Under pharmaceutical regulations, radiopharmaceuticals refer to medicinal products that contain radioisotopes (RI) and meet the following criteria:
- Drugs that emit radiation, as defined in Article 3, Item 5 of the Atomic Energy Basic Act (Act No. 186 of 1955), and fall under the scope of Article 2, Paragraph 1 of the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Act No. 145 of 1960).
- Unsealed compounds containing radioisotopes as part of their molecular structure, including their formulations.
Radiopharmaceuticals are used for diagnostic and therapeutic purposes in nuclear medicine.
Types of Diagnostic Radiopharmaceuticals
In vivo diagnostic radiopharmaceuticals:
Administered to the body to visualize radiation emitted by the RI for diagnostic imaging.
In vitro diagnostic radiopharmaceuticals:
Used outside the body, such as in blood or urine testing, without administration to the human.
The table below shows the regulatory classifications of radiopharmaceuticals and the corresponding review departments:
| Item | Category | Department in charge |
|---|---|---|
| In vivo diagnostic radiopharmaceuticals | Drug | Office of New Drug II |
| Therapeutic radiopharmaceuticals | Drug | Office of New Drug II |
| Generator | Drug | Office of New Drug II |
| Radiopharmaceutical synthesizer | Medical device | Office of Medical Devices I |
| In vitro diagnostic radiopharmaceuticals | In vitro diagnostic | Office of In Vitro Diagnostics |
This website describes radiopharmaceuticals intended for in vivo diagnostic and therapeutic use.
For information on diagnostic radiopharmaceuticals used to determine eligibility for therapeutic radiopharmaceuticals, please refer to 2. Diagnostic Radiopharmaceuticals.
Radiopharmaceuticals and the Minimum Requirements for Radiopharmaceuticals
Key Characteristics
Radiopharmaceuticals, both for diagnostic and therapeutic purposes, function by delivering and accumulating RI at specific target sites within the body. This targeted delivery is achieved either by combining RI with ligands—such as small molecules, peptides, or antibodies—that specifically bind to the target, or by utilizing the natural affinity of certain radionuclides for specific organs or tissues.
Once localized, the radiation emitted from the RI enables either diagnostic imaging or therapeutic action.
| Diagnostic radiopharmaceuticals | Therapeutic radiopharmaceuticals | |
|---|---|---|
| Purpose (e.g.) |
Visualization of molecular expression, organ/tissue function, blood flow | Treatment of malignant tumors |
| Radiation Type | γ- ray Note: Radiation with a long range and high permeability is used. |
β-ray; α-ray; Auger electron Note: Radiation with a short range and cytotoxic properties is used. |
| RI | 11C, 13N, 15O, 18F, 68Ga, 64Cu (nuclides for PET) 123I, 99mTc, 111In (nuclides for SPECT) Note: Nuclides with short physical half-lives are used. |
131I, 90Y, 177Lu (β-emitting nuclides) 223Ra, 211At, 225Ac (α-emitting nuclides) 64Cu (β-/Auger electron-emitting nuclides) Note: Nuclides with relatively long physical half-lives are used. |
Theranostics
"Theranostics" is a coined term that combines "therapeutics" and "diagnostics". Radiotheranostics is a medical approach that integrates radiopharmaceutical-based imaging and therapy. Diagnostic radiopharmaceuticals are used to evaluate disease status and predict the efficacy and safety of therapeutic radiopharmaceuticals with similar pharmacokinetics.
Radiotheranostics has been increasingly developed in recent years as one of the key strategies in personalized medicine.
The Minimum Requirements for Radiopharmaceuticals
Pursuant to the provisions of Article 42, Paragraph 1 of the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Act No. 145 of 1960), radiopharmaceuticals marketed in Japan must comply with the standards established for each product, including those concerning manufacturing methods, properties, quality, and storage methods.
When applying for marketing authorization of a new radiopharmaceutical in Japan, applicants need to submit a draft revision of the Minimum Requirements for Radiopharmaceuticals as part of the application dossier (CTD 1.13) to the Ministry of Health, Labour and Welfare (MHLW).
Note: The Minister of Health, Labour and Welfare may establish necessary standards for manufacturing methods, properties, quality and storage methods after obtaining opinions from the Pharmaceutical Affairs Council on pharmaceuticals and regenerative medicine products as those requiring special attention with regards to health and hygiene.
