1 Art. n. 14 f ministerial decree n. 593 f 8 august 2000 Minister dell Istruzine Cmplete filling lines and autmatic inspectin machine fr pharmaceutical and csmetic industries TYPICAL STERILIZATION PROCESS IN AUTOCLAVE FOR POLYPROPYLENE BAGS AND/OR POLYPROPYLEN BOTTLES 1.1 Sterilizatin: definitin and methds With the sterilizatin term we refer t any prcess, chemically r physically, that eliminates (remves) r kills all frms f pathgen life, including transmissible agents (such as fungi, bacteria, viruses, spre frms, etc.) present n a surface, cntained in a fluid, in medicatin, r in a cmpund such as bilgical culture media. Sterilizatin can be achieved by applying the prper cmbinatins f heat, chemical, irradiatin, high pressure and particular filtratin. There are many kind f sterilizatin prcess fr different applicatin and sectr: By heating: Steam sterilizatin; Biling in water; Super-heated water sterilizatin, etc. By chemical prcess: Ethylene xide; Ozne; Peracetic acid, etc. In the next pages we wuld like write a few descriptin f this prcess, a small reference n this applicatin.
2 Art. n. 14 f ministerial decree n. 593 f 8 august 2000 Minister dell Istruzine Cmplete filling lines and autmatic inspectin machine fr pharmaceutical and csmetic industries 1.2 ISBM technlgy and sterilizatin prcess The ISBM technlgy (Injectin- Stretch Blw Mulding) technlgy is a duble step prcess, cmpletely different frm the BFS (Blw Fill Seal) prcess. Duble means perfrm injectin first and bttles frming after. This prcess allws the peratr t keep under cntrl all the fundamental parameter and adjusts them in case it is required. The recvery time is als less than the BFS. With the ISBM technlgy the sterilizatin prcess is 100% allwed. The PP bttles and the PP bags made with the duble step technlgy are cmpletely sterilizable after the filling and clsing prcess, accrding the FDA statement and GMP prcess. In this field (sterilizatin prcess), GF S.p.A. experience suggest (please nte suggest) t use as sterilizatin methd based n a Super-heated water sterilizers. This kind f sterilizatin is designed t perfrm terminal sterilizatin f large vlume infusin and parenteral slutins in PP cntainers(bags and bttles). The sterilizatin prcess is made by an autclave and it is based n a differential pressure under heat expsure, a cunter pressure inside the chamber during the entire cycle in rder t minimize the differential pressure acrss the cntainer and avid excessive shrinkage r excessive defrmatin. A typically example f sterilizatin curve is shwed belw: Picture 1: Typically sterilizatin cycle fr PP bttles and bags 1 (1: web reference)
3 Art. n. 14 f ministerial decree n. 593 f 8 august 2000 Minister dell Istruzine Cmplete filling lines and autmatic inspectin machine fr pharmaceutical and csmetic industries Where in the pictures 1 are present several curves: - Internal Temperature autclave rm time; - Internal Pressure autclave rm time; - Internal Temperature cntainer time; - Internal pressure cntainer time. Picture 2: Sterilizatin curve f PP bttles btained by ISBM technlgy In the sterilizatin cycle, the F0 prcess (i.e. temperature and time) is fixed accrding the FDA prcess. Additinally, a) The sterilizer shuld equip with indicatr fr inside bttles pressure; b) The sterilizer shuld equip with cntrl fr dynamic pressure balance. In rder t btain the crrect pressure inside the bttles, the fllwing peratins can be cnsidered: 1) fix numbers f IV liquid filled PP cntainers as specimens inside sterilizer; 2) actual frmats shuld be cnsidered as specimens fr best simulatin; 3) lcatins f specimens are decided free frm regular autclave peratin; 4) all specimens must be capped and well sealed with pressure sensr tip inside; 5) cnnect sensing wires t cntrller utside f sterilizer fr cntinuus readut; 6) initial tests are essential t prgram cmpensatin fr each pint parameter; 7) the specimens can be used fr many cycles f actual sterilizatin prductin. Picture 3: The way t btain internal pressure
