Clean Air and Containment Reviewissn 2042-3268

Clean Air and Containment

Review ISSN 2042-3268 Issue 15 | July 2013

Real-time facility monitoring for quality and compliance Guidance on personal protection when working with cytostatics A guide to ductless fume hoods Activated carbon filters and cytotoxic drug vapours Real time measurement of particle deposition BSI Conference report: How to improve energy efficiency in cleanrooms Contents Editorial

Contents Editorial Clean Air and Main features 4 Last time I wrote Most pharmaceutical guidelines use about the issues the term CFU (colony forming unit) Containment Real-time facility monitoring for quality and compliance 4 that need to be as a measure of microbial contamination. Tim Russell resolved if E10 (or When we were writing BS 8568 (the Review Guidance on personal protection when working similar) filters are new cleanroom energy saving standard), with cytostatics and fabric testing methods 8 to be considered we were unable to find a good definition Ian Samson for pharmaceutical of CFU, so we wrote our own: “single Issue 15 | July 2013 A guide to ductless fume hoods 10 cleanrooms. One micro-organism or a single small mass of ISSN 2042-3268 X Q Lin of these derived from an apocryphal micro-organisms that when deposited on a Activated carbon filters and cytotoxic drug vapours: story that I had heard many years microbiological growth medium grows to form Euromed Communications Ltd Report on carbon filter project at The University of Bath 14 before: “Will such filters allow microbial a single visible colony that can be counted”. Passfield Business Centre, John Neiger growth from the dirty side to the clean In his various learned papers on the Lynchborough Road, side if the filter should accidentally subject, Bill Whyte prefers the term MCP Passfield, Liphook, Hampshire become wet with a nutrient solution?” (microbe-carrying particle). This term GU30 7SB, UK Innovations 16 This prompted a reply from Bill Whyte: was also used in BS 8568 and defined: T: +44 (0)1428 752222 Real-time measurement of particle deposition 16 “I think if you were to squirt nutrient “particle on which a micro-organism is F: +44 (0)1428 752223 Anton Duisterwinkel broth on a filter it would dry quite quickly. carried; it is normally dispersed into room e: [email protected] You would need to keep the broth and air by personnel as a skin cell, or fragment www.euromedcommunications.com Standards 18 filter wet if you wanted microbes to grow of skin cell, on which a skin microbe(s) CavendishCr t cal through the fibres, as they are aquatic is carried”. EDITOR Updates on the ISO 14644 series of standards and on filter standards 18 Design Install Upgrades and cannot grow in a dry environment There seems to me to be problems John Neiger John Neiger (they are hard pressed to survive). I am with both these terms. The number T: +44 (0)1494 882094 also fairly sure that the most efficient of CFUs that deposit on a settle plate or M: +44 (0)7967 572958 Regulatory reflections 19 filters have a pore size much larger than are collected in a biological sampler can e: [email protected] microbes and growth could occur through only be a representation of the number Just published: WHO guidance on quality risk management 19 all types of filters. I just do not think in the air and varies from method PUBLISHER Hans H. Schicht there will ever be the right circumstances”. to method. In addition, as Tim Sandle Joe Ridge www.cavendishcritical.net Here is a true story relating to two writes in CACR9, “there is no universal Conference report 20 horizontal unidirectional airflow benches culture medium or set of incubation Production Clare Beard 4th Annual Cleanrooms Conference Cleanroom Energy – that have just passed their in-situ aerosol conditions which will grow all How to improve energy efficiency in cleanrooms, IMechE, filter leak tests. Settle plates at the back microorganisms. Moreover there Subscriptions London, June 14 2013 20 of the work surface, i.e. near the filter are many viable but non-culturable Jill Monk John Neiger face, on both benches were picking up microorganisms found in cleanrooms”. microbial growths. The settle plate tests And a MCP might well be the most were repeated, with the same results, common form of microbial contamination Clean Air and Containment Review Book review 23 as were the filter leak tests, which that will land on the growth media to is a quarterly journal aimed at users, specifiers, designers, Review of ‘Cleanroom Management in Pharmaceuticals and continued to show no leaks. The mystery form a CFU, but there may be others manufacturers, installers and Healthcare’ edited by Tim Sandle and Madhu Raju Saghee 23 was eventually solved when the microbial that will do the same, including mold testers of clean air and containment James H Filer contamination was traced to the joint spores, sporulating bacteria (endospores) between the work surface and the filter and aerosolized bacteria (e.g. legionella equipment. It publishes articles of For useful information including: face. There was sufficient of a crack or from contaminated humidifiers or topical, technical and historical News 24 • Free downloads crevice to harbour microbial growth cooling towers). interest, updates on standards and • Links for ordering relevant books, Contec, Cavendish Engineers, Validair, Pharminox (1) 24 which had not been removed by cleaning Both these definitions are useful, regulations, news, views and standards, guidelines and other information on relevant events, CRC, Pharminox (2), DOP Solutions 25 or disinfection. The airflow from the but it important that we should fully publications HEPA filters was picking up this microbial understand their limitations too. especially training. • Links for booking events and growth and depositing it on the settle Events and training courses 30 training courses Clean Air and Containment Review plates. I am sure that there were many John Neiger Please visit the Clean Air and is published quarterly in lessons learnt from this incident. Vital vocabulary 31 Containment Review website January, April, July and October Readers will by now know that I www.cleanairandcontainment.com V is for … 31 have an obsession with terminology. Annual subscription rate £75.00 Standards can also be obtained

from national standards bodies and Views expressed in Clean Air and Containment Passfield Business Centre, Passfield ISO standards can be obtained from Review are those of the contributors and Liphook Hampshire, GU30 7SB ISO and IEST www.cleanairandcontainment.com not necessarily endorsed by the Publisher or Editor who accept no liability for the T: +44 (0)1428 752222 Permission to reproduce extracts A comprehensive source of information for clean air and containment consequences of any inaccurate or F: +44 (0)1428 752223 from British Standards is granted by the practitioners on relevant Standards, Publications, Guidelines, Events and misleading information e: [email protected] British Standards Institution (BSI). No Training courses with links for details, ordering/booking and free downloads. © 2013 Euromed Communications Ltd www.euromedcommunications.com other use of this material is permitted.

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Recent innovations in optical particle Detecting the root cause source shown in Figure 1. This information is Real-time facility monitoring for counting technology have made it The following example demonstrates commonly provided by a facility possible to determine airborne particle the impact of this new technology on monitoring system and is reviewed to quality and compliance viability in real-time. For example, TSI the outcome of root cause investigations help support root cause investigations of Inc.’s BioTrak Real-Time Viable Particle when compared with outcomes using airborne microbiological excursions. Tim Russell Counter counts airborne particles in traditional optical counting data. The question is: Which of these peaks compliance with ISO 21501-4 vii, the This example is based on real data corresponds to the viable particle event? calibration standard for particle taken by the BioTrak Particle Counter in The non-viable continuous particle Abstract cleanliness, has been a driver for Management (2005) for product counters. Then, each particle is analysed a supporting Grade C (ISO 7) area. A data is analysed and an excursion is Pharmaceutical industry regulators are pharmaceutical companies to install development and manufacturing process. for viability using a laser induced viable particle excursion did occur, identified. There were other candidates now encouraging quality rather than facility monitoring systems. The FDA’s Guidance for Industry fluorescence sensor. Finally, the particles which was supported by positive active where the particle counts appeared to compliance-based thinking. A facility PAT – A Framework for Innovative are captured on a filter to enable air sampling data received several days be high, but the event circled in green is monitoring system that includes real-time Quality-based monitoring Pharmaceutical Development, laboratory speciation. When integrated after the event took place. significant. In this example, one conclusion viable particle monitoring as well as The first facility monitoring systems to Manufacturing, and Quality Assurance directly into a facility monitoring system, The BioTrak Viable Particle Counter was that the event that caused the viable real-time total particle monitoring is include optical airborne particle counters (2004) v provides a regulatory framework it enables the continuous monitoring of “nonviable” total particle count (TCNT particle excursion occurred around 11 am. an extremely useful tool for achieving were installed in semiconductor and to facilitate innovation. The guidance airborne viable and non-viable particles. = viable + non-viable) trending data is There may not be enough granularity the necessary quality. A true example hard drive manufacturing facilities in recommends: “Sensor based in the environmental airborne is given of how real-time viable particle microbiological data to come to any counting can give different and more other conclusion. Production logs may reliable information than real-time total Recent innovations in optical particle counting technology even indicate that an operator activity particle counting. have made it possible to determine airborne particle was performed at the time associated with the particle spike, which could Introduction viability in real-time then be logically associated with the A facility monitoring system (FMS) is a viable particle excursion. process monitoring tool that collects Figure 2 shows the real-time viable data from sensors such as optical particle the early 1980s. There were no regulatory measurements provide a useful process particle count (VCNT = viable particles counters, differential pressure sensors, requirements to monitor particulate signature that may be related to only) trend data taken over the same and temperature probes in real-time. cleanliness of the air. A key driver was underlying process steps and could time by the same instrument. The red Other terms are independent monitoring – and continues to be – Six Sigma. The relate to product or process quality”. circle marks a clear candidate for a system (IMS) or environmental aim of Six Sigma is to reduce variation, The microbiological quality of the air single viable particle event around 12:30 monitoring system (EMS). Software waste and cycle times, while increasing surrounding the manufacturing pm. A closer look at the TCNT data in presents the collected data as information. the level of quality. This data-driven environment is one potential in-process Figure 1 around 12:30 pm does not Real-time alarms notify facility operators approach for analysing root causes of measurement; optical particle counters reveal a particle excursion (black oval), of alert limits to enable an immediate business processes and problems is used connected to facility monitoring systems and that time would give the end user response to an unwanted event or to achieve improved yields, cost savings, have been a surrogate measurement for no cause for concern. Real-time viable excursion. Reports and trend graphs and increased profits. It is quality-based this up until now. trending provides more insight to detect can be produced. decision making. Covering the entire product lifecycle root cause. This information can then be used Pharmaceutical industry regulators and strengthening the link between to help improve process understanding are now encouraging quality rather than pharmaceutical developments and Conclusion and enhance process knowledge. The compliance-based thinking and are manufacturing activities, ICH Q10 vi A facility monitoring system plays an quality of the data input into the facility keen to encourage industry to use the Pharmaceutical Quality System (PQS) Figure 1: Total particle counts (TCNTs) at ≥0.5 µm and ≥5 µm, TSI Inc. important role in supporting the ICH monitoring system will directly impact latest and best practices. Achieving the (2009) encourages an environment Q8, Q9, and Q10 guidelines in the the quality of the process information “desired state” is a term that is used to where quality is everyone’s responsibility. pharmaceutical industry. Data collected and knowledge gained from the system. describe the initiative: “A maximally This includes quality-based decision by the system provides useful real-time In the pharmaceutical industry, efficient, agile, flexible pharmaceutical making. Compliance-based decision and historical trending information aseptic processing is monitored – in manufacturing sector that reliably making is simply not sufficient. about the environment surrounding accordance with regulatory requirements produces high quality drug products Optical particle counters have critical processes. Over time, this – to prove the environment surrounding without extensive regulatory oversight”. 1 historically been the only way of information builds process knowledge. a process does not negatively impact Complementary guidelines provide monitoring the cleanliness of the air in Recent innovations in real-time product quality and, ultimately, patient a framework to encourage innovation real-time in pharmaceutical applications. airborne viable particle counting safety. Environmental parameters and quality-based thinking in the These instruments are installed based technology, when integrated into a facility monitored include temperature, relative pharmaceutical industry. For example, on the principles of quality risk monitoring system, enables real-time end humidity, differential pressure, and ICH Q8 (R2) iii Pharmaceutical management (QRM) in locations where user response to microbial excursions. airborne particles. Development (2009) encourages a there is the greatest risk of airborne Real-time detection of excursions in Compliance to regulatory guidelines greater understanding of pharmaceutical particle contamination to the process. process critical areas supports risk such as the EU GMP Annex 1 i and the and manufacturing sciences. Knowledge These instruments cannot determine reduction. Correlating excursions with US FDA cGMP ii, which require continuous is gained from the application of scientific particle viability; they can only count cleanroom activities at specific moments monitoring of airborne particle approaches and ICH Q9 iv Quality Risk and size particles in real-time. in time will lead to improved root cause investigations, which in turn will lead to more effective corrective and preventative 1. FDA’s Director of the Center of Drug Evaluation and Research (CDER), Janet Woodcock M.D. Figure 2: Viable particle count (VCNT) excursion appears to be at 12:30 pm, TSI Inc. actions. Opportunities exist to implement

