TYPICAL STERILIZATION PROCESS IN AUTOCLAVE FOR POLYPROPYLENE BAGS AND/OR POLYPROPYLENE BOTTLES
Sterilization: definition and methodsWith the “sterilization” term we refer to any process, chemically or physically, that eliminates (removes) or kills all form of pathogen life, including transmissible agents (such us fungi, bacteria, viruses, spore forms, etc.) present on a surface, contained in a fluid, in medication, or in a compound such as biological, irradiation, high pressure and particular filtration.
There are many kind of sterilization process for different application and sector:
- Steam sterilization
- Boiling in water
- Super-heated water sterilization, etc
By chemical process:
- Ethylene oxide
- Peracetic acid, etc
ISBM technology and sterilization processThe ISBM technology (Injection – Stretch – Blow – Moulding) is a double step process, completely different from the BFS (Blow – Fill – Seal) process.
This process allows the operator to keep under control all the fundamental parameter and adjusts them in case it is required. The recovery time is also less than the BFS.
With the ISBM technology the sterilization process is 100% allowed. The PP bottles and the PP bags made with the double step technology are completely sterilisable after the filling and closing process, according the FDA statement and GMP process.
In this field (sterilization process) G.F. experiences “suggest” (please note suggest) to use as sterilization method based on a Super-heated water sterilizers.
This kind of sterilization is designed to preform terminal sterilization of large volume infusion and parenteral solutions in PP containers (bags and bottles).
The sterilization process is made by an autoclave and it is based on a differential pressure under heat exposure under heat exposure, a counter pressure inside the chamber during the entire cycle in order to minimize the differential pressure across the container and avoid excessive deformation.
Are present several curves:
- Internal temperature autoclave room – time
- Internal pressure autoclave room - time
- Internal temperature container – time
- Internal pressure container – time
In the sterilization cycle, the F0 process (i.e. temperature and time) is fixed according the FDA process.
- The sterilization should equip with indicator for inside bottles pressure
- The sterilizer should equip with control for dynamic pressure balance
- In order to obtain the correct pressure inside the bottles, the following operations can be considered:
- Fix numbers of IV liquid filled PP containers as specimens for best simulation
- Actual formats should be considered as specimens for best simulation
- Locations of specimens are decided free from regular autoclave operation
- All specimens must be capped and well sealed with pressure sensor tip inside
- Connect sensing wires to controller outside of sterilize for continuous readout
- Initial tests are essential to program compensation for each point parameter
- The specimens can be used for many cycles of actual sterilization production
Furthermore, it is important consider the following items:
- The PP bottle linear dimensional change before and after autoclave, this is unavoidable, due to following principles:
- Shrinking/expansion exist with all substances, including high molecular weight plastics
- Material expands when its temperature goes up and/ore when ambient pressure drops
- Material shrinks when temperature goes down and/or when ambient pressure increases
- Plastic moulded products always have their tendency to go back to the original shape
- The shrinkages of a material between linear and cubic may not be the same
- The level of bottles linear dimensional change is depending on the rate of bottle being stretched, bottle internal stress level and process control (temperature, time and pressure etc.) during autoclave process.
2. The level of the geometric shape change also unavoidable, as it is a combined result of linear dimensional change mentioned above. The key to keep bottles in their proportional shape is to maintain the dynamic pressure balance between inside and outside of the bottles during the whole process of autoclave, no matter higher of lower rate of bottle linear dimensional changes
3. Preheating stage(e.g. temperature raised to 121°C). During this process, the pressure are increased both inside and outside of bottles but the pressure increasing speed between inside and outside of bottles must to be the same; pressure increasing speed of outside bottles is faster than that of inside bottles therefore, autoclave tank pressure should be discharged in order to keep dynamic pressure balance
4. Sterilization stage(e.g. temperature maintained at 121°C min). The temperature in this stage must be kept constant (eg.g 121°C), with no change both curves of the temperature and pressure must stay as much as possible in horizontally flat
5. Cooling stage(e.g. temperature dropped from 121°C in 40 min) special attention must be paid at this stage especially temperature 121 drop to around 85°C. during this process, the pressure are decreased both inside and outside of bottles but the pressure decreasing speed between inside and outside of bottles are not the same pressure decreasing speed of outside bottles is farest than that of inside bottles therefore, autoclave tank pressure should be compensated in order to keep dynamic pressure balance.
Please note that the above information must not be considered as a must. The sterilization conditions that best fit particular bottles are based on actual tests, since each product and equipment have their own factors to be adjusted case by case.