Cleanrooms may be considered as a ‘system’, with people typically accounting for the largest source of airborne particulate contamination and the cleanroom’s air handling system designed to remove this contamination. The balance between incoming contamination and the removal of contamination is designed to deliver the required air quality of the cleanroom ‘system’ to meet the requirements of the processes.
Why is data integrity important? Routine monitoring data can be trended to detect any deviations or tendency to drift towards an out-of-specification (OOS) situation that may threaten product quality. However, if the data integrity cannot be relied upon, either through frequent manual data transcription errors, or through poor particle counter-to-counter measurement issues, then the benefit of data trending can be called into question.
Improvements in data integrity are encouraged by the regulatory expectations of EU GMP Annex 11 and the FDA’s 21 CFR part 11 documents, driving users to seek more robust and secure methods of collecting and storing portable particle counter data. Manual data transcription from particle counter paper printouts into data trending and archiving systems is no longer an option.
Poor data integrity can lead to false data points that seem to indicate an OOS event. The resulting root cause investigation may not be able to identify that there had been a transcription error or that the error was due to poor particle counter performance and the investigation may be left unresolved.
Poor data and transcription errors prevent energy savings being maximised
Barrier to energy savings
The cleanroom air handling systems are typically one of the top three energy consumers on a pharmaceutical production site.1 Many cleanroom users are starting to look for potential energy savings from their cleanrooms to help meet carbon footprint reduction targets and also to help reduce operating overhead costs.
One area for energy savings under consideration is controlling the air handling systems to adjust cleanroom air change rates to match the varying contamination loading, especially in cleanrooms that were over-engineered in their original design. However, if the cleanroom monitoring data cannot be relied on, then these improvements in energy savings are difficult to realise with any confidence that quality will be maintained.
Equally, the maximum energy savings may not be realised, leaving cleanroom owners with excessive margins of air handling system over-performance and energy consumption due to lack of ability to get to the real performance data.
Cleanrooms as a system
To improve confidence in counter-to-counter performance, the revised ISO 14644-1 document,2 planned for publication in 2014, will provide a reference to ISO 21501-4, Determination of particle size distribution — Single particle light interaction methods — Part 4: Light scattering airborne particle counter for clean spaces,3 to direct the reader to a standardised test method for particle counter calibration.
ISO 21501-4 was originally published in 2007 and first appeared in the draft of the revised ISO 14644-1 published in December 2010. By the time the new ISO 14644-1 document is released in 2014, industries using portable particle counters will have had seven years’ notice to comply with ISO 21501-4 calibration method and to upgrade any non-compliant particle counters.
Before the publication of ISO 21501-4 there were no internationally recognised calibration standards for airborne particle counters, resulting in widely varying performance from particle counting instrumentation. Since 2007, most international manufacturers of particle counters designed for use in ISO 14644 applications have improved their particle counter designs where necessary so that they can now meet the more demanding expectations of this new calibration standard. Cleanroom users can now achieve a much higher level of confidence that their cleanrooms are delivering the required level of quality controlled environment for their processes.
In applications where large numbers of sampling locations with different sampling configurations are involved, manual configuration of the particle counter set-up at each location can lead to errors and the resultant unreliable data.
Advances in particle counter technology now allow the user to select the correct pre-programmed sub-set of sampling recipes and location labels through user log-on. So an operator carrying out a routine monitoring programme can simply log-on to the particle counter to be offered only the sub-set of the entire pre-programmed recipe library pertinent to their daily routine. Equally, a cleanroom classifier can utilise this functionality to enter a cleanroom suite dedicated log-on to be offered the appropriate sub-set of the entire pre-programmed recipe library pertinent to that specific cleanroom suite.
Manual processes associated with particle counters can take up to 20% of the working day
Paper trails and manual data
Most portable particle counters used for cleanroom classification or routine monitoring programmes provide particle count data reports via on-board thermal printers. Cleanroom classifiers and those people carrying out routine environmental monitoring programmes then have to tear off this paper and transfer it to a secure format in preparation for the batch release file and for archiving. However, thermal paper printouts are not stable and will become illegible over time.
So the particle counter operator then has to stick the printouts onto paper and scan them in, whether as a photocopy, or into a PDF file. To transfer the data from the paper printouts into the data archiving/data trending system, the particle counter operator then has to manually type the data in. Each of these steps is time-consuming and error-prone, with some particle counter user teams reporting that they spend up to 20% of their working day photocopying and manually entering data.
New advances in particle counter technology have allowed the elimination of paper printouts and manual data entry. Instead the new range of ‘paperless’ particle counters export the particle count data in secure PDF format for electronic batch release files and archiving and simultaneously in a format ready for Excel so that the data can be trended.
Going paperless removes the need for manual paper processing and data transcription, freeing up to 20% of operator time, while at the same time meeting the requirements of EU GMP Annex 11 and FDA 21CFR part 11 for data integrity.
As an added bonus, data transcription errors are eliminated and data can be reliably used for trending.
Paperless technology resolves data integrity issues and saves time
In conclusion, a recent FDA warning letter highlighted large gaps in environmental monitoring data for a manufacturer of a sterile drug product. Paperless particle counter technology removes manual data transcription errors and can save up to 20% of operator time, leading to increased efficiencies and cost savings, while helping to eliminate data gaps.
Particle counter accuracy and counter-to-counter reproducibility through ISO 21501-4 calibration improves confidence in particle counter trending data. Combined, paperless technology and ISO 21501-4 calibration deliver overhead efficiencies, improved data quality control and support initiatives to reduce energy consumption and carbon footprint.
Tony Harrison is a subject matter expert to the UK BSI cleanroom mirror group and one of the UK subject matter experts on ISO Technical Committee 209 Working Group 01 tasked with revising ISO 14644-1 and -2. He is employed by Hach as a Compliance and Applications Specialist.
1. Energy Efficiency Improvement and Cost Saving Opportunities for the Pharmaceutical Industry. Energy Analysis Department, Environmental Energy Technologies Division, Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720 March 2008. Ref: LBNL-57260-Revision.
2. ISO 14644-1:1999(E) Cleanrooms and associated controlled environments—Part 1: Classification of air cleanliness May 1, 1999. ISO Case Postale 56, CH-1211 Genève 20, Switzerland.
3. ISO 21501-4 Determination of particle size distribution — Single particle light interaction methods — Part 4: Light scattering airborne particle counter for clean spaces 2007. ISO Case Postale 56, CH-1211 Genève 20, Switzerland.