Cleanroom Contamination including Mould/Fungal contamination

Transcription

1 Cleanroom Contamination including Mould/Fungal contamination Brett Cole. Biosafety Pty Ltd Tuesday 25 th July

2 Cleanroom Contamination including Mould/Fungal contamination: 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 2

3 Professional Experience- 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 3

4 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. 4

5 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 5

6 What is mould? Some are good Some are bad 6

7 Sources of mould and contamination in cleanrooms. 7 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

8 How to minimise mould/fungal growth? Facilities should be constructed of nonporous material that do not absorb water and promote fungal growth (21 CFR ) 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. 8

9 Decontamination 9

10 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 10

11 11 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

12 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 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 12

13 Microbial Resistance: 13

14 Types of Antimicrobial applications: 14 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).

15 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. 15

16 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 16

17 Comparisons between technologies: Key H 2 O 2-1 = Wet VHP Process H 2 O 2-2 = Fogging Process H 2 O 2-3 = Dry VHP Process 17

18 Case Studies 18

19 19 Documented Mould Contamination Case Studies: 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 New England Compounding Centre shut down after 64 meningitis related deaths from fungal contamination of products

20 20 Case Study: BioSperix Cell Isolator: Tissue Culture Facility with mould in the isolator. Hard to reach with manual cleaning 20

21 21 Case Study: BioSperix Cell Isolator: 21

22 22 Case Study: Cell Culture Laboratory with Mould Contamination caused by Mould biofilm in the ceiling space: Source removal and application of antimicrobial 22

23 23 Case Study: Cell Culture Laboratory with Mould Contamination caused by Mould biofilm in the ceiling space: Source removal and application of antimicrobial 23

24 24 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) 24

25 25 Case Study: Facility Decontamination Animal Facility Pinworm Outbreak 25

26 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 26

27 Good References: IICRC S500 Guideline for Water Damage IICRC S520/R520 Guideline for Mould Remediation 27

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29 ANY QUESTIONS? Thank you for your time! Please feel free to me at 29