A system and method for transferring aseptically packaged aseptic material from a non-aseptic environment to an aseptic environment

Abstract

This invention discloses a system and method for transferring aseptically packaged sterile materials from a non-sterile environment to a sterile environment. The system includes recombinant air intake bags (RABs) and an isolator adjacent to the RABs. The laminar flow hoods of the RABs provide Class A unidirectional flow. Each RAB has a material transfer window at its front end, a waste discharge port on its side, and a rat hole at the connection point between the RABs and the isolator. The laminar flow hoods of the isolator also provide Class A unidirectional flow. The method involves transferring materials with at least one layer of sterile outer packaging through the material transfer window to a designated location within the RABs. Self-cleaning occurs under good Class A unidirectional flow. After self-cleaning, the outer packaging is removed, and the sterile material inside the bag is transferred to the isolator. This invention is suitable for the aseptic transfer of materials that cannot be sterilized by moist heat; it allows for continuous aseptic transfer; and each aseptic transfer is time-efficient.

Description

Technical Field

[0001] This invention relates to the field of aseptic transfer technology, specifically a system and method for transferring aseptically packaged sterile materials from a non-sterile environment to a sterile environment, applicable to industries such as pharmaceuticals, biotechnology, and food. Background Technology

[0002] Currently, the aseptic transfer technologies used in the domestic pharmaceutical and biotechnology industries mainly include RTP (Rapid Transfer Ports) and VHP (Vacuum-High Temperature) purification technology. RTP has several drawbacks: 1) it is not suitable for aseptic transfer of materials that cannot be sterilized by moist heat; 2) a single sterilization cycle is time-consuming; 3) for products requiring thorough drying after sterilization, it is difficult to guarantee complete drying; 4) continuous aseptic transfer of materials is not possible. VHP purification technology connects a VHP chamber to the aseptic production area. Aseptically packaged materials are placed in the VHP chamber, and after purification, the two are connected, allowing the materials to be transferred to the aseptic production area. This method has the following drawbacks: 1) a long VHP cycle time; 2) high cost of VHP chambers; 3) the risk of hydrogen peroxide permeation and residue. Summary of the Invention

[0003] In order to overcome the shortcomings of the prior art, the present invention aims to provide a system and method for transferring aseptically packaged materials from a non-sterile environment to a sterile environment, so as to achieve continuous aseptic transfer.

[0004] According to one aspect of the present invention, a system for transferring aseptically packaged sterile materials from a non-sterile environment to a sterile environment is provided. The system includes receptacles (RABs) and isolators adjacent to the RABs. The laminar flow hoods of the RABs provide Class A unidirectional flow. The front end of the RABs is provided with a material transfer window, the side of the RABs has a waste discharge port, and a rat hole is provided at the connection between the RABs and the isolator. The laminar flow hood of the isolator provides Class A unidirectional flow.

[0005] In the technical solution of the system described in this invention, preferably, the pressure inside the isolator is greater than the pressure inside the RABs, and the pressure difference is not less than 17.5 Pa, and this condition can still be met when the mouse hole is opened.

[0006] In the technical solution of the system described in this invention, preferably, the isolator is purified by VHP before operation so that the interior of the isolator is in a sterile environment.

[0007] In the technical solution of the system described in this invention, preferably, the cleanroom level where the RABs and isolators are placed is not lower than Class C. Here, Class C refers to the cleanroom for less critical operational steps in the sterile drug production process. Specific standards are as follows: Maximum permissible number of suspended particles / cubic meter: Static conditions: ≥0.5μm, 352,000 particles; ≥5μm, 2,900 particles; Dynamic conditions: ≥0.5μm, 3,520,000 particles; ≥5μm, 29,000 particles. The above information is derived from the Appendix on Sterile Drugs in the "Good Manufacturing Practice for Pharmaceuticals (2010 Revision)".

[0008] In the technical solution of the system described in this invention, preferably, the system further includes a wind speed detection probe respectively disposed in the RABs and the isolator.

[0009] According to another aspect of the present invention, the present invention provides an aseptic transfer method for transferring aseptically packaged sterile material from a non-sterile environment to a sterile environment using the system described above, the aseptic transfer method comprising the following steps: 1) transferring sterile material with a layer of sterile packaging into the RABs through a material transfer window at the front end of the RABs; 2) transferring the sterile material with a layer of sterile packaging to a designated location within the RABs; 3) self-cleaning the sterile material with a layer of sterile packaging under Class A unidirectional flow; 4) after self-cleaning, fixing the outer packaging and opening the opening of the outer packaging on the side adjacent to the mouse hole; 5) automatically transferring the sterile material inside the bag into the isolator; and 6) transferring the waste outer packaging material outside the RABs through a waste discharge port on the side of the RABs.