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real-time quality control strategies, version dated August 2009. (CDER), Center for Biologics Evaluation potentially including the immediate INTERNATIONAL CONFERENCE ON and Research (CBER), Office of Regulatory HARMONISATION OF TECHNICAL Affairs (ORA), September 2004, segregation of product that is at risk. REQUIREMENTS FOR REGISTRATION OF Pharmaceutical CGMPs PHARMACEUTICALS FOR HUMAN USE. Better real-time data presents more vi. ICH HARMONISED TRIPARTITE meaningful information, contributing to iv. ICH HARMONISED TRIPARTITE GUIDELINE: PHARMACEUTICAL GUIDELINE: QUALITY RISK QUALITY SYSTEM Q10, Current Step 4* a better knowledge and understanding MANAGEMENT Q9, Current Step 4* version dated 4 June 2008. of the process, an increase in product version dated 9 November 2005. INTERNATIONAL CONFERENCE ON Next Generation Air Filtration quality, and a safer product. Improved INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF For enhanced performance of critical processes and best energy savings yields, cost savings, and increased profits REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE. PHARMACEUTICALS FOR HUMAN USE. will be the result. vii. ISO 21501-4:2007 Determination of particle v. Guidance for Industry PAT — A Framework size distribution. Single particle light for Innovative Pharmaceutical Development, interaction methods. Light scattering Manufacturing, and Quality Assurance, airborne particle counter for clean spaces. i. EudraLex, The Rules Governing Medicinal U.S. Department of Health and Human * At Step 4 of the Process the final draft is Products in the European Union, Volume 4, Services: Food and Drug Administration, recommended for adoption to the regulatory EU Guidelines to Good Manufacturing Center for Drug Evaluation and Research Practice, Medicinal Products for Human bodies of the European Union, Japan and USA. and Veterinary Use, Annex 1 : Manufacture of Sterile Medicinal Products (corrected version), European Commission, Enterprise and Industry Directorate-General, Brussels, Tim Russell has 27 years’ experience in particle counting 25 November 2008 instrumentation. He was one of the founding Directors ii. Guidance for Industry, Sterile Drug at Facility Monitoring Systems Ltd, Malvern, England in Products Produced by Aseptic Processing 2000. Facility Monitoring Systems (now Validair Monitoring — Current Good Manufacturing Practice, U.S. Department of Health and Human Solutions) specialises in compliant environmental and Services: Food and Drug Administration, particulate monitoring systems. In 2009, Tim transferred Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation to TSI Instruments Limited where he is now Field Market and Research (CBER), Office of Regulatory Developer for life science applications. During Tim’s time in the industry Affairs (ORA), September 2004, Pharmaceutical CGMPs he has helped design, install and maintain hundreds of compliant monitoring systems throughout the world. iii. ICH HARMONISED TRIPARTITE GUIDELINE: PHARMACEUTICAL Contact: [email protected] DEVELOPMENT Q8(R2), Current Step 4*

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test method uses sodium chloride particles levels of permeability to both air and hood or collar, integrated socks, sewn or Guidance on personal protection when working at 0.6 micron sizes suspended in a fine water vapour to allow it to “breathe”. covered seams and thumb loops. Where spray in a test chamber. The 9 minute test additional protection is required, for with cytostatics and fabric testing methods (3 minutes standing, 3 minutes walking A range of solutions example where certain parts of the body and 3 minutes squatting) is repeated on 10 When choosing protective coveralls to may be more frequently or heavily Ian Samson suits. To pass the test 8 out of the 10 suits protect both the worker and the process it exposed to the hazardous substance, tested must have on average less than 15% is always advisable to carry out a detailed accessories are available. This includes inward leakage into the suits. This means analysis of the hazardous substance and sleeves, overboots, overshoes, lab gowns, Abstract during production, preparation, disposal, counter is used to sample the air. The that coveralls that have passed the Type 5 of the working environment to ensure aprons and back-fastening gowns that are This article, which was originally written storage and transportation of these sample is then used to determine the test offer a certain level of protection the right level of protection for the task. compatible with other products. by DuPont as an Educational Guide, substances. At the same time, it is average particle concentration in the air against fine particulates. It is important Tyvek® and Tychem® protective clothing For further information please visit describes the attributes of fabrics for important to protect the process from during the initial ten minutes of the test. to choose a coverall that offers the lowest offer a superior level of protection and www.chemicalprotection.dupont.co.uk. disposable coveralls used as personal human contamination, including hair, To ascertain the contamination of a level of inward leakage for the best exceed requirements for migrating protection equipment (PPE) for staff shedding skin and clothing fibres. If cleanroom by simulating the particle possible protection when working with particle efficiency and particle hold out, working with cytostatics. Fabrics and there is any risk of contact, the use of filtration of clothing and the particle cytostatic drugs. as well as offering comfortable, flexible i. http://www.who.int/mediacentre/news/ releases/2003/pr27/en/ garments have to be tested for barrier suitable personal protection equipment release of the person under real wear protection – see Figure 4. To offer the right ii. BS 6909:1988 – Method for generation and efficiency, particle shedding, particle (PPE) is mandatory to ensure effective conditions the BodyBox test is used. The importance of material protection where needed, protective counting of the airborne linting propensity emission and particle intrusion, and the full-scale protection. These protective During the test, a test person performs While most coveralls look similar, the clothing from DuPont is available in a of fabrics in the dry state relevant tests are described. Protective measures apply to all staff that come a series of defined movements ranging material used makes a difference in range of models, such as a suit with a clothing made from Tyvek® and Tychem® into contact with cytostatics, including from still to walking, knee bends and determining the end protection level. offer a superior level of protection whilst cleaning, maintenance and shipping arm movements in a cleanroom test There are three common types of exceeding requirements for these tests and staff. One of the most effective ways cabin. Particle counters determine the material; MPF (Microporous Film), SMS offering comfortable, flexible protection. of protecting both the worker and the quantity of particles generated by the (Spun Bond –Melt Blown–Spun Bond) process is through the use of disposable wearer and garment that are emitted and Tyvek®. When tested against BS Introduction coveralls. But with so many on the market into the chamber. One of the benefits 6909 ii these materials perform very Figure 1: Surface view of MPF (left) under According to the World Health it can be difficult knowing which one is of this method is that it is able to test differently. MPF (sometimes known a microscope x500 and a cross section of Organisation, between now and 2020 the right for you, so understanding what to what is commonly known as the as LMPF) is made using a spunbond MPF (right) cancer rate will rise by 50%, producing look for is key. ‘bellows effect’, where air can be drawn polypropylene and a film of polyethylene. 15 million new cases a year worldwide i. into the garment through movement. Due to the structure of the material it is As the number of cancer patients rises, so Particle emission barrier Further movement can push air not breathable and has a high particle does the use of chemotherapy treatments Barrier efficiency against migrating containing any fibres or skin that has shed count. SMS is a breathable material using cytostatic drugs. While effective in particles, such as those from clothing or been shed forcefully into the room but has poor liquid repellency. Due to treating disease, these drugs are also human skin, is a critical performance through the cuffs and ankles of the the short fibres in the material it sheds Figure 2: Surface view of SMS fibres (left) potentially hazardous for the oncology feature when working with cytostatics. coverall. Due to the high variation in fibres quickly so is unsuitable for under a microscope x500 and a cross section of SMS (right) nurses, pharmacists and other healthcare Protective coveralls are tested for barrier particle generation between individuals cleanroom environments. Tyvek®, professionals who handle them. efficiency against migrating particles no performance classification exists and manufactured only by DuPont, is made There are a wide range of potential and fibres through two different test there is no limit value for emission, but up of ultrafine endless high density effects on those exposed to cytostatic methods; the Helmke Drum and Body choosing the lowest possible filtration polyethylene fibres using specific drugs. The toxicity affects not only Box tests. rate is always recommended. spinning and bonding technology. tumour cells but also healthy cells; The Helmke Drum test method Because of the endless fibres it has a very Figure 3: Surface view of Tyvek® continuous therefore cytostatic drugs pose a quite simulates particle shedding of clothing Protection from particle intrusion low particle shed count. Surface and fibres (left) under a microscope x500 and a Figure 4: Full protection for working specific occupational risk to health care through movement and is a good When determining the level of protection cross section views of MPF, SMS and cross section with toxic substances workers. Yet research indicates that indication of the quantity of fibre that a from particle intrusion it is important to Tyvek® are shown in Figures 1, 2 and 3. insufficient care is being taken with coverall, both inside and out, will shed look at the Type 5 test results. The Type cytostatic agents. Studies report a Comfort is key Ian Samson is European Sales and Training Specialist for widespread, low-level contamination of Whilst protecting both the worker and protective clothing for DuPont, and is based in the UK. Ian areas where cytostatic drugs are used. When choosing protective coveralls to protect both the the process is crucial, a further, important has a wealth of experience of health and safety issues in the Traces of cytostatic drugs have been found worker and the process it is always advisable to carry issue is having coveralls that are manufacturing industry, gained through a career spanning on work benches, floors, vials and exterior comfortable. Comfort is closely linked nearly 40 years. surfaces. In some cases, traces have been out a detailed analysis of the hazardous substance and to protection – after all, if workers are Ian’s expert knowledge of limited-use protective garments ® found on the floor outside preparation of the working environment to ensure the right level comfortable they are more willing to and accessories such as those made of DuPont™ Tyvek and rooms which poses a contamination risk wear the protective garments and thus DuPont™ Tychem® and his extensive experience in the correct use of protective to supposedly ‘safe’ areas. of protection for the task. protection is heightened. Therefore the garments are combined with his in-depth knowledge of health and safety garments should ideally be designed legislation regarding protective clothing. Protecting the worker to be durable enough to allow for a During his 16 years with DuPont, Ian has trained a diverse range of and the process during normal working practices. The 5 test specifies the minimum requirements range of movement and flexibility, organisations to correctly “don” and “doff” protective garments and related Precautions must be taken to prevent garment is tumbled in a rotating drum for chemical protective clothing resistant without compromising safety through PPE, including international journalists, nuclear plant employees, industrial the formation of cytostatic aerosols and to release particles from the surface of to penetration by airborne solid particles. ripped seams. At the same time, the workers and the emergency services. dust and to avoid cytostatic contamination the garment whilst an automatic particle To test particle intrusion, the Type 5 fabric should offer sufficiently high

