Controlling facility contamination · • According to approved procedures for hand hygiene, glove...

Controlling facility contamination

Presented by Eoin Hanley1 July, 2016

Slide 2 © PharmOut 2015

Cleaning & Disinfection

Control of contamination:• Equipment cleaning (validated processes)• Cleaning of cleanrooms• Disinfection of cleanrooms

• Need clearly defined cleaning methods, use of detergents and correct disinfectants for microbial control

• Maintain appropriate levels of cleanliness• Important for sterile medicinal products that are not

terminally sterilised• Technical and operational controls


Microbiology: The basics

• Wide variety of microorganisms that could potentially contaminate product

• Microorganisms need to be controlled, killed and/or excluded in the process of making sterile product

• 4 main types of microorganisms:

Bacteria Fungi Yeast Virus


Types of Contamination

Contamination can enter cleanrooms or be generated within them

Viable and non-viable

Contamination can enter on solids, in fluids, on materials, personnel and air

Contamination can be generated by processes and movement of personnel

Large particles can settle on surfaces and small ones can be blown around

Facilities must be operated according to GMP ensuring the correct product quality


Sources of microorganisms

People Raw materials Equipment

Facility Clothing Processes

People are the greatest source of contamination to the manufacture of sterile product


What is a cleanroom?

Controlled environments

Classified or graded (ISO 14644) based on concentration of airborne particles.

HVAC systems with suitable air filtration/dilution

For sterile medicinal products, other physical and microbiological parameters must be met and maintained


What is a cleanroom?

Physical parameters include cleanable surfaces, controlled temperature & humidity

Microbiological alert & action levels (i.e. EU and US FDA for aseptic processing)

Control of personnel

Sanitisation and disinfection procedures must be validated


Cleaning practices

• Qualification of: • Facility• Systems • Equipment (& utilities)

• Cleaning Validation Plans, protocols and • reports for FSE

• Gowning/Dress codes

Cleaning effectiveness must be demonstrated


Cleaning Practices

Appropriate materials, movement of materials, product, process, waste and personnel

Effective training program with clear responsibilities

Understanding of cross-contamination risks

Cleaning and disinfectant procedures, programs and schedules


Cleaning Practices

• Removal of residues and soils from surfaces

• Visually clean• Defined methods for cleaning• Surfaces require adequate

cleaning prior to disinfection• Disinfectant effectiveness can

be inactivated by organic residues


Cleaning Practices

Cleaning will remove some microorganisms

Some cleaning agents also contain disinfection agents

Cleaning ≠ Disinfection, but can remove microbes

EU and US standards for disinfectant validation

Must reduce a microbial population to a certain log reduction (disinfectant validation)

Have a technical agreement with company who supplies the disinfectant and be able to track the lots.


Detergents and Disinfectants

Disinfectants:• Remove or eliminate microorganisms• Germicide-varying activity & effectiveness• Some are also sporicidal but usually called a steriliant

Detergents:• Cleaning agents• Removal of soils• The more soil removed, the better the disinfectant

effectiveness

Detergent


Detergents

• Chemical used to clean a surface by removing unwanted soil (capillary effects or electrostatic forces)

• Reduce the surface tension to allow removal

• Synthetic surfactants• Surfactant = Surface Active Agent• Hydrophilic and hydrophobic

aspects• Can also disassociate microorganisms

from the surface and then be removed by a water rinse or destroyed by a disinfectant


Selecting the correct Detergent

Two key considerations:• Chemical composition

• Typically neutral and non-ionic and low/non-foaming• Compatibility with the disinfectant

• Detergent must not leave a residue that neutralises the active ingredient in a disinfectant

• Common detergents include soaps, anionic/cationic/non-ionic/alkali/acidic/amphoteric detergents

• Other chemicals added to improve performance i.e. act against hard water/scaling, dispersal of fats etc.

Should be ARTG listed


Disinfection

• A disinfectant is a chemical agent which reduces number of microorganisms present by removing them or destroying them.

• Several terms depending on use:

Disinfectant

Antiseptic

Sanitiser

BiocideNormally applied to inanimate objects

Reduction of micro on living tissue


Disinfectant Efficacy and Performance

• #, type and location of microorganisms:• More effective against low numbers/low

cell density and a pure population• Unlikely to kill all but survival and

multiplication dependant on conditions they are left in

• Different types (cell membrane composition) have different resistances

• Easier to kill if in suspension. Biofilms difficult.



Temperature and pH:

• Will have optimal temperature and pH• Temperature influences rate of reaction but for cleanroom

use, made for use at ambient conditions• pH influences ionic binding• If outside ranges, will not be as effective

Water:

• Some do not work well in hard water. • Normally not an issue for cleaning of high grade

cleanrooms (WFI)



• Interfering Substances:• On surfaces and/or equipment• Require increased contact time or may not be

inactivated• Act as a barrier (dirt, oil, blood, protein etc)• Materials of construction & surface finish

Check the label claim for effectiveness (i.e. still effective in the presence of small amounts of organic matter?)


