Air quality control in reproductive laboratories: How important it is and how to implement, measure and control
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Air quality control in reproductive laboratories: How important it is and how to implement, measure and control
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Air quality control in reproductive laboratories: How important it is and how to implement, measure and control
- 1. Air quality control in reproductive laboratories How important it is and how to implement, measure and control 4th International Congress - Academy of Clinical Embryologists 18-20 September 2015, Kochi INDIA Sandro C. Esteves, MD., PhD. Medical & Scientific Director, ANDROFERT Andrology & Human Reproduction Clinic Campinas, BRAZIL
- 2. Outline 1. Importance of air quality in IVF 2. How to implement 3. How to measure and control ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 2 2015 ANDROFERT
- 3. Morbeck, JARG 2015; 32(7):1019-24. IMPORTANCE OF AIR QUALITY IN IVF ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 3 2015 ANDROFERT
- 4. IMPORTANCE OF AIR QUALITY IN IVF 25.0% 32.7% 14.1% 43.1% Miscarriage rate CPR General IVF Population (N=468) Cleanroon IVF lab (Central HVAC with particle + VOC filtration) Standard IVF lab equipped with portable filtration units P=0.01 P=0.03 Esteves et al. Fertil Steril 2004 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 4 2015 ANDROFERT
- 5. CPR Miscarriage rate 36.9% 23.0% 47.1% 15.0% Severe Male Factor Infertility (N=399) Standard IVF lab equipped with portable filtration units Cleanroon IVF lab (Central HVAC with particle + VOC filtration) Esteves et al. Fertil Steril 2006 IMPORTANCE OF AIR QUALITY IN IVF ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 5 2015 ANDROFERT
- 6. Van Voorhis et al. (F&S 2010) At least 7 of 10 consistently high-performing IVF centers in the USA used filtered laboratory air with HEPA and chemical, solid-phase filtration for VOCs Munch et al. (JARG 2015): Inadvertent removal of carbon filters resulted in significant drop of KPI Heitmann et al. (RBM Online 2015): Central HVAC (Particles + VOC) vs. Portable Units Higher IR (32.4% vs. 24.3%; p<0.01) Higher LBR (39.3% vs. 31.8%; p<0.05) RECENT EVIDENCE ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 6 2015 ANDROFERT
- 7. Importance of Air Quality in IVF Summary ANDROFERT ü High levels of VOC in unfiltered IVF lab air ü Mouse and human embryo development inversely correlated with VOC levels ü Efficient particle and VOC removal by dedicated air filtration systems ü Better IVF outcome (PR, IR, miscarriage) in laboratories with air particle and VOC filtration ü Central HVAC seems to work better than portable systems ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 7 2015 ANDROFERT
- 8. What regulatory agencies ask for ANDROFERTANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 8 2015 ANDROFERT
- 9. Social responsibility to protect public health from exposure to harm, when scientific investigation has found a plausible risk even though a scientific consensus had not been reached PRECAUTIONARY PRINCIPLE *Convention on Biological Diversity, UN 1992; Ratified by 192 countries and the EU, except USA, Andorra and South Sudan ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 9 2015 ANDROFERT
- 10. Region (directive) European Union (EU directive 2004/23/EC; 2006/86/EC) Brazil (Anvisa RDC33/2006; RDC23/2011) Particle filtration Equivalent to GMP Grade A air quality in the critical areas with a background environment at least equivalent to Grade D (exceptions apply) At least equivalent to ISO class 5 (NBR/ISO 14644–1) in the critical areas Microbial contamination Microbial colony counts equivalent to those of Grade A as defined in the current GMC guide with a background environment at least equivalent to Grade D Microbiological monitoring required; specifications not defined Volatile organic compounds filtration Not required Ventilation systems should be equipped with filters imbedded with activated charcoal ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 10 2015 ANDROFERT Reviewed by Esteves & Bento, RBM Online 2013.
