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E-Beam—a new transfer system for isolator technology
Radiation Physics and Chemistry 63 (2002) 587–589
E-BeamFa new transfer system for isolator technology Theo Sadata,*, Thomas Huberb a
Thomson-CSF Linac, 16 rue Nicolas Appert, 91400 ORSAY, France b Skan AG, Postfach, CH-4009 Basel, Switzerland
Abstract In every aseptic filling application, the sterile transfer of goods into the aseptic area is a challenge, and there are many different ways to do it. With isolator technology a higher sterility assurance level (SAL) is achieved. This SAL is only as good as the weakest segment in the chain of manufacturing. The transfer of goods into and out of the isolator is one of these critical segments. Today different techniques, some already well established, others still very new, are available on the market like: dry heat tunnel, autoclave, pulsed light, rapid transfer systems (RTP), H2O2 tunnel, UV light, etc. all these systems are either not applicable for continuous transfer, only good for heat-compatible materials like glass, or do not guarantee a 6 log spore reduction. E-Beam opens new perspectives in this field. With E-beam technology it is possible to transfer heat-sensitive (plastic), pre-sterilised materials at high speed, continuously into an aseptic area. E-Beam unifies three different technologies, that result in a very efficient and high-speed decontamination machine designed for the pharmaceutical industry. First, there is the electron beam that decontaminates the goods and an accurate shielding that protects the surrounding from this beam. Second, there is the conveyor system that guarantees the output and the correct exposure time underneath the beam. And third, there is the isolator interface to provide correct differential pressure and clean air inside the tunnel as well as the decontamination of the tunnel with H2O2 prior to production. The e-beam is a low-energy electron beam, capable of decontaminating any kind of surface. It penetrates only a few micrometers into the material and therefore does not deform the packaging media. Currently, machines are being built to transfer pre-sterilised syringes, packed in plastic tubs with a Tyvek cover into an aseptic filling isolator with the following data: decontamination efficiency of 106 (6 log spore reduction), decontamination speed of 6 tubs (600 syringes) per minute. This is just one of many applications for this new technology. r 2002 Published by Elsevier Science Ltd.
1. Description of the system
1.1. Shielding
The system is composed of: shielding, isolator, conveyor, accelerator, computerised control. The overall dimensions are 4 m 3 m 2.8 m.
The shielding is made of 1.5 cm thick lead alloy, built to a labyrinthine design in order to ensure complete biological protection (see Fig. 1 ). In the area immediately outside the shielding, the dose rate is o0.1 m rem/ h. For this reason, the system requires no official authorisations, and can be installed in a public area. All the calculations, however, were carried out by Thomson-CSF Linac and their subcontractor, with the approval of the French Atomic Energy Commissariat
*Corresponding author. Present address: Skan AG, Postfach, CH-4009 Basel, Switzerland. E-mail address: [email protected] (T. Sadat), [email protected] (T. Huber).
0969-806X/02/$ - see front matter r 2002 Published by Elsevier Science Ltd. PII: S 0 9 6 9 - 8 0 6 X ( 0 1 ) 0 0 6 3 9 - 9
T. Sadat, T. Huber / Radiation Physics and Chemistry 63 (2002) 587–589
588
Fig. 1. Conveyor layout inside biological protection.
(CEA). The external surface of the shielding is made of stainless steel.
1.2. Conveyor The conveyor belt carries the Hypak tubs from the handling area to the filling zone. The conveyor is divided into two parts, one circulating at the handling area side, the other at the filling zone side. This prevents contamination of the filling area by the conveyor. The space between the two conveyors allows the lower surface of the Hypak tub to be irradiated. The conveyor is built entirely of stainless steel components according to pharmaceutical standards. Conveyor speed is variable from 0.5 to 4 m/min.
1.3. Isolator The isolator consists of an outer housing, a decontamination tunnel and isolator interface. The outer housing is made of stainless steel and covers the entire installation including accelerator, lead shielding and decontamination tunnel. The purpose of the housing is cosmetic, protecting the surroundings from direct contact with the shielding. Access doors allow service activity on the e-beam and the decontamination tunnel.
