Pharmaceutical Microbiology and Sterility Assurance
Pharmaceutical Microbiology and Sterility Assurance covers sterilisation science, aseptic processing, microbial limits and endotoxin control. Numerical items on D-value and F0 are common.
Core rules
- Moist-heat sterilisation: 121 °C, 15 psi, 15 minutes as a minimum; F0 is the equivalent time at 121 °C with z = 10 °C.
- Dry heat: 160 °C for 2 hours or 170 °C for 1 hour for glassware and oils.
- Filtration and radiation: 0.22 µm membrane for heat-labile solutions; 25 kGy for single-use devices; ethylene oxide for plastics.
- SAL: 10⁻⁶ for terminally sterilised products; D-value is the time for a one-log reduction; a 12-log cycle is standard.
- Clean rooms: Grade A (critical zone), B (background for aseptic work), C and D; HEPA filters, pressure differentials, air changes and particle monitoring.
- Tests: sterility by membrane filtration or direct inoculation; bacterial endotoxin by LAL; microbial limit test; preservative efficacy test.
Worked example
A product has a bioburden of 10⁶ CFU and a D121 value of 1.5 minutes. To reach SAL 10⁻⁶, 12 log reductions are needed: 12 × 1.5 = 18 minutes. The cycle must therefore deliver an F0 of at least 18 minutes, not simply the conventional 15 minutes.
Traps
Autoclave tape indicates exposure, not sterility; the endotoxin test is not a sterility test; filtration does not reliably remove viruses or mycoplasma; and a media fill validates aseptic process capability, not terminal sterilisation.