Exhaust Ventilation Level 4 Special considerations with very

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

Outline n Overview of main ventilation controls for very hazardous substances n Testing for ventilated enclosures 2

Very Toxic Substances n Active Pharmaceutical Ingredients / Isolated Process Intermediates (APIs/IPIs), usually Pb. OEL 3 B 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 3

Ventilation systems The systems most commonly used for handling of very hazardous substances are: n n n Laminar air flow booths Vented balance safety enclosures Glove box isolators 4

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. 5

Laminar Flow Booth n n Typically re-circulate air Pre-filter and HEPA filters required Built-in alarm system Very limited for very toxic substances – additional controls must be implemented 6

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 7

Vented Balance Safety Enclosure Examples: weighing/transferring and manipulating milligram amounts of neat drug and lyophilized product 8

Vented Balance Safety Enclosure – more examples n n n HEPA filtered exhaust Connected to house system Smaller size mainly suitable to laboratory work 9

Glove Box Isolators • weighing/transferring and manipulating gram or higher amounts • Suitable for manufacturing activities 10

Isolators Alarm n n n Can also be mobile unit HEPA Filtered Exhaust Connected to house system 11

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 12

Test before every use n n Inspection and pressurisation test must be undertaken before each use Cease operation if alarm sounds All pressure gauges must be in “green” Check gloves are all in underpressure 13

Testing of Isolators n n n Installation Qualification (IQ) Test on installation Operations Qualification (OQ) Test as part of periodic maintenance Inspection undertaken prior to each use Frequent pressurisation tests The equipment should not be used if the equipment fails any of these test or if an alarm sounds during operation. 14

Installation Qualification Test n Main elements – – Define systems Review drawings and documentation Review installation Check all parts 15

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 16

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 17