1. Ventilation Controls Level 4: Basic principals of Ventilation Design, implementation and maintenance Part 1 of 2

2. 2 Outline n Approaches to ventilation systems n Key features n Good design considerations for local ventilation n Inspection and maintenance

3. 3 Two Main Types of Ventilation General/Dilution n Heat control and/or removal of contaminants (dilution ventilation) n Used for contaminant control ONLY when local exhaust is impractical n Not effective or economical Local n Captures contaminants at source n Preferred method of control –more effective –more economical Direct exposure: local ventilation/ controls Direct exposure: local ventilation/ controls Indirect exposure: general ventilation or control at source Most exposure is generally received directly

4. 4 General Ventilation: Once-through System with 100% makeup air Appropriate filtration or treatment Appropriate Filtration HEPAHEPA

5. 5 HEPAHEPA General Ventilation: Re-circulating System HEPA HEPAHEPA

6. 6 General Ventilation: Re-circulating System - with ~10% makeup air

7. 7 General Ventilation: Typical Ventilation Rates Chemical Operations or Labs: 15 OAC/hour Offices: 1 OAC/hour Pharmaceutical Operations: 5 OAC/hour Instrument or Biology Labs: 10 OAC/hour OAC: outside air change Rates

8. 8 General Ventilation: Limiting Factors for Control of IH Exposures n Contamination levels must not be too high or air flow rate necessary for dilution will be impractical n Workers cannot be near contaminant source n Toxicity of contaminant must be low n Evolution of the contaminant must be reasonably uniform

9. 9 General Ventilation Typical design failures n The air inlets are too close to the air outlet n The air will not circulate throughout the room

10. 10 General ventilation recommendations operating vehicles indoors n propane-fueled lift truck - 2.5 m 3 /s n gasoline-fueled lift truck – 4 m 3 /s n operating automobile – 2.5m 3 /s n operating truck - 5m 3 /s n Other diesel-fueled vehicles - 0.05 m 3 /s/horsepower

11. 11 Local Exhaust Ventilation LEV Consider contaminant characteristics: n Gas / vapour /fume / particles n Temperature n Particle size n Particle speed n Directionality of source n The perfect solution for one situation will fail in another n The solution must be tailored to the source

12. 12 Typical contaminant sources Source: BOHS

13. 13 Typical contaminant sources Source: BOHS

14. 14 Local Exhaust Ventilation: Hood Design Principles Main aspects influencing effective performance n Distance from source n Enclosure design n Design of openings Other aspects regarding velocity in the duct, duct design etc. are critical to a good functioning system, but won’t be covered here

15. 15 Distance from source Rule of thumb: Distance from source should be diameter of opening or less Air speed at emission point is called capture velocity

16. 16 Change in velocity with distance

17. 17 Recommended Capture Velocity You can measure the capture velocity easily with an anemometer Source:ACGIH

18. 18 Capture velocity and flow rate n At design, the flow rate is calculated to give the capture velocity you need

19. 19 Effect of enclosure design: Hood capture velocity with and without flange n With flange Source :EPA n Without flange

20. 20 Effect of enclosure design: The airflow required to give effective control n Plain extract opening n Enclosure added at sides and above bench n Flange added at rear n Transparent screen added at front 1m 3 /s 0.39m 3 /s 0.78m 3 /s 0.74m 3 /s BOHS

21. 21 Effect of enclosure design: Hood entry loss coefficient for various duct design n Air enters the duct more smoothly and efficiently when there is an smooth angled entrance to the duct

22. 22 Summary of Key Points affecting performance of LEV 1. The distance between the extract and the source must be similar to the dimensions of the extract 2. Increased enclosure greatly improves the effectiveness of the extraction 3. The design of the duct entrance should be smooth

23. 23 Examples of LEV –Charging Fluid Bed Granulator Would you expect this to work? How would you improve it?

24. 24 Charging Granulator – Improved Engineering

25. 25 Example of LEV- Charging Excipients n This is an enclosure – but not ventilated n The station is too small n There is nor provision for waste disposal n How would you improve it? n What is good and bad here?

26. 26 Charging Excipients - Improved design Integrated disposal of waste makes a big difference to exposure

27. 27 Examples of LEV – Weighing operation n Canopies never work for powders They even risk increasing the exposure for the operator n Leave them in the kitchen, over hot surfaces, where they work

28. 28 Examples of LEV – More weighing operation n Not appropriate for this scale of weighing... n..but a lot better than this. The “local” extract is in the ceiling

29. 29 Examples of LEV – larger scales weighing n The wall extract is likely to be very ineffective here - there is no “push” of air n There is also likely to be cross contamination between booths

30. 30 LEV – laminar air flow booths n Laminar air flow booths can be good for PbOEL 1 and 2 compounds n Exposure can be reduced further with good orientation, good techniques, drum lifters, and additional screening n PbOEL 3 & 4 need more containment however

31. 31 Laminar flow booth – typical design A: Filter/fan unit (HEPA or ULPA) BReturn duct directs air flow away from operator CExit filters (HEPA or ULPA) DFilter/Fan Units – create positive pressure of filtered air EAir Handler – exhausts air to create a negative pressure

32. 32 Worker orientation in laminar air flow booth n Tests showed an improvement of a factor of 2000 in large laminar air flow booths Source: ACGIH

33. 33 Design guidance n A selection of drawings from the ACGIH manual follow, showing recommended designs. Further details are provided in the manual

34. 34 Glove Box For High Toxicity Materials (ACGIH) ACGIH Ref. no.