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hoods. A ductless fume hood can Activated carbon filtration more feasible than bulky on board A guide to ductless fume hoods be placed on a bench and connected compression tanks in vehicles. to an electrical supply. No external 4. Gas purification: X Q Lin ducting, building work or changes Filters with activated carbon are to heating and ventilation systems usually used in compressed air and are necessary. gas purification to remove oil vapours, Abstract However, it should also be Advantages of ductless • An expensive ducting and external odours, and other hydrocarbons This article is a basic description of the remembered that ductless fume hoods fume hoods blower system that is often difficult Activated carbon from the air. Activated carbon design, advantages, applications, testing are not without limitations. Carbon • They protect the environment since to maintain is not required. Activated carbon (activated charcoal, filters and safe operation of ductless fume based filters are processed or treated toxic fumes are not released to the activated coal) is a form of carbon that are also used to retain radioactive hoods. Ductless fume hoods utilise to adsorb specific types of chemicals environment unlike in conventional • They are mobile and can be relocated has been processed to make it extremely gases from a nuclear boiling water activated carbon filters for the removal at low evaporation rates, thus ductless fume hoods. Activated Carbon easily to meet changing needs; porous, thus giving it a very large reactor turbine condenser. of fumes and the manufacture, physical fume hoods are not commonly used filters retain/neutralize pollutants perfect for schools and educational surface area for adsorption or chemical properties and applications of these in any applications involving a broad eliminating harmful discharge institutes. The hood may be easily reactions. One gram of activated carbon Activated carbon is produced filters are described in some detail. array of chemicals or forced evaporation. to the environment. re-positioned or filters changed to has a surface area around 500 m². by one of two methods: Another limitation is carbon filter suit new requirements at any time. • Fully installed systems ready to The effectiveness of activated carbon 1. Chemical Activation: Introduction saturation monitoring, which can prove operate are available at a lower cost • They allow energy savings since air, as an adsorbent is attributed to its This technique is generally used Fume hoods are ventilation devices to be difficult. than bulky conventional fume which is costly to air-condition unique properties, including large for the activation of peat and which remove chemical fumes, vapours, or to heat, is not removed from the surface area, a high degree of surface wood based raw materials. The gasses, dust, mist and aerosols. Fume laboratory. Recirculatory airflow reactivity, universal adsorption effect, raw material is impregnated with a hoods also serve as physical barriers eliminates the need for laboratory and favourable pore size. strong dehydrating agent; typically between reactions and the laboratory, make-up air and integration into Other than filtration of chemical phosphoric acid or zinc chloride offering a measure of protection against ventilation systems. fumes, activated carbon is often mixed into a paste and then heated inhalation exposure, chemical spills, used in purification, deodorization, to temperatures of 500 °C – 800 °C run-away reactions and fires. decolorization and separation. to activate the carbon. The resultant However, unlike conventional fume Description Activated carbon is usually derived activated carbon is washed, dried hoods, which are exhaust-ducted, Ductless fume hoods provide operator from wood, coal, coconut shell, or peat. and ground to powder. ductless fume hoods filter out chemical and environmental protection from toxic fumes using activated carbon filters and vapours, gases and fumes. The inflow Common areas of application 2. Steam Activation: recycle the air directly back to the working air, which moves from the ambient for activated carbon include: This technique is generally used environment. Personnel protection is environment into the work zone through 1. Environmental applications: for the activation of coal and coconut provided by drawing air at a controlled the hood front opening with an average Carbon adsorption has numerous shell raw material, which is usually rate across a front opening into the hood, velocity of 0.5 m/s flushes the work zone applications in removing pollutants processed in a carbonised form. thus preventing toxic vapours generated of the hood. Additional inflow air can from air or water streams both in Activation is carried out at during reactions from escaping into the be taken through perforations at the the field and in industrial processes temperatures of 800 °C – 1100 °C general laboratory environment. back of the work zone to prevent standing such as spill clean-up, groundwater in the presence of steam. Although conventional (ducted) vortices of fume accumulation. The inward remediation, drinking water The main mechanism for fume hoods remain the equipment of airflow maintains negative pressure filtration, air purification, and many physical adsorption in activated choice for ventilating hazardous airborne (relative to the ambient environment) other processes. carbon filters is the London materials from the laboratory, there are within the main chamber of the hood dispersion force, also known 2. Medical applications: situations that make ductless fume hoods in order to ensure that no chemical as one of the van der Waals Activated carbon is used to treat a logical solution. Such situations include: fumes or vapours escape, thus providing forces. The London force is an poisonings and overdoses following • laboratories located, for example, in operator protection. The air is then drawn intermolecular interaction that oral ingestion. Tablets of activated the center or bottom of a multi-story through a pre-filter and an activated is actually responsible for the charcoal are still used as a folk building where there may not be a carbon filter mounted in the interior. condensation of noble gases remedy and over-the-counter drug ducting option, The pre-filter is built into the activated (such as helium, neon, argon etc.) to treat diarrhoea, indigestion, carbon filter to prolong carbon filter life to liquid as well as the physical • laboratories that are ‘air-starved’ and and flatulence. by removing large particles before they adsorption of molecules onto where the make-up air available is Activated charcoal is also used enter the carbon filter. The activated activated carbon. therefore insufficient to accommodate for bowel preparation by reducing carbon filter removes fumes from the a ducted fume hood, intestinal gas content before Characteristic properties of the exhaust air stream so that filtered clean abdominal radiography to visualize London force are that it is: • laboratories where loss of conditioned air is exhausted directly back to the room bile, pancreatic and renal stones. • nonspecific, existing between air would result in a less energy from the top of the hood. The hood, all molecules, efficient heating and cooling system, with its activated carbon filter, provides 3. Fuel storage: i.e. in increased costs, protection for the operator and the • temperature independent from Key Gas storage in activated carbons is environment from volatile toxic chemicals, -273 °C to +1000 °C, • laboratories where the initial Carbon filtered air an appealing gas storage method even in trace amounts, which normally expense for ductwork and Unfiltered/potentially contaminated air because the gas can be stored in a • additive, i.e. the sum of would not be removed by an exhaust installation is significant, Room air/inflow air low pressure, low mass, low volume all interactions, ULPA filter. The airflow through environment that could be much • laboratories where portability Figure 1: Airflow through the Esco Ascent Max ductless fume hood, the hood is shown diagrammatically is essential. with the front panel and visor not shown in Figure 1.

