DP–IMP and PPQ Specification Examples
| Test/Specification | IMP Phase 1–2 | IMP Pivotal or Phase 3 | PQ Lots (PV Stage 2) | Reported Results Example |
|---|---|---|---|---|
| Appearance | Clarity: Clear to opalescent Color: Colorless to yellow liquid, Particles: Free from or practically free from visible particles | Clarity: NMT EP RS III Color: NMT Y5 Particles: Free from or practically free from visible particles | Clarity: NMT EP RS III Color: NMT Y5 Particles: Free from or practically free from visible particles | Clarity: RS I Color: Y7 Particles: Free from visible particles |
| Sub-visible particles | LT 6000 particles per container equal to or greater than 10 μm and LT 600 particles per container equal to or greater than 25 μm | LT 6000 particles per container equal to or greater than 10 μm and LT 600 particles per container equal to or greater than 25 μm | LT 6000 particles per container equal to or greater than 10 μm and LT 600 particles per container equal to or greater than 25 μm | 60 particles per container equal to or greater than 10 μm, 4 particles per container equal to or greater than 25 μm |
| Sub-visible particles (by MFI) | N/A | LT 500,000 particles per container for 2–10 μm | LT 100,000 particles per container for 2–10 μm | 4000 particles per container for 2–10 μm |
| Extractable volume (vial) | ≥1.0 mL | ≥1.0 mL | N/A | ≥1.0 mL |
| Deliverable Volume (APFS) | N/A | N/A | ≥1.0 mL | ≥1.0 mL |
| pH | nominal value ± 0.5 pH units | 6.5–7.5 | 6.5–7.5 | 6.9 |
| Osmolality | 240–360 mOsm/kg | 240–360 mOsm/kg | 240–360 mOsm/kg | 303 mOsm/kg |
| Total protein | Nominal value ± 10.0% | Nominal value ± 10.0% | Nominal value ± 10.0% | 1.05 mg/mL 10.2 mg/mL 52.0 mg/mL 103 mg/mL |
| cIEF | Release and Stability: Peak pattern consistent with Reference Standard; report % monomer, % total acidic peaks, % total basic peaks | Release: Peak pattern consistent with Reference Standard; monomer NLT 50%, report total % acidic peaks, report % total basic peaks Stability: Monomer NLT 40%, report total % acidic peaks, report % total basic peaks | Release: Peak pattern consistent with Reference Standard; monomer: NLT 65%, total acidic peaks: NMT 30% Stability: Monomer: NLT 55%, total acidic peaks: NMT 40% | Peak pattern consistent with Reference Standard; monomer: 72%, total acidic peaks: 14% |
| Target Binding Bioassay | 50–150% (symmetrical) of Reference Standard binding 60–167% (geometrical) of Reference Standard binding | N/A | N/A | 98% |
| MOA-simulated Bioassay | N/A | Release and Stability: 60–140% (symmetrical) of Reference Standard binding 70–143% (geometrical) of Reference Standard binding | Release: 90–120% (symmetrical) of Reference Standard binding 90–125% (geometrical) of Reference Standard binding Stability: 80–120% (symmetrical) of Reference Standard binding 80–125% (geometrical) of Reference Standard binding | 98% |
| Reducing gel electrophoresis | Electrophoretic peak pattern consistent with Reference Standard; area percent purity of heavy + light chains: NLT 95.0%; total area percent of impurities: NMT 5.0% | Release: Area percent purity of heavy + light chains: NLT 98.0%; total area percent of impurities: NMT 2.0% Stability: Area percent purity of heavy + light chains: NLT 97.0%; total area percent of impurities: NMT 3.0% | Release: Area percent purity of heavy + light chains: NLT 98.5%; total area percent of impurities: NMT 1.5% Stability: Area percent purity of heavy + light chains: NLT 98.0%; total area percent of impurities: NMT 2.0% | Area percent purity of heavy + light chains: 99.2%; total area percent of impurities: 0.8% |
| Non-reducing gel electrophoresis | Electrophoretic peak pattern consistent with Reference Standard; major product peak: NLT 95%; total area percent of impurities: NMT 5.0% | Release: Major product peak: NLT 98.0%; total area percent of impurities: NMT 2.0% Stability: Major product peak: NLT 97.0%; total area percent of impurities: NMT 3.0% | Release: Major product peak: NLT 98.5%; total area percent of impurities: NMT 1.5% Stability: Major product peak: NLT 98.0%; total area percent of impurities: NMT 2.0% | Major product peak: 99.2%; total area percent of impurities: 0.8% |
| HPSEC | Major product peak: NLT 95.0%; report % aggregates; report % fragments | Release: Major product peak: NLT 96.0%; aggregates: NMT 4.0%; fragments: NMT 4.0% Stability: Major product peak: NLT 95.0%; aggregates: NMT 5.0%; fragments: NMT 5.0% | Release: Major product peak: NLT 98.3%; aggregates: NMT 1.7%; fragments: NMT 1.7% Stability: Major product peak: NLT 97.0%; aggregates: NMT 3.0%; fragments: NMT 3.0% | Major product peak: 99.2.0%; aggregates: 0.5%; fragments: 0.3% |
| Sterility | No growth detected after 14 days | No growth detected after 14 days | No growth detected after 14 days | No growth detected after 14 days |
| Endotoxin (LAL) | NMT 0.30 EU/mg protein | NMT 0.30 EU/mg protein | NMT 0.10 EU/mg protein | 0.02 EU/mg protein |
| Break-Loose Force (Prefilled Syringe) | N/A | Report max. single value (in N) Report mean value (in N) | Max. single value ≤ 20 N Mean value ≤ 15 N | Maxvalue:8 N Mean value 6 N |
| Glide Force (Prefilled Syringe) | N/A | Report max. single value (in N) Report mean value (in N) | Max. single value ≤ 20 N Mean value ≤ 15 N | Maxvalue:8 N Mean value 6 N |
| CCI Dye Test (Prefilled Syringe) | N/A | No color observed | No color observed | No color observed |