Karen Snow, (ASCP)BB, CQA(ASQ)Quality Assurance Officer Bone Marrow Transplant Program &Cellular Therapeutics & Transplantation LaboratoryMassachusetts General HospitalBoston, Massachusetts, USA
How Effective is your Cleaning and Sanitization Process
A Review of Current Practices
Bonjour, Je m’appelle Karen
Cleaning & Sanitization Practices
Maintaining a clean laboratory is a critical element of Quality Manufacturing for cell therapy products.
Review of cleaning and sanitization practices reported by ISCT survey participants
Examine how regulatory and accreditation requirements influence cleaning practices
Discuss the needs of processing laboratories for standardization in cleaning and sanitization across the industry
5/12/20142 ISCT Annual Meeting, Paris France
Cleaning & Sanitization Reported byProcessing Facilities
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Does your facility: Undergo regulatory inspections & register with authority?
Participate in “voluntary” accreditation?
Have a Quality Program?
Follow published standards for cleaning (ISO)?
Follow standard operating procedures for cleaning?
Document cleaning?
Rotate cleaning agents?
Perform Environmental Monitoring ?
Use EM to measure cleaning procedures for effectiveness?
Monitor cleaning and effectiveness for Biological Safety Cabinet (BSC)?
Registered Reviewed & Why
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0%
25%
50%
75%
100%99%
53%
79%
21%
1%
47%
Yes
No
Accreditation
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0%
10%
20%
30%
40%
50%
60%
70%
AABB FACT CLIA CAP ASHI Other
Additional Regulatory & Accreditation
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State & local regulations
ISO 9001
TGA/NATA
Joint Commission
Health Canada
Other CNS, CNT
HTA
JACIE/AFSSAPS
College of MD & Surgeons
MHRA
EFI
Net Cord
Israel Ministry of Health
Processing Facilities
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0
10
20
30
40
50
60
70
8079
23
44
10 10
Total 166 Labs> 85% US /EU/AU/HC
Types Products Processed
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0%
10%
20%
30%
40%
50%
60%
70%
HPC-A, HPC, M Cord BB CB AdminBlood Products 351/IND
66%
41%
57%
64%
25%
10%
24%
16%21%
13%16%
21% 20%
7%
55%
7%
14%
7% 7% 8%
Unclassified
ISO 8
ISO 7
ISO 6
Quality Program
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0%
25%
50%
75%
100%
Quality Program Follow Published CleaningStds
99%
24%
1%
76%
Yes
No
A Clean Room Means A Controlled Environment
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Strict procedures followed to lower the risk & prevent contamination of cell therapy products
Mandated by EU, FDA, TGA & other competent authorities around the world
Objective: control environment where cell therapy products are manufactured
Laboratories are required to follow the regulations regardless of the type of facility they work in.
Contamination
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Dust, debris, microorganisms
Generated by:
Facilities: airflow, temperature, humidity, building materials
Processing activities: gowning, spills, products
Equipment: reagents, supplies, equipment operation
People: hair, skin, droplets, movement
Control:
Workflow: laboratory or clean room design
Airflow HEPA HVAC
Operations: process control
Cleaning & sanitization
Standard Operating Procedure & Documentation of Cleaning Based on Laboratory Classification
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0%
20%
40%
60%
80%
100%
Unclassified ISO 8 ISO 7 ISO 6
94%
68%
77%
55%
75%
47%
37%
57%
Cleaning SOP Cleaning Documented
Are Cleaning Agents Rotated?
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0%
20%
40%
60%
80%
Unclassified ISO 8 ISO 7 ISO 6
25%
53%
63%
43%
75%
47%
37%
57%
YES
NO
Cleaning Agents Utilized
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Chlorhexidine or similar
Hydrogen peroxide based
Qauternary disinfectants
Fungicidal solutions
Detergent solvents
Isopropanol reagents
Germicidal wipes
Sporeklenz, sporicidin
Virex 256
10% Bleach
70 % Alcohol
LpH, vesphene, phenolic
Asepticare
Actisan biozidal IPA
Percept , alcohol
Asepticare and alcohol mixture for hoods
SaniMaster 4 for floors
Bench Top & EquipmentHow often General Cleaning is Performed
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LaboratoryClassification
Monthly Weekly Daily After Each Use
Unclassified 1% 13% 59% 27%
ISO 8 3% 7% 72% 14%
ISO 7 0% 8% 43% 49%
ISO 6 0% 6% 33% 56%
** No one answered “Never” ** No one answered “Quarterly”
Frequency of General Cleaning:Bench Tops, Lab Equipment
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0%
10%
20%
30%
40%
50%
60%
70%
80%
After each use Daily Weekly Monthly
Unclassified lab ISO 8 ISO 7 ISO 6
Personal Gowning Practices
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Use of reusable/sterile lab coats
‘Bunny Suit’
Scrubs or other “non-street” clothes
Gloves (non-sterile/sterile)
Hair cover, face mask, shoe covers
Variation in practices in general and with:
Laboratory classification
Product type
Who is Responsible for General Facility Cleaning?