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• Keep laboratory personnel traffic • Hoods are easily assembled, portable Clinical/hospital • short-ranged, i.e. the magnitude • Sorption: The physical attachment • pH: adsorption capacity increases to a minimum while working in the and configured for high visibility • Industrial and commercial applications of the interaction is extremely of organic material onto the surface under pH conditions, which ductless fume hood. Substantial to improve classroom participation. range from quality control in cosmetic sensitive to the separation distance of active carbon in the meso-pores decrease the solubility of the cross drafts can be generated which production to photo-chemicals, of the molecules. and micro-pores of the active carbon. adsorbate (normally lower pH), • Installation costs are minimal; may affect containment. solvent extraction, purification and no ducting required. These characteristics make the • Contact time: sufficient contact other processes where fumes or Activated carbon has the following • Shut the sash when not working London dispersion force analogous to time is required to reach adsorption vapours are generated. adsorption parameters: in the hood. Life sciences the gravitational force, but short-ranged. equilibrium and to maximize • Particle size: smaller particles • Ductless fume hoods are ideal for adsorption efficiency. • Check filter saturation regularly, Cleanrooms The adsorption process takes provide quicker rates of adsorption, protocols using small quantities at least once every 60 hours of use. • Ductless fume hoods will not remove place in steps: Editor’s note: Activated carbon of solvents. • Temperature: lower temperatures tempered air from the cleanroom. • Macro transport: The movement filters are sometimes used in cytotoxic increase adsorption capacity except • Depending on the solvents used, A secondary HEPA filter can be of organic material through the safety cabinets and isolators. For more Testing in the case of viscous liquids, numerous vapour-generating installed to prevent particles generated macro-pore system of the active information on this application, see The ANSI/ASHRAE 110-1995 Method of laboratory processes such as HPLC during the work process from being carbon (macro-pore >50nm), • Concentration of adsorbate: article on page 14. Testing Performance of Laboratory Fume preparation and biochemistry recirculated to the cleanroom. adsorption capacity is proportional Hoods specifies three test procedures: • Micro transport: The movement protocols can be performed with to the concentration of adsorbate 1, 1. The face velocity grid test to measure of organic material through the improved safety and comfort. Other examples face velocity and gross draft velocity, meso-pore and micro-pore system • Touch-up painting of the active carbon (micro-pore 2. The flow visualization or smoke Forensics • Microscopy <2nm; meso-pore 2-50nm), test for local smoke visualization • Forensic laboratories frequently • Slide preparation and gross smoke visualization use sterilants and preservatives. • Histology Formaldehyde, often mixed with • Fingerprinting 3. The tracer gas containment test Safety precautions inside a ductless fume hood. Ignition Working procedures alcohols or phenols, is commonly • Dental laboratory whereby a tracer gas is released • Ductless fume hoods should not be sources such as electrical connections; • Ensure the hood is operating correctly used. OSHA has a specific standard • Spray adhesives inside the fume hood to measure used for laboratory work in which controllers and open flame can be before commencing work. for formaldehyde that stipulates • Solvent cleaning how much reaches the breathing chemicals of different types are used used inside a ductless fume hood initial and periodic monitoring, • Use appropriate personal protective zone outside. repeatedly. For example, the hood as long as there are no operations protective equipment and clothing, equipment including goggles and Conclusion should not be used for acid emitting involving flammable or explosive training and designating regulated gloves. Another test that is applicable for the Ductless fume hoods are very useful processes where hydrocarbon type vapours. If possible, ignition sources areas among others. ductless fume hood is BS 7989:2001 – devices for containing fumes in situations filters are installed. Ductless fume should remain outside the hood • Keep your head outside of the hood. Filter Efficiency and Capacity Test. This • Common chemicals used: where ducted fume hoods are not hoods should not be specified or used at all times. The operator should work at least test is to ensure that the ductless fume • formaldehyde practical or where the challenge is such for unknown chemicals or to contain 15 centimetres outside the plane of • Ductless fume hoods are potential hood is capable of meeting the filter • methyl methacrylate that the cost of ducted fume hoods is by-products of reactions for which the sash. locations for fires and explosions due capacity requirements specified in 8.5.2 • ammonia not justified. the characteristics are not known. to the types of reactions conducted • Work as far into the hood as possible of the BS 7989:2001 Standard. • Ductless fume hoods should not be in these hoods. The location of the and with slow, deliberate movements, used for multiple chemical processes ductless fume cabinets should be to minimize airflow disturbances. Common applications for where two or more chemicals could within the laboratory and be such The operator should attempt to slowly ductless fume hoods XQ Lin, currently the CEO and President of Esco, combine in the filter and cause that in the event of a fire or explosion approach and withdraw from the Education had his Bachelor’s Degree of Economics in the University reactions with toxic, exothermic within the fume hood, exit from the ductless fume hood. The opening • Ductless fume hoods are useful of Pennsylvania, USA. He has been part of the senior or explosive properties. The laboratory would not be difficult. and closing of the sash should be for secondary and post-secondary management team for more than 10 years, with responsibility chemicals may react later when the Depending on the types of reactions, done slowly. education, science classes and in for international sales, marketing, Research and Development second chemical is adsorbed even plastic hoods, which may not physically • Work with the sash as fully lowered laboratories where activated carbon and product management. if the chemicals are not present in withstand a fire, should not be used. as possible, utilizing the sash as a filtration offers safety from selected the ductless fume hood base at the • Ductless fume hoods should be natural barrier to accidents which aerosols and vapours. same time. located away from high traffic may occur in the hood. The operator • Ductless fume hoods should not be lanes within the laboratory because should make sure that the head and used with certain types of chemicals, personnel walking past the hood upper body remains outside the plane virus or bacterial emissions, high may disrupt the flow of air into the of the hood opening at all times. concentration acid emissions or hood and cause turbulence, drawing • Elevate the contaminants and processes with very high levels of fumes into the laboratory. equipment above the work surface of Save money and cut carbon chemical emissions such that the Gurney-Read • Safety devices such as drench showers, the hood so as to enable flow beneath We can help you achieve filter life would be very short. For savings of typically 20–50% Consulting Limited eye wash stations, fire extinguishers, and around the obstructions. such types of applications, standard without compromising Containment strategy, audits, first aid kits and fire blankets should compliance, quality and comfort. fume hoods, glove boxes or biological • Do not use the hood as a storage advice, concept design and be located convenient to the hood. safety cabinets should be used. area. Items can block airflow and awareness training Proper instructions should be posted interfere with containment. • Extreme caution should be taken as to their use and function. Email: [email protected] Tel: +44 (0)1428 725715 when working with ignition sources For more information contact: [email protected] Web: www.gurney-read.com

1. Adsorbate is the substance to be adsorbed

12 Clean Air and Containment Review | Issue 15 | July 2013 www.cleanairandcontainment.com www.cleanairandcontainment.com Clean Air and Containment Review | Issue 15 | July 2013 13 Main feature Advertisements

Activated carbon filters and cytotoxic drug vapours: Report on carbon filter project at The University of Bath John Neiger

The research project was carried out cytotoxic cabinets showed no traces of 3. Traces of Cisplatin were detected under the supervision of Professor these drugs, even after long periods either side of the carbon filters Graham Sewell whilst he was Professor of use, thus implying that the aerosols indicating that Cisplatin may vaporise of Clinical Pharmacy and Pharmacy generated by syringe-filling etc either at isolator temperatures and airflows. Practice at the School of Pharmacy and vaporised immediately, or, if arrested 4. Cisplatin was not adsorbed by the Pharmacology at the University of Bath. by the HEPA filters, vaporised over a carbon filters used for the tests. This report is based on a discussion in period of time afterwards. Some experts September 2004 between Professor considered this work to be flawed. Sewell and the author, who, as Chairman A test chamber was built to replicate Conclusions of Envair Limited at that time, was isolator conditions and cytotoxic drugs 1. Carbon filters do not adsorb responsible for commissioning the work. were injected into the airflow through all cytotoxic drugs that vaporise at room temperatures. Validated closed systems are the only effective way of 2. Carbon filters may adsorb some drugs that vaporise at room temperatures, containing those drug vapours that are not adsorbed by although these drugs have not yet carbon filters been identified. 3. Validated closed systems are the only effective way of containing those The object of the research project HEPA filters and activated carbon filters in drug vapours that are not adsorbed was to determine which cytotoxic drugs the sequence required. The test chamber is by carbon filters, e.g. Cisplatin. vaporise at room temperature; then for shown in figures 1 and 2. Samples of the 4. Neither carbon filters, nor closed those that do, whether activated carbon downstream air were taken and analysed systems address the problem of filters are effective, and for those that for each of the experiments. externally contaminated containers don’t, whether there are any other The results showed that: from drug manufacturers which processes (such as chromatography) 1. Cyclophosphamide, 5-flourouracil Complete solutions for HEPA filter, have been identified as a major whereby aerosols of drug, that are arrested and Paclitaxel were not detected source of cytotoxic contamination. cleanroom and safety cabinet testing by the HEPA, later vaporise off. either before the carbon filters or Previously published work by others, downstream of them, suggesting DOP Solutions notably in Germany, had suggested that these drugs did not vaporise at • Aerosol Generators and Photometers for HEPA Filter Testing at least two cytotoxic drugs, namely typical isolator working • Facility Monitoring Systems (with Lighthouse and Kimo) cyclophosphamide and 5-fluorouracil, temperatures (25-32°C). • Service and Calibration (inc. Mobile Lab) both exist in vapour form at room 2. If HEPA filters are loaded with these • Instrument Hire temperatures. This work included For more information drugs, there is no breakthrough. • Consumables and Accessories reports that exhaust HEPA filters from contact 01462 676446, • Consultancy and Technical Support [email protected] www.dopsolutions.com Academy for Cleanroom Testing (ACT) • Clean Air and Containment Systems Testing – Range of Courses