[0010] In the technical solution of the aseptic transfer method of the present invention, preferably, before self-cleaning, the outer surface of the aseptic packaging can be disinfected with a disinfectant. The disinfectant used here is a commonly used disinfectant.

[0011] In the technical solution of the aseptic transfer method of the present invention, preferably, the aseptic packaged aseptic material has at least one layer of aseptic outer packaging.

[0012] In the aseptic transfer method described in this invention, self-cleaning is performed under Class A unidirectional flow, where the velocity of the unidirectional flow is 0.45 m / s ± 20% vertically downward. Furthermore, the velocity of this unidirectional flow is constantly monitored by the wind speed probe 207 within the oRABs. If the velocity exceeds the range of 0.45 m / s ± 20%, the device immediately triggers an alarm.

[0013] In addition, when the designated location is less than 10cm away from the mouse hole II211, the outer packaging of the sterile material is fixed.

[0014] The beneficial effects of this invention are: 1) it is suitable for the aseptic transfer of materials that cannot be sterilized by moist heat; 2) it can perform continuous aseptic transfer; 3) it has a short time consumption for a single aseptic transfer. Attached Figure Description

[0015] Figure 1 This refers to a system for transferring sterile material in a single layer of aseptic packaging from a non-sterile environment to a sterile environment;

[0016] Figure 2 This refers to a system for transferring sterile materials in a three-layer aseptic package from a non-sterile environment to a sterile environment.

[0017] Explanation of reference numerals in the attached figures:

[0018] 101-RABs, 102-Wind speed detection probe, 103-RABs front-end material transfer window, 104-Waste discharge port, 105-Single-layer packaged sterile material, 106-Class A unidirectional flow, 107-Isolator, 108-Wind speed detection probe, 109-Rat hole, 110-Class A unidirectional flow, 201-Triple-layer packaged sterile material, 202-oRABs, 203-Material transfer window, 204-Double-layer packaged sterile material, 205-Rat hole I 206-oRABs waste discharge port, 207-oRABs internal wind speed probe, 208-oRABs internal Class A unidirectional flow, 209-cRABs, 210-one-layer packaged sterile material, 211-rat hole II, 212-cRABs internal wind speed probe, 213-cRABs waste discharge port, 214-cRABs internal Class A unidirectional flow, 215-isolator, 216-isolator internal wind speed probe, 217-isolator internal Class A unidirectional flow. Detailed Implementation

[0019] The present invention will be further described in detail through the following embodiments and accompanying drawings, but is not limited to the following embodiments and the range of process parameters in the embodiments.

[0020] Please see Figure 1 , Figure 1 This refers to a system that transfers a layer of aseptically packaged material from a non-sterile environment to a sterile environment. For example... Figure 1 As shown, the system includes RABs 101 and an isolator 107 adjacent to RABs 101; the laminar flow hood of RABs 101 provides Class A unidirectional flow 106, a material transfer window 103 is provided at the front end of RABs 101, a waste discharge port 104 is provided on the side of RABs 101, and a mouse hole 109 is provided at the connection between RABs 101 and isolator 107; the laminar flow hood of isolator 107 provides Class A unidirectional flow 110. Preferably, a wind speed detection probe 102 and a wind speed detection probe 108 are respectively provided in RABs 101 and isolator 107.

[0021] The pressure inside the isolator 107 is greater than the pressure inside the RABSs 101, and the pressure difference is not less than 17.5 Pa, which is still met even when the rat hole 109 is open. Preferably, the isolator 107 is purified by VHP before operation to ensure that the interior of the isolator 107 is in a sterile environment. The cleanroom level where the RABSs and the isolator are placed is not lower than Class C.

