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

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

3. 3 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

4. 4 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

5. 5 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.

6. 6 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

7. 7 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

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

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

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

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

12. 12 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

13. 13 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

14. 14 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.

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

16. 16 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

17. 17 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