Types of Disinfectants

Thousands of disinfectants available (also refer to ARTG)• Different spectra of activity, modes of action and differing

efficacies• Phenols• Alcohols• Aldehydes• Oxidisers


Selecting the correct Disinfectant

• Important decision for cleanroom managers & microbiologist• Compatible with detergents• Must have a wide spectrum of activity• Must have a fast action• Should not be neutralised by residual matter• Environmental conditions (temperature, pH)


Selecting the correct disinfectant

• Non-reactive/non-corrosive (i.e. may require rinse/wipe steps with sterile water)

• compatibility with the cleanroom surfaces • Personnel health & safety• Sporicidal properties• Different formats• Cost

Performance should be periodically reviewed based on results of microbial monitoring


Hand sanitisation and antiseptics

Hand sanitisers (removal of bacteria). Alcohol and non-alcohol types.

Hand antiseptics (bind to the skin giving a longer activity and destroy bacteria)

~80% of microorganisms are transferred by hands

Effectiveness of the sanitising agent and the integrity of the skin

Cannot have harsh chemicals on skin…but personnel also wear specific clothing/gloves for added protection

Cleaning of hands also prevents cross-contamination


Skin microflora

Resident:

• permanent inhabitants (i.e. Staphylococcusspecies)

Transient:

• picked up from surfaces or from aerosols (can be pathogenic i.e. E. Coli, as well as yeasts, moulds and viruses)

Need to distinguish between different microorganisms found on skin. Can be grouped into:

• Impossible to completely remove all microflora• Use of sterile disposable gloves


Common sanitisers/antiseptics

Alcohols (aqueous & gels)

Quaternary ammonium compounds (disinfectants and surfactants)

Bisbiguanides (cationic nature-binds strongly to skin and tissues. Wide range of effectiveness)

Poidone Iodide (surgical hand scrubs)

• All must be stored, controlled & used correctly. • Should not be transferred into secondary containers,

diluted or mixed.


Testing for efficacy

International Standards i.e. EN1500, ASTM E1174

Tests require a number of subjects/groups

Test organism ( S. marcescens or E. Coli) applied to their hands

Sanitising agent then applied (or a reference solution)

2 log reduction on each hand within 5 mins after the 1st use and 3 log reduction on each hand within 5 mins after the 10th use.


Hand washing techniques

• Must be carried out correctly• Physical rubbing and then agent applied• Time taken is important• Soap first, then the sanitiser/antiseptic

(pump dispensers/automatic)• Follow the manufacturer instructions• Awareness of activities/actions

Trainingis

key!

Frequent re-sanitisation & hand washing crucial


Hand washing techniques

• According to approved procedures for hand hygiene, glove application and contamination control

• Jewellery/watches removed• Short and tidy nails (must not puncture gloves)• No nail varnish/make-up• Wash according to a set procedure• Sanitiser can then be applied with vigorous

washing for a defined period• Rinsing not to re-contaminate the hands• Dry hands/arms• Gloving and apply alcohol. Leave to dry.


Hand dryers vs paper towels?

• Recent study at University of Leeds (Jan 2015)• Compared different hand drying methods and their

potential to spread bacteria from hands into the air• Modern hand dryers actually spread more germs than

paper towels• Airborne germ counts were nearly 30% higher around

hand dryers compared with paper towel dispensershttp://www.cleanroomtechnology.com/news/article_page/Hand_dryers_in_washrooms_spread_bacteria_and_diseases/105011

VS

http://www.cleanroomtechnology.com/news/article_page/Hand_dryers_in_washrooms_spread_bacteria_and_diseases/105011



Key findings:• Bacterial counts in the air close to jet

air driers were 4.5 times higher than around warm air dryers and 27 times higher compared with using paper towels

• Next to the dryers, bacteria persisted in the air well beyond the 15 second drying time, with 48% of microbes still airborne after five minutes.

• Lactobacilli were still detected in the air 15 minutes after hand drying



Key findings:• Drying with warm air and jet air driers resulted in

widespread droplet release; contamination was found on all areas of the body demonstrating potential for spread and inhalation to other washroom users

• Airborne bacteria were dispersed 1m away within the first five minutes of sampling and bacteria were found up to 2m away


Hand drying with single-use towels has the least risk of airborne microbial contamination



Other factors to consider

• Air filters on dryers• Location of sanitiser dispensers• IR beams for activation• Pressure of water• Distance of dryer from sink• Size of the sink• Glove dispensers• Automatic shoe covers


Cleaning a cleanroom

• Cleanrooms: transfer of materials and movement of personnel are sources of contamination

• Correct design of cleanrooms and AHUs to prevent cross-contamination

• Cleaning program dependant on:• Cleanroom size• Cleanroom grading/classification• Materials of construction/surfaces• Equipment in the room• Movement of materials and personnel• Product characteristics• Cleaning methods