KIMO Instruments • Anemometers, Flowhoods, Manometers, Thermometers, Hygrometers • Akivision Software for Laboratory Monitoring Systems • Sensors, Transmitters, Displays and Data Loggers

LIGHTHOUSE Worldwide Solutions • Handheld and Portable Particle Counters (for Air, Liquid and Gas) • Remote Particle Counters for Facility Monitoring Systems • Wireless Monitoring for Environmental and Laboratory Monitoring • LMS Software for Particle and Environmental Monitoring Systems Figure 1: Test chamber assembled showing the injection port Figure 2: Components of the test chamber showing the activated carbon filter and the HEPA filter

DOP Ad.indd 1 17/01/2012 20:39 14 Clean Air and Containment Review | Issue 15 | July 2013 www.cleanairandcontainment.com www.cleanairandcontainment.com Clean Air and Containment Review | Issue 15 | July 2013 15 Innovations Innovations

replacement depends on the quality inexperienced operator. Thus, APMON Conclusion Real-time measurement of particle deposition of the cleanroom and can vary between is ideally suited for training staff, as well We expect that APMON will cause two to three weeks. The system as for quality control in cleanrooms and a revolution in cleanroom control. Anton Duisterwinkel auto-calibrates itself when the new operating theatres. All the more reason Infrequent airborne particle witness cartridge is installed and therefore to set clear standards for PDC measurements will remain necessary to subsequently at every snap shot. in different cleanroom types. There is check air filtering, but the chief method Abstract Fall-out Consequently, this type of work is rarely Data are stored automatically and no doubt that cleanroom controllers and for contamination control will become Much attention in cleanrooms is currently In order to combat particle deposition done. Also, routine measurements of management reports are easily other experts understand the value of the particle deposition measurement. given to airborne particles. But product and thus increase yield of processes PDC are rarely in place if at all. And extracted from the system. AMPON. It recently won the Cleanroom For more information please visit: quality is not harmed by small particles in cleanrooms, it is essential to find the even when they are performed, results Innovation Award at Cleanzone 2012 in www.apmon.eu, email: in air that do not deposit, but by larger root causes of deposition. Therefore, it is are obtained after more than 24 hours, Standard Frankfurt, Germany where no less than [email protected] particles that do fall onto the product. essential to be able to measure it. All so that a considerable production loss Little labour is therefore involved in 80% of the visitors voted for APMON out or call on +31 53 737 0292. Particle deposition occurs even in the current methods for particle deposition, can have occurred meanwhile. Finally, setting up and maintaining PDC control of the five products that were nominated. best cleanrooms where people are working or particle fall-out, involve witness plates. no international standard on particle of cleanrooms using APMON. As or machines are running. This is amply These are placed on a surface for a deposition is accepted currently, because system investment costs are comparable demonstrated experimentally, with minimum period, typically 24 hours. no easy and affordable measurement to current systems, clearly APMON will Dr.ir. Anton Duisterwinkel is the manager responsible at cumbersome, slow and expensive These witness plates need to be carefully technique has been available up to now. be less expensive in use. But the main TNO, the Netherlands Organization for Applied Scientific methods. The award-winning invention placed and collected, in order not to advantage is that measurements are Research, who developed the APMON in cooperation with of Technology of Sense, The Advanced contaminate them due to handling. New rapid method real-time and at least a factor 150 times Technology of Sense. Particle deposition MONitoring system After collection they are hand-fed into The APMON, the Advanced Particle faster than current measurements. Anton Duisterwinkel Ph.D. was born in 1964 in the (APMON), shown in Figure 1, is some sort of surface analysis instrument. deposition MONitoring system, shown This allows for direct action to control Netherlands. He studied Chemical Engineering at the University affordable, stand-alone and the first These are typically slow and expensive. in Figure 1, is an optical system that damage due to bursts of particle of Twente and did his Ph.D. research in Delft, the Netherlands, and only system that is able to measure The instruments yield a particle size automatically takes a snapshot of a total deposition by, for example, stopping in physical chemistry. He has worked for TNO, an independent contract research the deposition of ≥25 μm particles distribution that can be translated surface of about 35 cm2 every few production or covering up patients. organization, since 1992 and specialized in contamination control since 1998, in real-time. Every ten minutes the to a PDC (particle deposition class). minutes. Each snapshot is compared to Also, it is very likely to point to the building up expertise in the control of both molecular and particulate APMON informs the user of the local All the hard work yields this small the previous one, counting and sizing event that caused the burst, for instance contamination. Since 2003, he is also active as independent scientific journalist, situation. It can be used as an alarm, amount of information, which is any additional particles. This is translated floor cleaning, a lunch break with specialising in chemistry and hygiene. for training staff, finding root causes valuable nevertheless. to PDC levels automatically and many people walking nearby or an of particle deposition and even for continuously. A system consists of setting standards on particle deposition Witness plates monitors (with a maximum of six in cleanrooms. Koos Agricola, cleanroom controller at monitors, so you can determine PDC Océ in The Netherlands, has shown that levels at six different locations at the Introduction determining the PDC can be used to same time) and a base unit that performs In cleanrooms, even with the best demonstrate the effectiveness of several the calculations and stores the data. precautions, large (> 25 μm) particles particle control measures, such as cleaning When more particles are deposited than deposit on surfaces that should remain more frequently and improved clothing. allowed in the time between the two APMON clean. That would seem impossible By placing numerous witness plates at snapshots, an alarm can be set off. The Advanced Particle deposition MONitoring Technology of Sense given the extensive air filtering and different locations, he also found user can set the alarm level (or allowed smart air flows, but is a reality in all machines (or workers) that are particularly PDC) as well as the location of the cleanrooms where people or machines effective particle spreaders. This requires alarm: either on the monitor itself, at the are working. Particle filtering ensures a huge amount of labour, a very meticulous central station or at the desk of the that the air entering the room is virtually way of working and a certain stamina. cleanroom controller. Maintenance of particle free and certainly devoid of The return on such an investment in APMON is simple. Once in a while, the such large particles. It is an essential effort is probably positive, but is measured disposable witness cartridge onto which condition for clean production, but not a in terms of yield improvement which the particles deposit needs to be sufficient one. Machines that are running may be difficult to quantify. replaced. The time in between and people that are working cause particle generation and deposition within the cleanroom. Walking and working produces particles, and cleaning and other ways of touching of surfaces causes re-suspension of settled particles into the air. The closer this happens to the critical surface of a product, the www.apmon.eu larger the probability that particles deposit on it. Although a good cleanroom is designed such that particles are pushed away from those surfaces, this protection is never complete. Large Webbased Auto Large Self Real-time particles in particular are least affected Wireless Battery Cartridge Software Report Surface Area Calibrating > 2 weeks & 24/7 ~2 weeks by the air flows. Figure 1: APMON, the Advanced Particle deposition MONitoring system

16 Clean Air and Containment Review | Issue 15 | July 2013 www.cleanairandcontainment.com www.cleanairandcontainment.com Clean Air and Containment Review | Issue 15 | July 2013 17 Standards Regulatory reflections

Updates on the ISO 14644 series of standards Just published: WHO guidance and on filter standards on quality risk management John Neiger Hans H. Schicht

