Terminal Sterilisation
Sterilisation of the final sealed pharmaceutical product, typically by heat (autoclaving) or radiation. Terminal sterilisation is preferred when feasible because it provides a higher level of sterility assurance than aseptic processing. However, most peptides are too heat-sensitive for this approach.
Technical Context
Terminal sterilisation methods: autoclaving (saturated steam at 121°C for ≥15 min — the gold standard, providing sterility assurance level SAL of 10^-6), dry heat (≥160°C for ≥2 hours — also depyrogenates), gamma irradiation (25-50 kGy from cobalt-60 or caesium-137), electron beam irradiation, and chemical sterilisation (ethylene oxide — primarily for devices). For peptide drugs, terminal sterilisation is rarely feasible because: most peptides denature above 50-60°C (excluding autoclaving and dry heat), gamma irradiation causes peptide bond cleavage, oxidation, and deamidation (degrading the product), and chemical sterilants may react with peptide functional groups. Exception: some small, robust peptide solutions can tolerate F0-based sterilisation cycles (lower temperature, longer time) if validated to achieve SAL 10^-6. Sterile filtration followed by aseptic processing remains the standard approach for most peptide injectable products.