Update on ISO Cleanroom Standards 14644 Amp 14698

8/19/2019 Update on ISO Cleanroom Standards 14644 Amp 14698

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Conor Murray

Chairman - Irish Cleanroom Society

Head of Delegation for Ireland at ISO TC 209

Update on ISO Cleanroom

Standards – 14644 & 14698

www.cleanrooms-ireland.ie

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Conor Murray, an Engineer by profession is an independent

Technical Expert on GMP Cleanrooms and Biosafety Labs

Conor is a founder member and Chairman of the Irish

Cleanroom Society, (ICS). Conor is a past Chairman of the

ICCCS, (International Confederation of ContaminationControl Societies) and currently Chairman of the ICEB,

(International Cleanroom Education Board)

Conor is Head of Delegation for Ireland representing the

NSAI at ISO TC 209 and is on WG 01 & WG 02

Conor is Convener of Sub Group 13, (Cleanrooms) on the

Health Care Standards Consultative (HCSC) committee

Conor's particular areas of expertise include Green and

Energy Efficient Modular Design, Lifecycle Sustainability,

Process Integration, RABS and Fast Track Clean

Build Construction

Conor Murray Bio


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Irish Cleanroom Society

ISO 14644 & 14698 Overview

ISO DIS 14644 -1 & -2:2011 – WG 01

14698 -1 & -2:2003 – WG 02

Presentation Content

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www.cleanrooms-ireland.ie


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The Irish Cleanroom Society (ICS) is a not for profit

membership subscription based organisation formed in

1998 to represent cleanroom professionals in Ireland

The ICS is affiliated to the International Confederation of

Contamination Control Societies (ICCCS)

The primary focus is to promote best practice knowledge

and skills, understanding and harmonisation ofcleanroom and contamination control technology and

standards among users and professionals in Life

Sciences, Healthcare, Food, Microelectronics and

Micromanufacturing


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ICS Objectives

Promote the development of cleanroom and

contamination control technologies throughout Ireland

Heighten the awareness of cleanroom and contamination

control technology among all users inc industry, educational,institutional establishments, government bodies & the public

Assist in the standardisation and harmonisation of

cleanroom and contamination control

Organise seminars, exhibitions and peer to peer forum

workshops for the dissemination of knowledge & experience

gained in cleanroom and contamination control technology

Represent Ireland on the international stage

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ICS & Education

Education and Training are at the core of ICS activities

The ICS has been a major contributor to the CTCB-I

(Cleanroom Testing and Certification Board -

International) since its inauguration in 2002 and

has provided nearly 20 Cleanroom Technology and

Testing courses with over 200 candidates from Ireland

and around the world Since 2005 the ICS has helped lead the ICEB initiative of

the ICCCS to accredit, harmonise & licence cleanroom

training courses across national cleanroom societies with

the emphasis on certification through examination

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ICS on the International Stage

The ICS represents Ireland at international level on ISO

TC 209 for cleanroom standarisation where Ireland is a

voting member

Conor Murray is Head of Delegation for Ireland & a

subject matter expert on the TC & a number of WGs

The ICS is an active member of the ICCCS, International

Confederation of Contamination Control Societies

ICS an active member of the International Cleanroom

Education Board (ICEB)

Ireland hosted the 21st biennial symposium in 2008

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ICS Linkages in Ireland

The National Standards Authority of Ireland are the

Irish representative body in CEN and ISO Standards

organisations

Their Health Care Standards Consultative (HCSC)

committee has established a subcommittee, SC 13

concerning cleanrooms

The Irish Cleanroom Society play a leading part in

this. Conor Murray is Convener of SC 13 andrepresents Ireland at ISO TC 209 concerning

Cleanrooms and associated controlled environments

The ICS works closely with FAS on cleanroom training

and up skilling

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International Cleanroom Education Board (ICEB)

Part of International Confederation of Contamination

Control Societies (ICCCS)

Set up in 2007

ICS playing a significant leadership role internationally

CTCB-I initiative set up with S2C2 in 2001

CTCB-I now includes Scandinavian Countries (R3) of

Norway, Sweden and Denmark & The Netherlands

(VCCN)

Capturing interest from the US, Baltic, Far East, South

Africa, Egypt

ICS Initiatives - Education

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5 ICEB accredited courses

Cleanroom Testing – CTCB-I (‘03 250)

Advanced Cleanroom Technology - CTCBi

(‘05 100)

Airborne Particle Counting – CTCB-I (‘08 20) Introduction to Cleanrooms - SSE (‘09 50)

Cleanroom Cleaning - FLO (‘09 40)

ICS Initiatives - Education

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ICS & International Associations

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Participation in Working Groups in TC 209 on

cleanroom standards

WG 01 - revision of ISO 14644 - 1 & 2 Classification by

total airborne particles

WG 02 - revision of ISO 14698 – Biocontamination

(Irish Biocontamination Mirror Group)

