FAQ
Drugs

What technical document regarding Chemistry, Manufacturing, and Controls (CMC), pharmacokinetics (PK), and pharmacology/toxicology (PT) should be submitted for radiopharmaceuticals in investigational new drug (IND) applications?

刊登日期:2019-11-11  |  點閱次數 : 492 次 

CMC part

Q1:What CMC data for radiopharmaceuticals in IND applications should be submitted?

A1:

1. Radionuclide

    (1) General information (including nomenclature, general properties)

    (2) Manufacture (including manufacturers, description of manufacturing process and process controls)

    (3)Control of radionuclide (including specifications, analytical procedures, batch analyses, justification of specifications)


2. Precursor(non-radioactive intermediate)

    (1) General information (including nomenclature, general properties)

    (2) Manufacture (including manufacturers, description of manufacturing process and process controls, control of materials)

    (3) Characterization

    (4) Control of precursor (including specifications, analytical procedures, batch analyses, justification of specifications)

    (5) Reference standards or materials

    (6) Container closure system

    (7) Stability


3. Drug substance*

    (1) General information (including nomenclature, general properties)

    (2) Manufacture (including manufacturers, description of manufacturing process and process controls, control of materials)

    (3) Control of drug substance (including specifications, analytical procedures, batch analyses, justification of specifications)

    (4) Reference standards or materials (when non-radioactive drug substance reference standard is produced in house or by a contract manufacturer, the non-radioactive drug substance reference standard information should be included method of synthesis used, structure characterization and batch analyses) *If drug substance and drug product are produced in a continuous operation, general information of drug substance and reference standards or materials should be submitted. The manufacture (including manufacturers, description of manufacturing process and process controls, control of materials) can be included in drug product section.


4. Drug product

    (1) Description and composition of the drug product

    (2) Manufacture (including manufacturers, description of manufacturing process and process controls, control of materials)

    (3) Control of excipients

    (4) Control of drug product (including specifications, analytical procedures, batch analyses, justification of specifications)

    (5) Reference standards or materials

    (6) Container closure system

    (7) Stability



Q2: Are stability data required for the submission of a radiopharmaceutical investigational new drug (IND) application?

A2:Yes, stability data should be required for the submission of a radiopharmaceutical IND application. Although radiopharmaceutical drugs have extremely short shelf lives, the expiration time and storage conditions should be established for each drug product. At least three production runs of the final product should be studied for a time period equal to the labeled shelf life of the drug product. The expiration time should be based on the results of stability testing.



Q3:How to calculate the endotoxin limit for parenteral radiopharmaceutical products?

A3:For radiopharmaceutical products not administered intrathecally, the endotoxin limit is calculated as 175/V, where V is the maximum recommended dose in mL. For intrathecally administered radiopharmaceuticals, the endotoxin limit is obtained by the formula 14/V. Please refer to USP <85> Bacterial Endotoxins Text.



PK part

Q1:What PK/PD information should be provided for IND application of radiopharmaceutical drugs?

A1:According to the guideline for clinical trial in radiopharmaceutical drugs, the sponsor should provide the drug tissue distribution, metabolic fate and excreted pathway/rate in animals in order to establish the optimal dose and sampling time in the clinical trial. If the drug has been used in human, human ADME information should be provided. Noted that if the PK information is from public literatures or not just same as the investigational medicinal product (IMP), it will be necessary to establish the relevance between products. Additionally, if there are new excipients or new carriers in IMP, the animal or human PK information of these new materials should also completely be collected and evaluated.

 

(中文版)




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