The control cabinet for the accelerator and conveyor belts is integrated into the housing. The stainless steel decontamination tunnel covers the conveyor system, provides class 100 conditions between the accelerator and the pealing isolator, provides positive differential pressure in the area between the accelerator and the pealing isolator, prevents O3 escaping into the surrounding room during production, and prevents H2O2 escaping into the room during decontamination. The tunnel has service openings and contains a fan for exhaust and air circulation, an HEPA filter with negative pressure plenum, two gas-tight flaps for exhaust and air circulation, and a mousehole with cover at tub infeed and tub outfeed. The surface decontamination of the tunnel before production is performed in combination with that of the pealing/filling isolator. The H2O2 required for the decontamination mode is vapourised inside the isolator and guarantees a 6 log spore reduction on all surfaces inside the e-beam tunnel and the pealing/filling isolator. All components required for the control of the isolator are integrated into the control cabinet of the filling isolator (Fig. 2).
1.4. Accelerator With the aim of obtaining homogeneous dosage on the entire surface of the tub, three accelerators are used, installed at 1201 from each other, thereby creating an electron beam ‘‘curtain’’. The tub passes through the curtain, which provides homogeneous sterilisation. Each accelerator delivers up to 200 KeV energy and up to 5 mA current. The beam is scanned on the product with a 20 cm scan width. In order to compensate the edge effect, a specific sinusoidal is used. The goal is to have minimum 25 kGy on the surface of the tub and also 25 kGy just beneath the Tyvek sheet,
Fig. 2. E-Beam integration in isolator: production mode showing airflow (diagram by Skan AG).
T. Sadat, T. Huber / Radiation Physics and Chemistry 63 (2002) 587–589
589
Fig. 3. Accelerator layout showing shielding structure; photograph of prototype (tub is upside down in this view).
without any dose reaching the syringes. That is why the energy has to be correctly tuned in order to avoid: (a) ozone production inside the tub and (b) glass coloration. The power of the machine has to be selected according to the requested throughput, which in this case is 6 Hypak boxes per minute (Fig. 3). 1.5. Dosimetry results We used dosimetric films from Far West Technologies and GEX Corporation, placed in strategic areas. The dose measurements show that 25 kGy dose minimum is attained on the entire surface of the tub. The dose distribution rate ranges from 25 to 37 KGy (Fig. 4).
2. Conclusion This system has been developed as an isotropic, single-pass treatment for a large company because
Fig. 4. Dose measurements were made on tub cover and on Tyvek sheet under tub cover.
the existing methods (pulsed light, hydrogen peroxide) were not very satisfactory, in particular due to the lack of standards. The e-beam system gives high throughput allied with monitoring effectiveness and reliability.
E-BeamFa new transfer system for isolator technology Theo Sadata,*, Thomas Huberb a
Thomson-CSF Linac, 16 rue Nicolas Appert, 91400 ORSAY, France b Skan AG, Postfach, CH-4009 Basel, Switzerland
Abstract In every aseptic filling application, the sterile transfer of goods into the aseptic area is a challenge, and there are many different ways to do it. With isolator technology a higher sterility assurance level (SAL) is achieved. This SAL is only as good as the weakest segment in the chain of manufacturing. The transfer of goods into and out of the isolator is one of these critical segments. Today different techniques, some already well established, others still very new, are available on the market like: dry heat tunnel, autoclave, pulsed light, rapid transfer systems (RTP), H2O2 tunnel, UV light, etc. all these systems are either not applicable for continuous transfer, only good for heat-compatible materials like glass, or do not guarantee a 6 log spore reduction. E-Beam opens new perspectives in this field. With E-beam technology it is possible to transfer heat-sensitive (plastic), pre-sterilised materials at high speed, continuously into an aseptic area. E-Beam unifies three different technologies, that result in a very efficient and high-speed decontamination machine designed for the pharmaceutical industry. First, there is the electron beam that decontaminates the goods and an accurate shielding that protects the surrounding from this beam. Second, there is the conveyor system that guarantees the output and the correct exposure time underneath the beam. And third, there is the isolator interface to provide correct differential pressure and clean air inside the tunnel as well as the decontamination of the tunnel with H2O2 prior to production. The e-beam is a low-energy electron beam, capable of decontaminating any kind of surface. It penetrates only a few micrometers into the material and therefore does not deform the packaging media. Currently, machines are being built to transfer pre-sterilised syringes, packed in plastic tubs with a Tyvek cover into an aseptic filling isolator with the following data: decontamination efficiency of 106 (6 log spore reduction), decontamination speed of 6 tubs (600 syringes) per minute. This is just one of many applications for this new technology. r 2002 Published by Elsevier Science Ltd.
1. Description of the system
1.1. Shielding
The system is composed of: shielding, isolator, conveyor, accelerator, computerised control. The overall dimensions are 4 m 3 m 2.8 m.
