Back to Explorer

Developing Medical Imaging Drug and Biological Products Part 2: Clinical Indications

FinalCenter for Drug Evaluation and Research Center for Biologics Evaluation and Research06/22/2004
Blinding

Description

This guidance is one of three guidances intended to assist developers of medical imaging drug and biological products (medical imaging agents) in planning and coordinating their clinical investigations and preparing and submitting investigational new drug applications (INDs), new drug applications (NDAs), biologics license applications (BLAs), abbreviated NDAs (ANDAs), and supplements to NDAs or BLAs. The three guidances are: Part 1: Conducting Safety Assessments; Part 2: Clinical Indications; and Part 3: Design, Analysis, and Interpretation of Clinical Studies.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

9
Medical Imaging Drug

Subject of the guidance document

biological product

Products subject to section 506C notification requirements

investigational drug

The drug being tested in clinical trials for MDS.

Reference product

single biological product licensed under section 351(a) of the PHS Act; U.S.-licensed reference product used for comparative analytical assessment; analytical studies that demonstrate that the proposed product is highly similar to the reference product

Biological Products

Requires analytical comparability per ICH Q5E

Contrast Agents

Category of medical imaging agents

Diagnostic Radiopharmaceuticals

Low doses not expected to elicit late radiation toxic effects; Usually gamma emitters given in lower activities than therapeutic radiopharmaceuticals

Diagnostic Radiopharmaceutical

An article intended for use in the diagnosis or monitoring of a disease exhibiting spontaneous disintegration of unstable nuclei.; A diagnostic radiopharmaceutical may be intended to evaluate patients in an emergency room.

Medical imaging agent

diagnostic or therapeutic patient management indication

Stakeholders

1
Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

8
Phase 3 studies

Using information from phase 3 studies to characterize impact of renal function

Drug Approval

regulatory goal supported by early endpoints

IND

Investigational New Drug submissions

NDA

New Drug Application

BLA

Biologics License Application

ANDA

Abbreviated New Drug Application

New Drug Application

Rule does not apply to products marketed under an NDA

Biological License Application

Submission requirement for vaccine labeling

Document Types

1
Label

performing label review for each new batch

Attributes

8
Immunogenic

Property of biological medical imaging agents that may pose significant patient risk.

Precision

Closeness of agreement between a series of measurements from multiple samplings.; Performance characteristic measured by intermediate precision; Performance characteristic to be validated

Accuracy

Performance characteristic assessed via linearity experiment

Reliability

reliability includes accuracy, completeness, and traceability

Negative predictive value

measure of test validity

Positive predictive value

measure of test validity

Specificity

Ability to detect intended mechanism of action without interference; Performance characteristic to be validated

Sensitivity

Analysis by sex of clinical performance measures such as sensitivity

Technical Details

Substances

10
Iodinated compounds

iodinated compounds used in radiography and CT

Prostate Specific Antigen

Men presenting with abnormal prostate specific antigen testing.

Contrast agent

risk of use of a contrast agent should also be considered

Diagnostic radiopharmaceutical

developed as an aid in the diagnosis of lung cancer

Gadolinium

Active ingredient in gadolinium products is considered the entire complexed molecule

Microbubbles

microbubbles, microaerosomes, and related microparticles used in diagnostic ultrasonography

Technetium-99m

Radionuclide component of a radiopharmaceutical

Iodine-123

Example of a radionuclide detected in vivo.

Indium-111

Example of a radionuclide detected in vivo.

Radiolabeled monoclonal antibody

Used to detect unique tumor antigens.

Testing Methods

10
Single Photon Emission Computed Tomography

Imaging modality for diagnostic radiopharmaceuticals

Truth standard

An independent method of measuring the same variable being measured by the investigational drug

standard deviations

measures used to express precision

confidence intervals

measures used to express precision

Pathology

Compare the new test added to the current standard test battery to a truth standard such as pathology.

Randomized Clinical Trial

Prospective study comparing interventions against a control

Colonoscopy

recommended to document disease activity in all involved segments

Mammography

Safety assessment for patients undergoing screening during the study

Coronary angiography

invasive diagnostic testing for cardiac patients

Positron Emission Tomography

Source of radiological data

Processes

8
Radiography

diagnosis or monitoring with a variety of modalities, such as radiography

Image Acquisition

processes that took place during the conduct of the trial

Chemotherapy

evaluate the effect of investigational drugs added to standard chemotherapy

Tumor resection

Optical imaging during oncologic surgery aims to optimize tumor resection

Computed Tomography

diagnosis or monitoring with a variety of modalities, such as computed tomography (CT)

Ultrasonography

diagnosis or monitoring with a variety of modalities, such as ultrasonography

Magnetic Resonance Imaging

diagnosis or monitoring with a variety of modalities, such as magnetic resonance imaging (MRI)

Radionuclide Imaging

diagnosis or monitoring with a variety of modalities, such as radionuclide imaging

Clinical Concepts

10
Structure Delineation

Indications for medical imaging agents including structure delineation; A category of labeled indications for medical imaging agents.

Myocardial Infarction

Number of events for Nonfatal Myocardial Infarction in trials

Breast Cancer

Example of a cancer type treated by tissue agnostic drugs

Prostate Cancer

Disease state not addressed by the general indication in this guidance.

Cardiac ejection fraction

functional evaluation of cardiac anatomy

Mortality

include estimates of acute morbidity and mortality; Deaths included in the public health impact evaluation.

Morbidity

include estimates of acute morbidity (i.e., acute illnesses); Acute illnesses included in the public health impact evaluation.

Disease Detection

Disease or pathology detection or assessment

Disease or Pathology Detection

A category of labeled indications for medical imaging agents.

Functional, Physiological, or Biochemical Assessment

A category of labeled indications for medical imaging agents.

Identified Hazards

Hazards

1
Unnecessary invasive procedures

potential harm from imaging results without defined benefits

Standards & References

Specifications

5
Truth Standard

Independent method of measuring the same variable being measured by the investigational drug.

Negative Predictive Value

NPV requirement for supporting de-escalation of treatment

Positive Predictive Value

PPV requirement for supporting escalation of treatment

Specificity

ability to assess unequivocally the analyte in the presence of components which may be expected to be present

Sensitivity

Index used for quantifying bias in exposure validation

Related CFR Sections (4)

See Also (8)