1. The ISO 14644 series of standards The 2013 report of the WHO Expert development through manufacturing, perceived significance of risks and to The following table summarises the Committee on Specifications for packaging, testing, storage and determine the level of scrutiny accordingly. status of all the parts of this comprehensive Pharmaceutical Preparations i has distribution. It embraces the entire life A risk rating for manufacturers is set of standards. just been published. From the GMP cycle of pharmaceutical products and recommended to be adopted in order perspective, only a single new guideline the corresponding manufacturing and to determine the optimum frequency Standard Title: Cleanrooms and associated Status has been approved this year: the WHO distribution processes. The objective is of inspections, with suggested inspection clean environments guideline on quality risk management. to optimise the benefit-risk balance of intervals ranging between 6 months for ISO 14644-1:1999 Part 1: Classification of air cleanliness Under revision ref ISO/DIS 14644-1, With this guideline, WHO adopts the products and processes. It applies both the least compliant, and 36 months for planned completion 2014. See article same risk-focussed and science-based to industry and to the respective the most compliant companies. by Gordon Farquharson in CACR13. approach that distinguished recent regulatory authorities. In a final chapter, the different risk ISO 14644-2:2005 Part 2: Specifications for testing and monitoring to Under revision ref ISO/DIS 14644-2, developments in the GMP compendia The subject of quality risk management management tools are assessed, with a prove continued compliance with ISO 14644-1 planned completion 2014. See article of the leading pharmaceutical regulatory is split into three main chapters: short description of their attributes and by Gordon Farquharson in CACR13. authorities. • an introduction to the elements the potential application areas. The FMEA ISO 14644-3:2005 Part 3: Test methods Under revision ref ISO/CD 14644-3. The objective of the new WHO of the quality risk management procedure is recommended for the See article by Stephen Ward in CACR13. guideline is to push the philosophy of process itself; evaluation of equipment and facilities, ISO 14644-4:2001 Part 4: Design construction and start-up Current. Systematic review under assessment quality risk management to a worldwide for analysing manufacturing processes • its application in industry during ISO 14644-5:2004 Part 5: Operations Current level, i.e. for all WHO member and for identifying their critical high-risk product and process development, ISO 14644-6:2007 Part 6: Vocabulary Current but will hopefully go on-line on the ISO/TC nations developing, manufacturing and elements and/or critical parameters. the qualification and validation website so it can be kept constantly up to date with distributing pharmaceutical products. stages and commercial manufacturing, new terms from new documents. The definition for Quality risk management is perceived with a life-cycle approach; the term ‘cleanroom’ will be reviewed so it takes by WHO as a most effective rationale i. WHO Expert Committee on Specifications for Pharmaceutical Preparations, 47th into account all cleanliness classifications not just for understanding risks and for • its application for the medicines report. WHO Technical Report Series no. the classification by particle concentration. mitigating them through appropriate regulatory authorities. 981, World Health Organization WHO, Geneva (2013). ISO 14644-7:2004 Part 7: Separative devices (clean air hoods, Current. Review initiated and robust controls. Regarding inspection activities, gloveboxes, isolators and mini-environments The new WHO risk management ii. ICH Q9: Quality risk management. WHO recommends the inspection plans International Conference on Harmonization ISO 14644-8:2013 Part 8: Classification of air cleanliness Current philosophy is based upon the provisions of Technical Requirements for Registration to focus on quality risk aspects. by chemical concentration (ACC) Note: the new 2013 version was published in of the ICH Q9 guideline ii developed by of Pharmaceuticals for Human Use ICH, Inspections are expected to consider the Geneva (January 2006). February 2013. the International Conference on ISO 14644-9:2012 Part 9: Classification of surface particle cleanliness Current Harmonization and published in 2006. ISO 14644-10:2013 Part 10: Classification of surface cleanliness by Current The quality risk management approach Hans H Schicht, Dr. sc. Techn, has over 40 years’ chemical concentration replaces the HACCP (Hazard Analysis experience in cleanroom and contamination control ISO 14644-12 Part 12: Classification of air cleanliness by ISO/DIS 14644-12 now being considered and Critical Control Points) procedure, technology. He has represented Switzerland on the nanoscale particle concentration until now the basic WHO guidance CEN and ISO cleanroom TCs for many years, and ISO 14644-13 Part 13: Cleaning of surfaces to achieve defined Proposal ref ISO/NP 14644-13 – standard being for quality risk management in the has served as Chairman of ICCCS and President of levels of cleanliness in terms of particle and developed pharmaceutical industry. SRRT. He is a Fellow of the IEST and an inductee chemical classifications Quality risk management is intended to the Cleanrooms Hall of Fame. ISO 14644-14 Part 14: Assessment of suitability of equipment and Proposal ref ISO/NP 17910 – standard being to cover all activities from research and materials for cleanrooms developed. See article by Richard Roberts in CACR13. ISO 14698-1:2003 Biocontamination control. Part 1: General Current but working draft for new standard principles and methods being worked on. See articles by Tony Harrison in CACR13 and by Tim Sandle in CACR14. ISO 14698-2:2003 Biocontamination control. Part 2: Evaluation and As above interpretation of biocontamination data Clean Air Test & Certifi cation 2. Filter standards that terms and definitions are no longer For a complete catalogue of The EN 1822 series of standards High included. Instead they are in EN standards relevant to cleanrooms, clean cGMP Compliance & Validation Support efficiency air filters (EPA, HEPA and 14799:2007 Air filters for general air air, containment and contamination GAMP Compliant Continuous Monitoring Systems ULPA) was revised and reissued in 2009, cleaning. Terminology. This might be a control, with ordering links, please as already reported in Clean Air and useful standard to have, especially for look at our associated website: Cleanroom Design, Construction & Project Management Containment Review (Issue 2: April those readers who are interested, as they www.cleanairandcontainment.com. www.validair.com www.diamondscientifi c.co.uk www.fmonsys.com 2010), but what was not mentioned was should be, in using correct terminology!

18 Clean Air and Containment Review | Issue 15 | July 2013 www.cleanairandcontainment.com www.cleanairandcontainment.com Clean Air and Containment Review | Issue 15 | July 2013 19 Conference report Conference report

practical examples. Various oil crises chillers with modern variable speed have included excessive design margins 4th Annual Cleanrooms Conference Cleanroom resulting from the 1973 Arab-Israeli War screw compressors and close controls for heat gains, particle loads etc., so and the Gulf War were major drivers available data should be used to reduce, The next speaker was Gordon Energy – How to improve energy efficiency in the move towards more compact for example, air volume to a level that Farquharson who spoke about energy clean air environments such as mini still maintains the required air quality. saving opportunities in HVAC systems in cleanrooms, IMechE, London, June 14 2013 environments, tents, softwall Further energy savings can be made and utilities, much of it from his own cleanrooms and fan filter units. Now in what Gordon termed ‘black utilities’, experience. He showed that savings can John Neiger we are facing the threats of global the main one of these being cooling be made a) in the choice of design warming and oil depletion. systems. There are opportunities in both concept, e.g. outside air pre-treatment Dick gave two case studies. These the design concepts, as already mentioned, with zonal recirculation and fan filter This conference was arranged by BSI in • An appreciation of potential emissions. The possible adverse impacts are shown in Figures 1 and 2 and are and the water chiller components and units (FFUs) vs. central air handling association with the IMechE (Institution reduction opportunities are increased cost and personnel self-explanatory. specifications. Energy efficient chillers units (AHUs), b) in component selection, of Mechanical Engineers) to mark the discomfort. Cleanroom operator Dick then described the history of the with ‘Turbocor’ compressors, electronically • A quantification of the relationship e.g. efficient fans and drives and low publication in March 2013 of BS 8568:2013 competence is achieved by training development of BS 8568, which started commutated (EC) motors, refrigerant between energy and application resistance system components, and c) in – Cleanroom energy – Code of practice people in personal hygiene, gowning and in 2011, and the constitution of the team liquid pressure amplification (LPA), (energy performance indicators) operational aspects, e.g. set-back (turn for improving energy efficiency in the performance of all the required tasks of experts that wrote it. He concluded electronic expansion valves and free down) including air volume, temperature cleanrooms and clean air devices. • A plan or schedule for in a controlled and deliberate manner. by quoting several of the energy saving cooling coils have been reported by and relative humidity. The conference was opened by continuous improvement There are no adverse impacts. Both these opportunities that are given in the Gordon in a comprehensive article in Taking the choice of design concept, Gordon Farquharson with a dramatic opportunities ensure that fewer particles standard. These included: CACR14. Dehumidification using liquid • An effective monitoring/targeting Gordon gave an example of the savings slide showing photographs of the are generated so that energy savings can • matching supply air volume flow rate and solid desiccant systems instead of approach (the energy baseline) that were achieved in a 24 m2 Grade A Upsala Glacier in Argentina taken in be made by allowing the airflow volume to the contamination source strength less energy efficient cooling coils is unidirectional airflow cleanroom by the 1928 and again in 2004. What had been • The establishment of standardised flow rate to be reduced while maintaining (determined using Bill Whyte’s described in the same article. use of 34 FFUs instead of one central a thick ice sheet was now a lake! processes and procedures the specified standard of air cleanliness. formula for dispersion rate and Gordon concluded by commenting AHU. The total fan power required by Pharmaceutical facilities are very large The relationship to other standards estimated sedimentation velocities) that regulations concerned with medicines the single AHU was 25 kW compared users of energy and two examples were Implementation should lead to and guidelines was described. ISO instead of air changes per hour quality (GMP) and bio-safety containment with 11 kW for the 34 fans of the given. At Pfizer 50-80% of site energy effective and pro-active management 50001 is generic and has no practical (ACPD/SAPO) do not yet include a • replacing IE1 fans with IE3 fans as FFUs. This gave an annual saving of is used in HVAC, mostly for fan power of the reduction of energy and emission guidance that is specific to cleanrooms. green/sustainability requirement. As fan efficiency can vary from 20% approximately 70 tonnes of CO based and cooling systems. At Novo Nordisk costs. David showed a case study in ISO 14644-4:2001 ‘Cleanrooms and 2 energy efficient systems are likely to have to 80% (concept of specific fan power on UK electrical grid power. the climate strategy and clEAN® which the filter manufacturer Camfil associated controlled environments – Part smaller margins of error as well as possibly explained: the ratio of the electric He then went through all the programme together are well on target Farr had used ISO 50001 to help 4: Design, construction and start-up’ barely greater complexity, the importance of power that is needed to drive a fan components where energy could be saved to reduce CO emissions from 210,000 achieve a reduction in energy costs from mentions energy reduction and certainly risk assessments, when considering 2 relative to the amount of air that by careful selection including fans with tons per annum in 2004 to 190,000 in £500,000 in 2008 to £300,000 in 2011. gives no guidance. However, energy energy saving measures, was stressed. is moved) efficient frequency converter variable 2014 against an increase of almost 100% The next talk, which was given by reduction is entirely compatible with the The final speaker was Nigel Lenegan, speed drives and filters where larger filter in production output. Having set the the author, described the scope, process core concept of this standard. • efficient filter selection using the an expert who has been directly involved areas reduce energy consumption. scene, Gordon introduced BS 8568 by structure and content of BS 8568:2013, EU GMP Annex 1 gives guidance LCC (life cycle costing model) in the subject for a number of years. Operational aspects where energy going through the different standards the new British Standard. The energy values for unidirectional airflow velocities, Nigel started by making the point that, • allowing RH to float between wider can be saved include set-back, but some organisations and professional bodies evaluation and implementation process particle concentrations and pressure in the past, pharmaceutical companies limits (30% to 70%) if electrostatic systems to control air volume may be that have or should have (!) produced of the standard sets the Plan-Do-Check- differentials between rooms. Values for have been very profitable and could charge is not a product issue quite complex so that the potential guidance on best practice in energy Act principles of ISO 50001, including these parameters derived from an energy afford to take a “compliance at any energy reduction needs to be assessed management for HVAC in cleanrooms. the selection of an implementation team saving exercise might be in conflict with • reducing cooling costs by using cost” approach. This resulted in over- carefully against the cost and risk of The second talk was given by from the key business functions, in a the guidance values expected by regulators latent cooling for humidity control specification, over-sizing, over-capacity failure. Another operational aspect is to David Fatscher, Head of Market practical cleanroom context. such as the European Medicines Agency and sensible cooling for room and over-performance of facilities, which re-evaluate a facility after it has been Development – Sustainability at BSI. Two annexes give information on and the FDA. BS 8568 recommends that, heat load control, with separate are now increasingly costly to run and running for 12-18 months to check if it David first explained that his role 25 energy saving opportunities specific where such conflicts arise, it is distribution and control loops use excessive amounts of energy. has been over-designed. In many cases covers economic sustainability (profit), to cleanrooms, Annex A being a checklist important to write a justification and Pharmaceutical company profitability, • as an alternative, utilising DX the original design assumptions will environmental sustainability (planet) that can be used to select and prioritise obtain the approval of the regulator. and social sustainability (people) but energy saving opportunities and A later speaker made the point that Case 1: Seven year study of electrical power consumption Case 2: Cleanroom energy usage in an inkjet plant he had been invited to talk about Annex B going into much more depth the strongest opposition to deviations in a UK disc drive plant (2,300 m2 ISO 5 ballroom) (230 m2 ISO 6 ballroom) ISO 50001:2011 – Energy Management on each opportunity. from guidance values is more likely to Millions kWh Energy team Lighting System. ISO 50001 is one of a series of The language of the standard, which come from internal rather than external 8 18% 20% airspeed redn. 500k MJ load Boilers management standards along with is a code of practice, was briefly explained. quality auditors and that it was therefore 7 30% weekend redn. Fans 6% rd reduced to ISO 9001 (Quality management systems) Recommendations are identified by important to include the internal quality 6 3 shift 25% sequential control 53% Chillers 400k MJ 23% and ISO 14001 (Environmental the word ‘should’ with additional auditors in any incentivisation so that 5 2nd shift = 26% energy management systems) that adopt the or background information coming they become stakeholders in the energy 4 3 reduction continuous improvement Plan-Do- in the form of notes. reduction process. 1 shift work Air speed reduction 0.5 to 0.4 m/s = 12% overall 2 Check-Act approach. Compliance with Two examples of energy saving BS 8568 has been put forward as Lighting down to 723 lux = 5% overall 1 500 changes/hour UDAF Make-up air reduction to 8% = 2% overall these standards is seen as evidence of opportunities were given to illustrate the basis for a CEN standard on energy 0 Leak sealing = 1% overall corporate social responsibility and helps how they are treated in the two annexes: reduction in cleanrooms. Yr 1 Yr 2 Yr 3 Yr 4 Yr 5 Yr 6 yr 7 YR 8 Plus 32% boiler reduction manage customer – client requirements. garment requirements and operator The conference continued with Dick Total reduction 20% power plus 30% CO The main components of ISO 50001 are: competence. Garments should be selected Gibbons giving the background to the 2 • An energy audit to maximise containment of people decision to write BS 8568 and some very Figure 1: Case study 1 Figure 2: Case study 2

