Table 3.
Summary of the specifications used for the cGMP radiosynthesis of [11C]UCB‐J for multi dose vials
| QC Test (Parameter/Method) | Release Criteria | Production 1 | Production 2 | Production 3 |
|---|---|---|---|---|
| Appearance | Clear colourless solution | Confronts | Confronts | Confronts |
| pH | 4.5‐8.5 | 6.4 | 6.1 | 6.1 |
| HPLC system suitability test | Retention time difference less than 8 s in two injections of reference solution | pass | pass | pass |
| Radiochemical identity | Retention time of [11C]UCB‐J corresponds to that of reference UCB‐J standard, corrected for the dead‐volume between UV and radio‐detector | pass | pass | pass |
| Chemical amount of UCB‐J | ≤10 μg/dose | 8.8 | 8.6 | 6.8 |
| Chemical amount of desmethyl UCB‐J | ≤1.5 μg/dose | 0.97 | 0.59 | 0.6 |
| Chemical amount of unidentified impurity | ≤1.5 μg/dose | 1.44 | 1.38 | 1.00 |
| Total unidentified impurity | ≤3.0 μg/dose | 2.40 | 2.29 | 2.00 |
| Radiochemical purity of [11C]UCB‐J | ≥95% | 100 | 100 | 100 |
| Molar activity (GBq/μmol) | N/A | 33.0 | 23.4 | 32.1 |
| Strength (MBq in 0.1 mL) | N/A | 9.1 | 6.3 | 6.8 |
| Bacetiral endotoxins (postrelease test) | ≤175 EU/dose (≤17.5 EU/mL) | ≤2.5 EU/mL | ≤2.5 EU/mL | ≤2.5 EU/mL |
| Filter integrity (postrelease test) | Bubble point ≥46 psi (3.17 bar) | 3.8 bar | 3.7 bar | 3.8 bar |
| Sterility (postrelease test) | Pass test | pass | pass | pass |
| Residual solvent DMF (postrelease test) | ≤0.88 μg/day (≤880 ppm) | ND | ND | 1.5 |
| Formulation solvent EtOH (postrelease test) | ≤10% | 7.7% | 9.8% | 10% |
Note. The limits are per injected dose. The desmethyl UCB‐J competes with UCB‐J for the binding site for which reason the specification for desmethyl UCB‐J is stringent. The unidentified impurities include all impurities in the final formulated product, and they were calculated using 258 nm wavelength absorbance response.