Leak & Integrity Testing
Container-Closure Integrity for Peptide Products
Purpose
Container-closure integrity testing (CCIT) ensures vials remain sealed throughout shelf life, preventing microbial ingress and moisture penetration.
Test Methods
| Method | Type | Sensitivity | Destructive | Application |
| Dye ingress | Probabilistic | 5–10 µm | Yes | Development |
| Helium leak | Deterministic | 1–5 µm | No | Production |
| Vacuum decay | Deterministic | 5–15 µm | No | Production |
| High-voltage (HVLD) | Deterministic | 5–10 µm | No | Liquid-filled |
| Bubble emission | Probabilistic | 20–50 µm | Yes | Package development |
| Microbial challenge | Probabilistic | — | Yes | Validation |
Vacuum Decay Method
Principle
- Place vial in sealed test chamber
- Apply vacuum
- Measure pressure change
- Leak = pressure increase above threshold
Parameters
| Parameter | Setting |
| Test pressure | −250 to −400 mbar |
| Test time | 10–30 seconds |
| Leak threshold | 1–5 µm equivalent |
| Reference | ASTM F2338 |
Regulatory Requirements
| Market | Standard | Requirements |
| USP | <1207> | Deterministic method preferred |
| EU | Annex 1 | CCIT for all sterile products |
| FDA | 21 CFR 211 | Container-closure integrity verified |
🔗 Related: Packaging Guide | Stability Testing | Quality Control Overview