- 11. CONTAMINATION Any undesirable material or substance that may affect the quality of final product Contaminants are generated by laboratory personnel, processes, furniture and equipment ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 11 2015 ANDROFERT Indoor air Personnel Material and Equipment Cell, tissue and fluids
- 12. 1. Airborne particles Residues of cleaning agents and clothing, skin shedding; temporary suspension; 1< µm <100 2. Microorganisms Viruses, spores, bacteria; constant suspension in air; size <1 up to 8µm ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 12 2015 ANDROFERT Contamination
- 13. CONTAMINATION 3. Indoor Volatile Organic Compounds Chemical compounds that evaporate and react with indoor ozone Result in submicronic particles and harmful by- products (eg. toluene, benzene, alcohols, acetone, refrigerating gases, aldehydes) Cigarette smoke, automobile exhaust, detergents, lubricants, dyes, furniture, rubber, plastics, resins, synthetic fibers, nylon, particle-board, plywood Some are genotoxic/mutagenic ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 13 2015 ANDROFERT
- 14. VOC in REPRODUCTIVE LABORATORIES 0 1000 2000 3000 Outside Air Indoor IVF Lab Air 533 2769 5-fold increase in VOC Anderson et al. 1997 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 14 2015 ANDROFERT
- 15. HOW TO PROTECT GAMETES AND EMBRYOS FROM CONTAMINATION Bacteria and other contaminants can attach themselves to particles, a decrease in particles equates to an increase in air quality Pre-Filters: >10µ Fine dust filters: 1<10µ HEPA filters: 0,3µ = 99,97% Removal of air particulates by forced air movement using positive air pressurization through a series of filters with increased efficiency ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 15 2015 ANDROFERT
- 16. Particle size/m3 of air: ISO 14.644-1 0.3 µM 0.5 µM 1 µM 5 µM ISO 1 ISO 2 10 4 ISO 3 102 35 8 ISO 4 1,020 352 83 IVF lab ISO 5 10,200 3,520 832 29 ISO 6 102,000 35,200 8,320 293 OR ISO 7 352,000 83,200 2,930 Transfer ISO 8 3,520,000 832,000 29,300 ISO 9 35,200,000 8,320,000 293,000 CLEAN ROOM CLASSIFICATION ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 16 2015 ANDROFERT
- 17. VOCs are 100–1000x smaller than the effective pore size of HEPA filters Spaces between the carbon particles contain a cloud of delocalized electrons that act as electronic glue to chemical contaminants Alcohols and ketones are oxidized and thereby detoxified by potassium permanganate HOW TO PROTECT GAMETES AND EMBRYOS FROM CONTAMINATION Removal of VOCs by forced air movement using positive air pressurization through a series of filters containing activated carbon and potassium permanganate ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 17 2015 ANDROFERT
- 18. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 18 2015 ANDROFERT PORTABLE SYSTEMS HEPA filter VOC filter Pre- filter
- 19. Central HVAC SYSTEMS ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 19 2015 ANDROFERT
- 20. BEFORE IMPLEMENTATION Risk assessment analysis • New or existing facility • Age and size of laboratory • Equipment/furniture (low off gassing?) • Constructing materials • Atmospheric air pollution • Disposable materials (storage location) • Human activity No. per workspace, Use of protective clothing Cosmetics, etc. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 20 2015 ANDROFERT
- 21. HOW WE IMPLEMENTED ANDROFERTANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 21 2015 ANDROFERT
- 22. AIR-HANDLING VENTILATION SYSTEM (with carbon + KMnO4 filtration) ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 22 2015 ANDROFERT
- 23. 23 - S. Esteves, August 2015 2015
- 24. ISO 5 Cleanroom IVF lab + Chemical filtration ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 24 2015 ANDROFERT
- 25. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 25 2015 ANDROFERT ISO 5 Cleanroom IVF lab + Chemical filtration
- 26. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 26 2015 ANDROFERT
- 27. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 27 2015 ANDROFERT
- 28. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 28 2015 ANDROFERT
