Table 1.
Summary of the quality and safety assessment of SL PAV batch 1 and batch 2.
| Parameters (unit) | Testing method | Results | Regulatory requirement (WHO, 2016)14 | |
|---|---|---|---|---|
| SL PAV B1 | SL PAV B2 | |||
| Appearance | Visual observation of colour, and physical appearance of the powder (in case of freeze-dried preparations) | White in colour and powder like appearance, more cake-like structure is observed | White in colour and powder like appearance, less cake-like structure than B1 | Compliance with the description of the marketing dossier |
| Residual moisture (freeze-dried preparations) (%) | Heat dying method | < 3 | < 3 | Less than 3% |
| Solubility (freeze-dried preparations) (min) | Addition of solvent and observation of time to reach solubility and of appearance | ~ 5 | ~ 5 | Product should be completely dissolved within 10 min |
| Turbidity (NTU) | By using a turbidimeter | 15.3 ± 0.6 | 11.1 ± 0.8 | Solution should not be cloudy but threshold level is not mentioned in the guidelines |
| pH of solution | By using a potentiometer (pH meter) | 6.95 ± 0.2 | 6.89 ± 0.3 | Specifications of Pharmacopeias and regulatory agencies (generally neutral pH) |
| Total protein concentration (g/dL) | Lowry method | 7.3 ± 0.2 | 7.5 ± 0.4 | Not more than 10 g/dL |
| Serum albumin content (%) | LC–MS/MS | 1.54 | 0.66 | Ideally should be within 1% |
| Test for pyrogen substances (EU/mL) | Limulus Amebocyte Lysate (LAL) test when validated and approved by national regulatory agency | 1.55 ± 0.07 | 1.8 ± 0.05 | Accepted limits by the pharmacopeia in use |
| Sterility test (microbial cfu) | Filtration through membranes, neutralization (when preservatives are used), and addition to culture media (trypticase soy broth and thioglycolate) | No microbial growth | No microbial growth | Absence of microbial growth |
| Concentration of preservative (g/L) | RP-HPLC-based method (cresol) | 0.4 ± 0.03 | 0.3 ± 0.02 | Phenol: maximum 2.5 g/l |
| Cresol: maximum 3.5 g/l | ||||
| Complement activation (CH50/mL and AP50/mL) | Biochemical assay to determine CH50 and AP50 value for classical and alternative pathway, respectively | CH50/mL (%)–61.6 ± 3.2 | CH50/mL (%)–64.5 ± 2.9 | Threshold level is not mentioned |
| AP50/mL (%)–69.1 ± 4.1 | AP50/mL (%)–65.7 ± 3.9 | |||
| Fc content of IgG (%) | Immunological assay (ELISA and immunoblotting) by using anti-Fc specific antibody | 13.9 ± 0.6 | 11.8 ± 0.5 | Threshold level is not mentioned |
Detailed methodologies are described in the text.