[0022] Please see again Figure 2 , Figure 2 This refers to a system for transferring triple-layered aseptically packaged materials from a non-sterile environment to a sterile environment. For example... Figure 2As shown, after unpacking the three-layered sterile material 201 into a two-layered sterile outer packaging, the material transfer window 203 at the front of the oRABs is opened, and the operator transfers the material to the oRABs 202. The operator, wearing oRABs gloves, places the two-layered sterile material 204 in a designated location. Self-cleaning is performed under good Grade A unidirectional flow 208. This unidirectional flow is a vertically downward unidirectional flow with a velocity of 0.45 m / s ± 20%, and the velocity is constantly monitored by the wind speed probe 207 inside the oRABs. If the velocity exceeds the range of 0.45 m / s ± 20%, the device immediately alarms. The self-cleaning time is monitored. After the self-cleaning time is reached, the automatic unpacking device inside the oRABs 202 cuts open the outer packaging of the two-layered sterile material 204. A robotic arm inside the cRABs 209 uses a mouse hole I 205 to grab the single-layered sterile material 210 into the cRABs 209. Operators, wearing oRABs gloves, pass packaging waste from oRABs 202 out through the waste discharge port 206 on the side of oRABs 202. Aseptic material 210, with one layer of packaging, enters cRABs 209 and is then transported to a designated location via an automatic transfer track. The designated location is less than 10cm from the mouse hole II 211, securing the outer packaging of the aseptic material. Self-cleaning is performed under good Grade A unidirectional flow 214, where the unidirectional flow velocity is 0.45m / s ± 20% vertically downward, and the velocity is constantly monitored by the wind speed probe 212 inside the cRABs. If the velocity exceeds the range of 0.45m / s ± 20%, the equipment immediately alarms. The self-cleaning time is monitored; after the self-cleaning time is reached, an automatic unpacking device automatically opens the opening of the outer packaging on the side adjacent to the mouse hole and uses a vacuum suction cup to prop the opening open. Inside isolator 215, a robotic arm uses a rat hole II 211 to grab sterile materials and place them into the isolator for later use. The isolator has been pre-purified using VHP and is in a sterile state. The isolator contains a unidirectional airflow 217 at a vertical downward speed of 0.45 m / s ± 20%. The velocity of this unidirectional flow is constantly monitored by an air velocity probe 216 inside the isolator; if the velocity exceeds the 0.45 m / s ± 20% range, the device immediately alarms. After the transfer is complete, the operator, wearing cRABs gloves, transfers the waste from cRABs 209 out of cRABs 209 through the waste discharge port 213 on the side of cRABs 209. The technology of this invention 1) is applicable to the aseptic transfer of materials that cannot be sterilized by moist heat; both VHP purification technology and this patented technology can achieve aseptic transfer of materials that cannot be sterilized by moist heat, while RTP rapid transfer technology cannot achieve this; 2) can perform continuous aseptic transfer; only this patented technology can achieve continuous aseptic transfer, while RTP rapid transfer technology and VHP purification technology can only achieve batch transfer.

[0023] In particular, the method of this invention shows that the time for a single transfer is approximately 7 minutes, indicating a short time for a single aseptic transfer. In contrast, the RTP rapid transfer technology takes approximately 3 hours for a single batch of sterilization transfer, and the VHP purification technology takes approximately 45 minutes for a single batch of purification transfer.

[0024] The above description only illustrates preferred embodiments of the present invention and should not be construed as limiting the scope of the claims. The present invention is not limited to the above embodiments, and variations in its specific structure are permitted. All modifications made within the scope of the independent claims of this invention are also within the scope of protection of this invention.

Claims

1. A method for aseptically transferred aseptically packaged materials from a non-sterile environment to a sterile environment, comprising a system for transferring aseptically packaged aseptic materials from a non-sterile environment to a sterile environment, the system comprising receptacles (RABs) and isolators adjacent to the RABs; the laminar flow hoods of the RABs provide Class A unidirectional flow, the front end of the RABs is provided with a material transfer window, the side of the RABs is provided with a waste discharge port, a robotic arm is located inside the isolator, and a mouse hole is located at the connection between the RABs and the isolator; the laminar flow hoods of the isolators provide Class A unidirectional flow; the pressure inside the isolator is greater than the pressure inside the RABs, and the pressure difference is not less than 17.5 Pa, and this pressure difference is still met even when the mouse hole is open; the aseptic transfer method comprises the following steps: 1) Sterile materials with a single layer of aseptic packaging are transferred into the RABs through the material transfer window at the front end of the RABs; 2) Sterile material with a single layer of aseptic packaging is delivered to a designated location within the RABs; 3) Aseptic materials with a single layer of aseptic packaging undergo self-cleaning under Grade A unidirectional flow; 4) After self-cleaning is complete, secure the outer packaging and open the opening of the outer packaging on the side adjacent to the mouse hole; 5) Automatically transfer the sterile material inside the bag to the isolator; and 6) Transfer the waste outer packaging material outside the RABs through the waste discharge port on the side of the RABs.

2. The aseptic transfer method according to claim 1, characterized in that, Before self-cleaning, the outer surface of the aseptic packaging is disinfected with a disinfectant.

3. The aseptic transfer method according to claim 1, characterized in that, The aseptic packaged aseptic material has at least one layer of aseptic outer packaging.

4. The aseptic transfer method according to claim 1, characterized in that, The isolator is first purified by VHP before operation to ensure that the inside of the isolator is in a sterile environment.

5. The aseptic transfer method according to claim 1, characterized in that, The cleanroom level where the RABs and the isolator are placed is no lower than Class C.

6. The aseptic transfer method according to claim 1, characterized in that, A wind speed detection probe is installed in both the RABs and the isolator.

Images