Layout of an Ethylene Oxide Sterilization Unit

Interministerial Ordinance 482/1999 establishes the minimum conditions for the physical area, facilities and environmental safety. Companies that perform ethylene oxide (EtO) sterilization must have a specific Operating License obtained from the Health Surveillance agencies and are responsible for biological control and ethylene oxide residue control of sterilized materials.

Sterilization units consist of at least five environments with restricted access to authorized personnel:

a. Command area

b. Sterilization room

c. Ventilation room

d. Ethylene oxide container storage room or area

e. Treatment area

Figure 1: Example of layout of an EtO sterilization plant according to Chapter II of Interministerial Ordinance 482/99

The sterilization room must have:

a. Construction that allows adequate direction for the expansion of gases in the event of an accident, through a fragile ceiling or wall, ensuring an external radius without the movement of people or vehicles compatible with the risks inherent to the facilities.

b. Air renewal system independent of other sectors that guarantees 25 (twenty-five) air changes per hour, as well as negative pressure in relation to the ventilation room.

c. Electrical installations in accordance with specific legislation for Electrical Installations in Potentially Explosive Atmospheres. It is recommended that an area classification study be carried out prior to applying the requirements for electrical installations in potentially explosive atmospheres.

d. Exclusive emergency door with unlocked exit and no possibility of being locked with keys, and opening in the direction of escape.

Special attention should be given to requirement “b” above regarding the air renewal system. The purpose of the air renewal system is to eliminate any possible presence of EtO in the environment. Considering that EtO is heavier than air, there will be a tendency for concentrations to be close to the floor. Therefore, in addition to the flow rate, it is recommended to carry out a careful study of the air flow.

Figure 2: Detail of the positioning of the ventilation grille in the sterilization room close to the floor. Although it is not a requirement, it is good practice.

Ethylene Oxide Cylinder Room

The EtO Cylinder Room or Cylinder Warehouse must have:

a. Construction that allows adequate direction for the expansion of gases in the event of an accident, through a fragile ceiling or wall, ensuring an external radius without the movement of people or vehicles compatible with the risks inherent to the facilities.

b. Electrical installations in accordance with specific legislation for Electrical Installations in Potentially Explosive Atmospheres. It is recommended that an area classification study be carried out prior to applying the requirements for electrical installations in potentially explosive atmospheres.

The Aeration Room must have an air renewal system independent of the other sectors that guarantees 25 (twenty-five) air changes per hour, as well as negative pressure in relation to the other environments.

The treatment area must have electrical installations in accordance with specific legislation for Electrical Installations in Potentially Explosive Atmospheres. It is recommended that an area classification study be carried out prior to applying the requirements for electrical installations in potentially explosive atmospheres.

General observations

Companies must also:

Have means of continuous monitoring of EtO concentration in the environments of sterilization rooms, quarantine, ethylene oxide container storage and gas treatment area, ensuring maintenance of the established Tolerance Limit:

• 1 ppm (1.8 mg/m3) concentration in air for a normal eight-hour day

  
  

• 5 ppm (9.0 mg/m3) concentration in the air for periods of up to 15 minutes per day

The Ethylene Oxide Sterilization Unit must also have:

• Automatic protection devices against overcurrents and overvoltage, in accordance with Brazilian Technical Standard - NBR 5.410 - Low Voltage Electrical Installations.

  
  

• Lightning protection system in accordance with Brazilian Technical Standards, NBR-5.419 - Protection of Structures Against Atmospheric Discharge.

  
  

• Fire-fighting system compatible with local Fire Department standards, with carbon dioxide (CO 2 ) extinguishers being essential;

  
  

• Automatic sound and light alarm system for emergency cases of gas leaks.

The layout development must be carried out based on a careful study of the flow of materials and people and activities to be developed in each environment. For example:

• Sizing of waiting areas must take into account the balance between sterilization and previous manufacturing steps and subsequent handling, in order to ensure a continuous production flow in accordance with Good Manufacturing Practices. Cycle time and takt time are essential elements for optimized sizing.

  
  

• Forecast of cargo handling conditions and sample placement and removal.

  
  

• It is advisable to evaluate the maintenance and operation activities to be carried out in each area so that the necessary conditions can be foreseen. Access to the vacuum system, steam generator, EtO treatment system, heat exchangers, instrumentation, etc. must be sufficient so that the activities can be carried out in safe and ergonomic conditions.

  
  

• Convenient escape routes studied for failure modes mapped in risk mapping study.

In addition to complying with legislation, the layout of an EtO sterilization facility must be based on a detailed multidisciplinary process study so that optimal safety and operating conditions are achieved.