20 Clean Air and Containment Review | Issue 15 | July 2013 www.cleanairandcontainment.com www.cleanairandcontainment.com Clean Air and Containment Review | Issue 15 | July 2013 21 Conference report Book review corporate social responsibility and energy of an international medical devices airflow reduction risk more supply security are now under pressure manufacturer where the cost of carefully in these areas. Review of ‘Cleanroom Management in and as such companies are looking at electrical consumption was reduced • Challenges from quality must be ways to reduce their energy use, cost from £26,000 pa to £6,000, a saving Pharmaceuticals and Healthcare’ edited addressed – fact / calculation / proof. and emissions. Therefore facility energy of 76%. This was largely achieved by use is now under the spotlight. savings on fan power because of the • Cleaning strategy must be robust. by Tim Sandle and Madhu Raju Saghee Nigel reported that discussions he had cubed relationship with flow. A 50% • Be aware that reduced airflow may had personally with MHRA inspectors reduction on flow gives an 88% James H Filer result in over-sized ductwork and about energy reduction confirmed they reduction in power. The programme low velocities which could be hard are happy for companies whose facilities, was rolled out to other facilities. This is a comprehensive guide to current simulations combines regulatory of cleanroom performance, the chapter to measure. and processes are “under control” to One of Nigel’s last slides gave thinking about cleanrooms, made up of expectations and current best practice on airflow studies is a must-read, as it undertake energy reduction projects – some useful learning points. Here • Reduced pressures in the ventilation 26 separate papers, each by one or more to allow users to ensure their program discusses the criteria for a useful smoke following a risk based, scientific approach. is a selection of these: system may cause some control recognised experts, covering multiple is both compliant and representative of visualisation of the airflows in a clean They are keen to ensure that the UK • You can’t just turn down or switch hardware to operate across a lower aspects of design, commissioning, real process risk, based on actual air process and, most importantly, the pharmaceutical industry is sustainable. off cleanroom HVAC, or make any range, e.g. ΔP sensors and switches. validation and operation of cleanrooms process data. Management of microbial limitations, including the effects of As all the other speakers have argued, uncontrolled change. and isolator systems. The introductory contamination by risk is covered by an selecting an inappropriate type of • DX cooling coils may give HVAC is in many cases the biggest chapters, on the evolution of cleanrooms excellent detailed section which suggests smoke and other common pitfalls. • Ensure you have a strong technical/ temperature control problems opportunity for energy and cost reduction. and the applicable regulations, set the risk management scores based on real The final chapters relate to the quality team including subject under lower flow conditions. Because it may impact the quality compliance background for the whole data, allowing process risk from a range operation of cleanrooms, from selection matter experts. assurance and GMP status of the facility, Nigel’s concluding comment was book. The chapters on design and of sources to be determined. Relevant of clothing to the design of cleaning the energy reduction strategy must be • Assess ventilation performance – that quite often it is possible to find qualification offer extensive checklists examples are given. The chapter on and disinfection programs, and there transparent, risk assessment based, before and after. This is critical the biggest savings in the lower grade to facilitate protocol design, especially environmental monitoring discusses the is a chapter on energy management, scientific, toll-gated (formal reviews to ensure ventilation effectiveness cleanroom ancillary areas, which are useful for anyone looking to commission current debate between industry bodies which is becoming increasingly important before proceeding to further stages), is maintained at reduced airflow. less critical. a new cleanroom. This approach is also regarding environmental monitoring globally, both economically and robust, reliable, repeatable and include Gordon Farquharson brought the used in subsequent chapters on selection limits vs. incidence rates and the pros environmentally. • Utilise calculated airflow requirements a disaster recovery plan. meeting to a close by thanking BSI and validation of isolators for aseptic and cons of different monitoring Overall I found this to be an as a basis for minimum air-changes Nigel gave an example of the and IMechE, who had laid the operations. methods. Especially useful is the section excellent reference book, well suited successful implementation of this • Change areas are notorious for conference on, and also thanking The challenges of aseptic processing discussing how to use (and how not to to those who design, validate, monitor strategy. This was at the facility high microbial counts – consider those who had attended. are well covered, looking at both use) environmental monitoring data. or operate cleanrooms and isolators. current best practice, and the future With airflow visualisation becoming of the science. The chapter on process such an important tool in the verification

22 Clean Air and Containment Review | Issue 15 | July 2013 www.cleanairandcontainment.com www.cleanairandcontainment.com Clean Air and Containment Review | Issue 15 | July 2013 23 News News

