Table 2. Release requirements1 of plain and adjuvanted sIPV.
Cell culture | ||
Identity | Vero cells | |
Mycoplasma | Absent | |
Extraneous viruses | Absent | |
Virus harvest | ||
Sterility | Absence of growth (Tryptic Soy Broth & Thioglycollate broth) | |
Mycoplasma | Absent | |
Extraneous viruses | Absent | |
Purified virus | ||
Purity (ratio total protein and D-antigen) | ≤0.1 µg DU-1 | |
Sterility | As above | |
Identity | PV type 1, 2 OR 3 | |
Residual host cell proteins | Consistent clearance | |
Monovalent Bulk | ||
Inactivation kinetics | PV titer below detection limit after 120h | |
Formaldehyde | >2 mM | |
Sterility | As above | |
PV identity | Contains PV type 1, 2 OR 3 | |
Inactivation | Full absence of active PV after 10 and 13 days | |
D-antigen content | Information for calculation | |
Trivalent bulk | ||
Inactivation | Full absence of active PV in 1,500 calculated human doses | |
Sterility | As above | |
D-antigen content | Information for calculation | |
Final bulk | Plain | Adjuvanted |
pH | 6.8-7.4 | 6.8-7.4 |
Phenoxyethanol | 31-42 mM | 31-42 mM |
Formaldehyde 2 | 0.7-2.4 mM | 0.7-1.3 mM |
Sterility | As above | As above |
D-antigen content | ≥75% nominal value | ≥75% nominal value |
Final lot | Plain | Adjuvanted |
Appearance | Bright red-orange fluid | Turbid red-orange fluid |
PV identity | Contains type PV 1, 2 and 3 | Contains type PV 1, 2 and 3 |
D-antigen content | ≥75% nominal value | ≥75% nominal value |
Residual host cell DNA 3 | ≤100 pg shd-1 | ≤100 pg shd-1 |
Bovin Serum Albumin 3 | ≤50 ng shd-1 | ≤50 ng shd-1 |
Total protein | ≤20 µg mL-1 | ≤20 µg mL-1 |
Endotoxin | ≤10 IU mL-1 | ≤10 IU mL-1 |
Extractable volume | ≥0.5 mL | ≥0.5 mL |
pH | 6.8-7.4 | 6.8-7.4 |
Sterility | As above | As above |
Free D-antigen | Not applicable | < 1% |
Aluminium | Not applicable | 0.26-0.36 mg mL-1 |
Abnormal toxicity (in mice and guinea pigs) | No illness | No illness |
1 Most important release tests drafted for the production of the phase I clinical lots are given. It should be noted that the release criteria could change due to further product development. 2 Formaldehyde requirement is dependent on the amount of monovalent bulk used to prepare the final bulk. 3 Test is performed at an earlier stage in view of the lower detection limit.