“Filtration” alludes to the division of minuscule strong particles or spray particles in liquids (gases and fluids) from the liquid, and the gadget used to accomplish this partition is a filtration gadget, which should be fitted with a filtration layer, and just when the film has a high filtration effectiveness would the liquid be able to become unadulterated or sterile. “Refinement” is additionally a sort of partition, yet broad decontamination gadgets, for example, tornado separators, vortex tube separators, gas-fluid separators, and so on don’t have channel films, depending on logical and sensible mechanical construction configuration, can isolate bigger particles, the overall cleaning exactness are above 1μm. In the biopharmaceutical and other aging businesses, air filtration and refinement innovation is broadly utilized in the planning of sterile air frameworks.
Collapsed film air channels, which can supplant the conventional air channels with cotton and actuated carbon as media, have shown extraordinary predominance as far as energy saving, ecological security and utilization decrease. In almost 30 years, our organization has fostered an assortment of sterile air framework hardware, which have been applied to the aging business and have been generally welcomed and supported by clients. The new energy-saving aseptic air filtration framework containing five public patent items, for example, one-piece collapsed film channel is displayed in Figure 1.
1 New energy-saving aseptic air filtration framework stream outline (the graph is “one-piece collapsed layer channel”)
1-Air blower pre-processor 2-Air blower 3-Air stockpiling tank 4-Cooler 5-Gas-fluid separator 6-Heater
7 – Scroll tube separator 8 – Master air channel 9 – Steam channel 10 – One-piece collapsed film channel
11-Stopping gadget 12-Fermenter 13-Escape trap
1 Structural investigation of aseptic air channels
The aseptic air channels utilized in the aging business have gone through a course of change from low effectiveness and high energy utilization to high proficiency and low energy utilization. At the point when the channel media of absolute air channel and sub-channel are cotton and actuated carbon, it is called cotton charcoal + cotton charcoal channel; when the channel media of all out air channel and sub-channel are cotton, initiated carbon and glass fiber, it is called cotton charcoal + covered plate channel; when the channel media of all out air channel and sub-channel are glass fiber and metal composite layer, it is called glass fiber + metal film channel; when the channel media of complete air channel and sub-channel are glass fiber and metal composite film, it is called glass fiber + metal film channel; when the channel media of all out air channel and sub-channel are glass fiber and metal composite layer channel, it is called glass fiber + metal layer channel. At the point when the channel vehicle of the sub-channel is glass fiber and PTFE film, it is called collapsed layer + polymer film channel.
1.1 Cotton carbon channel structure
China’s maturation industry creation started during the 1950s, from that point until the mid-1980s, has been utilizing cotton, initiated carbon as the primary vehicle of sterile air filtration gear.
Inside the shell of the cotton-carbon channel, cotton and initiated carbon are put in layers and fixed by parts and screws. The air enters from the lower part of the shell and is released from the top after a few layers of cotton and actuated carbon.
Figure 2 shows a sketch of the construction of a cotton charcoal channel. The cotton charcoal channel is partitioned into two kinds, to be specific the absolute air channel and the sub-channel. Contingent upon the size of the stream rate, their outer aspects are unique, however the interior design is something very similar. The headspace channel is the primary phase of filtration and captures principally oil fog, water fog and bigger particles. The sub-channel is the second phase of filtration. In the event that the separated air doesn’t arrive at the necessary filtration exactness of the aging fluid, one more phase of filtration can be added to guarantee that the sifted air meets the prerequisites of the aging system.
Benefits of the cotton carbon channel.
(1) Fewer gadgets are designed in the framework, which works with incorporated plan and the board.
(2) Cotton and initiated carbon, media materials, are effectively accessible, generally modest and have a long assistance life.
(3) Through the aggregate and sub-stage sterile filtration, it is not difficult to design and often supplant the sub-channel media, and each clump of media can be autoclaved prior to entering the tank, which can all the more dependably give the sterile air needed to the maturation cycle. Considering these benefits, making the cotton carbon channel in the previous many years, in the development of Chinese and unfamiliar maturation industry has been involving an indispensable predominant position.
Nonetheless, as per the attributes of cotton and actuated carbon itself, as a channel mechanism for sterile air channels, it has a few difficult imperfections.
(1) Large strain misfortune, the complete loss of tension drop of 0.06 to 0.07 MPa for two-stage filtration.
