How Effective is your Cleaning and Sanitization Processc.ymcdn.com/sites/ · Standard Operating...

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

5/12/2014ISCT Annual Meeting, Paris France 3

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

5/12/2014ISCT Annual Meeting, Paris France 4

0%

25%

50%

75%

100%99%

53%

79%

21%

1%

47%

Yes

No

Accreditation

5/12/2014ISCT Annual Meeting, Paris France 5

0%

10%

20%

30%

40%

50%

60%

70%

AABB FACT CLIA CAP ASHI Other

Additional Regulatory & Accreditation

5/12/2014ISCT Annual Meeting, Paris France 6

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

5/12/2014ISCT Annual Meeting, Paris France 8

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

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