Contec introduces Soft Landings* and building Ground-breaking cancer imaging DOP Solutions to new range controls conference cleanroom project wins award provide Bioreset® Cavendish Engineers is set to hold another conference on soft A cutting edge cancer imaging cleanroom project, designed and built by Clean of cleanroom landings and building controls in the autumn at the Institute Room Construction (CRC), has scooped a major award at the annual S-Lab Awards range of Hydrogen of Directors. in Liverpool. disinfectants Following the success of low energy cleanrooms and controlled environment Newcastle University’s Department of Chemistry was named Winner of the Peroxide conference last year, Cavendish have decided to arrange another event, this time Refurbished Laboratory category for its innovative cyclotron design to allow the with HydroPure™ partnering with clients British Land. Cavara Training will be hosting the event. integrated production of pre-clinical and clinical radiopharmaceuticals. The award Generators The conference will bring together facility management specialists and engineers recognises the safest, most successful and most sustainable laboratories which can DOP Solutions Ltd is very pleased to discuss important issues around energy efficiency and the built environment. demonstrate enhanced performance, high levels of user satisfaction and lower levels for product to announce that it now offers a CACR, who covered last year’s conference, is looking forward to this new event. of energy consumption. versatile range of Vapour Phase For information on the conference including how to book a place and latest CRC designed and built the specialist environment to house the Biomark contact areas Hydrogen Peroxide (VPHP) details, please visit www.cavendishengineers.net. Generator, an ultra-compact cyclotron which is the first of its kind in Europe. The Product contact areas require very Generators capable of use in many cyclotron was funded by the university and the largest donation ever made by the specific disinfectants. Not only do *Soft Landings means designers and constructors staying involved with applications including isolators, Sir Bobby Robson Foundation. they need to be sterile, but the level buildings beyond practical completion. This will assist the client during the first safety cabinets and rooms. CRC Director Steve Lawton said: “Clean Room Construction is experienced in of endotoxins has to be extremely months of operation and beyond, to help fine-tune and de-bug the systems, The Bioreset® range includes providing bespoke environmentally sustainable cleanroom solutions for the expanding low. Furthermore, disinfectants and ensure the occupiers understand how to control and best use their buildings. the Smart, Pro and Plus models PET tracer technology market. We are very proud to be associated with this which leave surface residues are BSRIA (The Building Services Research and Information Association) to accommodate budgets and groundbreaking, potentially life-saving and now award-winning project in Newcastle.” not appropriate. applications ranging from a www.crc-ltd.co.uk Contec is launching its new consumption over time manual range of cleanroom disinfectants process to a GMP recipe driven with a disinfectant which is Validair provides additional automated process. The Pro model specifically designed for product is for OEM integration meaning the contact areas. Contec HydroPure™ disaster recovery support VPHP Generator is built in and runs is a blend of stabilised 6% hydrogen through the isolator control panel. A well designed validated monitoring system (VMS) will provide built-in redundancy. peroxide in water for injection (EP) The equipment has been in use This is typically achieved by a well distributed system structure that may include a which, uniquely, is sterilised by around the world for some years buddy stand-by backup for the main system server. gamma irradiation. It has a and so it is an exciting opportunity Validair now offer an additional layer of disaster recovery support, by providing guaranteed endotoxin level of for the UK and Ireland to have secure off-site storage of system configuration details. This information is securely less than 0.25EU/ml*. access to this affordable alternative, and reliably stored on Validair’s network infrastructure. Sporicidal in 15mins, Contec backed by DOP’s flexible approach No matter what disaster event occurs on the client’s IT system, such as fire or HydroPure™ breaks down to water to support. flood damage etc., this configuration backup enables our engineers to restore all and oxygen leaving no surface This support ranges from of the sensor information and alarm settings, without any additional delay. residue. Manufactured using the equipment supply, for those As well as the benefits that aid disaster recovery, this system configuration highest grade of pharmaceutical experienced in the application backup also helps to simplify planned IT maintenance tasks such as server hydrogen peroxide, this product and validation, up to full lifecycle replacements or upgrades. complements the hydrogen peroxide validation including URS, DQ, This additional service is available for both existing and new VMS systems. used in vaporised systems. FAT, SAT, IQ and OQ, with cycle For further information please contact: Validair Monitoring Solutions Ltd, Telephone For more information please development and microbiology 01684 576452. Email [email protected] Website www.validair.com Pharminox Isolation Ltd receives first contact Karen Rossington at for those with less experience. ® [email protected] order for Optima TS Rapid Transfer Ports Consumables such as hydrogen *EU/ml is Endotoxin Units per peroxide and biological indicators The directors of Pharminox Isolation Ltd are delighted to announce the first sale of ml. One EU is of the order of 0.1 ng are also provided. the new Optima TS rapid transfer port range. Launched in the UK and Ireland just depending on the endotoxin. Pharminox to provide VPHP The Bioreset® brand is backed a few months ago, the ‘Optima TS La Calhene-compatible transfer port system has by experience from the principal attracted a lot of interest and further orders are expected in the near future. support to DOP Solutions and manufacturer and from DOP’s Tim Coles, Pharminox director said: “The pharmaceutical industry, in general, Pharminox Isolation Limited is pleased to announce a co-operation agreement with multi-disciplined UK team, tends to be quite conservative and sales of new capital equipment often take quite a DOP Solutions Limited to provide technical support on VPHP application, design, which includes collaboration with long time, sometimes years, to materialise. We are therefore pleased to make the installation, commissioning, gassing cycle development and maintenance – both Pharminox Isolation Ltd, to ensure first sales after what might be considered a short time since the initial launch. We planned and unplanned. This will help DOP provide a comprehensive service to the that customers have available are also able to offer an option of an annual maintenance contract with the product growing number of VPHP users in the pharmaceutical and healthcare industry. everything that they need for their which means that our clients don’t have to worry about remembering the service Tim Triggs, a Director of DOP Solutions said, ‘We are delighted that Pharminox hydrogen peroxide gassing process. dates – we’ll do that for them.” will join our team in this specialised area. Their experience and expertise is key to Email [email protected] , Jon Nottingham, ‘Optima TS director said “We have worked closely with Pharminox providing our customers with a complete support package.’ +44 (0)1462 676446, or www. and are very satisfied with their active marketing and sales venture. We expect Tim Coles, Managing Director of Pharminox said, ‘We have worked with DOP dopsolutions.com or www.bioreset.it Pharminox to become one of our largest and most effective agents in the future.” on a number of projects over many years and it is exciting to be able to provide DOP This first UK order for Optima equipment is to be fitted to isolators built by CTS with additional VPHP expertise through our long standing experience in this area.’ Ltd, and destined for a large pharmaceutical company. Website: www.pharminox-isolation.com Website: www.pharminox-isolation.com

24 Clean Air and Containment Review | Issue 15 | July 2013 www.cleanairandcontainment.com www.cleanairandcontainment.com Clean Air and Containment Review | Issue 15 | July 2013 25 Advertisements Advertisement

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28 Clean Air and Containment Review | Issue 14 | April 2013 www.cleanairandcontainment.com www.cleanairandcontainment.com Clean Air and Containment Review | Issue 14 | April 2013 29 Events and training courses Events and training courses/Vital vocabulary

Events

Dates Event Organiser PHSS

2013 Dates Event Location October 2-4 16th GERPAC Conference/11th European GERPAC Conference, GERPAC September 17-19 PHSS and UHOVI Quality Assurance GMP and GDP Principles Nr. Cardiff, UK Giens Peninsula, France

October 9-10 PHSS Annual Members Conference & Exhibition: PHSS Academy for Cleanroom Testing* Bio-contamination Control and Monitoring guidance Dates Event Location and best practice, Crewe, UK September 10 HEPA Filter Testing Letchworth, UK October 22-23 Cleanzone, Frankfurt, Germany Messe Frankfurt September 11-12 Safety Cabinet Testing Letchworth, UK October 24 PHSS India Conference, Hyderabad, India PHSS December 2 Cleanroom Technology Letchworth, UK November 11-14 2013 IEST Fall Conference: Gateway to Enhancing your Education, IEST St Louis, Missouri December 3 Airflow Testing Letchworth, UK November 13-14 European Isolator & RABS Conference and Exhibition 2013, PHSS December 4 HEPA Filter Testing Letchworth, UK Dublin, Ireland December 5 Particle Counting – Introduction Letchworth, UK 2014 * The Academy for Cleanroom Testing (ACT) is a part of DOP Solutions, a commercial company May 13-16 ESTECH 2014, the 60th Annual Technical Meeting of IEST, IEST that provides cleanroom testing and monitoring equipment, and training San Antonio, Texas October 13-17 ICCCS 2014 – International Symposium on ICCCS Contamination Control, Seoul, Korea

Training courses V is for …

IEST (Institute of Environmental Sciences and Technology) Vocabulary Validation master plan (VMP) Virtual impactor The body of words used in a particular A coordinating document describing Instrument to separate the particle used Dates Event Location language or in a particular sphere the validation of a total system comprising [sic] sizing by inertial force to collide on July 23-24 Risk Assessments for Cleanrooms and Arlington Heights, of activity. individual pieces of equipment the hypothetical (virtual) surface. Controlled Environments Illinois, USA Concise Oxford English Dictionary and/or processes. Note: Large particles pass through Pharmaceutical Isolators, the surface into a stagnant volume and September 25 Aerosol Photometers – The Gold Standard in Arlington Heights, Validation Pharmaceutical Press, 2004 small particles deflected with the bulk HEPA Filtration Testing Illinois, USA The accumulation of documentary of the original airflow. evidence to show that a system, equipment Viable particle ISO 14644-6:2007: Vocabulary ICS (Irish Cleanroom Society) or process will consistently perform as Particle that consists of, or supports, Editor’s note: At least this definition expected to a predetermined specification, one or more live organisms. makes the point that small particles Dates Event Location and will continue to do so throughout ISO 14644-6:2007: Vocabulary follow the airstream and large particles November 5-7 CTCB-I* Certification & Validation Course & Examination Swords, Co Dublin, Ireland its life cycle. tend to carry straight on when the CTCB-I*/ICEB* Certification It establishes documented evidence Viable unit (VU) airstream changes direction. which provides a high degree of assurance One or more viable particles that December 2 CTCB-I* Technology Advanced Course & Examination Letchworth, UK that a specific process will consistently are enumerated as a single unit. Vortex ICEB* Accredited Course ICEB* Certification produce a product meeting its Note: When viable units are A region within a fluid where the flow * ICEB and CTCB-I certifications are explained on the ICS, ICEB and CTCB-I websites predetermined specifications and enumerated as colonies on agar media, is mostly a spinning motion about an quality attributes (GAMP/FDA). it is common usage to name them colony imaginary axis, straight or curved. Safety Ventilation Pharmaceutical Isolators, forming units (CFU). One CFU may Wikipedia Pharmaceutical Press, 2004 consist of one or more VU. Dates Event Location Editor’s note: There are numerous ISO 14644-6:2007: Vocabulary September 10-12 CTCB-I Certifiering CTCB-I Associate Level Göteborg, Sweden definitions of validation including those Editor’s note: The last sentence in ISO 14644-6:2007: Vocabulary and in of the note is rather odd and spoils September 10-12 CTCB-I Certifiering CTCB-I Professional Level Göteborg, Sweden the ISPE Glossary, but the one given the whole definition! including Exam here is one of the more comprehensive.

30 Clean Air and Containment Review | Issue 15 | July 2013 www.cleanairandcontainment.com www.cleanairandcontainment.com Clean Air and Containment Review | Issue 15 | July 2013 31