Attachment IV - Page 5 
3. Equipment Validation and Inactivation Assurance Program 
No plant or process design is complete without validation. Hence, an 
equipment validation and an inactivation assurance program have been 
established to ensure that the containment features and process safeguards 
designed to prevent the release or escape of recombinant organisms function 
properly . 
Prior to use of recombinant organisms: 
o Biological safety cabinets are certified. 
o The fermenter systems, inoculation and sampling assemblies are tested 
for leaks under steam pressure. These are then checked as part of 
the sterilization cycle prior to use for each batch. 
o Each vessel, line, and piece of equipment that is designed for steam 
sterilization is tested to ensure that the inactivation temperature 
selected is achieved. 
o Thermal oxidizers used to sterilize exhaust gases are tested to 
ensure they achieve design temperature at the desired air flow. 
o The emergency containment system (dike) for catastrophic spills is 
validated with water. 
o The method of culture inactivation is validated using the parent 
strain. 
o Filter integrity is tested at some facilities using an aerosol 
generator. 
Once the plant goes on stream, the following tests are made: 
o Biological safety cabinets are tested annually and each time the HEPA 
filter is changed. 
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