cleanroom contamination including mould/fungal … · • member of anzlaa, absanz, scria, ispe and...
TRANSCRIPT
© PharmOut 20171
Cleanroom Contamination
including Mould/Fungal
contamination
Brett Cole. Biosafety Pty Ltd
Tuesday 25th July 2017
© PharmOut 20172
1. Introduction
2. What is Contamination?
3. What is Mould?
4. Sources of Mould/Fungal contamination
5. How to minimise mould/fungal contamination
6. Cleanroom decontamination
7. Planning, Execution and Validation
8. The various common and emerging technologies used for manual
and rapid decontamination and sterilization
9. Case Studies
10. Conclusion
11. Questions
Cleanroom Contamination including Mould/Fungal contamination:
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• Bachelor of Science with Honours Degree – Microbiology (Monash University)
• Masters Degree in Occupation Hygiene and Toxicology (Edith Cowan University)
• Over 15 Years experience in Infection, Waste and Contamination Control (Healthcare, Pharmaceutical and Laboratory)
• IICRC Certified for Water Damage and Mould/Microbial Remediation • Committee Member of ABSANZ Regulatory Committee (OGTR, DAFF
and AS/NZS)• Internationally Certified Biorisk and Biowaste Management
Professional (IFBA)• Member of Australia Institute of Occupational Hygiene (MAIOH)• Member of Australian Standards Committees (CH-029) Safety in
Laboratories Standards• Licensed Fumigation Company (Dept of Health and Human Services)• Member of ANZLAA, ABSANZ, SCRIA, ISPE and ACPIC• 2017 Australian Restoration Awards – Most Innovative Specialised
Restoration Project – Microbial Infestation Restoration of a Medical Research Facility
Professional Experience-
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What is contamination?Contamination is the introduction of unwanted material or substance into a process, person or product.
It is particularly critical in controlled environments such as
➢ Food
➢ Pharmaceutical
➢ Healthcare
➢ Life Science
How does a facility get contaminated?
How does your product get contaminated?
Contamination can occur at any step in the process—during production,
processing, distribution, transportation, preparation, etc.
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What is mould?
• From the Kingdom Fungi
• Not Animal or Plant
• Form of multicellular thread-like structures called hyphae.
• Some Fungi exist as single cells are called yeasts.
• Can cause disease or food/product spoilage, others play an
important role in biodegradation or in the production of various
foods, beverages, antibiotics and enzymes
• Can reproduce sexually or asexually via spore release
• Require high relative humidity to exist (>60% RH)
• Cannot produce their own energy
• Require organic material to feed on
• Can release airborne Mycotoxins
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Sources of mould and contamination in cleanrooms.
• Primary source of mould/microbial contamination into cleanrooms is
via personnel/humans
• Poor gowning procedures
• Poor Ingress and egress/access control
• Poor Heating, Ventilation and Air Conditioning (HVAC) maintenance
and hygiene
• Equipment and raw material introduction into clean rooms
• Cellulose material such as cardboard, paper and wooden pallets
• Contaminated Packaging
• Flooding introducing spores from external environments
• Poor or improper decontamination processes
• Inappropriate cleanroom construction materials
• Leaks in cleanroom structure
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How to minimise mould/fungal growth?
• Facilities should be constructed of nonporous material that do not
absorb water and promote fungal growth (21 CFR 211.42)
• If floods occur, there is a need to react quickly to water damage
within a facility aggressively and fully dry or replace damaged walls
and ceilings within 72 hours to prevent mould growth.
• Temperature and humidity controls must be in place to discourage
fungal growth, that is, RH < 60% RH.
• Minimise cellulosic materials such as cardboard and wooden pallets
from GMP areas as they can become wet and support fungal
growth.
• Cleaning and disinfection procedures must be in place to prevent
people and mobile equipment introducing fungi into facilities.
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Why Decontaminate?
➢To create a Sterile baseline
➢Renovation (Before or after)
➢Between Population / Production Batches
➢Commissioning
➢De-Commissioning
➢Contamination/Infection
➢Preventative Maintenance
➢Regulatory compliance
➢GMP/Best Practice
➢Other…
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What makes for a good decontamination?
