The harmonisation of standards, sustainability and nanotechnology were key topics at the 2nd Annual Cleanrooms Conference held by the British Standards Institution in June. Susan Birks reports.
All cleanroom operators, whether in a new build or an existing facility, need to be aware of the current harmonisation of the ISO standards for cleanrooms and to have prior notice of proposed changes so that they can plan ahead. The BSI’s 2nd Annual Conference on Cleanrooms in June not only provided an update on future ISO proposals and revisions, but also discussed issues of cleanroom sustainability and the rise in new nano-technologies.
Gordon Farquharson, principal consultant, Bovis Lend Lease, in his overview of recent legislative changes to ISO 14644 parts 1-10, noted that work would start in early autumn on new ISO standards for airborne microbiological contamination and on a microbiological standard for surfaces.
When all the above work is finished, he said, the result will be that ISO classifications will exist for:
1. Airborne particulate cleanliness;
2. Surface particulate cleanliness;
3. Airborne (chemical) molecular cleanliness;
4. Surface chemical cleanliness;
5. Airborne viable cleanliness and
6. Surface viable cleanliness.
Meanwhile, some 10 years after their introduction, the review of parts 1 & 2 of ISO 14644 (Classification by airborne particles and Monitoring for compliance) is already underway and revisions were posted in January this year for industry comment. The ISO TC 209 Working Group 1 is due to meet in September to consider the comments made and Farquharson said we could see revised standards published by mid 2010.
Farquharson reviewed some of the proposed changes to ISO 14644 parts 1 & 2, the main one being a change in calculating cleanroom classifications. This is currently calculated using a formula but, in future, will be identified through an ISO 14644-1 Classification table, with the use of a formula for intermediate classes. Farquharson suggested that this change was unlikely to have a major impact on business and could help to prevent poor selection by companies in terms of facility size versus class.
However, there are still some issues with the proposed revisions in terms of statistical calculation that remain to be ‘ironed out’, said Farquharson, and companies might have to redefine their classification sampling and data evaluation – one of the implications of the revision could be that more sampling is required in small- and medium-sized zones.
Annex 1 in practice
AstraZeneca’s sterile manufacturing specialist, Tim Eaton shared his experiences in implementing Annex 1 of the EU Guide to Good Manufacturing Practice (GMP) at the company’s plant in Macclesfield, UK. This plant is used for the manufacture of a parenteral implant and has two aseptic manufacturing facilities and some 15 cleanrooms, with EU grade A, B and C areas.
Annex 1 of the EU Guide to GMP was published in November 2008 and came into operation on 1 March, 2009. It includes recommendations on the standards of environmental cleanliness of cleanrooms. Eaton found several issues arose when following the new guidelines.
One of the changes the EU GMP guide has introduced is the need to monitor particles of >5µm, which is not required in the US. Eaton pointed out that the values for the maximum number of permitted particles/m3 for the >5µm range allowed in operation is different in the EU and harmonised US versions of the ISO guidelines (see table 1). In grade B and C areas it is 2,900 under Annex 1 and 2,930 in the US harmonised ISO guidelines. The difference is more significant in the grade A areas where the maximum permitted is 20 vs 29 in the US. This means one could end up with two different cleanroom classification numbers (5 and 4.8) for the same area, he said.
He also pointed out that under the new particle monitoring requirements for Annex 1, the old manifold particle counting systems are no longer suitable. AZ has installed 60 individual counters with a sample rate of 1ft3/min and a sample volume of 1ft3 monitoring particles >0.5µm and >5µm continuously and simultaneously. However, the company soon found that it had problems in non-unidirectional airflow areas with the use of hand disinfection aerosols, which were producing airborne particle counts above the permitted levels for ISO 5.
The sprays were used for local disinfection and the particles forming the aerosolised mist were meant to evaporate in a matter of seconds. But that was not happening, instead they were remaining in the air causing high counts and triggering alarms.
After much research, the company found that to prevent IPA particles reaching the data collection point (DCP) it had to identify ‘safe’ spray zones and also moved to a hand spray with a jet delivery rather than a mist, or to pre-wetted wipes.
Variable results
When an autoclave door malfunctioned and an engineer had to be brought in to fix it, Eaton also found that continuous monitoring provided some interesting information. It showed that during maintenance, the >0.5µm counts showed a large rise and ratios were relatively consistent over the period of intervention. However, the >5µm counts had such low values that counting was difficult and the results were very variable.