(2) Easily tainted with microorganisms, bringing about a lot of steam and misuse of natural substances.
(3) tedious and work concentrated to supplant the media, laborers work force, genuine ecological contamination. As biopharmaceuticals and other aging items are delivered persistently, the yearly energy utilization is extremely enormous, so the utilization of cotton charcoal channel will carry a significant weight to the venture, the aging business energy saving and utilization decrease needs are especially noticeable, the market and clients earnestly need more dependable and proficient filtration media and filtration framework to meet the creation needs of the aging business.
1.2 QJX high-effectiveness gas sanitization framework
The advancement of QJX high-proficiency gas refinement membrane filter press framework (hereinafter alluded to as metal film channel) began in 1985. Confronting the dire interest for new air filtration framework in the maturation business, our experts applied the mechanical advancement of military partition layer to regular citizen items and effectively created metal film channel with filtration accuracy of 0.01μm, what broke the circumstance that cotton charcoal channel overwhelmed in the aging business.
Metal film is an exceptional layer utilized in the atomic business. Metal film channels utilize surface and profound filtration systems, and the liquid structure is vortex shear cross stream. The outer layer of the metal film is not difficult to perfect, the profound filtration has a huge residue limit, and the vortex shear cross-stream structure can ceaselessly release dust, consequently guaranteeing the long assistance life of the metal film channel can arrive at over 5 years. Its particular elements are: (1) high framework dependability; (2) progressed filtration instrument; (3) high framework cost adequacy. The filtration accuracy of the metal layer channel made with nanotechnology can reach 0.01μm.
The metal film channel mostly incorporates pre-channel, primary channel and non-turn around gadget. The framework takes on the type of pre and fundamental channels associated upward. The pre-channel cartridge is barrel shaped, with gas bay outside and outlet inside, enormous single branch stream volume and simple establishment and substitution. The film tube is organized in a cluster, and the heading of wind current is internal and outward. The film tube and the cylinder plate are associated by chilly welding innovation, and the entire machine has no joints. The sanitization temperature can arrive at 180°C, and rehashed sterilization won’t make the framework execution break down. The float of the gadget is planned as a twofold float structure, which can successfully keep harm to the primary channel from backpressure and fluid reverse, and ensure the fermenter, and help to keep the tension of the fermenter if there should arise an occurrence of unexpected power disappointment, gas disappointment or different mishaps. The metal film channel and the metal layer tube are displayed in Figure 3.
Figure 3 Metal layer channel and metal film tube
From the last part of the 1980s, metal film channel in North China Pharmaceutical Factory, Jiangxi Dongfeng Pharmaceutical Factory, Shandong Lu Anti Group, Nanyang Pu Kang Pharmaceutical Company and other almost 100 aging endeavors have been effectively applied, maturation items aging unit/normal yield, single tank yield, the pace of pollution of microorganisms and different pointers have been enormously improved and improved, have accomplished impressive financial advantages.
Simply North China Pharmaceutical Factory 108 aging studio, for instance, the full utilization of metal film channels after the outcomes are self-evident: (1) the seed tank pollution rate fell by over 30%, financial advantages added up to 1.428 million yuan/year. (2) hundred tons of maturation tank microorganisms pollution rate diminished by over half, this by itself, the yearly monetary advantages of 980,000 yuan. Because of the improvement of air quality, the expense per unit of item was fundamentally diminished, and the yearly pay produced added up to RMB 4.57 million. (3) Completely supplanted the cotton charcoal channel, saving cotton and initiated carbon assets of 173,000 yuan each year. (4) Annual reserve funds of north of 1,000 t of sterilization steam, worth 20,000 yuan. The complete yearly financial advantage is 7,171,000 yuan.
By utilizing metal film channels, the key homegrown cleanomycin makers have supplanted the obsolete cotton and charcoal channels, bringing about a principal improvement in air quality and clear advantages. The important markers when the improvement of sterile air channels are looked at as displayed in Table 1.
Table 1 Comparison of important markers when the improvement of sterile air channels
Highlights of the one-piece channel
3.1 Novel plan and sensible design
The one-piece channel works on the design of the split channel (medium and high productivity channels are associated by valves, and the medium effectiveness channel can’t be sanitized), and interfaces the medium and high proficiency channels upward. Under a similar wind current, the incorporated channel occupies less room than the split channel, and the channel component is not difficult to introduce and supplant.
