alternative technologies Flashcards
how do you select the sterilising agent?
- Balancing the advantages of available methods against their disadvantages
- No requirements to specify which method should be used
- Choice of method made at the design / development stage
- Terminal sterilization of product in final container is preferred to aseptic processing
- Agent in contact with all parts of product
- Process variables are controlled and monitored
- Process does not present hazards to operators or environment
- Process does not leave toxic residues within the product
what are the new and emerging sterilisation technolgies?
- X-ray Irradiation
- Pulsed light
- Microwaves
- Gas plasma
what is x-ray irradiation?
- ionising radiation, expensive, low penetration power.
this limits the type of products which can be used for x-ray radiation
what is pulsed light?
broad spectrum white light, short pulses, UV output.
used for in-line sterilisation and intravascular medical devices
what is microwave techology?
intense heating, short cycle (seconds) used for solutions in vials and contact lenses.
usually for batch processes
what is gas plasma?
- mixture of ions, free radicals, electrons and neutrons
- used for medical devices
- the mixture are what cayse the sterilising agent
- heat to around 50 degrees
- exposure time 1-1.5 hours
- no residuals ro remove, short processing time
what the current problmes with new technologies?
- Unknown lethal effects
- Kill kinetics different to traditional processes not your usual kill curve
- Validation compliance
- Monitoring
- No established regulatory requirements
what are the generic tests for quality control?
- Bioburden estimation
- Test for sterility
- Test of sterility
- Test for pyrogens (LAL test)
what is the test of sterility?
Performed on devices exposed to a fraction of the specified sterilization process, ie, part of Process Development
Purpose: Validation of a sterilization process
what is a false positive?
• Frequency of occurrence
• Perform simulated test of “sterile” samples
• Precautions to minimise level
– use environmentally controlled area/room
– use aseptic techniques
– avoid introducing contamination
– decontaminate test surfaces
– sterilize test equipment and materials
– minimise manipulations
– monitor and control incubator environment
– minimise aerosol production train personnel
what is a false negative?
- Inadequate culture conditions
- Presence of microbiostatic / cidal substance
- Interval between treatment and testing
how do you test for sterility?
• Defined in Pharmacopoeia
• Testing for a negative – i.e absence of Microorganisms
• Probability of rejecting a batch as a function of
o Frequency of contamination
o Number of times tested
• Probability of rejection = 1 - (1 - p)n
where p = proportion contaminated
n = number of items tested
• Presumption is that the sample tested represents the batch
what are the failures in sterility tests?
• Up to 2 further re-tests allowed
o Reject batch on 2nd test if same microorganisms found
o Retest if 2nd fail due to a different microorganism. If it still fails this is when you could fail the batch
• Additional tests therefore increase chance of passing the test
what are the tests fo sterility?
• Destructive test • Statistical test o Imprecise o The greater the number of samples tested, the greater proability of rejection • Correct conclusion
what is pyrogen testing?
Pyrogens are endotoxins produced by the LPS from Gram-negative bacteria
liquid A is the pyrogen that can cause death.
Gram -ve bacteria will shed pyrogens and these can be quite toxic.
