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Slide 1 © PharmOut 2017
Cleanroom vs. Isolator ConceptPerformance and cost comparison
Guy Turner, General ManagerBioquell Asia [email protected]
Slide 2 © PharmOut 2017
Requirements for Sterility Testing Environment
• Sterility testing is a key step in the release of sterile products
• To ensure a correct result the procedure must be performed under aseptic conditions
• The various guidelines point to Sterility testing being performed in a Grade A environment
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Achieving a Grade A Environment
To meet these requirements 2 set-ups are possible: BSC or LFC in clean-room or isolator.
LFC/BSC in Grade B Cleanroom Isolator
Slide 4 © PharmOut 2017
What is this presentation about?
This presentation is about answering these 2 questions :
1. Which setup is the best to reduce the risk of a false positive?
2. Which setup is most economical?
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Performance comparison - qualitativeThe spectrum of protection
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Clean-room or isolator?Comparison of infrastructure requirements
Clean-room Isolator
Room classification Grade BISO 6 for LFCISO 7 for BSC
Unclassified (restricted access)
Overall surface for1 workstation
Test room 15 m2 grade BMaterial and Personnel Air
Locks 20-30 m2
Twice the surface
20 m2
Gowning Required Not required
Gowning time (for each operator access) according to GMP and ISO
in ISO 6: 20 minutesin ISO7: 10 minutes
~ 10 min each access20% loss of effective
operator time
3~5 minutes
HVAC requirements 7,800 m3/hr8.7 times more
900 m3/hr
Energy consumption(per year)
$ 23,4002.7 times more
$ 8,600
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Clean-room or isolator?Risks of assay contamination
Clean-room Isolator
Positive swabs 1.3%6.8 times bigger risk
0.19%
In case of power failure Classification breach Classification maintained
Alcohol disinfection HPV biodecon
Process control ManualBy SOP
AutomatedMonitored
Sterility Assurance Level (claimable)
3 log reduction 6 log reduction
Finger dab failures (according to literature)
3-4%30-40 times bigger risk
< 0.1%
Sporicidal No Yes
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Why the operator needs to be isolated from the process?
Particle generation for one person per minute according to activity (Takasago Thermal Engineering Co, Fiski)
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Why the operator needs to be isolated from the process?
Airborne particle count inside a barrier enclosure in a clean-room and inside the same clean room (Abuzeid, Microcontamination Jul 1993)
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Clean-room or isolator? Costs comparisonApplication: sterility testing
Clean-room Isolator
T. Krebsbach publication Oct 2012 (sterility testing, Europe)
Investment for rooms, air locks and enclosure(equipped)
Low $ 250,000High $ 320,000
Low $ 250,000High $ 320,000
Equal with an isolator worth $200~250,000
Annual operating cost, excluding labour cost
$ 60,450 $ 16,64072% cheaper
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Clean-room or isolator? Costs comparisonApplication: sterility testing
Clean Room Isolator
LFC Isolator
10 100
Grade B
MAL PAL
Grade C
Unclassified
120100120
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Clean-room or isolator? Costs comparisonApplication: sterility testing
Clean-room Isolator
T. Krebsbach publication Oct 2012 (sterility testing, Europe)
Investment for rooms, air locks and enclosure(equipped)
Low $ 250,000High $ 320,000
Low $ 250,000High $ 320,000
Equal (biggest cost here is the isolator)
Annual operating cost, excluding labour cost
$ 60,450 $ 16,64072% cheaper
R. Gardino case study 2007 (sterility testing, USA)
Annual cost for consumables (gowning and disinfectants)
- $ 20,000 cheaper
Labour impact - 372 work hours saved per year per workstation
(21% effective operator time)
Down time upon yearly maintenance break
2 weeks extra per year -
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Clean-room or isolator? Cost comparisonApplication: small scale aseptic operations
Clean-room Isolator
B. Dekyndt publication Feb 2014 (hospital pharmacy, Europe)
Investment for infrastructureand equipmentYearly depreciation
$ 42,613 $ 30,22929% cheaper
Annual operating cost, excluding labour cost
$ 71,073 $ 49,83630% cheaper
Panasonic case study (cell processing, Japan)
Nominal annual budget, excluding labour cost
$ 91,600 $ 60,10034% cheaper
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Clean-room or isolator? Cost comparisonApplication: large scale aseptic filling
Clean-room Isolator
D. Sierakowski publication Feb 2012 (Aseptic filling, France)
Total investment for aseptic filling suite equipped, ready for operation
$ 5,970,000 $ 6,930,00016 % more expensive
Annual operating cost, including labour cost
$ 989,000 $ 331,00067% cheaper
Jacobs Engineering case study Nov 2009 (Aseptic filling, USA)
Total investment for whole facility, ready for operation
$ 36,710,000 $ 45,572,00024 % more expensive
Annual operating cost, including labour cost
$ 4,196,000 $ 2,091,00050% cheaper
Overall investment and operating cost after 10 years of operation
$ 78,870,000 $ 66,942,00015% cheaper
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However... clean-room can be more suitable for these situations
• Very high throughput (> 40 tests per day and above)
• Testing of LVP (large volume parenterals)
• Testing of samples in packaging permeable to Hydrogen Peroxide (eg medical devices)