3.2 Reduced beginning tension, great energy-saving impact
Because of the sensible underlying model, the one-piece channel lessens the quantity of lines with 90º turns in the wind stream from one perspective, and takes on a high stream rate and low opposition of the collapsed chamber construction of the medium-impact channel component then again, which decreases the air obstruction. The two angles together serve to decrease the strain drop all around framework, making the underlying tension drop more modest than that of the split channel.
3.3 Overall sterilization and high unwavering quality
The medium and high effectiveness channels of the split channel are associated by valves, and the medium proficiency channel can’t be sanitized, which builds the chance of bacterial tainting of the maturation material. The coordinated channel successfully defeats this inadequacy, as the medium and high effectiveness channels can be sanitized simultaneously at a high temperature of <150 °C.
3.4 Cost decrease and significant expense execution
The one-piece channel saves the shell of the split channel, for example the lower shell of the medium-execution channel and the upper shell of the great productivity channel, and saves the treated steel valve utilized for association between the medium and high-effectiveness channels. The over two things represent around 1/3 of the cost of the split channel, decreasing the expense of the one-piece channel.
3.5 Eradicating stowed away issues and forestalling them before they happen
After sanitization of the channel or under states of high air moistness, it is not difficult to shape fluid water in the lodging of the medium and high productivity channels. In light of the present circumstance, the internal pit of the one-piece channel is keenly planned with an inflow hydrophobic plate gadget. Under the activity of pneumatic stress, the fluid water is released along the planned inflow channel, which generally wipes out the chance of bacterial pollution of the aging fluid.
3.6 Online identification capacity to forestall defilement
An identification valve is introduced on the exhaust line of the great proficiency channel, which can be associated with the laser molecule counter for air accuracy testing through plastic cylinder. Under working condition, in view of the information identified by the incorporated channel, it very well may be decided whether the air accuracy meets the necessities of the aging system. In the event that the information doesn’t satisfy the guideline, successful measures can be taken on schedule, for example, supplanting the channel cartridge or researching other potential issues that might cause bacterial pollution of the material.
An examination of the exhibition of the aseptic air channels is displayed in Table 3.
Table 3 Aseptic air channel execution examination table
4 Notes on issues connecting with one-piece channels
4.1 Cartridge establishment activity
The cartridge is a collapsed structure with high transition and low obstruction, and is not difficult to introduce and supplant. The cartridge interfaces all take on the worldwide normal standard CODE7, twofold 226 silicone elastic ring.
(1) After opening the cartridge bundle, the cartridge ought to be painstakingly checked whether the presence of the cartridge is smooth, regardless of whether there is any harm, and whether the silicone elastic ring is flawless, and the establishment ought to be done after the check is right.
(2) It is by no means permitted to open the channel lodging when the collapsing channel lodging is feeling the squeeze. Possibly open the channel lodging assuming you are certain that the compacted air is separated and the channel is totally decompressed.
(3) After destroying the channel component to be supplanted, clean the connector attachments on the channel lodging with a non-destructive cleaning specialist and don’t introduce the channel component until the attachments are adequately dry.
(4) Open the plastic sack containing the cartridge (the end with the twofold elastic ring), don’t eliminate the plastic pack, uncover just the two elastic rings, grease up the elastic rings appropriately, jam the opposite finish of the cartridge with two hands, embed the finish of the cartridge into the lower part of the attachment, and afterward lock the cartridge by turning clockwise. Be mindful so as not to hold the top finish of the cartridge for the establishment activity, any other way it will prompt extremely durable harm of the cartridge.
(5) After every one of the cartridges have been introduced, set up the back fixing toss and try not to over-fix the locking nut now to keep the cartridge from being squashed.
4.2 Precautions for channel sterilization
(1) the utilization of soaked steam should be sifted through the steam channel, the pollutants in the steam and condensate will be cleaned by the valve release, contingent upon the steam arrives at an apparently hazy, and afterward open the valve into the steam channel to forestall untimely harm to the steam cartridge.
(2) When involving soaked steam for sterilization, it is suggested that the steam pressure be controlled at 198-270kPa, the temperature be controlled at 120-130 ℃, and the time be controlled at around 30min.