35. 35 Typical Isolator n Excellent protection is provided by an isolator – but the design still influences the performance

36. 36 Weigh Hood, Powders (ACGIH)

37. 37 Drum Filling (ACGIH)

38. 38 Typical Laboratory Hood

39. 39 Grinding Wheel Hood n The manual includes details on flow rates for various week sizes. n No more than 25% of the wheel should be exposed

40. 40 Evaluation – smoke tubes n Smoke tubes/generators help to visualise the air movement and can be a good indicator of performance n They are useful in training operator in how their behaviours influences exposure The LEV may appear better than it is, as the s moke is diluted in the air

41. 41 Evaluation – measurement of capture velocity n Capture velocity is measured with an anemometer n Compare it with recommended / design values n Face velocity can also be measured, compared with design values and used to calculate the air flow

42. 42 Periodic Inspection and Maintenance n A detailed plan of periodic maintenance of both general and local ventilation must be established and adhered to n The objective is to verify that –the system is performing to specifications –Proper maintenance, cleaning and chemical treatment (if necessary) is undertaken to inhibit growth of microorganisms in the complete ventilation system –Any faults, abraded surfaces contamination are detected and corrected. –acceptable quality of air is entering the structure n The periodic maintenance frequency will vary with task but is typically quarterly

43. 43 Conclusion n There are two main approaches to ventilation, general and local n With hazardous substances, local ventilation is preferred n Simple considerations in design and use greatly increase the effectiveness n Recommended designs are given in the ACGIH ventilation manual n Ventilation systems must be regularly inspected and maintained

44. Exhaust Ventilation Level 4: Special considerations with very hazardous substances Part 2 of 2

45. 45 Outline n Overview of main ventilation controls for very hazardous substances n Testing for ventilated enclosures

46. 46 n Active Pharmaceutical Ingredients / Isolated Process Intermediates (APIs/IPIs), usually PbOEL 3B and 4 n The “gens”: Carcinogens / Mutagens / Reprogens n IDLH : Immediately Dangerous to Life and Health n The use of ventilation controls must be managed very carefully when very toxic substances are handled Very Toxic Substances

47. 47 Ventilation systems The systems most commonly used for handling of very hazardous substances are: n Laminar air flow booths n Vented balance safety enclosures n Glove box isolators

48. 48 Key Point for very toxic substances Ventilation systems that are essential to the safe operation of a process or procedure must be equipped with automatic warning systems which are activated when the ventilation system fails to meet required performance criteria.

49. 49 Laminar Flow Booth n Typically re-circulate air n Pre-filter and HEPA filters required n Built-in alarm system n Very limited for very toxic substances – additional controls must be implemented

50. 50 Limitations of a Laminar Flow Booth n Requires supplemental PPE for Category 3 n Standard design protects against particulate n Special design needed for solvent handling n Exposure is very dependant on operator technique

51. 51 Vented Balance Safety Enclosure Examples: weighing/transferring and manipulating milligram amounts of neat drug and lyophilized product

52. 52 Vented Balance Safety Enclosure – more examples n HEPA filtered exhaust n Connected to house system n Smaller size mainly suitable to laboratory work

53. 53 Glove Box Isolators weighing/transferring and manipulating gram or higher amounts Suitable for manufacturing activities

54. 54 Isolators n Can also be mobile unit n HEPA Filtered Exhaust n Connected to house system Alarm

55. 55 Limitations of Isolators n Size of material handled n Bringing material in/out n Risk of back and shoulder strain with prolonged use –Must include ergonomics in design n May be residual risk with material outside isolator

56. 56 Test before every use n Inspection and pressurisation test must be undertaken before each use n Cease operation if alarm sounds All pressure gauges must be in “green” Check gloves are all in underpressure

57. 57 Testing of Isolators n Installation Qualification (IQ) Test on installation n Operations Qualification (OQ) Test as part of periodic maintenance n Inspection undertaken prior to each use n Frequent pressurisation tests n The equipment should not be used if the equipment fails any of these test or if an alarm sounds during operation.

58. 58 Installation Qualification Test n Main elements –Define systems –Review drawings and documentation –Review installation –Check all parts

59. 59 Operational Qualification Test n Main Elements –key component check –inflow velocities –HEPA filter integrity –Filter pressure drops/magnehelic gauges –Illumination and noise levels –Motor –Alarms

60. 60 Summary n Great care must be taken in control of exposure to very hazardous substances n All equipment for very hazardous should be fitted with alarms n Regular testing must be scheduled and documented