www.cleanrooms-ireland.ie Update on ISO Cleanroom Standards – 14644 & 14698 Conor Murray Chairman - Irish Cleanroom Society Head of Delegation for Ireland at ISO TC 209 2 Conor Murray Bio 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 Contamination Control 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 3 Presentation Content Irish Cleanroom Society ISO 14644 & 14698 Overview ISO DIS 14644 -1 & -2:2011 – WG 01 14698 -1 & -2:2003 – WG 02 4 Irish Cleanroom Society www.cleanrooms-ireland.ie 5 Irish Cleanroom Society 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 of cleanroom and contamination control technology and standards among users and professionals in Life Sciences, Healthcare, Food, Microelectronics and Micromanufacturing 6 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 7 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 8 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 9 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 and represents Ireland at ISO TC 209 concerning Cleanrooms and associated controlled environments The ICS works closely with FAS on cleanroom training and up skilling 10 ICS Initiatives - Education 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 11 ICS Initiatives - Education 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) 12 ICS & International Associations 13 ICS Initiatives - ISO TC 209 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 14 ICS & ISO TC 209 15 ISO 14644 & 14698 - Overview 16 ISO 14644 & 14698 Standards ISO Document Title Status ISO-14644-1 Classification of Air Cleanliness - 1999 WG01 ISO-14644-2 Testing for Continued Compliance to -1 - 1999 WG01 ISO-14644-3 Test Methods & Metrology - 2005 WG03 ISO-14644-4 Design, Construction & Start Up 2001 ISO-14644-5 Cleanroom Operations 2004 ISO-14644-6 Terminology - 2007 SG06 ISO-14644-7 Separative Enclosures 2004 ISO-14644-8 Classification of Airborne Molecular Contamination - 2007 WG08 ISO-14698-1 Biocontamination: General Principles - 2003 WG02 ISO-14698-2 Biocontamination: Eval’n & Interpretation of Data - 2003 WG02 17 ISO 14644 & 14698 Standards ISO Document Title Status ISO-14644-1 Classification of Air Cleanliness - 1999 WG01 ISO-14644-2 Testing for Continued Compliance to -1 - 1999 WG01 ISO-14644-3 Test Methods & Metrology - 2005 WG03 ISO-14644-4 Design, Construction & Start Up 2001 ISO-14644-5 Cleanroom Operations 2004 ISO-14644-6 Terminology - 2007 SG06 ISO-14644-7 Separative Enclosures 2004 ISO-14644-8 Classification of Airborne Molecular Contamination - 2007 WG08 ISO-14698-1 Biocontamination: General Principles - 2003 WG02 ISO-14698-2 Biocontamination: & Interpretation of Data - 2003 2 new standardsEval’n under development to cover SCP via WG9 & -9 and SCC via WG8 & -10 WG02 18 ISO 14644 TD Proposal Deals with the role of an ISO 14644 Technical Document as an Overview, Introduction, Explanation and Context in dealing with updates 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 19 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 20 ISO 14644 Issues 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 21 ISO 14664/ 14698 Structure Total Particles Viable Biocontamination Chemical Nanoparticles Airborne ACP ACV ACC ACN ? Surface SCP SCV SCC SCN ? Total Particles Viable Biocontamination 14698-1 14698-2 14698-1 14698-2 Chemical Nanoparticles 14644-8 14644-? 14644-10 14644-? Airborne 14644-1 Surface 14644-9 22 ISO Support Standards Standard Existing Testing for Ongoing Compliance to 14644-1 New Testing for Ongoing Compliance to 14644-1 14644-3 Test Methods Supporting Test Methods 14644-4 Design, Construction & Startup Design, Construction & Startup 14644-5 Operations Operations 14644-6 Terminology Terminology 14644-7 Separative Devices Separative Devices 14644-2 14698-? Supporting ? 