4 Art. n. 14 f ministerial decree n. 593 f 8 august 2000 Minister dell Istruzine Cmplete filling lines and autmatic inspectin machine fr pharmaceutical and csmetic industries Befre t btain the ptimized sterilizatin prcess and curve and the crrect bttles shape, it is necessary t perfrm several tests with the bttles, by adjusting chamber pressure, chamber temperature, pre heating and cling time. Furthermre, it is imprtant cnsider the fllwing items: 1. The PP bttle linear dimensinal change befre and after autclave, this is unavidable, due t fllwing principles: a. shrinking / expansin exists with all substances, including high mlecular weight plastics; b. material expands when its temperature ges up and/r when ambient pressure drps; c. material shrinks when its temperature ges dwn and/r when ambient pressure increases; d. plastic mulded prducts always have their tendency t g back t the riginal shape; e. the shrinkages f a material between linear and cubic may nt be the same; f. the level f bttles linear dimensinal change is depending n the rate f bttle being stretched, bttle internal stress level and prcess cntrl (temperature, time and pressure, etc.) during autclave prcess. 2. The level f bttle gemetric shape change is als unavidable, as it is a cmbined result f linear dimensinal change mentined abve. The key t keep bttles in their prprtinal shape is t maintain the dynamic pressure balance between inside and utside f the bttles during the whle prcess f autclave, n matter higher r lwer rate f bttle linear dimensinal changes; 3. Preheating stage (e.g. temperature raised t 121 C). During this prcess, the pressure are increased bth inside and utside f bttles but the pressure increasing speed between inside and utside f bttles must t be the same; pressure increasing speed f utside bttles is faster than that f inside bttles therefre, autclave tank pressure shuld be discharged in rder t keep dynamic pressure balance; 4. Sterilizatin stage (e.g. temperature maintained at 121 C fr 20 min). The temperature in this stage must be kept cnstant (e.g. 121 C), with n change bth curves f the temperature and pressure must stay as much as pssible in hrizntally flat; 5. Cling stage (e.g. temperature drpped frm 121 C t 50 C in 40 min) special attentin must be paid at this stage especially temperature 121 drp t arund 85 C. During this prcess, the pressure are decreased bth inside and utside f bttles but the pressure decreasing speed between inside and utside f bttles are nt the same pressure decreasing speed f utside bttles is faster than that f inside bttles therefre, autclave tank pressure shuld be cmpensated in rder t keep dynamic pressure balance. Please nte that the abve infrmatin must nt be cnsider as a must. The sterilizatin cnditins that best fit particular bttles are based n actual tests, since each prduct and equipment have their wn factrs t be adjusted case by case.
5 Art. n. 14 f ministerial decree n. 593 f 8 august 2000 Minister dell Istruzine Cmplete filling lines and autmatic inspectin machine fr pharmaceutical and csmetic industries When yu fixed the parameters and yu decide the crrect way, a typically examples f sterilized bttles are shwed: Picture 4: Entire prcess fr LVP prducts Picture 5: Example f sterilized bttle and bag
6 Art. n. 14 f ministerial decree n. 593 f 8 august 2000 Minister dell Istruzine Cmplete filling lines and autmatic inspectin machine fr pharmaceutical and csmetic industries In rder t help ur custmer t define the crrect sterilizatin parameters, we wuld like t shw yu a real autclave curve. The curves are btained after several tests n the finished bttles. The parameters presents in the curves are explained belw: X axis TIC22xC is ChamPrs Bar LdTem2 C BtPrsBar is the time; the temperature Indicatin Cntrller, the temperature f autclave Chamber; is the sterilizer chamber pressure; is the Internal Bttles Temperature; is the Internal Bttles Pressure Typically Sterilizatin curve These curves are btained after several tests n the bttles. With the ISBM prcess many advantages can be btained. Cntact us fr additinally infrmatin and details. Fr mre infrmatin, please visit ur website:
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