The submitted draft monograph of the Minimum Requirements for Radiopharmaceuticals will be reviewed in parallel with the approval review and will be subject to public comments, WTO notification, and other necessary procedures conducted by MHLW. The Pharmaceutical Affairs Council will then deliberate on both the draft revision of the Minimum Requirements for Radiopharmaceuticals and the marketing application of the product.
Based on the results of the deliberation, the Minimum Requirements for Radiopharmaceuticals will be revised concurrently with the marketing approval of the product.
To ensure the smooth progress of both the review of the Minimum Requirements for Radiopharmaceuticals and the approval review, applicants who plan to submit a marketing authorization application for a radiopharmaceutical that may require a revision of the Minimum Requirements for Radiopharmaceuticals should refer to the following notification and request a Pre-consultation meeting to confirm whether a revision of the Minimum Requirements for Radiopharmaceuticals is necessary and to review the contents of the documents to be submitted for the Prior Assessment Consultation for Drugs (Quality).
Utilization of Prior Assessment Consultation for Drugs (Quality) for Marketing Authorization Applications of Radiopharmaceuticals[124KB]
October 2, 2025 PSB/PED Notification No. 1002-2
Diagnostic Radiopharmaceuticals
Guidelines and Guidance
- Guideline for Clinical Evaluation of Diagnostic Radiopharmaceuticals[286.37KB]
June 11, 2012 PFSB/ELD Notification No. 0611-1
- Considerations for Non-Clinical Studies in the Development of Diagnostic Radiopharmaceuticals (Early Consideration) [126.12KB]
March 26, 2025 Office of New Drug II, Pharmaceuticals and Medical Devices Agency
The necessity of safety pharmacology studies and repeated-dose toxicity studies in the development of diagnostic radiopharmaceuticals is shown in the "Guidelines for Clinical Evaluation of Diagnostic Radiopharmaceuticals" issued in 2012. However, discussions frequently arise regarding the non-clinical study items, timing of their implementation, etc. Therefore, in order to clarify the regulatory viewpoint, and to explain how to evaluate drug-drug interactions and the safety of degradation products in diagnostic radiopharmaceuticals based on the newly issued ICH guidelines, key considerations regarding non-clinical evaluation of diagnostic radiopharmaceuticals have been compiled in this "Early Consideration".
Lecture Materials
The following materials were used by PMDA reviewers during presentations on diagnostic radiopharmaceuticals. Please note that the views expressed in the presentations are those of the presenter and do not necessarily reflect the official views of the PMDA.
| Lecture name/Materials | Supplementary explanation |
|---|---|
| PMDA-ATC Radiopharmaceuticals Webinar 2024 for FDA Philippines(2024, November) Session1 [1.08MB], Session2 [786KB], Session3 [426KB] |
This section outlines the review of radiopharmaceuticals (mainly diagnostic radiopharmaceuticals) and the points of quality, non-clinical and clinical evaluation for foreign regulatory authorities. |
Information on Diagnostic Radiopharmaceuticals Used for Determining Eligibility for Therapeutic Radiopharmaceuticals
In recent years, various therapeutic and diagnostic radiopharmaceuticals have been developed to enable the clinical implementation of theranostics (see Section 1). In light of this situation, it is important to ensure that diagnostic radiopharmaceuticals used to determine eligibility for therapeutic radiopharmaceuticals can be used rationally and smoothly, taking into account factors such as the feasibility of conducting tests at medical institutions.
Therefore, regarding diagnostic radiopharmaceuticals used for eligibility determination, approved indications are not limited to a one-to-one correspondence between diagnostic and therapeutic radiopharmaceuticals. Instead, for diagnostic radiopharmaceuticals determined as suitable for determining eligibility for therapeutic radiopharmaceuticals during the application review, relevant information will be provided on this website in a timely manner.
When developing such therapeutic and diagnostic radiopharmaceuticals, please also refer to the FAQ.
- Information on Diagnostic Radiopharmaceuticals Approved in Japan for the Purpose of Determining Eligibility of Patients for Therapeutic Radiopharmaceuticals
Updated September 19, 2025 [210KB]
FAQs
Q1: What is the process for obtaining marketing approval for diagnostic radiopharmaceuticals?
A1: Please refer to this link for the overall marketing authorization process, including radiopharmaceuticals. Also see the "Guidelines and Guidance" section above for details on nonclinical and clinical evaluation.
