BRIEFING

 〈1823〉 Positron Emission Tomography Drugs—Information. This proposal is based on the version of the chapter official as of May 1, 2017. The comments received on the proposal published in PF 49(5) [Sep.–Oct. 2023] informed this updated proposal. The previous proposal has been canceled and replaced with this new proposal. It is proposed to make the following changes:

1. Revise the chapter title from "Positron Emission Tomography Drugs—Information" to "Positron Emission Tomography Drugs for Diagnostic Imaging—Information” to better describe the scope of the chapter.

2. Renumber the sections to reflect the reorganization and any newly added content to the general chapter. Please note that most sections have been renumbered.

3. Revise the section titles as needed. Please note that most of the updated titles resemble their original versions.

4. Revise 1. Introduction to be consistent with current terminology and practices, as well as:

   • Indicate the scope is “Positron emission tomography (PET) drugs used for diagnostic imaging”.

   • Add zirconium-89 to Table 1, which includes examples of positron emission tomography (PET) radionuclides and their associated half-lives.

   • Revise the term "[¹⁸F]fluorinated" to "¹⁸F-fluorinated" in Figure 1 to be consistent with current convention, and update the figure to include the reaction with mannose triflate precursor.

   • Expand the requirements associated with PET drug products and biologically active PET drug products.

   • Remove the reference to compounding from the self-verification requirement within the characteristics defining PET drug products.

5. Add 2. Typographic Conventions for PET Radionuclides to provide information about typographic conventions.

6. Add 3. Regulatory Framework for PET Drugs to provide information about regulations related to PET drugs.

7. Add 4. Precursors to provide information about precursors related to PET drug products.

8. Add 5. PET Drug Substance versus PET Drug Product to provide definitions for a PET drug substance and PET drug product.

9. Rename 3. Quality Assurance as 7. Quality Assurance, update to be consistent with current terminology and practices, and add 7.2 Structural Characterization of the PET Drug Substance.

10. Rename 4.2 Equipment for Automated Synthesis and 4. Production as 8.2 Equipment for Automated Synthesis and 8. Production and update to allow remote manipulators to be used in addition to robots.

11. Rename 5. Quality Control as 9. Quality Control and clarify that “PET drug” refers to a “PET drug product”.

    • Delete 5.3 Conditional Release because the information has been included in Production of Diagnostic Positron Emission Tomography Drugs for Investigational and Research Uses 〈823〉, 11.4 Conditional Final Release Tests.

    • Rename 5.4 Out-of-Specification Results as 9.3 Out-of-Specification Results and update to be consistent with current practices.

12. Rename 6. Analytical Methodologies as 10. Analytical Methodologies and make the following changes:

    • Move the paragraph about calibration from 6.3 High-Performance Liquid Chromatography to a new subsection, 10.1 Calibration and System Suitability, and provide additional information about calibration and system suitability tests.

13. Rename 7. Quality Attributes as 11. Quality Attributes and make the following changes to be consistent with current terminology and practices:

    • Add a paragraph acknowledging that the section includes typical quality attributes for PET drugs and that other attributes and test methods may be appropriate beyond those described therein.

    • Rename 7.7 Chemical Purity as 11.7 Chemical Purity and add a statement about stabilizers and other additives.

    • Rename 7.8 Total Mass of the Active Pharmaceutical Ingredient and Specific Activity as 11.8 Total Mass of the Active Pharmaceutical Ingredient and Specific Activity and clarify that the total mass of the active pharmaceutical ingredient (API) includes the nonradioactive carrier.

    • Add 11.9 Potency to address the quality of biologically active PET drug products.

    • Rename 7.9 Bacterial Endotoxin as 11.10 Bacterial Endotoxin and include a reference to Bacterial Endotoxins Test 〈85〉.

14. Rename 8. Sterility Assurance as 12. Sterility Assurance and make changes to be consistent with current terminology and practices:

    • Rename 8.1 Sterile Membrane Filtration as 12.1 Sterile Membrane Filtration and update to include both closed-filled and open-filled injectable PET drug products.

    • Rename 8.3 Presterilized Components as 12.3 Presterilized Components and add a preference for commercially presterilized components, a statement about in-house sterilized components, and a risk statement.

    • Rename 8.4 Environmental Controls as 12.4 Environmental Controls and add Table 2 titled ISO Classification of Particulate Matter in Area Air.

    • Rename 8.5 Media Fills as 12.5 Aseptic Simulations and replace references to media fills with simulations or aseptic simulations. Provide additional information about positive and negative controls.

    • Rename 8.6 Suitability of Media as 12.6 Suitability of Media and clarify that media should be stored according to the manufacturer's instructions.

    • Delete 8.9 Operator Training and Qualification because it is included in 〈823〉, 3.1 Training and Qualification Requirements.

15. Delete 9. Labeling because it is included in 〈823〉, 14. Labeling.

16. Add 13. Record Retention to be consistent with current practices.

17. Update the Glossary to include additional definitions for Potency and Precursor, remove the entry for Active Pharmaceutical Ingredient, rename the entry for PET drug as PET drug substance, and revise the entries for PET drug product and Strength.

 Additionally, minor editorial changes have been made to update the chapter to current USP style.

 (SM4: N. Myers)

 Case ID—SUB-1918