PZ Cussons – Industrial Hygiene

Training

Module Four

Cleaning and Sanitization

Phil Greaves
BiotiQ Consulting
 Slide 2

Cleaning & Sanitization

Cleaning & Sanitization are fundamental to our production

processes to ensure that product is safe for use and stable in
storage

Effective cleaning and sanitization can compensate for some

weaknesses in hygienic design – but not all!
 Slide 3

Cleaning & Sanitization

• We clean factories to reduce contamination from the manufacturing

environment
• We clean production equipment to remove residues of product and
contaminants to:
– Reduce the level of nutrients available for microbial growth
– Prevent one product contaminating the products subsequently
manufactured on that equipment
• We sanitize production equipment to reduce micro-organisms to very low
levels that are safe for products during production
• Good hygienic design and time limits after sanitization prevent the micro-
organisms growing back to levels that are dangerous for products
 Slide 4

Cleaning & Sanitization

We can never eliminate all contamination from our

factories

Cleaning & Sanitization controls contamination at levels

below which product quality if affected
 Slide 5

Factory Cleaning – Floors, Walls and External Surfaces

This is how we want our

factories to look!
 Slide 6

Factory Cleaning – Floors, Walls and External Surfaces

• Buckets, mops and wipes must be managed well to prevent cleaning

being a source of contamination!
• One bucket results in dirty mop or wipe being rinsed in the cleaning
water
• Two bucket system is best practice
– Bucket One with cleaning water & detergent
– Bucket Two for rinsing out mop and wipes
• Cloths used for wiping should be single use disposable
– Not recycled rag or clothing that can shed fibres into equipment
– No left wet or soaking in sanitizer as this will still allow bacteria to
grow
 Slide 7
Preventing Contamination of Production Equipment –
Cleaning & Sanitization

Cleaning:
The chemical or physical process of removing material and product residues
to acceptable levels
• Prevents cross-contamination
• Allows for effective disinfection

Sanitization:
The destruction of micro-organisms (but usually not spores)
• May not kill all micro-organisms present but reduces their number to
an acceptable level
• Term ‘disinfection’ often used - restricted to chemical treatments
(disinfectants)
 Slide 8

Preventing Contamination - Sanitization

Sanitization often used to describe the destruction of micro-organisms:

•Includes both chemical (disinfectant) or physical (heat) ways of killing micro-

organisms
•Still not an absolute – reduces numbers to acceptable levels
•Not to be confused with the term ‘sterilization’ – total removal or destruction
of all living organisms. Used in hospitals and injectable pharmaceutical
processes
 Slide 9

Preventing Contamination – Effective Cleaning

• Effective cleaning achieved by:

• Mechanical disruption – high flow rate / pressure
• Chemical cleaning agents
• Choice of chemical depends on type of residue
• Heat – hot water generally increases cleaning efficiency
• Beware of products that may ‘gel’ or cake with heat!

• Automated clean-in-place preferable to manual processes

• Spray balls in vessels to ensure full coverage
• Cleaning should be validated – demonstrates that acceptable residual
levels are routinely and consistently achievable
 Slide 10

Preventing Contamination – Effective Cleaning

Some equipment may need to be disassembled for effective cleaning and can
be contaminated during re-assembly. These pictures show a well-managed
process.
 Slide 11
Preventing Contamination – Effective Cleaning
Washdecks / Washbays

Designed for process flow:

Dirty

Clean

Sanitized

Dry
 Slide 12
Preventing Contamination – Effective Cleaning
Washdecks / Washbays

• Water and humidity must be controlled and removed from the washdeck
and prevented from entering production areas:

• Screen / curtain / door into washdeck

• Drainage channels in floor
• Air extract

• Often design and installation of water pipework in washdecks is poor –

deadlegs and lots of flexible pipework!
 Slide 13

Preventing Contamination – Effective Sanitization

Sanitization should be performed:

•After a contamination incident
•Before bringing new plant into production use
•After invasive plant maintenance
•Routinely after cleaning to control the level of bioburden
•Before high risk products

•Sanitization may be achieved with chemicals or heat (thermal)