WG 03 - revision on ISO 1464 - 3 Metrology

ICS Initiatives - ISO TC 209

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ICS & ISO TC 209

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ISO 14644 & 14698

- Overview

ISO 14644 & 14698 Standards

ISO Document Title

ISO-14644-1 Classi fi cat ion o f A ir Clean liness - 1999

ISO-14644-2 Testing for Cont inued Compl iance to -1 - 1999

ISO-14644-3 Tes t Met ho ds & Met ro lo gy - 2005

ISO-14644-4 Des ign, Construc tion & Star t Up

ISO-14644-5 Clean ro om Op er at io ns

ISO-14644-6 Terminology - 2007

ISO-14644-7 Sep ar at ive En clos ur es

ISO-14644-8 Classif ication of Airborne Molecular Contaminat ion - 2007

ISO-14698-1 Biocontaminat ion: General Pr inciples - 2003

ISO-14698-2 Biocontaminat ion: Eval ’n & Interpretat ion of Data - 2003

Status

WG01

WG01

WG03

2001

2004

SG06

2004

WG08

WG02

WG02

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ISO 14644 & 14698 Standards

ISO Document Title

ISO-14644-1 Classi fi cat ion o f A ir Clean liness - 1999

ISO-14644-2 Testing for Cont inued Compl iance to -1 - 1999

ISO-14644-3 Tes t Met ho ds & Met ro lo gy - 2005

ISO-14644-4 Des ign, Construc tion & Star t Up

ISO-14644-5 Clean ro om Op er at io ns

ISO-14644-6 Terminology - 2007

ISO-14644-7 Sep ar at ive En clos ur es

ISO-14644-8 Classif ication of Airborne Molecular Contaminat ion - 2007

ISO-14698-1 Biocontaminat ion: General Pr inciples - 2003

ISO-14698-2 Biocontaminat ion: Eval ’n & Interpretat ion of Data - 2003

Status

WG01

WG01

WG03

2001

2004

SG06

2004

WG08

WG02

WG022 new standards under development to cover2 new standards under development to cover

SCP via WG9 &SCP via WG9 & --9 and SCC via WG8 &9 and SCC via WG8 & --1010

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ISO 14644 TD Proposal

Deals with the role of an ISO 14644 Technical

Document as an Overview, Introduction,

Explanation and Context in dealing withupdates and changes to ISO 14644 & ISO

14698 re airborne and surface cleanliness

classification by total particles, viable, chemical

and nano particles

Approved in Milan 2011- to be presented to ISO

TC 209 in Zurich, September 2012

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ISO 14644 Issues

Historical development and focus on Airborne

Particles

New standards deal with surfaces, chemicals

and nanoparticles

Need backward compatibility

Where to put the history, context, perspective,

objectives, usage & application notes

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Existing definition of cleanroom relates to

airborne particles ie total particle

concentration in air

New definition needs to address the

concept of a controlled environment where

the control could be total particles, viables or

chemicals in air and/or on a surface

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ISO 14644 Issues


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ISO 14664/ 14698 Structure

Total

Particles

Viable

Biocontamination Chemical

Nano-

particles

ACC

SCC

Airborne

Surface

ACP

SCP

ACN ?

SCN ?

ACV

SCV

TotalParticles

ViableBiocontamination

ChemicalNano-

particles

14698-1

14698-2

14698-1

14698-2Surface

Airbo rne 14644-1

14644-9

14644-8

14644-10

14644-?

14644-?

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ISO Support Standards

Standard

14644-6 Terminology Terminology

14644-7 Separative Devices Separative Devices

Design, Construction &

Startup

14644-5 Operations Operations

14644-4 Design, Construction & Startup

Testing for Ongoing

Compliance to 14644-1

14644-3 Test Methods Supporting Test Methods

14644-2Testing for Ongoing Compliance to

14644-1

Existing New

14698-? Supporting ?

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ISO DIS 14644 -1 & - 2

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Apply good science and statistics

Remove confusion and inconsistencies

Simplify terms

Use more precision

Use a Table for Classification instead of the

universal formula

ISO DIS 14644 -1 & -2


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DIS Vote May ‘11 – unanimous but > 200

comments

Differences over no of samples for confidence level

and maximum area to determine classification

Differences over method of selection of samplelocations, application of statistics – random selection

Differences over treatment of 5 micron particles

Differences over normative use of ISO 21501-4

ISO DIS 14644 -1Copenhagen

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DIS Vote May ‘11 – unanimous

Decided to remove classification and keep to

Periodic Testing & Monitoring

Agreed that Classification and Periodic Testing are

NOT the same – amount of testing

Differences over inclusion of Differential Pressure

ISO DIS 14644 -2

Copenhagen


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ISO 14698 -1 & -2:2003

- Biocontamination WG 02

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ISO 14698 -1 & -2: 2003


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ISO 14698 not in line with ISO 14644

No Tables of Classification

Not up to date with Risk Assessment & Risk

Management techniques (eg ICH Q9 QRM)

No Check Lists of “Things to Consider”

Not up to date with technology advances in

Rapid Microbiological Methods (RMM) &

Instantaneous Microbiological Detection (IMD)

