Product release criteria (radiopharmaceutical quality control)

Product release criteria are the specific quality-control tests and pass/fail limits a radiopharmaceutical must meet before it is dispensed or administered. Under USP General Chapter <825>, licensees preparing or compounding radiopharmaceuticals on site must complete a quality assessment before use, appropriate to the preparation, which can include radionuclidic purity, radiochemical purity, chemical purity, pH, and physical appearance, in addition to sterility and bacterial endotoxin testing for injectable preparations made from non-sterile or non-pyrogen-certified components. Compliance with these tests is not optional: the chapter states that quality testing is mandatory for validating radiochemical purity of the final product through to its beyond-use date, particularly whenever a preparation deviates even slightly from the manufacturer's kit directions.

A representative numeric release criterion is the 99Mo/99mTc radionuclidic purity limit: USP monographs for 99mTc radiopharmaceuticals require that 99Mo not exceed 0.15 microcurie per millicurie of 99Tc-99m at the time of administration, a limit that must be recalculated forward in time because the 99Mo-to-99mTc ratio rises continuously as the shorter-lived daughter decays away faster than the parent. Generator eluates must also be tested for radionuclide "breakthrough" of the parent isotope under 10 CFR 35.204, with eluates exceeding the specified limits barred from use and any exceedance reported to the generator manufacturer.

Except for unopened manufacturer unit-dose containers, the final patient dose or ordered amount must be radioassayed in a dose calibrator immediately before release, with the measured activity mathematically decay-corrected to the scheduled administration (calibration) time; the assayed activity must fall within federal, state, and institutional tolerance limits of the prescribed activity. Radiopharmaceuticals should not be administered if any impurity level exceeds the package insert or USP monograph specification. Records of every preparation, including quality-control results and final disposition, must be retained and are the primary evidence a regulator or accreditor reviews to confirm release criteria were actually met before a dose reached a patient.