 Slide 14

Typical Sanitization Methods

Method Typical Criteria Comments

Thermal – hot water 80° C for 10 minutes Leaves no residue but plant
wet after sanitization
Thermal - steam > 100° C for 10 minutes Leaves no residue, plant ~ dry
after sanitization
Available chlorine (e.g. > 300 ppm for 20 minutes Rinse required; inactivated by
hypochlorite) residual organic product

Peracetic acid > 400 ppm for 20 minutes Rinse required; highly
inactivated by residual organic
product
Hydrogen peroxide 6% for 30 minutes Rinse not required but high
toxicity; not affected by
product residue
Amphoteric 1% for 30 minutes Efficacy reduced significantly
by product residue
Alcohol e.g. isopropranol 70% for 5 - 20 minutes Ineffective against fungi and
spores
 Slide 15

Effective Sanitization Methods

Sanitization can only work if internal

surfaces of equipment are in contact
with the sanitizer!
Beware of trapped air bubbles
 Slide 16

A Common Problem!

• Where there are no sprayballs

installed, some factories ‘part-fill’
the mixer and recirculate
sanitizer for the required contact
time

• This often fails to reach the

upper surfaces of the mixer!
 Slide 17

Preventing Contamination – Thermal Sanitization

• Hot water applied to all product contact surfaces – either through total
immersion / filling or sprayball recirculation, or steam
• Requires at least 70° C to be achieved (ideally 80 ° C) for at least 10
minutes
• Very effective at killing micro-organisms BUT energetic cost is high
• Safety issues with hot surfaces

• Where temperature is measured may not be representative of temperature

further down the plant – risk of not achieving the required temperature &
time!
• This requires validation testing
 Slide 18

Preventing Contamination – Chemical Sanitization

• Best performed with sodium hypochlorite solution or peracetic acid

• Corrosive to 304 stainless steel!
• If using alternative (proprietary) disinfectants – ensure they are validated
against typical contaminants in the presence of residual product on
surfaces (typical laboratory challenge tests are not representative!)
• The active chemical will be used up by organic material, product residues
and bacteria / fungi
– Sufficient quantity and concentration must be provided to ensure
enough chemical is left at the end of the line
– This requires validation testing
 Slide 19

Preventing Contamination – Chemical Sanitization

• After sanitization we may need to rinse the chemical out of the equipment
– Sanitizer chemical may affect product quality – odour or colour

• Rinse water must be of the same microbiological quality as process /

production water or it will re-introduce contamination

• Rinse water must be fully drained after the rinse process; residual water
will allow bacteria to grow
 Slide 20

Holding Times

• Because some bacteria / fungi will always remain after sanitization (and
rinsing) we must limit the time that equipment is empty before next product
is made – hold time

• Safe hold time depends on how good our sanitization process is, how
hygienically designed equipment is, and how robust product preservatives
are

• Typical hold times:

– For High Risk equipment or products: Never exceed 8 hours
– Medium Risk equipment or products: Never exceed 24 hours
– Low Risk equipment or products: Never exceed 48 hours
 Slide 21

Holding Times

• But what if we have a combination of risks e.g. Medium Risk formula made
on very hygienic (low risk) equipment?
• May need a matrix approach, with different times for different mixers or
lines

• Always default to the safest – reduce time rather than extend it

• IF the maximum hold time is exceeded, you must resanitize again before
product manufacture

• Do not leave equipment cleaned but not sanitized for more than 8 hours!
– Cleaning will introduce bacteria from water that can grow to levels
beyond the capability of the sanitization process
Validation Testing Slide 22
Confidence that Cleaning and Sanitization are Repeatedly
Effective
• Cleaning and sanitization should be validated
– Repeat testing (typically three times)
– Agreed acceptance or pass criteria
– Documented

• Do we validate all equipment for all products and processes?