➢All Decontamination methods can work based on
the following:
➢ Must reach ALL surfaces for a prescribed
amount of time, which means you must have:
1. Good and Complete Distribution
2. Thorough and Total Penetration
3. Sufficient Contact Time
4. At specified concentration
5. At required Environmental conditions
(temp/RH)
➢Any decontamination method requires a complete
and thorough distribution of the sterilant or high
level liquid disinfectant to get an effective
decontamination or kill
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Planning for decontamination:
• Define purpose and scope: rooms, equipment, HVAC
• Identify the players, area production managers,
• OH&S, facilities engineering, QC validation, security, emergency
services, other facility users
• Establish responsibilities (SWMS, SOP, Who’s who)
• Select decontaminating agent (Best fit-for-purpose)
• Establish the schedule and ordering
• Write SOPs, fumigation management plan (AS 2467 24 hour
notification) where required
• Define validation: Microbial Testing, full PQ, target dosage
• Hand back procedure
References: Harris (2010)B & V Testing, INC.
AS 2467 (2008) General Requirements for Fumigation
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Sterilizers (Sporicides): Used to destroy or eliminate all forms of microbial life including fungi, viruses, and all forms of bacteria and their spores. Spores are considered to be the most difficult form of microorganism to destroy. Therefore, EPA considers the term Sporicidal to be synonymous with "Sterilizer.“ (Log 6 Reduction)
Disinfectants: Used on hard inanimate surfaces and objects to destroy or irreversibly inactivate infectious fungi and bacteria but NOT necessarily their spores. Disinfectant products are divided into two major types: hospital and general use. (Log 4 Reduction)
Sanitizers: Used to reduce, but not necessarily eliminate, microorganisms from the inanimate environment to levels considered safe as determined by public health codes or regulations. (Log 2 Reduction)
Antiseptics and Germicides: Used to prevent infection and decay by inhibiting the growth of microorganisms. Because these products are used in or on living humans or animals, they are considered drugs and are thus approved and regulated by the Food and Drug Administration (FDA).
http://www.epa.gov/oppad001/ad_info.htm
Types of Antimicrobial applications:
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Types of Antimicrobial applications:Liquid Treatments:
• For mould/fungal decontamination, the antimicrobial must be sporicidal and fungicidal
• Sterile cleaning equipment must be used in conjunction with the appropriate antimicrobial of choice.
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Rapid Decontamination Systems:
• Formaldehyde
• Ozone (Cold Plasma/UV Generated)
• Vapourised Hydrogen Peroxide
• Ionised Hydrogen Peroxide
• Chlorine dioxide
• Nitrogen dioxide (small volumes)• All of the above fumigants are sporicidal and fungicidal
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Comparisons between technologies:
Key
➢H2O2-1 = Wet VHP Process
➢H2O2-2 = Fogging Process
➢H2O2-3 = Dry VHP Process
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Documented Mould Contamination Case Studies:
2015 - Mould in a anti-tuberculosis manufacturing facility in India. WHO issued
a Notice of Concern (NOC) for black mould found in GMP facility. Product recall
and shortage of supply.
http://www.in-pharmatechnologist.com/Regulatory-Safety/Black-mould-and-
rusty-equipment-lands-Indian-TB-drugmaker-WHO-warning
2012 – New England Compounding Centre shut down after 64 meningitis
related deaths from fungal contamination of products.
https://www.cemag.us/blog/2017/01/pharmacists-fatal-meningitis-outbreak-
facing-trial
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Case Study: BioSperix Cell Isolator:
Tissue Culture Facility with mould in the isolator. Hard to reach with manual
cleaning
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Case Study: Cell Culture Laboratory with Mould Contamination caused by
Mould biofilm in the ceiling space:
Source removal and application of antimicrobial
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Case Study: Cell Culture Laboratory with Mould Contamination caused by
Mould biofilm in the ceiling space:
Source removal and application of antimicrobial
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Case Study: Facility Decontamination – Animal Facility – Pinworm Outbreak
Facility with single stage physical clean and pinworm egg Inactivation using
Chlorine dioxide gas
Total Project Duration = 7 days (6 day clean, 1 day gas)
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Summary:
• Identify possible sources or routes of contamination• Control environmental factors such as relative humidity to reduce
the chance of fungal growth• Control the introduction of organic or cellulose based materials
into your cleanroom• Have GMP processes in place to correctly measure and mitigate
the opportunity for fungal contamination, ie; cleaning regimes, HVAC hygiene etc
• Understand the physical properties and behaviour of your decontaminant of choice to ensure efficacy and safety and is a sporicide and fungicide
• Different decontaminants may be appropriate for different applications
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Good References:
• IICRC S500 Guideline for Water Damage• IICRC S520/R520 Guideline for Mould Remediation• http://www.ivtnetwork.com/article/understanding-preventing-and-
remediating-mold-cleanrooms
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ANY QUESTIONS?
Thank you for your time!
Please feel free to email me at [email protected]