Aseptic Production 2 Flashcards
Sterility
- Sterilisation processes must be specified to ensure that the probability of microorganisms surviving is low enough to ensure patient safety. The accepted low probability is that there should be not more than one chance in one million of viable micro‐organisms surviving.
- Called a sterility assurance level (SAL) of 10‐6
Sterility definition
• The total absence of viable microorganisms and an absolute state (Winfield and Richards)
What are we trying to destroy?
Anything that causes harm to patients
• All viable microorganisms
• Bacterial spores
• Pyrogens
– Produced by Gram‐negative bacteria on cell death
– Endotoxins ‐ lipopolysaccarides from cell walls
– Cause inflammatory response on injection; starts with a
fever, can result in cardiogenic shock (multi-organ failure)
– Distillation of aqueous products the most effective method of removal
What are bacterial spores
what bacteria are reproduced from, they are not living themselves but are able to reproduce
When are pyrogens released
released from bacteria upon cell death
Sterilisation – the main processes
• Heat – Moist heat – Dry heat • Gaseous – Ethylene oxide – Formaldehyde • Irradiation • Filtration
Which sterilisation process is commonly used
- used most commonly are moist heat, ethylene oxide and irradiation
- size of batch affects choice of methodology
D value
• Decimal reduction time
• Time taken at a fixed temperature to reduce the number of viable organisms by 90% (i.e. 1 log cycle reduction)
• Also applies to radiation
– D value is the radiation dose required to achieve the above (where time taken at a fixed temp to the time taken at a radiation dose to achieve a 1 log cycle reduction)
What is D value used for
D value is what we use to calculate the amount of time a particular product will need in the sterilisation process to achieve your sterility assurance level of 10-6
-D value = time taken to reduce at a fixed temp the amount of contaminant you have by 90%
Z value
• Only applies to heat sterilisation
• Assesses the influence of temperature changes on thermal resistance
• Increase in temperature required to reduce the D‐value by 90% (i.e. 1 log cycle)
-so its an additional value on top of D value. Allows you to reduce time exposure to heat if you have a product that can withstand higher temp
How to measure D value and Z value
D value - Time (horizontal axis)
Z value - Temp (vertical axis)
Bioburden
- Need to know at beginning of process
• Concentration of microorganisms in a material
• Normally given by the supplier of a raw material
• Specifications within pharmacopoeial entries, or from product development
• In order to assure sterility, the bioburden must be as small as possible at the start of the process (if bioburden is too large, product will be exposed to sterilising agent for too long which could denature product)
Inactivation factor (IF)
With a bioburden of 103 organisms prior to sterilisation, an inactivation factor of 109 would be required to achieve sterility (10‐6). I.e. the product would have to be exposed to 9 times the D value of a reference organism to achieve sterility.
Inactivation factor (IF) equation
IF = 10t/D
Where t = contact time or dose and D = the D‐value appropriate to the process being used.
IF is expressed as a log value for reference.
Heat Sterilisation
- Most reliable and most widely used method (but decreasing now)
- Destroys enzymes and other essential cell components
- Used with thermostable products
- Moisture sensitive products use dry heat
- Moisture resistant products use moist heat
