GMP dry heat ovens for depyrogenisation and sterilisation

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1 GMP dry heat ovens for depyrogenisation and sterilisation Product Concept Standard specifications Options and accessories Commisioning services

2 What s a GMP sterilizer? The term GMP sterilizer has no official definition or specific requirements for the pharmaceutical industry. However, it is frequently used in the commercial literature to transmit a certain design, construction and performance of a sterilizer. In general, we consider that a GMP sterilizer must be designed and constructed to deliver effective desired cycles in a consistent and reproducible manner.

3 When to use a GMP sterilizer? Laboratory: GMP and non-gmp sterilizers are used, but do not require validation of performance, unless used for sterilization of release test articles such as sterility test media or equipment. Production: As validation for all load types is required, GMP sterilizers are widely used for this purpose.

4 Main concerns of hot air sterilisation and depyrogenation processes Microbiological patterns in depyrogenation: Bacillus subtillis, Tr = 250º C, Z = 46º C, typically 30 min depyrogenation time (USP XX) Temperature uniformity acceptable range ± 15ºC (USP XXIV), but optimum is ± 7.5ºC Integrity of chamber filters to guarantee Class 100 rate is one of the most critical issues unit shall pass periodical OQ DOP tests Load chamber configuration to allow air unidirectional flow in order to provide proper temperature distribution Cycle time depends on: Electrical power: the more electrical heaters are supplied, the faster is the oven to reach the temperature of depyrogenation Desired load temperature at the end of the cycle in order to unloading it: The lower is the desired temperature, the longer it takes to finish the cycle. The size of the cooling heat exchanger and the temperature/flow of the cooling water

5 Chamber and doors Chamber body, frame and doors are made of stainless steel AISI 316L sheet. All welds are properly treated. Front panels made of SS AISI 304 Chamber is heat insulated with rock wool and protected with SS AISI 304 stainless steel external cladding. All interior chamber surfaces in contact with the product are mirror polished.

6 Chamber and doors At both sides there are stainless steel AISI 316 perforated plates, in order to produce a uniform horizontal air flow. The metal sheet of the inner face is assembled as a sandwich between a PTFE and the door frame so it s floating. This design allows the expansion on the inner face without warping on the outer, which is submitted to much lower temperatures.

7 Chamber and doors Each door is supported on two shifting hinges so that the effort on the seal can be adjusted and leaks through it are prevented. Non-toxic silicone lip-shaped profiles housed in the chamber perimeter. The door has an angular piece forming a heat barrier and protecting the seal against direct contact with chamber air, thus prolonging its life.

8 Main components Prefiltering system 75% efficiency external air inlet pre-filter (F8). 90% efficiency external air inlet pre-filter (G4) % DOP efficiency HEPA type external air inlet filter (H14).

9 Main components Chamber inlet filters Camfil Termikfil 2000 (option) Protection of ultra-clean processes at high temperature, sterilisation tunnel for the pharmaceutical industry. Efficiency DOP: >= 99.99%. Frame: Composite ceramic. Gasket: Rolled glass fiber paper + 6 mm dia. glass braid. Grid: Upstream and downstream in stainless steel. Media: Glass fiber. Advantages: Meets FDA requirements - continuous 350 C, 99.99% at 0.3 µm Ceramic frame Exclusive precuring process at 300 C carried out in the plant Efficiency tested after precuring

10 Main components Chamber outlet filter CAM FRK CAM Termikfil Camfil Absolute 1FRK Protection of ultra-clean processes at high temperatures. Efficiency DOP: 99.97%. Frame: Stainless steel. Gasket: Glass fibre. Media: Glass fibre paper. Sealant: Ceramic, glass fibre. Separator: Aluminium. Temperature: 350 C in continuous service (400 C peak).

11 Main components A centrifugal fan/s SS AISI 316 for airflow chamber recirculation. A external centrifugal fan for air renewal. A set of electrical heaters SS AISI 316. Static contactors to switch on/off the heating resistors. Tubular heat exchanger SS AISI 316L, water-cooled, to cool down the load after sterilisation cycle. Two pressure transducers for control and monitoring: Differential pressure between inside chamber and room Pressure drop of internal chamber filters (recirculation). Two differential pressure switches to control pressure drop at inlet and outlet filters (renewal).

12 Main components Two Pt 100 temperature probes, at chamber air inlet and outlet, for control and monitoring the maximum and minimum chamber temperatures. This Pt 100 temp. probe is used to control sterilisation temperature. The other one located in the filtering system is for regulation of electrical heaters functioning

13 Working principle

14 Typical depyrogenation cycle Degrees Temp. Chamber Temp. Product Time

15 MicroSter Standard supervisory system Emergency Stop Colour touch-screen Control lights Locked doors Alarm Cycle running End of cycle Push buttons Open door Close door Alarm acknowledgement

16 MicroSter Standard supervisory system 3-channel graphic recorder for chamber pressure and temperature recordings. A thermal printer for recording main events and parameters of the cycle.

17 SCADA PharmaSter control system (option) Host PC computer for data logging and supervision Computer, PLC and chart recorder interconnected Synoptic diagrams Synoptics Self diagnostics On-line variables and alarms display Variable trends stored in historic files History Graphs Recipe confection

18 Accessories Additional temperature probe Pt channel dotted graphic recorder (instead of std. 3-channel) Loading carts Transfer trolleys Shelves or product support trays Set of spare parts for 1/2 year/s

19 Start up and training The unit is fully tested at our facilities simulating working conditions User s manual to set up, connection to utilities and start up. Start up and training is necessary when the customer is not very familiar with the process and sterilization technology

20 Validation Master Plan: FS/DS, DQ, FAT, IQ/OQ VMP protocols are submitted to customer DQ is recommended to assure all user requirements have been covered before manufacturing FAT is carried our at our facilities to demonstrate full achievement of the main critical issues involved in the project IQ and OQ is performed at customer facilities, separated from start up and training activities

21 Typical FAT testings Documentation checking; instruments and materials certificates, etc. Installation checking: Drawings and diagram conformity, instruments and component list Calibration of critical instruments (Temperature probes and pressure transducers) PLC input and output checking Access levels checking Alarm checking Thermal mapping of sterilisation cycles (a full cycle of empty chamber, 3 times) DOP test (filtering systems are DOP tested once installed) Velocity map Particle counting (Option)

22 Typical SAT (IQ/OQ) testings Documentation checking; instruments and materials certificates, etc. Installation checking: Drawings and diagram conformity, instruments and component list Calibration of critical instruments (Temperature probes and pressure transducers) PLC input and output checking Access levels checking Alarm checking Thermal mapping of sterilisation cycles (a full cycle of empty chamber, 3 times) DOP test (filtering systems are DOP tested once installed) Velocity map Particle counting to check achievement of Class 100 (Option)