BRIEFING

 〈825〉 Radiopharmaceuticals—Preparation, Compounding, Dispensing, and Repackaging. This proposal is based on the version of the chapter official as of January 1, 2024. Revisions to the chapter are proposed at the direction of the Small Molecules 4 Expert Committee and in conjunction with previously received public comments. The revision is also used to align terminology and subjects discussed in Pharmaceutical Compounding—Nonsterile Preparations 〈795〉 and Pharmaceutical Compounding—Sterile Preparations 〈797〉. It is proposed to make the following changes:

1. Throughout the revised general chapter, and where applicable, replace the term “buffer area” with “buffer room”, replace the term “personnel” with “individuals”, and replace the term “sterile compounding” with “radiopharmaceutical processing”.

2. Revise 1. Introduction to include examples of specialty clinic settings, including but not limited to endocrinology, urology, neurology, and oncology settings.

3. Clarify in 1.2 Sterile Radiopharmaceuticals that 70% isopropyl alcohol (IPA) must be allowed to dry, prior to initial needle puncture, when wiping vial septa.

4. Revise 3. Immediate Use of Sterile Radiopharmaceuticals as follows:

   • Add the requirement that intrathecally administered radiopharmaceuticals not be dispensed according to the immediate use standards.

   • Add requirements that nondirect infusion generators may not be eluted according to the immediate use standards and that nondirect infusion generators are required to be stored and eluted in a segregated radiopharmaceutical processing area (SRPA) in ISO 8 total airborne particles or better. Garbing and aseptic qualifications for the environment must be performed.

5. Make the following changes to 4. Personnel Qualifications, Training, and Hygiene:

   • Delete "sunburn" from conditions that may pose a higher potential of contaminating the radiopharmaceutical and the environment.

   • Clarify requirements in 4.1 Aseptic Qualifications under Gloved Fingertip and Thumb Sampling.

   • In 4.2 Reevaluation, Retraining, and Requalification:

     • Clarify the requirement that gloved fingertip and thumb sampling is not required but may be allowed to be in conjunction with media-fill testing.

     • Clarify the requirement for reevaluation and requalification after a pause in sterile radiopharmaceutical processing.

   • Update 4.3 Ancillary Personnel to 4.3 Ancillary Individuals as follows:

     • Clarify the requirements for ancillary individuals with regard to whether or not they handle sterile radiopharmaceuticals directly.

     • Clarify the expectation for all personnel entering ISO classified areas to meet the requirements for the specific classified area that they access.

   • Make the following changes in 4.4 Hand Hygiene and Garbing for Immediate Use Preparations.

     • Rename 4.4 Hand Hygiene and Garbing for Immediate Use Preparations to 4.4 Hand Hygiene and Garbing for Immediate Use Preparations and Nonsterile Processing.

     • Clarify requirements for hand hygiene, garbing, and gloving when radiopharmaceuticals are prepared or dispensed for immediate use.

   • Make the following changes to 4.5 Hand Hygiene and Garbing for Buffer Rooms and Segregated Radiopharmaceutical Processing Area:

     • Clarify that alcohol-based hand rub must be used if hand hygiene takes place outside the classified area prior to donning garb.

     • Update requirements so that the designated person can make personnel preparation accommodations if the quality and environment are not adversely affected.

6. Make the following changes to 5. Facilities and Engineering Controls:

   • In 5.1 Facility Design and Environmental Controls:

     • Clarify that in the event of excursions, temperature and humidity readings must be reviewed.

     • Update the requirement for smoke studies and environmental monitoring to be repeated whenever a change is made to the placement of equipment within the room or any other alteration is performed with the cleanroom suite that affects the quality of the air.

     • Add the requirement of a permanent line of demarcation in the anteroom.

     • Clarify that tacky surfaces such as tape or tacky mats are not acceptable as a line of demarcation.

   • Update 5.2. Creating Areas to Achieve Easily Cleanable Conditions to clarify ceiling requirements for sealing and securing inlaid panels.

   • Remove 5.5 Classified Areas.

   • Clarify 5.5. Remote Aseptic Processing Involving a Hot Cell to outline personnel garbing requirements in the event of verification failure, or lack of verification (e.g., by airflow smoke pattern tests or other specified methods), showing that the staging of supplies and materials into the demarcated PEC area does not allow intrusion of less than ISO Class 5 air into the designated ISO Class 5 space.

   • Make the following changes to 5.6. Environmental Controls:

     • Add pressure differential requirements for buffer rooms specific for leukocyte labeling.

     • Revise the requirement for pressure monitoring devices to be tested for accuracy every 12 months.

7. In 6. Microbiological Air and Surface Monitoring, delete requirements for incubation of samples in separate incubators.

8. Make the following changes to 7. Cleaning and Disinfecting:

   • Update the frequency requirement for cleaning and disinfecting surfaces.

   • Update Table 5 to include a requirement for cleaning and disinfecting the surfaces of handwashing sink(s) used as part of aseptic garbing.

   • Update 7.2 Cleaning Supplies to add a requirement for cleaning, disinfecting, and sporicidal agents used within the PEC to be sterile with the exception of tool handles and holders.

   • In 7.6 Cleaning and Disinfecting Items from Patient Care Area, update to include syringe-carrying containers.

9. Make the following changes to 8. Assigning BUD:

   • Add a parameter column to Table 7 and update the table title.

   • Revise the BUD for “direct infusion system, one puncture only” from 10 to 12 h.

   • Clarify that the BUD for “radiolabeled blood components” is 6 h after the blood sample is obtained from the patient.

   • Clarify that a radiopharmaceutical may exceed the BUD of its components if specified in the approved product labeling.

   • Add a requirement for multiple-dose radiopharmaceutical that contains an antimicrobial preservative.

10. Revise 9. Documentation as follows:

    • In 9.1 Master Formulation Record, add prescribing information as an example of validated documentation for ingredients.

    • Rename 9.2 Records for Preparation/Compounding to clarify applicability to all preparations and not just preparations with minor deviations.

11. Update the requirements outlined in 10.3 Preparation of Radiolabeled Blood Components for clarity and flow of information.

12. In 11.1. Compounding Nonsterile Radiopharmaceuticals, add a requirement for hand hygiene and garbing as detailed in 4.4 Hand Hygiene and Garbing for Immediate Use Preparations and Nonsterile Processing.

13. Make the following changes to 12. Dispensing:

    • Revise 12.1 Dispensing and Radioassay to allow exemptions listed in the facility's RAM license and to correct activity based on requested calibration time.

    • Make the following changes to 12.3. Direct Infusion Systems:

      • Revise the section heading from 12.3 Direct Infusion Systems to 12.3 Direct Multidose Radiopharmaceutical Infusion Systems.

      • Revise aseptic handling in ambient air for direct infusion systems from a maximum BUD of 10 to 12 h.

      • Revise the expiration time for the IV solution bag attached to infusion system from 10 to 12 h after puncture.

    • Add 12.4 Nondirect Infusion Generator Systems outlining standards for including the appropriate environment for set up, storage, and elution of the generators, BUD of the multiuse eluent, training, garbing, and aseptic qualification requirements included.

14. In 13. Repackaging, add clarification for exemptions allowed by RAM license.

15. In the Glossary, add definitions for the following terms: “low-lint”, “nondirect infusion generator systems”, “radiopharmaceutical processing”, “remote manipulation system”, “validation”, and “verification.” Additionally, revise “direct infusion system” and remove “low-lint wiper”.

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

 (SM4: B. Wagner)

 Case ID—SUB-2534