(3) When steam sanitization, all valves ought to be opened, leaving no dead space, and toward the finish of sterilization, compacted air should be passed gradually, and the speed of ventilation should not be too quick to even think about forestalling wellbeing mishaps brought about by grating with the channel media through the wind stream.
(4) Steam sanitization end into the compacted air, to rigorously control the strain drop of the channel, cautiously notice the progressions in the tension table when the channel pipeline, to wipe out the peculiarity that the strain before the channel film is lower than the tension after the layer, to try not to twist the channel component.
(5) After steam sanitization, assuming the cycle permits, completely open the channel valve of the channel and ventilate for 30 min to totally blow dry the channel prior to placing it into activity. Assuming the channel is placed into activity in a wet state, it might make the maturation fluid be defiled with microscopic organisms.
(6) Steam channel after use, to shut its import and commodity shut-off valve, make certain to completely open the channel valve at the lower part of the steam channel to forestall valve spillage, steam condensate drainage into the aging tank, causing pointless misfortunes.
(7) When utilizing superheated steam to clean the channel, make certain to decrease the strain and temperature of the superheated steam to arrive at the tension and temperature necessities of the maturation business before use.
(8) Under the reason of guaranteeing ordinary creation, the occasions the channel is sanitized ought to be decreased however much as could be expected to drag out the help life of the cartridge. Because of the various items and working conditions created by maturation undertakings, the units giving filtration hardware for the most part don’t give sterilization cycles. Undertakings should work out pragmatic sterilization cycles as indicated by the development of the aging fluid to accomplish the reason for both diminishing creation costs and guaranteeing safe creation.
5 On-line recognition and laser molecule counters for across the board channels
5.1 Online assessment of the coordinated channel
Sterile air filtration is a vital piece of the maturation interaction, as the development and development of microbes and the blending of the aging stock all include sterile air. The tried and true way of thinking is that air is the principal wellspring of tainting for debased microscopic organisms in the maturation interaction.
By and by, bacterial defilement of the feed arrangement is brought about by an assortment of reasons, most fermenters with huge areas of tainting, assuming it happens in the beginning phase, it could be brought about by seeds with microorganisms or even sterilization hardware issues; assuming the pollution happens in the center and late stages and similar microbes, almost certainly, the air channel isn’t spotless, air with microscopic organisms or renewal framework with microscopic organisms caused. Furthermore, releasing valves, inadequate sanitization and staff blunders can all cause microorganisms in the material.
A somewhat logical test strategy is expected to decide if sterile air is the reason for a polluted material. There is no bound together norm for the testing of collapsing layer channels, and every producer follows its own technique for testing. When testing the filtration precision of aseptic collapsing layer channels, there is a trying strategy for reference, for example a laser molecule counter with a molecule size precision of 0.3μm is utilized to test the nature of the incorporated channel and cartridge on the web, as displayed in Figure 8. The laser molecule counter is aligned utilizing a 0.1 μm or higher precision instrument.
The laser molecule counter is associated with the discovery valve on the exhaust line of the incorporated channel by means of a plastic line for internet testing, which permits a more precise assurance of whether the air exactness at the power source of the great productivity channel is up to norm. Assuming the test falls flat, successful measures can be taken on schedule, for example, testing every high productivity channel cartridge, supplanting the bombed cartridge or checking for other potential issues that can cause bacterial pollution individually. Laser molecule counters can likewise be utilized to check the nature of individual cartridges, which require exceptional apparatuses.
On location online review of the nature of coordinated channels and cartridges
For instance, 100 ton fermenter in a huge aging organization in Henan area was viewed as sullied with microbes from an example taken during the maturation interaction. In the event that the reason for the tainting can be recognized on schedule at the underlying phase of the maturation cycle, then, at that point, the effect on the unit yield of the fermenter isn’t incredible. In the event that the tainting happened in the center or late phases of the aging cycle, it would have caused a huge loss of creation, regardless of whether the whole maturation stock must be unloaded. The professionals showed up on location on schedule and, with the dynamic participation of the studio staff, did web based testing of the air through laser molecule counters and investigated that there was to be sure an issue with the air, then, at that point, went to viable lengths on schedule to reestablish creation by supplanting the back-up channels on schedule and checking the channel components in the substitution channels individually to observe the tricky ones, subsequently limiting the harm brought about by the mishap. The justification behind this was that the cartridge sterilization temperature was excessively high because of a worker’s functional mistake, making a couple of cartridges fall flat.
