ETHYLENE OXIDE GAS (EtO) STERILIZERS

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ETHYLENE OXIDE GAS (EtO) STERILIZERS DE LAMA holds the Quality System certificates ISO 9001 and EN 46001 ISO 9001 - Cert. n 0351/2 EN 46001 - Cert. n 1275/0 ISO 9001 - Cert. n IT - 4018 EN 46001 - Cert. n IT - 7773

Ethylene oxide gas (EtO) sterilizers DE LAMA DLOG and DLOG/V Ethylene oxide sterilizers of DE LAMA DLOG and DE LAMA DLOG/V series have been specifically designed for sterilization of products sensitive to high temperatures and to humidity (syringes, defluxers, catheters, cartridges for dialysis, plastic articles, bandages, sutures, etc.). Such autoclaves can be used even for sterilization of powders which deteriorate by heating exposure. For the wide range of product that can be treated, such sterilizers find application in parapharmaceutical and pharmaceutical industry, in laboratories and hospitals. Ethylene oxide autoclaves can be realized in two versions to satisfy different requirements: DE LAMA DLOG series for working under pressure ( abs. bar + vacuum) with mixtures of ethylene oxide and carbon dioxide (usual composition 10% EtO + 90% CO2) DE LAMA DLOG/ Vseries for working under vacuum (1,45 abs. bar + vacuum) with mixtures of ethylene oxide and carbon dioxide (usual composition 90% EtO + 10% CO2) or with 100% ethylene oxide. On request, DE LAMA can supply EtO sterilizers which are able to perform even saturated steam cycles. Sterilizer DE LAMA DLOG/V-Ex 561 type, capacity 0 lts., with automatic sliding door MAIN CONSTRUCTION FEATURES Sterilizers are designed, manufactured and tested according to current Directives for construction of pressure vessels (PED), in full compliance with cgmp Guidelines, European Standards and EN 1422, with procedures fixed by ISO 9001 and Quality Systems and are suitable to be validated according to European Standard EN 550. DE LAMA DLOG (equipment under pressure) and DE LAMA DLOG/V (equipment under vacuum) are distin- - double wall body - sterilization chamber in AISI 316 or AISI 316L stainless steel - front panels and eventual side walls in satin finish AISI 304 stainless steel - piping and valves directly connected with the chamber in stainless steel - loop for heating and circulation of water inside the jacket, complete of pump - efficient insulation with minimum heat loss and high power economies Sterilizers are available with single or double door, hinged or automatic sliding type.

PROCESS CONTROL All DE LAMA control systems are provided with marking and are in compliance with European Directive EMC 89/336 relevant to electromagnetic compatibility. To satisfy Customers several production needs, DE LAMA has realized different and flexible control system configurations. All controllers give the possibility of data processing and to issue detailed process documentation. DE LAMA MASTER 6 Distributed architecture modular control, processing and recording system with industrial PC connected to a PLC VGA colour LCD monitor (TFT x600) multifunction keyboard membrane type track-ball colour graphic printer with printout size A4 interface Ethernet IEEE 802.3 and Profibus self-diagnostic and self-test graphic programming configurable dynamic synoptic panel human / machine interface (HMI) with graphic management Windows-NT / 2000 Professional operating system integrated management of all process parameters and sequences up to 35 standard storable programmes self-diagnostic data holding in case of black-out possibility of connection to an external PC for real-time logger and data storage functions On Customer s request, DE LAMA can supply: - customized systems able to interface with supervisors (SCADA) and external control facilities - independent recording system for process data (according to European Standard EN 1422) STERILIZATION PROGRAMMES High flexibility of control systems mounted on autoclaves DE LAMA DLOG and DE LAMA DLOG/V allows to perform cycles, automatic control cycles (vacuum leak test pressure leak test) and cycles free programmable by It is possible to choose operating parameters (time, humidity, gas concentration, etc.) according to type load, packaging and product placing inside the chamber. Standard operating values are the following: Sterilization time: usual gas exposure time is 3 4 hours. Sterilization time depends on both type of packaging and other process parameters. Product temperature: 40 60 C Set temperature value is non-stop holded by forced circulation of water inside the jacket and, optionally, inside the This system is very reliable with no risk of overheating and temperature differences by steam use. Product humidity: 40 70 RH% Such value is obtained with sterilizer under vacuum condition to allow best conditioning of sterilization load. Gas concentration inside the sterilizer: variable on the basis of used gas mixture and operating pressure. PC/PLC integrated logic computerized control system Master 6 type unlimited possibility of programmes configuration and memorization data holding in case of black-out software in compliance with GAMP3 Guidelines Multilevel password and full compliance with FDA Regulations Guidelines relevant to electronic signature (CFR 21-Part 11). DE LAMA OLIMPYA/EXP3 Control, regulation, management and recording system equipped with high speed microprocessor: monitor LCD multifunction keyboard membrane type synoptic panel colour graphic printer with printout size A4 serial interface wide programming and management of all process parameters Q (kg) 140 120 100 80 60 40 20 0 Graphic of changes in mixture consumption (10% EtO + 90% CO2) to different concentrations 10 20 V (m3) C= mg/l 4.8 bar (480 kpa) C= 700 mg/l 4.2 bar (420 kpa) C= 600 mg/l 3.6 bar (360 kpa) C= 500 mg/l 3 bar (300 kpa) C= 400 mg/l 2.4 bar (240 kpa) C= 300 mg/l 1.8 bar (180 kpa) C= 250 mg/l 1.5 bar (150 kpa) C= 200 mg/l 1.2 bar (120 kpa) C= 150 mg/l 1 bar (100 kpa)

