Pharmaceutical Technology: Unit Operations, Sterilisation and Validation
This domain tests manufacturing technology: unit operations, equipment, sterilisation, aseptic processing, validation and utilities. Questions often ask why a parameter is controlled, or calculate a lethality or sterility value.
Unit operations and controls
- Milling and mixing: particle size, uniformity and segregation risk; granulation: wet or dry, binder choice, endpoint.
- Drying: tray or fluid-bed, inlet temperature, moisture endpoint.
- Compression: force–hardness–friability relationship, tooling, capping and lamination.
- Coating: pan or fluid-bed, inlet air, spray rate and pan speed.
Sterilisation and aseptic processing
- Moist heat: typically 121 °C for 15 minutes; dry heat: 160–180 °C; filtration: 0.22 µm; radiation; ethylene oxide.
- F0 integrates lethality at 121 °C; the SAL for terminally sterilised products is 10⁻⁶.
- Aseptic processing relies on Grade A/B environments, HEPA filtration, validated gowning and media fills.
Worked example
Bioburden is 10⁶ CFU and D₁₂₁ is 1.5 minutes. To achieve SAL 10⁻⁶: F0 = D₁₂₁ × (log N0 − log N) = 1.5 × (6 − (−6)) = 18 minutes. Reasoning: the cycle must deliver at least 18 minutes at 121 °C equivalent; verify with biological indicators and heat-penetration data.
Traps
Confusing D-value (decimal reduction time) with z-value (temperature change for a 10-fold D change); using SAL 10⁻³ for terminally sterilised products; assuming filtration sterilises a suspension; accepting a filter without integrity testing; skipping cleaning validation because equipment looks clean.