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LaboratoryClassification
Lab Staff Hospital Staff Contract Staff
Unclassified 25% 51% 24%
ISO 8 39% 18% 43%
ISO 7 49% 26% 26%
ISO 6 67% 20% 13%
Employee training documentation on cleaning procedures is critical. This training should (shall) be conducted for all staff charged with cleaning functions and often extends beyond laboratory staff
Walls, floors, ceilings…
Training Documentation for Cleaning Staff
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0%
25%
50%
75%
100%
Training Documentation
61%
93% 91%
100%
Std Lab
ISO 8
ISO 7
ISO 6
Frequency of Extended Cleaning:Equipment, Walls, Ceilings
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0%
5%
10%
15%
20%
25%
30%
35%
40%
Never Quarterly Monthly Weekly Daily Aftereach use
Unclassified lab ISO 8 ISO 7 ISO 6
HVAC Vent Cleaning
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0%
5%
10%
15%
20%
25%
30%
35%
40%
Weekly Monthly Quarterly SemiAnnually
Annually Never
Unclassified lab ISO 8 ISO 7 ISO 6
Cleaning and Effectiveness
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Viable & non-viable particles
Air sampling
Settle plates/swabs/RODAC plates
Testing areas:
General facility cleaning
Personnel
Critical equipment: BSC, water baths, centrifuges
Hematology analyzer, cell sorter or other instrumentation
Small equipment: weight scale, heat sealer
Ventilation, HEPA filters (maintenance dept)
Bench tops
Environmental Monitoring
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Unclassified Lab
Class 100,000 (ISO 8)
Class 10,000 (ISO 7)
Class 1,000 (ISO 6)
Similar % for EM SOP
Not used as a measure of cleaning effectiveness *****
73%
93%
97%
100%
Is Effectiveness of Cleaning Measured?*****
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0%
20%
40%
60%
80%
Unclassified ISO 8 ISO 7 ISO 6
41%
54%
61%
42%
59%
46%
39%
57%
YES
NO
Environmental Monitoring: Surface Microbial Sampling (Touch Plates)
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0%
10%
20%
30%
40%
50%
60%
After Each Product Daily Weekly
12%
17%19%
0%
33%31%
59%
33%
50%
29%
17%
0%
Unclassified ISO 8 ISO 7 ISO 6
Biological Safety Cabinet
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Critical piece of equipment
The Biological Safety Cabinet (BSC)
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BSC certified by trained/certified professional at least annually
½ reported annual & ½ bi-annual certification
A small percentage reported quarterly certification
General cleaning SOP
Airflow on for specified amount of time prior to processing
UV light utilized by many facilities
Clean/disinfect BSC before/after processing each product
BSC ‘deep cleaning’ taking apart to clean
The Biological Safety Cabinet
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Is there an SOP to describe BSC cleaning?
Is cleaning documented?
Unclassified 93% 94%
ISO 8 89% 89%
ISO 7 100% 100%
ISO 6 92% 83%
BSC General Surface Cleaning
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0%
10%
20%
30%
40%
50%
60%
70%
Unclassified ISO 8 ISO 7 ISO 6
How Often is ‘Deep Cleaning’ of the BSC Performed
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Before/AfterEach Use
After a Spill
Daily Wkly Mnly Q 2X Year
1XYear
N/A
Unclassified
2% 2% 0% 21% 36% 17% 10% 6% 5%
ISO 8 8% 0% 0% 8% 44% 16% 4% 8% 12%
ISO 7 15% 0% 0% 15% 53% 15% 0% 3% 0%
ISO 6 18% 0% 0% 36% 27% 0% 0% 18% 0%
Effectiveness of Cleaning MeasuredGeneral vs BSC
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0%
20%
40%
60%
80%
Unclassified Class100,000 Class 10,000 < Class 1,000
41%
54%
61%
42%43%
72% 71%
64%
General
BSC
How Cleaning Effectiveness is Measured for BSC
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Validation of cleaning methods
Touch plates for viable organisms
Touch plates weekly, air sample & particle counts monthly
Swab of surfaces after cleaning
Settle plates
Culture of surfaces monthly/quarterly
Swab & blood agar plates before & after cleaning
Many variations on these answers
Summary
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Maintaining a clean laboratory is a critical element of Quality Manufacturing for cell therapy products
Cleaning & sanitization practices differ widely and this is not solely limited by facility type, regulatory requirements, or accreditation standards
It is important to find a balance in manufacturing a safe product with data driven, cost-effective cleaning
& sanitization practices that can be applied anywhere in the world
Thank You to Members of the Laboratory Practices Committee, Past & Present
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Andrew Havens
Michele Sugrue
Steve Konings
Joe Mierski
Martin Hildebrandt
Nadim Mahmud
Karl Stasko
Federico RodriguesQuezada
Varda Deutsch
Deb Lamontagne
Eugenia Ioannidi
Fen Fen Hsieh
Heather Garrity
Doug Padley
Tom Leemhuis
Richard Meagher
Merci beaucoup
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ISO 14664 Cleanrooms and Associated Controlled Environments
United States Pharmacopeia (USP) Chapter 1116 and 797
21 CFR 1271 Human Cells, Tissues and Cellular and Tissue Based Products, current Good Tissue Practices, Final Rule May 25, 2005