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Microbiology and Sterility Assurance
Dr. Tim Sandle
www.pharmamicroresources.com
Microbiology Activities
• Laboratory:– In-coming raw materials
• Bioburden• Specific pathogens
– Processing of plasma• Hygiene swabs• Bioburden
– Intermediate product• Bioburden• Endotoxin
– Finished product• Sterility• Endotoxin• Pyrogens• Toxicity
Microbiology Activities
• Testing of environment• Viable samples
• Particle counting
• Testing of water– WFI
– Purified
– Mains
• Microbial identification– What?, Why?, Where?
Impact on Sterile Supplies
• Sterile Supplies is an EU GMP Grade C facility (ISO 14644 class 8)
– Certified cleanroom: annual
– Environmental monitoring, based on risk:
• Types of activities
• Whether there are water sources
• Room history
– Water samples are taken from outlets
Impact on Aseptic Filling
• Routine monitoring programme of support rooms– Monitored according to risk e.g. corridors monitored
more often than infrequently used rooms– Monitoring is:
• Twice weekly• Weekly• Fortnightly • Monthly
– Monitoring is for:• Viable counts• Particles• Fungi
Impact on Aseptic Filling
• Batch monitoring
– Filtration of the product
– Unloading stoppers
– Machine set-up
– Pre-fill period (target 4 hours)
– Filling
– Post-fill monitoring
– Machine clean down
Environmental Monitoring
• Samples
– Settle plates (deposition rate / 4 hours)
– Active air (cubic metre)
– Contact plates
– Swabs
– Finger plates (staff)
– Gloveport plates
– Gown plates
Environmental Monitoring
• Routine, support samples taken by Microbiology
• Batch samples taken by Sterile Operations
• Samples contain tryptone soya agar
– Some contain neutraliser
– Samples incubated at a regime designed to encourage the growth of bacteria and fungi.
Important Points #1
• Pre-final filtration TVAC– Taken in Sterile Operations
for certain samples– Bioburden assessment of
product prior to sterilisation through 0.22 µm filter
a) Sample must be placed at 2-8oC within 2 hours
b) Samples must be tested within 24 hours
c) Bioburden must not exceed 10 CFU / 100mL
• Any of the above will lead to batch rejection.
Important Points #2
• Media fills
– Qualify the filling line and the people
– Different vial sizes and numbers in rotation
• Maximum broth fill size sets maximum batch size
– Require a set number of aseptic interventions
– Contain the maximum stoppage
– Run every six-months per line
– Each person must participate once per year and carry out an intervention
Important Points #3
• AFS qualification– Gown test
• Visual check of change procedure against SOP
• Samples relating to environment and individual
– Aseptic qualification test• Test of aseptic technique
– Conducted• Three times for new staff or after a prolonged absence
• Six-monthly for qualified staff
• Zero tolerance for staff who miss due dates
Important Points #4
• Data is reviewed every month and summaries are sent out to Sterile Ops Management
• Includes staff performance
– Each staff member is rated green, amber or red
– Includes:
• Gown test results
• Finger plate trends
• Exit suit plate trends
• Behavioural issues
Current issues
• There is currently an upward trend in the AFS relating to environmental monitoring data.
• Trend began after the winter 2013 shutdown.
• Primarily relates to people, behaviours and aseptic practices.
• Some issues linked to cleaning.
Current issues
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Jan-12 Feb-12 Mar-12 Apr-12 May-12 Jun-12 Jul-12 Aug-12 Sep-12 Oct-12 Nov-12 Dec-12 Jan-13 Feb-13 Mar-13 Apr-13 May-13 Jun-13
Total number of samples OOL: batch and routine 2012 - 2013
No. OOL 2012 average 3 per. Mov. Avg. (No. OOL)
Current issues
• Importance of:– Good gowning practices.– Not being the AFS for more than four hours (four hour
gown change policy).– Slow, deliberate movements.– Spraying gloves before each activity.– Using the 1 minute hand rubbing procedure.– Spraying gloves every 10 minutes.– Reporting broken hand dispensers and fabric issues to
a supervisor.– Cleaning and disinfecting surfaces to standard.
Thank you
Any questions?