5.2 Precautions for web based testing of laser molecule counters
(1) Before testing, the plastic cylinder and the channel testing valve should be flushed clean with liquor and affirmed to be blown dry prior to being placed into utilization.
(2) Before testing, open the channel identification valve so the released gas is liberated from water and different contaminations and ensure that the air is dry prior to testing. If not, the test can’t be completed.
(3) Before testing, the float in the instrument ought to be shown in the right position and the quantity of particles with a molecule size of 0.3 μm circling in the demeanor of the molecule counter should be adjusted to show 0. When testing, the examining wind current rate is 2.83 L/min to guarantee the precision of the test esteem.
(4) Before recording, the program show (or perception gear) shows the quantity of various molecule sizes for around 3 to 4 cycles, the information show settles prior to recording is more exact.
(5) For the situation of typical wind current, notice the float in a more steady state prior to testing the channel, in any case the information identified isn’t precise.
(6) During the testing system, assuming that the quantity of particles with a molecule size of 0.3 μm shows 0, or irregularly or consistently, it very well may be viewed as qualified. Assuming that time permits, a few additional cycles can be estimated, the worth will be more precise.
(7) Detection of molecule size information, you can pick the program show record, as indicated by the 6 molecule size channel for a cycle show, that is, every molecule size channel to show the quantity of particles for 10 s, 6 molecule size channel to show the quantity of particles for 1 min. or then again select the perception document, as indicated by the second whenever to show the quantity of particles in the predetermined channel. Two recognition strategies can be chosen, as indicated by various requirements, can likewise be utilized get over.
(8) during the time spent channel testing, the applicable upsides of various cycles and molecule sizes can be recorded to work with relative investigation of item execution.
Take a drug plant in Chifeng as an illustration subsequent to utilizing collapsed film channel for one year, the air accuracy in the wake of sifting is identified by molecule counter to decide if it meets the necessities of matured air, Table 4 to Table 6 is the air molecule information discovery report.
Table 4 101 tank air molecule information testing report
The three arrangements of information in Tables 4 to 6 completely meet the maturation air precision necessities. It ought to be noticed that during channel testing, on the off chance that the 0.3μm molecule count doesn’t will generally diminish dramatically throughout a more extended timeframe or on the other hand on the off chance that 0 doesn’t show up, the associated part outside the channel should initially be checked for neatness and breaks. Assuming the internal pit of the plastic cylinder and the test valve is cleaned again with liquor and blown dry with no impact, the channel cartridge is then tried individually. For the identified hazardous cartridge, it ought to be supplanted on schedule to guarantee ordinary aging creation.
6 The application and viewpoint of the one-piece channel
Ltd. in Qingdao in the plan of sodium gluconate project, are utilized in the energy effective one-piece channel, gas-fluid separator, get away from trap and other filtration items. In a sum of four sodium gluconate projects in Shandong and Tongliao, the high-productivity and energy-saving one-piece channels created by our foundation were embraced, which enjoy clear cutthroat benefits contrasted and split channels and are in front of comparative items in the channel business from one side of the country to the other.
A drug organization in Inner Mongolia Chifeng has utilized many 10 m3/min, 20 m3/min and 70 m3/min across the board channels in two maturation plants, and has been keeping a decent creation record. In the extension of the maturation project, the new energy-saving across the board channel was utilized again and has been effectively placed into utilization for over 5 years.
An innovation organization in Weifang, Shandong, has utilized various 10m³/min, 20m³/min, 100m³/min high-effectiveness and energy-saving across the board channels, get away from traps and other related filtration items, which have been in need for over 4 years, and the hardware has been running in great condition, making remarkable commitments to wiping out the secret risk of bacterial pollution of the feed arrangement and balancing out creation, carrying great financial and social advantages to the undertaking.
According to the point of view of the homegrown market, many endeavors in the maturation business have effectively utilized the high-productivity and energy-saving one-piece channel, and the quantity of units (sets) utilized has arrived at hundreds, which has gotten consistent acclaim and acknowledgment from clients, with a wide market improvement prospect and will carry better monetary advantages to undertakings. As most of clients have a more profound comprehension of this item, the one-piece channel will positively possess a more extensive market and advance further development and improvement of homegrown channel items.