(eg ATP, Bioluminescence)

ISO 14698 Issues

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Cannot “Monitor a process into Control”

Not enough clarity on differences, issues and

guidance on Aseptic vs Non Sterile applications Not enough guidance on Airborne vs Surface

biocontamination risks and control

Overall seen as not easy to read & use

ISO 14698 Issues


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ISO/TC 209 N 187

Reso lu t ions f rom ISO/TC 209 Meet ing 9-10 Nov ember 2007Résolut io ns de l ' ISO/TC 209 (19èm e réun ion, 9 et 10 Novemb re 2007)

Resolu t ion 1 IS O/TC 209 resolves that WG 2 commence s work on these two docum ents:

a. Classification of airborne bioconta mination in cleanrooms, including metho ds ofmeasurem ent and their valida tion.

b. Classification of surface bioc ontaminatio n in cleanrooms, including m ethods of

measurem ent and their valida tion.

At t he appr op ria t e ti me du rin g the de vel op men t o f these do cu men ts, t he po si ti on of IS O 14 698Parts 1 and 2 sh ould be considered, as well as a Risk Managem ent Standard.

(All in fa vor)

ISO TC 209Preliminary Work Items WG02

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ISO Standards are NOT industry specific -

Bird’s Eye view from 25,000 feet

Normative (Must do) & Informative (Should do) Based on good science with clear and

independent guidance

Short & concise, easy to read & use

Check Lists, flow charts, suggested methods,

options on best practice methods, choices,

examples.

ISO Standard Principles


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Working Group is a team of international experts

nominated by each member country

Terms of reference set by TC 209

Duration varies but typically 2 - 5 years

Act as Subject Matter Experts (SMEs) in their

field

ISO Working Group Principles

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Capture best science and international expertise

“Get all the toys on the table” and play with them

Everything on the table Open dialogue encouraged until the end

Let “good science” prevail

ISO Working Group Principles


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Current measurement ‘technologies’ limited to

orders of magnitude resolution, especially in low

density populations

Species recovered using these technologies

limited due to incubation methodology (inc

media, temperature, pH, aerobic/anerobic, etc.)

“Environmental microbiologists recent research

indicate that some species are inter-dependant

& one species will not culture successfully

without the presence of the other”

ISO 14698 Challenges- Limitations of Quantitation

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People are the greatest source of

biocontamination

Unpredictability and uncertainty of Humanbehaviour

“80% of the species found in the human upper

respiratory tract cannot be recovered”

ISO 14698 Challenges

- Diversity of People

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Below limit of resolution for current

technologies

i.e. 1 cfu recovered may be indicative of 1cfu

or perhaps >10cfu, impossible to accurately

and repeatably determine

Risk of false positives high due to likelihood ofaccidental contamination during collection and

incubation

ISO 14698 Challenges- Issues in clean spaces

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In some cases, all species are considered

harmful

In some cases there is ‘background counts’ ofcfu of species considered ‘normal and non-

harmful’

In some cases, some species are considered

‘objectionable’ and are not tolerated at all

ISO 14698 Challenges

- Process/ Application Specific

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“In Grade A and B zones, the monitoring of the

≥ 5.0 μm particle concentration count takes on

a particular significance as it is an important

diagnostic tool for early detection of failure.”

“... consecutive or regular counting of low

levels (of ≥5.0 μm) is an indicator of a possible

contamination event and should beinvestigated.”

Particles ≥5.0 μm could be skin particles

carrying biocontamination

Aseptic Processing- 5μm Particles & EU GMPs

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ISO 14698

- Proposed New Structure

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New ISO 14698 Flowchart

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Risk Analysis/ Assessment

Risk Management

Establishing (Risk) Control

Proposed New ISO 14698 -1

- Establishing Control


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Identify ‘typical, non-harmful’ species

- typical in cleanroom

- not harmful to product or

application/customer

Identify ‘objectionable’ species

- atypical in cleanroom

- harmful to product and/or harmful to

customer

ISO 14698- Establishing Control Step 1

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For “normal, non-harmful”:

- establish typical ‘background counts’, e.g.


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For “Objectionable”:

- establish acceptable incidence, including

maximum number process will tolerate

- anything above incidence rate or maximum

triggers investigation

ISO 14698- Establishing Control Step 3

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Classify your process/cleanroom:

“Normal, non-harmful”

- species- by ‘background counts’

- by acceptable incidence of ‘higher thannormal’ (maximum limit is defined)

“Objectionable”

- establish acceptable incidence, includingmaximum number process will tolerate perincidence

ISO 14698

- Establishing Control Step 4

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ISO 14698- Airborne Classification

Class *Airborne limit In

Operationcfu/m

3

ACVx 1


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Next meeting – Zurich Sept 2012

New Work Item Proposal (NWIP)

Formal Vote required for approval

ISO timetable of CD, DIS FDIS, & IS

over 3 years

ISO 14698- WG 02

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Thank You for Your Attention

Update on ISO Cleanroom Standards 14644 Amp 14698

Documents

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