• Various materials and equipment used• Hand wipes, mop wipes, tacky rollers, • multiple bucket systems etc• Physical removal of contamination • Dry and also wet for distribution of cleaning agent (but

they must not be source of contamination)• Can clean and disinfect at the same time• Wipes usually polyester/cellulose/cotton/multilayer and

non-shedding• Can be sterilised but needs control



• Mops need to be abrasive but robust• Cleaning of floors, walls, doors and

ceilings• Multi layer wipes/foam heads, or

microfiber heads with electrostatic charge

• Need to be careful of damage/ snagging etc

• Various shapes and sizes for ease of use to fit a handle system

• Single use or cleaned• Tacky rollers also useful in low grade

areas



Mop heads with pieces or telescopic

handleLightweight but

rotate and easy to move

Full surface contact during the cleaning

process

Aluminium shaft and a PVC head

Must be easy to clean and sterilise



• Multiple bucket system with a ringer• Three bucket system the best but more storage room

required

• Other equipment may include:• Cleanroom vacuum cleaners • Steam cleaners • VHP cleaning systems


Three bucket system

Outer bucket holds cleaning agent

Middle bucket used to rinse contamination off

the mop head

Inner bucket used to collect waste solution

under wringer



Broad spectrum against bacteria, fungus, spores and virus

Easy to apply and safe for personnel

Prepared and effective immediately

Non-corrosive, evaporates quickly, no residues



Effectiveness dependencies already discussed

Expectation to rotate between two or more different agents on a routine basis

Irradiated solutions in high grade areas or filtration.


Cleaning Techniques

• Robust procedures as part of a sanitisation program:• Reduction of airborne and viable contamination to

specified limits (separate activities)• Cleaning/disinfection/rinsing stages and techniques,

frequencies, rotation, surfaces, area classification/grade

• Environmental Monitoring program to demonstrate effectiveness

• Periodic training/re-training• Periodicity appropriate using validated methods

Shutdown, commissioning and start-up


Cleaning Techniques

• Solutions and equipment prepared/controlled according to validated SOPs

• Application of agents must be applied evenly over the whole surface

• Cleanrooms must be designed without crevasses, ledges, recesses etc

• “Pull and lift” technique with overlapping (10%) unidirectional strokes

• If using hand wipes wipe is re-folded to expose clean fabric


Cleaning Techniques

• Define how often each rooms is cleaned and the surfaces.• Horizontal surfaces will require more frequent cleaning and• the higher the grade and the greater the activity, the

more often it will be cleaned• Use the correct gowning & PPE

• Clean the cleanest areas first-from room of highest grade towards CNC

• Start in area furthest away from the exit door• Start with high surfaces and work downwards: clean

ceilings before walls, and walls before floors


Cleaning Techniques

• Clean walls with downwards overlapping strokes and avoid the mop head touching the floor

• Log of cleaning & disinfection activities to be maintained• Care when transferring cleaning materials and waste

between rooms using correct transfer hatches and appropriate cleaning of packaging

• Take care around HVAC grilles and vents• Also attention to stationary and non-stationary

equipment as well as doors, handles, windows, step-overs, transfer hatches etc)


Other considerations

Various regulations on authorisation of cleaning agents

Must be safe for use or use the correct PPE

MSDS available

Stability, storage and handling instruction

Risks, exposure, health assessments, surveillance

Correct disposal


Peel off mats

80% of cleanroom contamination by feet or wheels• 27% prevented

by peel-off mats

Effective decontamination needs at least 6 footfalls or 3 full wheel rotations

Not possible to decontaminate

wheel traffic using a peel-off mat


Peel off mats

• Switching from peel-off mats to Dycem proven to reduce airborne particles by 75%• 99.9% prevented by Dycem

• Tests demonstrate that 200,000 particles released during peeling (and a lot of waste)

http://www.dycem-cc.com

http://www.dycem-cc.com/


Environmental monitoring

• Demonstrates effectiveness of cleaning & disinfection program

• Sample surfaces and equipment• Swabs, contact plates and surface sampling• Contact plates more efficient than swabs• Agar with neutralising agent to eliminate disinfectant

residues and to allow any recovered organisms to grow• Dual incubation step to pick up a range of environmental

microorganisms• Review results and look for trends


Validation of Disinfectants

• Demonstrate its efficacy-documented evidence• EU and US FDA requirement (there are differences)• Performance testing: can reduce the microbial

bioburden either in suspension or from cleanroom surfaces to an acceptable level

• Bactericidal, fungicidal, and or sporicidal activity• Suspension Tests (quantitative testing with

interferences)• Surface Tests (effective concentrations)• Field trials (effectiveness in cleanroom)• Other tests for hand sanitisers (EN 1500)


Various Standards

• Basic Suspension tests:• EN 1275 (fungicidal)• EN 1040 (bactericidal)

• Quantitative Suspension tests:• EN 1650 (fungicidal)• EN 1276 (bactericidal)

• Surface/carrier tests:• EN 13713• EN 13697• AOAC 991,47

GlobalStandards


Thank you for your time.Questions?

Eoin Hanley

[email protected]

Technical Manager

www.pharmout.net

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Controlling facility contamination · • According to approved procedures for hand hygiene, glove...

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