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Let’s ask again…
1. Which setup is the best to reduce the risk of a false positive?
2. Which setup is most economical?
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Sterility testing in Isolator – Traditional Process
• To ensure a EU GMP Grade A environment gaseous decontamination methods are often used in isolators.
• Traditionally these were slow. Which means sterility test becomes very much a batch process.
• A larger isolator = greater daily throughput.
• So typically isolators used for sterility testing are large to manage the volume of samples than need to be processed.
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Semi-batch or semi-continuous concept
• Use of smaller, and in some cases modular, isolators
• Fast decontamination allows batch sizes to be reduced
• Multiple smaller batches are then processed in the same day to achieve a similar throughput as the traditional method
Slide 19 © PharmOut 2017
Sterility testing in Isolator – Semi-Continuous process
Test Pump
Gassing Sterility Testing
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Test Pump
Sterility testing in Isolator – Semi-Continuous process
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Sterility testing in Isolator – Timeline
Load Decontamination Processing
Traditional
“Semi-Batch”
Semi-Continuous
Processing
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Choosing your Grade A Environment
IsolatorLAF in Grade B room Isolator
• Consider all the options:
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Summary
• The reduction in risk with using an isolator for sterility testing is clear. The economics are more complex.
• Remember to compare the complete costs of both setups and not just the equipment costs
• Use of new isolator technologies concepts can help to reduce footprint and capital equipment costs for a comparable throughput
• For existing facilities the picture is not so clear but don’t forget to consider return on investment due to reduced running costs
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ReferencesT. Krebsbach publication (sterility testing, Europe)
Article in French: Comparaison des couts. Test de stérilité: salle propre ou isolateurin Salle Propres N° 81 - Oct 2012 http://www.processpropre.fr/revue/ficherevue/?id=29Presentation video in English: http://www.youtube.com/watch?v=V2L4ETF_RcU
R. Gardino case study (sterility testing, USA)
Isolator Quest: Perseverance necessary to find the right fitin Contamination Control 3:16-19 – 2007http://pharmaceuticalvalidation.blogspot.sg/2010/01/isolator-quest.html
B. Dekyndt publication (hospital pharmacy, Europe)
Economic assessment of aseptic compounding rooms in hospital pharmacies in five European countriesIn Journal of Oncology Pharmacy Practice, Feb 2014http://www.ncbi.nlm.nih.gov/pubmed/24519187
Panasonic case study (cell processing, Japan)
http://us.sanyo.com/dynamic/product/Downloads/CPWS_Brochure_v2_LOW-17147437.pdf
D. Sierakowski publication Feb 2012 (Aseptic filling, France)
Article in French: Répartition aseptique sous isolateur ou open RBAS? Evaluation des couts totaux: investissement et fonctionnementIn La Vague N°33 - Feb 2012http://www.calameo.com/books/0027705829ef318ef1ad3
Jacobs Engineering case study (Aseptic manufacturing, USA)
A Comparison of Capital and Operating Costs for Aseptic Manufacturing Facilities Using Conventional Clean Room Technology, Restricted Access Barriers (RABS), or Isolation TechnologyPresented that the ISPE Annual meeting San Diego USA - Nov 2009 http://www.pharmamanufacturing.com/assets/wp_downloads/pdf/Jacobs_10.pdf
Finger dab failuresM. Oldcorne
Considerations for an ideal hospital aseptic pharmacyHospital pharmacy Europe, 64:45–47, 2012.http://www.hospitalpharmacyeurope.com/featured-articles/considerations-ideal-hospital-aseptic-pharmacy
Positive swabsH. Van Doorne
Industrial manufacture of parenteral products in The Netherlands. A survey of eight years of media fills and sterility testingPDA J Pharm Sci Technol. 1998 Jul-Aug;52(4):159-64.http://www.pharmtech.com/pharmtech/data/articlestandard//pharmtech/152005/155377/article.pdf
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ANY QUESTIONS?
