DRAFT-For Review Only

Protocol to Establish a Standardized Media Fill Test for Compounding Injectable Radiopharmaceuticals

Overview

USP Chapter <797> Pharmaceutical Compounding-Sterile Preparations requires training and evaluation of personnel aseptic technique through media fill testing.

There is a need for a standardized media fill protocol for compounding injectable radiopharmaceutical unit dosages. The purpose of this protocol is to field-test the utility of a proposed media fill exercise for low-risk compounding that will be supported by the nuclear pharmacist community.

After the protocol has been successfully field-tested, it will be submitted for approval by the Nuclear Pharmacy Practice Section of the APPM of the American Pharmacists Association. The intention is for this protocol to become an industry “standard of practice” to assure the quality of dispensed injectable radiopharmaceutical dosages.

Scope

The initial media fill protocol to be tested will be limited to low-risk compounding, which will be defined hence as including the following routine nuclear pharmacy activities:

1) Preparing a radiopharmaceutical kit using the eluant from step 1; and

2) Drawing unit radiopharmaceutical dosages from the kit in step 2.

Consistent with the USP definition of low-risk compounding, all ingredients, containers and devices will be sterile.

Selected nuclear pharmacies from the major companies, independents and hospital sites will participate in the protocol. Thus, both commercial and not-for-profit facilities will be involved, as well as nuclear pharmacy educators, preceptors and other highly qualified nuclear pharmacists.

Personnel

The personnel involved in the protocol will include authorized nuclear pharmacists having completed a training program in aseptic manipulation in compliance with state board of pharmacy requirements. They will be proctored by a nuclear pharmacist experienced in media fill testing and aseptic technique and having completed a training program in aseptic manipulation in compliance with state board of pharmacy requirements.

Methods

Materials and Equipment:

  • Sterile, evacuated 20-mL or 30-mL vials simulating Tc 99m elution vials
  • Sterile 10-mL evacuated vials simulating radiopharmaceutical kits
  • 1 sterile 30-mL syringe for transfer of media
  • 48 sterile 10-mL syringes for transfer of media (simulation of dilution with normal saline)
  • 48 sterile 5-mL syringes for transfer of media (simulation of addition of Tc 99m)
  • 2448 sterile 3-mL syringes for simulation of unit doses
  • 48 sterile 10-mL empty vials for accumulation of syringe contents and incubation
  • Vial and syringe shields necessary to simulate actual manipulations
  • Sterile 100-mL vials of Soybean Casein Digest Broth (Tryptic Soy Broth, USP/EP (TSB))
  • Incubator or Eenclosed area with thermometer temperature monitoring device for incubation at 25-35 ºC
  • Alcohol swabs for critical-site sanitization
  • Laminar Air Flow Workbench (LAFW) with unidirectional flow. Note: LAFW shall be in good working order and certified within the previous 6-months.
  • Appropriate PPE (personal protective equipment).
  • Manufacturer’s certificate for media growth promotion.

Notes

  • The critical site will be sanitized with an alcohol swab and allowed to dry, prior to any punctures., unless otherwise specified.
  • Strict aseptic technique must be adhered to.
  • All manipulations must be conducted within the LAFW.
  • TSB will be used as the microbial growth media as it supports the growth of a wide variety of microorganisms including aerobic, facultative and anaerobic bacteria and fungi.

Procedure:

  1. In a LAFW, using a 30-mL syringe and an 18-gauge needle, draw up 20 mL of Tryptic Soy Broth (TSB) from a manufacturer’s source vial and transfer to a shielded 20-mL or 30-mL sterile evacuated vial. Keep the source vial in the LAFW. Note: This step and subsequent steps require sanitization of the critical puncture site prior to the procedure.
  1. Using a 5-mL shielded syringe, transfer 2 mL of TSB media from the shielded, simulated elution vial to a shielded 10-mL empty vial that simulates a kit vial. Also, using a fresh, unshielded 10-ml syringe, draw 6 mL of media from the source TSB vial and add to the kit vial to simulate dilution with Sterile Normal Saline. Gently invert the vial several times. Repeat this step 7 3 more times to reach a total of 8 4 simulated kit vials, each containing 8 mL of media. This step and subsequent dose drawing tasks must be conducted in an LAFW. Apply a numbering scheme to track the syringes filled from a specific simulated kit vial.
  2. Using a 3-mL shielded syringe, draw up 0.8 mL of media. Repeat this step 5 more times and repeat with 7 3 additional vials to reach a total of 6 syringes loaded from each of 48 simulated kits vials.
  3. Transfer the contents of the 6 media syringes from each vial into a sterile, empty 10-mL vial. Repeat this step until all syringes are transferred into sterile vials. There should be eight four vials at the end of the transfers. Label the incubation vial with the number of the original kit vial, such as one through eightfour.
  4. Incubate the vials at 25-35 ºC in a controlled environment with a calibrated thermometer for 14 days. An observer will write an assessment of the candidate’s ability to use proper aseptic technique throughout the simulation, according to written procedures
  5. Observe the contents (Tryptic Soy Broth) of each vial for cloudy turbidity or discrete colonies that indicate microbial growth. Record the results on the assessment form provided for this study.

Data Collection

Data will be collected as follows:

  • Temperature reading of the area in which the protocol is being conducted
  • Daily media observations until turbidity noted, up to 14 days.
  • Daily recording of incubation temperature
  • Observer’s notes on aseptic technique of test candidate

Evaluation

The results of the study will be submitted to the steering committee for evaluation. A coding system will be designed to preserve the anonymity of each participating pharmacy.