Radiopharmaceutical Production Quality Control Testing Sterility STOP

Sterility According to the pharmacopeia, a sterility test must be started within 24 h of the final manufacture of the radiopharmaceutical. Sterility tests are designed to determine the presence of bacteria and fungi in solutions. The tests are normally carried out over a 14 day period. Normally samples are sent out to a commercial laboratory for these tests. Contents Acceptance Criteria Discussion Procedure STOP

Acceptance Criteria Acceptance Criteria: FDG must comply with the requirement for parenteral preparations, and must pass the sterility test. The product is released for patient use prior to completion of the test. Procedure: The test must be initiated within reasonable period of time allowing for decay of the radioactivity. Sterility test entails incubation of the test sample with two different growth media (Soybean Casein Digest Medium and Fluid Thioglycolate).

Discussion Discussion: The test can be performed in house or outsourced depending upon the availability of resources. It may be necessary that the test sample has decayed sufficiently enough to transport as non-radioactive materials. It has to be ensured through validation studies that the sample is stored in a way not to influence the test outcome. In situations when a preparation fails the test, it becomes necessary to investigate the entire production routine for possible breach in the processes employed in manufacturing. Non-compliance with aseptic processing, and people behaviour should be examined for corrective and preventive actions, and to evaluate need for retraining of staff. As described in next section, the filter integrity test should be required prior to release of product if the product is not steam sterilized.

Sterility Procedure Validation: Bacteriostasis and fungistasis (2 media and 6 organisms) tests must be performed once before first use in humans. It must be tested for sterility on three separate syntheses. Each of the three validation syntheses must give a negative sterility result. If an established radiotracer has not been produced for 6 months, one sterility test will be performed on a “practice” synthesis and serves to re-validate sterility procedures and quality control. Testing Frequency: This test is required to be performed once per day for each compound that is delivered to a human subject (i.e. if the same compound delivered multiple times, only one of the deliveries is tested, usually the first batch). Usually these samples are sent out on every batch for testing.

Sterility Procedure QC Aliquot: Remove 0.6 – 0.7 mL from the product vial immediately after Millipore filtration using the 1 mL syringe that is part of the standard multi-injection vial assembly. This sample is called the QC aliquot and is used for all batch testing. Sampling of QC aliquot: Take ~ 0.3 mL of the QC aliquot and put into a sterile pyrogen-free (SPF) multi-injection after swiping the top of the SPF vial with an alcohol swab. Link to Demonstration (UNDER CONSTRUCTION)

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