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 Small Molecules 4 Expert Committee is proposing to update this chapter with the following key 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", respectively, 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. Make the following changes to the Introduction section:

   • Replace "dedicated couriers" with "appropriately trained couriers that transport radioactive materials".

   • 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.

5. Add a Documentation section to provide the documentation standards for PET drugs for investigational and research uses.

6. Make the following changes to the Personnel section:

   • Expand the Training Requirements subsection to include a statement regarding personnel with limited roles.

   • Limit the scope of the Aseptic Operations Training subsection to address the ISO Class 5 environmental conditions where designated. Move text regarding the evaluation of personnel involved in aseptic operations to a new subsection titled Aseptic Qualifications.

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

7. Revise the Quality Assurance section 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.

8. Make the following changes to the Facilities and Equipment section:

   • Update the Environmental Controls for Parenteral PET Drug Products by clarifying that facilities and equipment must be designed and operated to promote sterile PET drug product production. Replace many of the references to an “aseptic workstation” with references to a “PEC” (primary engineering control station). Accommodate additional concepts such as a cleanliness rating of better than ISO Class 5, a description of the PEC location applying when it is operated, details about the work area inside of the PEC, and the surface sampling frequency. The paragraph about alert and action limits is removed.

   • Expand the Cleaning Equipment and Components subsection to provide standards for appropriate working environments to be aligned with current expectations. The topics addressed include design, controls, monitoring, sampling, cleaning and disinfecting, and data evaluation and action levels.

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

   • Add a new subsection titled Water Sources.

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

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

   • Add a new subsection titled Environmental Controls.

   • Remove “reagent delivery volumes” from the Day-of-Use Checks subsection.

   • Simplify the System Suitability for QC Equipment subsection by replacing several paragraphs with a reference to the chapter Positron Emission Tomography Drugs—Information 〈1823〉, which is also being revised in this issue of PF.

9. Add an Environmental Monitoring section to provide the related standards for PET drugs for investigational and research uses.

10. Add a Cleaning and Disinfecting section to provide the related standards for PET drugs for investigational and research uses.

11. Update the Control of Components, Materials and Supplies section to be consistent with the current terminology and practices.

12. Make the following changes to the Process and Operational Controls section:

    • Remove the Aseptic Techniques subsection and provide details about the performance of sterility tests and sample timing in the Aseptic Operations for Parenteral PET Drug Products subsection.

    • Update the Sterility Test Inoculations subsection to be consistent with the current terminology and practices.

13. Make the following changes to the Controls and Acceptance Criteria for Finished PET Drug Products section:

    • Clarify that half-life measurement is one option to determine the radionuclidic identity of all dosage forms in the Quality Control Tests subsection.

    • Remove the phrase "rather than on a batch-to-batch basis" from the Periodic Quality Indicating Tests subsection.

    • Remove statements about testing with regard to the first batch prepared each day and pooled samples from the Microbiological Tests for Sterile PET Drug Products subsection.

14. Update the section titled If a PET Drug Product Does Not Conform to Specifications to be consistent with current terminology and practices.

15. Update the Reprocessing section by adding an example of secondary dilution and by removing the example of a second passage through a purification column to remove an impurity.

16. Update the Labeling section to be consistent with current terminology and practices.

17. Update the Glossary to include additional definitions, to remove the entry for compounding, and to revise the entries for PET drug substance, PET drug product, Specific Activity, and Strength.

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

 (SM4: G. Hsu)

 Correspondence Number—C319934