Cleanroom vs. Isolator Concept Performance and cost comparison. Guy Turner, General Manager Bioquell Asia Pacific

Transcription

1 Cleanroom vs. Isolator Concept Performance and cost comparison Guy Turner, General Manager Bioquell Asia Pacific Slide 1 PharmOut 2017

2 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 Slide 2 PharmOut 2017

3 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 3 PharmOut 2017

4 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? Slide 4 PharmOut 2017

5 Performance comparison - qualitative The spectrum of protection Slide 5 PharmOut 2017

6 Clean-room or isolator? Comparison of infrastructure requirements Room classification Overall surface for 1 workstation Clean-room Grade B ISO 6 for LFC ISO 7 for BSC Test room 15 m 2 grade B Material and Personnel Air Locks m 2 Twice the surface Isolator Unclassified (restricted access) 20 m 2 Gowning Required Not required Gowning time (for each operator access) according to GMP and ISO HVAC requirements Energy consumption (per year) in ISO 6: 20 minutes in ISO7: 10 minutes ~ 10 min each access 20% loss of effective operator time 7,800 m 3 /hr 8.7 times more $ 23, times more 3~5 minutes 900 m 3 /hr $ 8,600 Slide 6 PharmOut 2017

7 Clean-room or isolator? Risks of assay contamination Clean-room Positive swabs 1.3% 6.8 times bigger risk Isolator 0.19% In case of power failure Classification breach Classification maintained Process control Sterility Assurance Level (claimable) Finger dab failures (according to literature) Alcohol disinfection Manual By SOP HPV biodecon Automated Monitored 3 log reduction 6 log reduction 3-4% times bigger risk < 0.1% Sporicidal No Yes Slide 7 PharmOut 2017

8 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) Slide 8 PharmOut 2017

9 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) Slide 9 PharmOut 2017

10 Clean-room or isolator? Costs comparison Application: sterility testing Clean-room T. Krebsbach publication Oct 2012 (sterility testing, Europe) Investment for rooms, air locks and enclosure (equipped) Annual operating cost, excluding labour cost Low $ 250,000 High $ 320,000 Isolator Low $ 250,000 High $ 320,000 Equal with an isolator worth $200~250,000 $ 60,450 $ 16,640 72% cheaper Slide 10 PharmOut 2017

11 Clean-room or isolator? Costs comparison Application: sterility testing Clean Room Isolator LFC Grade B Isolator Unclassified MAL PAL Grade C Slide 11 PharmOut 2017

12 Clean-room or isolator? Costs comparison Application: sterility testing Clean-room T. Krebsbach publication Oct 2012 (sterility testing, Europe) Investment for rooms, air locks and enclosure (equipped) Annual operating cost, excluding labour cost Low $ 250,000 High $ 320,000 R. Gardino case study 2007 (sterility testing, USA) Annual cost for consumables (gowning and disinfectants) Isolator Low $ 250,000 High $ 320,000 Equal (biggest cost here is the isolator) $ 60,450 $ 16,640 72% cheaper - $ 20,000 cheaper Labour impact work hours saved per year per workstation (21% effective operator time) Down time upon yearly maintenance break 2 weeks extra per year - Slide 12 PharmOut 2017

13 Clean-room or isolator? Cost comparison Application: small scale aseptic operations Clean-room B. Dekyndt publication Feb 2014 (hospital pharmacy, Europe) Investment for infrastructure and equipment Yearly depreciation Annual operating cost, excluding labour cost Panasonic case study (cell processing, Japan) Nominal annual budget, excluding labour cost Isolator $ 42,613 $ 30,229 29% cheaper $ 71,073 $ 49,836 30% cheaper $ 91,600 $ 60,100 34% cheaper Slide 13 PharmOut 2017

14 Clean-room or isolator? Cost comparison Application: large scale aseptic filling Clean-room D. Sierakowski publication Feb 2012 (Aseptic filling, France) Total investment for aseptic filling suite equipped, ready for operation Annual operating cost, including labour cost Isolator $ 5,970,000 $ 6,930, % more expensive $ 989,000 $ 331,000 67% cheaper Jacobs Engineering case study Nov 2009 (Aseptic filling, USA) Total investment for whole facility, ready for operation Annual operating cost, including labour cost Overall investment and operating cost after 10 years of operation $ 36,710,000 $ 45,572, % more expensive $ 4,196,000 $ 2,091,000 50% cheaper $ 78,870,000 $ 66,942,000 15% cheaper Slide 14 PharmOut 2017

15 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) Slide 15 PharmOut 2017

16 Let s ask again 1. Which setup is the best to reduce the risk of a false positive? 2. Which setup is most economical? Slide 16 PharmOut 2017

17 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. Slide 17 PharmOut 2017

18 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 18 PharmOut 2017

19 Sterility testing in Isolator Semi- Continuous process Gassing Sterility Testing Test Pump Slide 19 PharmOut 2017

20 Sterility testing in Isolator Semi- Continuous process Test Pump 20 Slide 20 PharmOut 2017

21 Sterility testing in Isolator Timeline Traditional Load Decontamination Processing Semi-Batch Semi-Continuous Processing Slide 21 PharmOut 2017

22 Choosing your Grade A Environment Consider all the options: LAF in Grade B room Isolator Isolator Slide 22 PharmOut 2017

23 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 Slide 23 PharmOut 2017

24 References T. Krebsbach publication (sterility testing, Europe) R. Gardino case study (sterility testing, USA) B. Dekyndt publication (hospital pharmacy, Europe) Panasonic case study (cell processing, Japan) D. Sierakowski publication Feb 2012 (Aseptic filling, France) Jacobs Engineering case study (Aseptic manufacturing, USA) Finger dab failures M. Oldcorne Positive swabs H. Van Doorne Article in French: Comparaison des couts. Test de stérilité: salle propre ou isolateur in Salle Propres N 81 - Oct Presentation video in English: Isolator Quest: Perseverance necessary to find the right fit in Contamination Control 3: Economic assessment of aseptic compounding rooms in hospital pharmacies in five European countries In Journal of Oncology Pharmacy Practice, Feb Article in French: Répartition aseptique sous isolateur ou open RBAS? Evaluation des couts totaux: investissement et fonctionnement In La Vague N 33 - Feb A Comparison of Capital and Operating Costs for Aseptic Manufacturing Facilities Using Conventional Clean Room Technology, Restricted Access Barriers (RABS), or Isolation Technology Presented that the ISPE Annual meeting San Diego USA - Nov Considerations for an ideal hospital aseptic pharmacy Hospital pharmacy Europe, 64:45 47, Industrial manufacture of parenteral products in The Netherlands. A survey of eight years of media fills and sterility testing PDA J Pharm Sci Technol Jul-Aug;52(4): Slide 24 PharmOut 2017

25 ANY QUESTIONS? Slide 25 PharmOut 2017