    Specify an expiration period, post preparation or repackaging of the radioactive drug,

    wherein there is evidence that each of the designated minimum acceptance criteria

    will be retained. Summarize the studies that have been performed or provide a

    literature reference justifying this expiration period.

    6. Labeling

The final container for the radioactive drug shall be labeled to include the following:

? The statement “Caution: Federal law prohibits dispensing without a prescription.”

    ? The statement “To be administered in compliance with the requirements of Federal

    regulations regarding radioactive drugs for research use (21 CFR 361.1).”

    ? Identity of the radioactive drug to include the name and half-life of the radionuclide.

    ? The identity and quantity of the active ingredient.

    ? The total quantity of radioactivity within the immediate container at a designated

    reference time.

    ? The amount of radioactivity per unit volume or unit mass at a designated reference


    ? The net quantity of contents.

    ? The route of administration if it is for other than oral use.

    ? An identifying lot or control number from which it is possible to determine the complete

     preparation/repackaging history of the batch of radioactive drug.

    ? The name and address of the manufacturer, preparer, repackager, or distributor.

    ? The expiration date.

    ? If the drug is intended for parental use, a statement as to whether the contents are


    ? If the drug is for other than oral use, the identity of all active ingredients.

    Instructions for HUSC-RSC Form 1002

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