Patent Application
20150033828
1. Field of the Invention
The present invention relates to an automated test apparatus for risk and integrity testing for pharmaceutical filtration membranes and method thereof, in particular relates to the risk and integrity testing for pharmaceutical filtration membranes for preparation of aseptic pharmaceutical production, and its isolated apparatuses.
2. Description of related Art
Conventional method of medicine liquid filtration often used a filter to exert pressure and then a 0.2 μm membrane for filtration. The membrane needs to undergo an integrity testing before and after the filtration to ensure complete blocking of microorganisms in the medicine liquid as a quality control standard to release the products. European GMP (PIC/S GMP Annex 1, Article 113) requests that membranes used as a filter for aseptic medicine preparation shall be sterilized and tested for its integrity before use, and shall also be verified after use with an appropriate test, for example, blistering point, diffusion flow or holding pressure test.
Although a confirmation of membrane integrity prior to use may reduce filtrate waste. Nevertheless, the approach of filtration test (Pre-Use Post Sterilization Integrity Test, PUPSIT) is still controversial, and a test operation in any form may increase the risk of contamination to the membrane, and the use of pre-test of integrity is to enhance the chance of contamination to the membrane. Moreover, if it is really damaged the membrane, the integrity test after use can be performed and detected, it is unnecessarily that the integrity testing has to be done prior to use. The only consensus reached is to adopt a risk assessment approach to determine whether to perform PUPSIT.
Although the confirmation of membrane integrity before use may reduce filtrate waste, one of disadvantages of the conventional approach is that any operation for the membrane integrity testing is likely to increase the risk of contamination, and the integrity test before use is one that increased probability of membrane contamination.
Another drawback of the conventional approach is that after completion of radiopharmaceuticals labeling, the present filter integrity testing begins with manual operation, that not only has the problem of radioactive exposure, there are test reproducibility and accuracy of the process need to be improved. If the drawback in these issues receives no proper treatment, it may result in excessive exposure and test result accuracy shortcomings to occur.
U.S. Pat. No. 7,770,434 disclosed a method of medicine dispensing in-process integrity testing without dismantling filter membranes. However, it did not disclose a computer controlled automated integrity and risk testing for filter membrane, respectively, after and before filtration, and the outputs of filter membrane were not concurrently connected to bubble generating bottles and pharmaceutical product bottles, respectively.
In view of the above described drawbacks arising after the completion of radiopharmaceutical labeling during filter membranes integrity testing before and after filtering process, the inventors of the present invention are aiming for solving drawbacks in a way of continuous study and research and eventually this invention is presented.
The primary object of the present invention is to provide an automated test apparatus for risk and integrity testing of pharmaceutical filtration membranes that is operable by a computer automatic control system, for example, by measuring a bubble point pressure of the filter maximum aperture for a 0.2 μm membrane risk and integrity testing to ensure the effectiveness of the 0.2 μm membrane integrity in production and subsequent process. The present invention is applicable to the production of nuclear medicine injections for the treatment and diagnosis with PET (Positron Emission Tomography) and SPECT (Single Photon Emission Computed Tomography), as well as nuclear medicine industry research and development, other related biologics pharmaceutical manufacturing processes and applications.
Another object of the present invention is to provide an automated test apparatus for risk and integrity testing of pharmaceutical filtration membranes. It is to provide an integrated automated control system for membrane risk and integrity testing in place of traditional method that is dependent from other devices, or manual operation, or indirect proof of test result, and effectively prevent outside environment from polluting to pharmaceutical bottles. It is also an object of the present invention to reduce the pollution from manual operation and exposure radioactive dose to person's hand to mitigate the stringent requirements for environmental equipments, and adequately save the cost of production and investment while retaining production efficiency and simplification in principle.
Another object of the present invention to provide an automated test apparatus for risk and integrity testing of pharmaceutical filtration membranes for filtering medicine while monitoring whether its steep drop exists in filtration pressure. It has sufficient evidences to prove that the level of damage probability of the filter membrane in the filtration process is properly controlled, and after the completion of filtration, the membrane integrity test is performed. The pre-use post sterilization integrity test (PUPSIT) and post-filtration integrity test are also considered in the present invention in order to achieve the requirements of risk assessment and good manufacture practice (GMP) regulation.
Another object of the present invention is to accomplish a sterility assurance in an automatic manner, including membrane risk test, membrane integrity test, as well as a device isolating process. In accordance with the sterile filter membrane specification, the membrane risk test is conducted and completed in process to justify the integrity of then used filter and confirm immediately after use with an automated method for bubble point pressure test, wherein the flow lines and bottle sets were sterilized or cleaned with procedures in line with GMP requirements. The present invention uses computer implemented automation to replace traditional manual method to achieve the risk control that couldn't be done previously. The control method of the present invention can effectively obviate the complexity in pharmaceutical production, and address the issue of personnel radioactive exposure and the likes, and in compliance with current economic efficacy.
Another object of the present invention is to provide an automated test apparatus for risk and integrity testing of pharmaceutical filtration membranes, which is capable of conducting an independent operation for filter membrane testing and connecting with other automation modules to carry out on-line filter membrane testing.
To achieve the above objects, the technical features of the automated test apparatus for risk and integrity testing of pharmaceutical filtration membrane of the present invention comprising a liquid inlet, a pump, a fluid pressure gauge, a gas pressure gauge, a plurality of solenoid valves, a plurality of membranes, a gas pressure regulating valve, a bottle of pharmaceutical product, and a bottle of bubble generation. The present invention is controlled by computer software and connected with a pharmaceutical automatic synthesis device for automatic testing operation. To use the automated test apparatus for risk and integrity testing of pharmaceutical filtration membrane of the present invention, when the pharmaceutical synthesis is completed, it only needs to start the operation system of the automated test apparatus, one can complete filter membrane risk and integrity testing in a short time to provide important references for pharmaceutical quality assessment.
As aforementioned, the automated test apparatus for risk and integrity testing of pharmaceutical filtration membrane of the present invention can be operated independently or in connection with other automation modules for online filter membranes testing.
The technical features of the automated test apparatus for risk and integrity testing of pharmaceutical filtration membrane of the present invention comprising:
1. Risk testing by gas, comprising at least the following steps:
2. Risk testing by liquid, comprising at least the following steps:
3. Integrity test by gas, comprising at least the following steps:
The above and other objects, features and advantages of the present invention will become apparent from the following detailed description taken with the accompanying drawings.
In one preferred embodiment of the present invention, when the membrane 5 is dry, the exerting pressure of gas pressure gauge is subject to about 5 psi.
In one preferred embodiment of the present invention, when the membrane 5 is wet and having holes, the exerting pressure of the gas pressure gauge is subject to in a range about 5˜12 psi.
In one preferred embodiment of the present invention, when the membrane 5 is wet and in integrity without holes, the exerting pressure of the gas pressure gauge is subject to in a range about 20˜25 psi.
From the above it is understood that the automated test apparatus for risk and integrity testing of pharmaceutical filtration membrane of the present invention can improve production efficiency, simplify operational processes, reduce the risk of contamination with radioactive pharmaceuticals, and resolve issues of personnel exposure of radioactive dose.
The foregoing invention has been described in detail by way of illustration and example for purposes of clarity and understanding. It will be apparent to those of ordinary skill in the art that variations, changes, modifications and alterations may be applied to the compositions and/or methods described herein without departing from the true spirit, concept and scope of the invention.