• Can we use a matrix approach to cover ‘worst case’ cleaning and

sanitization?
Validation Testing Slide 23
Confidence that Cleaning and Sanitization are Repeatedly
Effective
• Worst case conditions may be:
– Experience of which product / s are most difficult to clean
– Experience of different mixers and filling lines
– Maximum holding times

• A worst case matrix for validation is not valid if mixers are of different
design (e.g. some with, some without sprayballs) or different designs of
filling equipment

• Each cleaning and sanitization procedure requires separate validation

testing
 Slide 24

Validating Cleaning

• Typically three cleaning runs of worst case product

• Acceptance criteria:
– Visually clean. Can any residues or uncleaned areas within equipment
/ lines be seen?
– Lack of colour or foam in final rinse water
– Freedom of odour

• All of the above are subjective (but good!) criteria. For regulated products
health authorities may require quantitative methods:
– Total organic carbon
– Specific measurement of active component e.g. by HPLC
 Slide 25

Validating Sanitization - Thermal

• Measurement of temperature at various locations across the equipment

and line

Thermal test strips – Dataloggers with external Thermal / IR imaging

low cost and can be thermocouples – provide camera – good for
attached to test graph of complete visual checks of cold
protocol as evidence heating and cooling cycle spots
 Slide 26

Validating Sanitization - Thermal

• Where do we locate our temperature measuring equipment?

• At locations that will be slowest to heat – large thermal masses like pump
housings
• At most distant point in the line being sanitized

• Good practice to mark these on a schematic drawing or photographs and

attach to the validation report
 Slide 27

Validating Sanitization - Chemical

• How do we know that the concentration of our sanitizing chemical is being

achieved at all locations in the plant?

• Measurement of the chemical concentration at the start of the line, at the

start of the contact time, and measurement at the far end of the line, at the
end of the contact time

• At least 70% of the starting concentration should be present at the end of

the line, at the end of the contact time …. If not indicates that the plant was
not sufficiently clean prior to sanitization

• Supplier of sanitizer chemical often sell the ppm concentration

measurement kits
 Slide 28

Validating Sanitization - Drainage

• After sanitization (and rinsing if necessary) we must inspect inside the

equipment and line to ensure it is drained of water

– May require disassembly of pipework at low points and pumps

– Use of a boroscope to look down pipes for any product residues that
were not cleaned sufficiently or trapped water

• Some trapped water may be expected but 20 – 50 ml is a sensible limit; if

greater than this we need to make improvement actions to the procedures
for cleaning and sanitization, or plant modifications to improve ‘drainability’
 Slide 29

Validating Sanitization – Microbiological Criteria

• After sanitization and after our maximum hold time, we should verify that
the level and type of bacteria present is within acceptable limits
• Micro testing may be performed by:
– Swabbing internal surfaces
• Access may be limited; you may need to disassemble pipelines to
enable microbiologists to reach inside
– Analysis of final rinse water
• Not as good as swabbing as some bacteria will remain attached to
equipment surfaces
• Good limits are < 20 CFU / 100mm2 for swabs and < 1 cfu / ml (or limit of
rinse water)
• Absence of high risk Gram negative bacteria e.g. Psuedomonas,
Burkholderia
 Slide 30

Validating the Person

• We cannot ‘validate’ the person as they may vary how they perform
manual processes
• We can ‘qualify / certify’ that an operator can perform the procedure
effectively after training … and only trained persons perform the cleaning
and sanitization

• A programme of routine inspection (watch what people do!) and swab

testing helps to provide confidence that routine cleaning and sanitization is
performed effectively
– The programme should rotate through different mixers and filling lines
– Aim to ‘verify’ each operator performing cleaning and sanitization at
least annually
 Slide 31

Finally …. If It All Goes Wrong!

• ‘Deep’ sanitization and biofilm removal

– Performed periodically (e.g. 6 to 12 monthly) as a preventative process
(less frequent for very good hygienic design equipment; more
frequently for high risk poor hygienic design equipment)
– In response to a micro problem

• Typical procedure:
1. Hot caustic soda (10% solution @ 60⁰C for 30 minutes)
2. Neutralise
3. Hot phosphoric acid (10% solution @ 60⁰C for 30 minutes)
4. Neutralize
5. Hot peracetic acid (> 800 ppm @ 60⁰C for 30 minutes)
Any Questions?