BRIEFING

 〈823〉 Positron Emission Tomography Drugs for Compounding, Investigational, and Research Uses. This proposal is based on the version of the chapter official prior to 2013. 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 for Compounding, Investigational, and Research Uses" to "Production of Diagnostic Positron Emission Tomography Drugs for Investigational and Research Uses” to better describe the scope of the chapter and to support the removal of references to the compounding of positron emission tomography (PET) drugs.

2. Replace “should” with “must” throughout the chapter, as appropriate, to be consistent with the current compliance standards. Replace "preparation" and "make" with "production" and "produce" throughout the chapter, as appropriate, to support the removal of compounding from the scope of this chapter.

3. Incorporate the relevant components of Radiopharmaceuticals—Preparation, Compounding, Dispensing, and Repackaging 〈825〉.

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

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

6. Make the following changes to 1. Introduction:

   • Remove the requirement of using dedicated couriers for PET drug product delivery.

   • Limit the scope of this chapter to diagnostic PET drugs for human administration.

   • Exclude the production of PET drug products used for therapeutic purposes and the manufacturing of PET drugs under 21 CFR Part 212.

   • Exclude the activities as defined in 〈825〉.

7. Add 2. Documentation to provide the documentation standards for PET drugs for investigational and research uses.

8. Rename 2. Personnel as 3. Personnel and make the following changes:

   • Rename 2.1 Training Requirements as 3.1 Training and Qualifications Requirements and expand to include a statement regarding personnel with limited roles.

   • Rename 2.2 Aseptic Operations Training as 3.2 Aseptic Operations Training and limit the scope to address the ISO Class 5 environmental conditions where designated.

   • Add a new subsection titled 3.3 Aseptic Qualifications. Move text regarding the evaluation of personnel involved in aseptic operations from 2.2 Aseptic Operations Training to 3.3 Aseptic Qualifications.

   • Add a new subsection, 3.4 Reevaluation, Retraining, and Requalification, to provide standards for these activities.

9. Rename 3. Quality Assurance as 4. Quality Assurance and update to ensure that PET drugs have adequately defined potency (if applicable) and they are produced, tested, labeled, released, and distributed according to the facility's established procedures and practices based on investigational new drug (IND) or Radioactive Drug Research Committee (RDRC) protocols for PET drug products.

10. Update 4. Facilities and Equipment to 5. Facilities and Equipment and make the following changes:

    • Replace many of the references to an “aseptic workstation” with references to a “PEC” (primary engineering control station).

    • Rename 4.1 Environmental Controls for Parenteral PET Drug Products as 5.1 Environmental Controls for Parenteral PET Drug Products and update by clarifying that facilities and equipment must be designed and operated to promote sterile PET drug product production.

      • Rename Asceptic Workstation as 5.1.1 Aseptic Primary Engineering Control to accommodate cleanliness ratings better than ISO Class 5, describe the operating locations of PECs, add a cleaning and disinfecting frequency, revise the certification frequency, and remove a reference to Microbiological Control and Monitoring of Aseptic Processing Environments 〈1116〉.

      • Rename Microbiological Testing as 5.1.2 Microbiological Testing and update to be consistent with current practices. Remove the paragraph about alert and action limits.

      • Add subsections 5.1.3 Engineering Controls and Design, 5.1.4 The PET Drug Product Production Environment, and 5.1.5 Types of PECS and Placement

    • Rename 4.3 Cleaning Equipment and Components as 5.3 Cleaning Equipment and Components and expand to provide standards for appropriate working environments and align with current expectations.

    • Add a new subsection titled 5.4 Creating Areas to Achieve Easily Cleanable Conditions.

    • Add a new subsection titled 5.5 Water Sources.

    • Add a new subsection titled 5.6 Placement and Movement of Materials.

    • Add a new subsection titled 5.7 Remote Aseptic Processing Involving a Hot Cell.

    • Rename 4.4 Day-of-Use Checks as 5.8 Day-of-Use Checks and replace “(e.g., temperature, pressure integrity, gas supply, vacuum supply, proper delivery line selection, reagent delivery volumes, gas flow rates, radiation monitors, and other process sensors)” with “as applicable”.

    • Rename 4.5 System Suitability for QC Equipment as 5.9 System Suitability for QC Equipment and simplify by replacing several paragraphs with a reference to Positron Emission Tomography Drugs for Diagnostic Imaging—Information 〈1823〉, which is also being revised in this issue of PF.

11. Add 6. Environmental Monitoring to provide the related standards for PET drugs for investigational and research uses.

12. Add 7. Cleaning and Disinfecting to provide the related standards for PET drugs for investigational and research uses.

13. Rename 5. Control of Components, Materials, and Supplies as 8. Control of Components, Materials, and Supplies and update to be consistent with the current terminology and practices.

14. Rename 6. Process and Operational Controls as 9. Process and Operational Controls and make the following changes:

    • Remove the Aseptic Techniques subsection and provide details about the performance of sterility tests and sample timing in 3.3 Aseptic Qualifications.

    • Rename Sterility Test Inoculations as 9.3.3 Sterility Test Inoculations and update to be consistent with the current terminology and practices.

15. Rename 8. Controls and Acceptance Criteria for Finished PET Drug Products as 11. Controls and Acceptance Criteria for Finished PET Drug Products and make the following changes:

    • Rename 8.1 Quality Control Tests as 11.1 Quality Control Tests and clarify that half-life measurement is one option to determine the radionuclidic identity of all dosage forms .

    • Rename 8.2 Periodic Quality Indicating Tests as 11.2 Periodic Quality Indicating Tests and remove the phrase "rather than on a batch-to-batch basis".

    • Rename 8.3 Microbiological Tests for Sterile PET Drug Products as 11.3 Microbiological Tests for Sterile PET Drug Products and remove statements about testing with regard to the first batch prepared each day and pooled samples.

16. Rename 10. Reprocessing as 13. Reprocessing and update by adding an example of secondary dilution and by removing the example of a second passage through a purification column to remove an impurity.

17. Rename 11. Labeling as 14. Labeling and update to be consistent with current terminology and practices.

18. Update the Glossary to include additional definitions, remove the entry for Compounding, and revise the entries for PET drug, PET drug product, Specific activity, and Strength.

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

 (SM4: N. Myers)

 Case ID—SUB-1913