CYCLE BASIC PHASES Load of product to be sterilized Product heating by heated water circulating inside the jacket and by internal fans preventing stratification which make heat exchange easier. Pre-vacuum with value that can be automatically set up to 40 mbar (4 kpa) max. Vacuum leak test of the chamber before gas inlet Product conditioning by humidification up to a preset value Inlet of preheated and vaporized gas up to selected pressure value Sterilization with gas pressure constant holding for a preset time (up to 24 hours) Flushing by gas evacuation through vacuum pump and sterile air inlet (pulsations) for a prefixed number of times. CONDITIONING STERILIZATION FLUSHING 240 360 60 3 bar (300kPa) Sterilizer DE LAMA DLOG 931 type, capacity 37734 lts., with hinged motorized door 2 bar (200kPa) 1 bar (100kPa) 60 C (333 K) 50 C (328 K) 40 C (313 K) ATMOSPHERIC PRESSURE 0,2 bar (20kPa) Functional diagram PRESSURE GAS INLET HUMIDIFICATION VACUUM LEAK TEST AIR REMOVAL Typical sterilization cycle Gas heater Magnetic coupling fan Air inlet CPU EtO gas mixture bottle CPU Heater of water recirculating inside the jacket TE01 TE02 TE03 TP RH % Jacket Temperature probes Chamber Pressure transducer Humidity probe Steam generator Separating tank Drain to be conveyed to neutralization system

AUXILIARY EQUIPMENT Gas feeding, vaporizing and preconditioning equipment Microprocessor system for control of relative humidity Exhausted gas neutralization equipment Device for continuous monitoring of EtO pollution arising from eventual escapes of gas indoor OPTIONALS Doors heating through hot water flushing Doors motorization system with electronic control Automatic translation system for doors opening/ closing Internal ventilation system, with magnetic coupling fan groups, to optimize homogeneity conditions throughout the chamber (according to European Standard EN 1422) Gas injection pipes washing system by nitrogen flux Exhaust hoods for suction of eventual residual gas on doors opening Electronic gas weighing system ADPE explosion-proof execution for sterilizers under vacuum ( DE LAMA DLOG/V) QUALITY CONTROL AND VALIDATION Equipment and relevant supervision systems are designed and manufactured to be easily validable in compliance with European Standard EN 550 and with quality standards for pharmaceutical processes required by FDA. Careful tests, specific controls and high technical professionality in pre-validation activities assure that plants are fully in compliance with highest required standards. Sterilizer DE LAMA DLOG 541 type, capacity 10875 lts., with hinged door TECHNICAL DOCUMENTATION AND ADDITIONAL ACTIVITIES To complete the supply, plants are always provided with following basic documentation: - installation and operation manuals - P&I and technological diagrams - dimensional drawings and lay-out - bill of materials and components - materials and calibration certificates On request, DE LAMA supplies: FAT and SAT protocols/documentation for pre-validation Validation documentation customizable by the end-users Full documentation for EN or FDA activity of validation Theoretical/practical trainings reserved to Customers production and maintenance staff. ASSOCIATED EQUIPMENT AND ACCESSORIES TO COMPLETE THE PLANT Stainless steel trolleys for internal loading and external moving, trays and boxes Idle/motorized rollers internal conveyor for europallets Full customized systems for loads handling Sterilizer DE LAMA DLOG 631 type, capacity 23392 lts., with automatic product loading system

TECHNICAL DATA ETHYLENE OXIDE (EtO) GAS STERILIZERS DE LAMA DLOG and DLOG/V type MODEL CAPACITY CHAMBER INTERNAL DIMENSIONS MAXIMUM WORKING PRESSURE lts. HEIGHT WIDTH DEPTH mm mm mm abs. bar kpa LOADING CAPACITY IN EUROPALLETS (dimensions mm.x1200) DLOG 101 640 --- DLOG 201 --- DLOG 211 1250 --- DLOG 311 1250 1250 1 DLOG 411 2925 1300 900 2500 2 DLOG 501 3625 2500 2 DLOG 511 5510 3 3 DLOG 521 7250 5000 4 DLOG 531 8990 6200 5 DLOG 541 10875 6 DLOG 551 12470 8600 7 DLOG 561 0 0 8 DLOG 611 16864 6200 10 DLOG 621 20400 12 DLOG 711 21675 12 DLOG 631 23392 8600 14 DLOG 651 27200 0 16 DLOG 811 24225 1900 12 DLOG 911 25994 2150 1950 6200 10 DLOG 931 37734 2150 1950 9000 14 Models indicated in above table are only some of standard sizing for DE LAMA DLOG and DLOG/V. Apart from the standard configurations indicated in the table, sterilizers can be proposed even with other dimensions, on request, according to Customer's production needs. Working parameters are for indication only and and can be modified in relation to Customer s working requirements. DLOG IN. 06-02 DE LAMA advises that technical data and features indicated in this folder are subject to without notice, owing to the continuous development of the technology and the research in the field. S T E R I L I Z E R S Via Piemonte, 21-27028 San Martino Siccomario (PV) - Italy Phone 0039 0382 559501 (5 lines) - 0039 0382 556627 ISDN - Fax 0039 0382 556224 http://www.delama.it - E-mail (Sales Dept.): sales@delama.it S.p.A.