As a result of this and other recent experiences with monitoring >5µm counts Eaton suggested that monitoring the >0.5µm particles provides “more meaningful and consistent information than monitoring >5µm particles and that monitoring both sizes in the same area may not add any value.”
The topical issue of energy-saving in cleanrooms was addressed by Tim Trigg of DOP Solutions. The recent hike in fuel prices and downturn in the economy has forced businesses to look seriously at cutting operating costs while adhering to ever stricter standards. “If you can influence the energy usage in your facilities, now is the time to do it,” Trigg suggested, as it makes a noticeable difference to the bottom line.
Savings could be made quickly and simply by replacing faulty ductwork and preventing leakages. “Poorly fitting housings account for 10% of cleanroom energy wastage,” said Trigg. He also suggested it was important to use the “best fit” size of facility, as smaller rooms will save energy over time. He added that companies should always ensure they use the class of filter required for the job and not something higher.
“ULPA filters are creeping in from the electronics sector into pharma cleanrooms but they are not necessary,” he said.
Finally, something that is often overlooked but that can immediately save wasted energy, is the removal of redundant equipment. Among the case studies Trigg presented was an (un-named) non-silicon semi-conductor wafer producer with a 50,000ft2 (4,645m2) cleanroom at ISO Class 5 which made a $100,000 p.a. cost reduction by reducing the fan speed on its HVAC system.
Experimental air change rates
Trigg explained that staff at this facility carried out a series of air change rate experiments and used a grid of 25 remote particle counters to collect results every minute. The company lowered the fan speeds and monitored particle counts until they were below the specification of the ISO Class 5. It then carried out experiments in which the fan speed was increased to achieve a zone for safe operation, and the situation within this zone was then monitored for eight weeks.
Remote monitoring devices were also installed in process equipment for yield enhancement. In addition the company installed a 40-point sequential particle monitoring system. The result was a 5% reduction of fan speed, which led to a six figure annual cost reduction with no effect on product quality or yield. The return on investment of the monitoring system was achieved within the first year.
The lesson, said Trigg, is that “air change rates are key but you need to put time and effort into collecting the data to show that the changes are safe.”
Another option is to turn down HVAC systems when facilities are not in use. For example, facilities that do not have production runs over the weekend have found that they can reduce the number of air changes over this period of inactivity, and then ramp them up again before operations restart on the Monday. One company was able to make a 61% energy reduction, which equates to an annual cost-saving of €97k, by shutting down the HVAC system in its warehouse when the facility was not in use (see Figure 1). While total shutdown may not be possible in critical facilities such as a cleanroom, the principle of “reduce when you can” still applies.
He also suggested that companies should look at the latest HVAC filter systems with particle pre-ionisation. Pre-ionisation of the particles by running energy through a carbon brush can improve filter operation such that an F6 filter has the performance of an F7 filter. In addition, the lower starting pressure of the filters increases their lifespan, reducing costs over long periods.
Spending to save
A little more spent on initial filter costs could bring large savings in energy costs, Trigg said. For example, with today’s use of widespread particle monitoring providing large amounts of report data, “smart buildings” could use low energy filtration systems (LEFS) that can be increased to protect a building when there is a particular environmental problem, such as a smog, and which can then be turned down again when the threat has passed.
Another simple option proposed by Trigg was the use of lighting motion sensors in facilities that turn the lights off when the facilities are not being used. Finally, he suggested energy generation from renewable sources should also be considered. He cited one pharmaceutical company with a five-acre facility that is currently using a wind turbine to provide 75% of its energy.
The conference closed with a presentation by Professor Michael Kraft from Southampton University’s department of Electronics and Computer Science (ECS). He outlined some of the research projects being carried out at the Mountbatten Building in Southampton, UK. This building provides a world-class interdisciplinary cleanroom to meet the research needs of the ECS and the Optoelectronics Research Centre and covers research in nanotech, bio-nanotech and photonics.
Kraft outlined how the ability to visualise and operate at the nano scale means many novel micro-electro-mechanical system (MEMS) fabrication processes are on the horizon. A major problem when operating at this scale is not only the elimination of airborne contaminants but also vibration, and this requirement makes many current cleanroom practices and equipment non-viable in fabs of the future. New standards and test methods will need to be evolved to meet the new nanotech era, which is advancing so rapidly.
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