23 ISO DIS 14644 -1 & - 2 24 ISO DIS 14644 -1 & -2 Apply good science and statistics Remove confusion and inconsistencies Simplify terms Use more precision Use a Table for Classification instead of the universal formula 25 ISO DIS 14644 -1 Copenhagen 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 sample locations, application of statistics – random selection Differences over treatment of 5 micron particles Differences over normative use of ISO 21501-4 26 ISO DIS 14644 -2 Copenhagen 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 27 ISO 14698 -1 & -2:2003 - Biocontamination WG 02 28 ISO 14698 -1 & -2: 2003 29 ISO 14698 Issues 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) 30 ISO 14698 Issues 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 31 ISO TC 209 Preliminary Work Items WG02 IS O/T C 2 09 N 187 Re so lution s from ISO/ TC 20 9 M ee ting 9-10 No v em be r 2007 Ré sol utio ns de l' IS O / T C 20 9 (1 9 èm e réu nion, 9 et 1 0 Nov e mbr e 2 00 7) Re so lution 1 IS O/T C 209 reso lv es th at W G 2 co m m ence s w ork on thes e tw o doc um ents : a. C lassi fication of airb orne bi oc onta m inatio n in c leanroo m s, inc luding m etho ds of m eas ure m ent a nd their v alida tion. b. C lassi fication of s urf ace bioc ontam inatio n in c le anroo m s, including m ethod s of m eas ure m ent a nd their v alida tion. At t he appropriat e time during the de velopm ent of these docu m ents, t he position of IS O 14 698 Parts 1 a nd 2 sh ould b e cons idered, as w ell as a Risk M anage m ent St andard. (All in fa vor) 32 ISO Standard Principles 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. 33 ISO Working Group Principles 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 34 ISO Working Group Principles 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 35 ISO 14698 Challenges - Limitations of Quantitation 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” 36 ISO 14698 Challenges - Diversity of People People are the greatest source of biocontamination Unpredictability and uncertainty of Human behaviour “80% of the species found in the human upper respiratory tract cannot be recovered” 37 ISO 14698 Challenges - Issues in clean spaces 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 of accidental contamination during collection and incubation 38 ISO 14698 Challenges - Process/ Application Specific In some cases, all species are considered harmful In some cases there is ‘background counts’ of cfu of species considered ‘normal and nonharmful’ In some cases, some species are considered ‘objectionable’ and are not tolerated at all 39 Aseptic Processing - 5μm Particles & EU GMPs “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 be investigated.” Particles ≥5.0 μm could be skin particles carrying biocontamination 40 ISO 14698 - Proposed New Structure 41 New ISO 14698 Flowchart 42 New ISO 14698 Flowchart 43 New ISO 14698 Flowchart 44 Proposed New ISO 14698 -1 - Establishing Control Risk Analysis/ Assessment Risk Management Establishing (Risk) Control 45 ISO 14698 - Establishing Control Step 1 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 46 ISO 14698 -Establishing Control Step 2 For “normal, non-harmful”: - establish typical ‘background counts’, e.g. <10cfu - establish acceptable incidence of higher than normal counts, where maximum limit is defined - anything above incidence rate or maximum triggers investigation 47 ISO 14698 - Establishing Control Step 3 For “Objectionable”: - establish acceptable incidence, including maximum number process will tolerate - anything above incidence rate or maximum triggers investigation 48 ISO 14698 - Establishing Control Step 4 Classify your process/cleanroom: “Normal, non-harmful” - species - by ‘background counts’ - by acceptable incidence of ‘higher than normal’ (maximum limit is defined) “Objectionable” - establish acceptable incidence, including maximum number process will tolerate per incidence 49 ISO 14698 - Airborne Classification Class *Airborne limit In Operation cfu/m3 ACVx 1 ACVx 2 ACVx 3 ACVx 4 <10# < 100 < 1000 < 10000 1. *Combined with an appropriate incidence rate 2. ‘x’ is the species of interest 3. # still under discussion (added error by air collection method) 4. Intermediate classes are permitted, eg SVCx 3,5 50 ISO 14698 - Surface Classification Surface Contamination Class (SCV) *Surface Count Limit (CFU) Sampled Area SVCx 1 <4 1 m2 SVCx 2 <40 1 m2 SVC x3 <40 1 cm2 SVCx 4 <300 1 cm2 SVC x5 >300 1 cm2 1. Numbers are open for further discussion 2. *Combined with an appropriate incidence rate 3. ‘x’ is the species of interest 4. Intermediate classes are permitted, eg SVCx 3,5 51 ISO 14698 - WG 02 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 52 Thank You for Your Attention