- 29. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 29 2015 ANDROFERT
- 30. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 30 2015 ANDROFERT
- 31. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 31 2015 ANDROFERT
- 32. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 32 2015 ANDROFERT
- 33. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 33 2015 ANDROFERT
- 34. LAYOUT AND CONSTRUCTION In situ wet construction Low off-gassing materials Surfaces and Coatings Lighting fixtures Flush-mounted and sealed Coved junctures Stainless steel & aluminum Furniture, doors, windows, air vents, workstations ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 34 2015 ANDROFERT
- 35. 0 50 100 before after % TQE 0 20 40 before after % miscarriage 0 50 before after % LBR2.3 3.2 Average No. Top Quality Embryos ET Conventional lab (with portable filters) Cleanroom lab (Central HVAC with particle & VOC filtration) P=0.01 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 35 2015 ANDROFERT N=2,315 cycles
- 36. Cumulative live birth rates 40.4% 48.0% ANDROFERT, Referral Center for Male Reproduction ET #3 (FET) 49 ET #2 (FET) 239 ET #1 (fresh) 822 50.5% +18.8% +25.0%Female Age ≤38 ANDROFERT 332/822 63/239 17/49
- 37. HOW TO MEASURE AND CONTROL ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 37 2015 ANDROFERT
- 38. TEST EQUIPMENT Air volume flow rate Termoanemometer Air exchange rate Termoanemometer Air and room pressure differential Microanemometer and balometer HEPA-filter integrity leak Aerosol generator Airborne particle counts Electronic particle counter Recovery performance Smoke generator Lighting level Luxmeter Noise level Decibelmeter Temperature and humidity Thermometer and hygrometer Third-part certification company (CCL, Brazil); semi-annually IEST 006.2 standards ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 38 2015 ANDROFERT
- 39. TEST Air volume flow rate Air exchange rate Air and room pressure differential HEPA-filter integrity leak Airborne particle counts Recovery performance Lighting level Noise level Temperature and humidity ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 39 2015 ANDROFERT
- 40. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 40 2015 ANDROFERT
- 41. Settle plates Mold and blood-agar Petri dishes Surface sampling Swabs and contact plates Five-finger glove printing Incubators, workstations, air, floor, wall Limits Colony Forming Unites (CFU) Settle plates (90mm diameter) CFU/4 hours Contact plates (55mm diameter) CFU/plate Glove print CFU/ glove <3 <3 <3 Microbiological Monitoring ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 41 2015 ANDROFERT
- 42. VOC Monitoring 1. Activated-carbon life-time estimates Carbon tetrachloride activity method 2. Active air sampling on Tenax TA sorbent and 2,4 dinitrophenyl hydrazine Summa canisters; Thermal desorption Gas chromatography (Limits <2 mcg/m3 TVOC) 3. Direct reading Snapshot reading using VOC probes Photo ionization detector ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 42 2015 ANDROFERT
- 43. Esteves & Bento. RBM Online 2013 ü APPROVED ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 43 2015 ANDROFERT
- 44. Key messages 1. Air quality (particulate matter and VOC) associated to in vitro embryo development in animal and human studies 2. Regulatory agencies have issued Directives with specific requirements for air quality in IVF labs based on precautionary principle 3. Air cleanness in IVF should integrate both particulate matter and VOC filtration ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 44 2015 ANDROFERT
- 45. Key messages (2) 4. Risk assessment analysis needed before implementing air quality control to IVF units 5. Validation “in operational state” after AQC implementation ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 45 2015 ANDROFERT 6. Ideally, measure and control should be guided by third-part certification companies
- 46. Thank you This presentation is available at http://www.slideshare.net/ sandroesteves 4th International Congress - Academy of Clinical Embryologists 18-20 September 2015, Kochi INDIA