Q2: What are the key points in clinical evaluation of diagnostic radiopharmaceuticals?
A2: To evaluate the clinical utility of diagnostic radiopharmaceuticals, it is essential to demonstrate both i. the accuracy of the imaging-derived information and ii. its clinical significance. For example, these may be explained as follows:
- The accuracy of imaging-derived information should be demonstrated based on the results of diagnostic performance evaluations conducted in clinical trials. In principle, the diagnostic performance of the product should be assessed based on its sensitivity (the probability that the test is positive in patients with the disease) and its specificity (the probability that the test is negative in patients without the disease) compared to standard diagnostic methods.
- The clinical significance of the imaging results can be explained based on the expected clinical benefits for the target patients, such as leading to the appropriate treatment option, or improvement of clinical outcomes. The approach to such explanation may vary depending on the availability of existing diagnostic methods or the current clinical algorithms.
Refer to the above "Guidelines for Clinical Evaluation of Diagnostic Radiopharmaceuticals" for more details.
Q3-1: When submitting a new application for a therapeutic radiopharmaceutical that requires patient eligibility to be determined using a diagnostic radiopharmaceutical, what information should be included in the application documents regarding the diagnostic radiopharmaceutical?
A3-1: If the diagnostic radiopharmaceutical was used for patient enrollment in the major efficacy trial of the therapeutic radiopharmaceutical, the applicant should explain that patient eligibility can be determined using that diagnostic agent, based on evidence demonstrating the clinical efficacy of the therapeutic radiopharmaceutical in the patient population enrolled through the use of the diagnostic agent.
On the other hand, if the diagnostic radiopharmaceutical was not used for patient enrollment in the major efficacy trial of the therapeutic radiopharmaceutical, it is necessary to explain, with supporting evidence, that the diagnostic radiopharmaceutical can appropriately identify a patient population equivalent to that of the clinical trial.
Since the necessary considerations for evaluating whether a diagnostic radiopharmaceutical can be used to identify eligible patients for a therapeutic radiopharmaceutical may vary depending on factors such as whether it was used in the major efficacy trial of the therapeutic product, it is recommended to consult with PMDA in a timely manner, for example during the planning stage of the major efficacy trial.
The basic approach is the same when developing new diagnostic radiopharmaceuticals intended for eligibility determination of therapeutic radiopharmaceuticals.
Q3-2: For a new therapeutic radiopharmaceutical targeting the same indications (disease, biomarkers) as an already approved product, if it is considered that the eligible patients for the new therapeutic agent can be identified using an already approved diagnostic radiopharmaceutical, are any regulatory procedures required for the diagnostic radiopharmaceutical, such as applications for partial change or revisions to precautions in the package insert?
A3-2: If, during the application review, it is determined that an already approved diagnostic radiopharmaceutical can be used to determine eligibility for a new therapeutic radiopharmaceutical, information on such diagnostic radiopharmaceuticals will be provided on this website as those usable for eligibility determination of therapeutic radiopharmaceuticals.
Therefore, no application for partial change is required for the already approved diagnostic radiopharmaceutical upon approval of the new therapeutic radiopharmaceutical. However, revisions to precautions in the package insert may be necessary based on the data submitted in the marketing authorization application for the therapeutic agent.
Q4: When submitting a new application for a precursor formulation to be radiolabeled and used at medical institutions, what information should be included in the application documents regarding the supply method of the radionuclide used for radiolabeling (e.g., generator system)?
A4: It is necessary to provide an explanation, supported by evidence, that the radionuclide supply method used for radiolabeling the formulation enables proper and reliable radiolabeling.
For example, such explanations are expected to be based on data confirming the quality of the radiolabeled drug prepared using the combination of the precursor formulation and the radionuclide supply method intended for use, as demonstrated in clinical trials, including evidence that appropriate patient enrollment was conducted using this radiolabeled drug. In addition, explanations should be supported by comparative data regarding the quality of the radiolabeled drug prepared using this combination versus that used in clinical trials, such as batch analysis and impurity profiles. Comparisons of the acquired imaging results should also be provided.
Therapeutic Radiopharmaceuticals
Guidelines and Guidance
Clinical evaluation of therapeutic radiopharmaceuticals may differ depending on the disease area. Refer to this link for guidelines and guidance in targeted disease areas.