The shielding is made of 1.5 cm thick lead alloy, built to a labyrinthine design in order to ensure complete biological protection (see Fig. 1 ). In the area immediately outside the shielding, the dose rate is o0.1 m rem/ h. For this reason, the system requires no official authorisations, and can be installed in a public area. All the calculations, however, were carried out by Thomson-CSF Linac and their subcontractor, with the approval of the French Atomic Energy Commissariat
*Corresponding author. Present address: Skan AG, Postfach, CH-4009 Basel, Switzerland. E-mail address: [email protected] (T. Sadat), [email protected] (T. Huber).
0969-806X/02/$ - see front matter r 2002 Published by Elsevier Science Ltd. PII: S 0 9 6 9 - 8 0 6 X ( 0 1 ) 0 0 6 3 9 - 9
T. Sadat, T. Huber / Radiation Physics and Chemistry 63 (2002) 587–589
588
Fig. 1. Conveyor layout inside biological protection.
(CEA). The external surface of the shielding is made of stainless steel.
1.2. Conveyor The conveyor belt carries the Hypak tubs from the handling area to the filling zone. The conveyor is divided into two parts, one circulating at the handling area side, the other at the filling zone side. This prevents contamination of the filling area by the conveyor. The space between the two conveyors allows the lower surface of the Hypak tub to be irradiated. The conveyor is built entirely of stainless steel components according to pharmaceutical standards. Conveyor speed is variable from 0.5 to 4 m/min.
1.3. Isolator The isolator consists of an outer housing, a decontamination tunnel and isolator interface. The outer housing is made of stainless steel and covers the entire installation including accelerator, lead shielding and decontamination tunnel. The purpose of the housing is cosmetic, protecting the surroundings from direct contact with the shielding. Access doors allow service activity on the e-beam and the decontamination tunnel.
The control cabinet for the accelerator and conveyor belts is integrated into the housing. The stainless steel decontamination tunnel covers the conveyor system, provides class 100 conditions between the accelerator and the pealing isolator, provides positive differential pressure in the area between the accelerator and the pealing isolator, prevents O3 escaping into the surrounding room during production, and prevents H2O2 escaping into the room during decontamination. The tunnel has service openings and contains a fan for exhaust and air circulation, an HEPA filter with negative pressure plenum, two gas-tight flaps for exhaust and air circulation, and a mousehole with cover at tub infeed and tub outfeed. The surface decontamination of the tunnel before production is performed in combination with that of the pealing/filling isolator. The H2O2 required for the decontamination mode is vapourised inside the isolator and guarantees a 6 log spore reduction on all surfaces inside the e-beam tunnel and the pealing/filling isolator. All components required for the control of the isolator are integrated into the control cabinet of the filling isolator (Fig. 2).
1.4. Accelerator With the aim of obtaining homogeneous dosage on the entire surface of the tub, three accelerators are used, installed at 1201 from each other, thereby creating an electron beam ‘‘curtain’’. The tub passes through the curtain, which provides homogeneous sterilisation. Each accelerator delivers up to 200 KeV energy and up to 5 mA current. The beam is scanned on the product with a 20 cm scan width. In order to compensate the edge effect, a specific sinusoidal is used. The goal is to have minimum 25 kGy on the surface of the tub and also 25 kGy just beneath the Tyvek sheet,
Fig. 2. E-Beam integration in isolator: production mode showing airflow (diagram by Skan AG).
T. Sadat, T. Huber / Radiation Physics and Chemistry 63 (2002) 587–589
589
Fig. 3. Accelerator layout showing shielding structure; photograph of prototype (tub is upside down in this view).
without any dose reaching the syringes. That is why the energy has to be correctly tuned in order to avoid: (a) ozone production inside the tub and (b) glass coloration. The power of the machine has to be selected according to the requested throughput, which in this case is 6 Hypak boxes per minute (Fig. 3). 1.5. Dosimetry results We used dosimetric films from Far West Technologies and GEX Corporation, placed in strategic areas. The dose measurements show that 25 kGy dose minimum is attained on the entire surface of the tub. The dose distribution rate ranges from 25 to 37 KGy (Fig. 4).
2. Conclusion This system has been developed as an isotropic, single-pass treatment for a large company because
Fig. 4. Dose measurements were made on tub cover and on Tyvek sheet under tub cover.
the existing methods (pulsed light, hydrogen peroxide) were not very satisfactory, in particular due to the lack of standards. The e-beam system gives high throughput allied with monitoring effectiveness and reliability.