Technical exchange on maintenance and major repairs of Dongfulong pharmaceutical lyophilizers, with complimentary basic learning materials*

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I have my own unique insights regarding the major repairs and maintenance of freeze-dryers, and I hope to discuss them with everyone! Progress together: Nowadays, with the continuous advancement of freeze-drying technology and freeze-dryers, freeze-drying is being used more and more widely in the development of sterile preparations. Throughout the process of producing freeze-dried sterile formulations, the freeze-drying step is the most critical one. Lyophilization technology is widely used in the pharmaceutical industry for antibiotics, antitoxins, interferons, bacteria, viruses, vaccines, blood products, diagnostic agents, enzyme preparations, vitamins, hormones, culture media, traditional Chinese medicine preparations, and more ； In aseptic pharmaceutical manufacturing, the main components include active pharmaceutical ingredients, as well as lyophilized injections and tablets. A flowchart of the lyophilization process is attached below. The two most important systems in a lyophilizer are the refrigeration system and the vacuum system. The refrigeration system is the heart of the freeze-drying system. It mainly consists of the following components: compressor, refrigerant, oil separator, water condenser, dry filter, intercooler, sight glass, solenoid valve, manual valve (roof valve), expansion valve, evaporator (plate exchanger, rear box condensing coil), vapor-liquid separator, return air filter, pressure gauge, pressure control relay, CPCE (energy regulator), safety valve, and refrigeration pipes. The system diagram is attached below: 1. Routine maintenance of the refrigeration system (1) A routine inspection should be carried out before each startup ； Are all stop valves (compressor suction and discharge valves, liquid supply valves, manual valves, etc.) in the open position? ； Are the readings of all pressure gauges normal (0.6–0.7 Mpa)? Is the level of the compressor oil normal (1/4–3/4)? Are the pressure and temperature of the cooling water normal (above 0.1 Mpa)? (2) After power is supplied, pay attention to whether the compressor automatically collects liquid ； Whether the oil pressure difference has been reset, etc ； Check the heating performance of the crankcase heater; the temperature of the crankcase should be 20°C higher than the ambient temperature. (3) After turning it on, pay attention to whether the sound of the compressor operating is normal ； Are there any abnormal vibrations in the refrigeration piping? ； Whether the vibration of the compressor itself is minimized depends on whether the sight glass flow is normal ； Frosting on the expansion valve ； Compressor defrosting condition ； (4) The compressor refrigeration oil should be replaced every six months or once a year, depending on the circumstances. (5) The water condenser needs to be cleaned regularly, usually once a year. It can be disassembled for cleaning, or cleaned cyclically using a water-based cleaning agent. For air-cooled units, clean the outer surface of the condenser promptly. (6) Be careful not to start the compressor frequently. (The startup interval should be greater than 3 minutes.) The following figures show repair cases of Kobe Steel two-stage screw compressors and Maekawa two-stage screw compressors as well as Bizerba piston pumps in Toyo Fuse freeze-dryers: The vacuum system is an important component of a freeze-dryer; it mainly consists of a drying chamber, a condenser, a vacuum pump, a Roots pump, small butterfly valves, chamber isolation valves (large butterfly valves, mushroom valves), vacuum testing equipment (vacuum gauges, vacuum tubes (pressure sensors)), venting devices, auxiliary devices, and vacuum pipes. Daily maintenance of vacuum systems: (1) Before starting the vacuum pump, check its oil level (it should generally be at 1/2 of the oil sight glass).   (2) Before turning on the vacuum pump and the small butterfly valve, ensure that the front box door is closed and all valves are in the closed position. Before starting to evacuate the chamber with the vacuum pump, it is essential to ensure that the rear chamber is dry. If there is moisture present, the temperature of the condenser must be kept below -45°C, and this temperature must remain below -45°C throughout the entire freeze-drying process, in order to prevent moisture from being drawn into the pump and affecting its operation. (3) If the vacuum pump and rotary vane pump used require water cooling, it is essential to ensure that the cooling water is available before the vacuum pump is turned on; during operation, one can touch the temperature of the pump body to check this. The Roots pump should not be started too early (controlled by a contact pressure gauge). (4) The vacuum pump oil needs to be replaced regularly, usually once a year. When the vacuum pump is in operation, pay attention to the changes in the color of the oil shown on the level gauge. If a white turbidity appears in the upper part of the oil during operation, consisting of small white droplets, it indicates that moisture or organic solvents have entered the vacuum pump. In such cases, open the air vent valve for a certain period of time (depending on the actual situation; generally around 1 hour) ； If the pump oil remains milky white, black, or of some other color for an extended period of time, it indicates that the oil has deteriorated and emulsified, and it is necessary to replace the vacuum pump oil. (5) After starting the vacuum pump, do not open the small butterfly valve yet; let the vacuum pump evacuate the vacuum tube for some time first, and check whether any abnormal noises are produced during its operation Can an ultimate vacuum be achieved within a normal time frame? If there are any changes, please first check whether the vacuum pump oil has deteriorated, whether the solenoid valve on the pump head is functioning properly, and whether there are any loose connections on the pump head. Below are several common vacuum pumps used in Toyo Engineering’s freeze-dryers: AirTAC vacuum pumps, Edwards vacuum pumps, Edwards Roots pumps, and Shanghai Kaini Roots pumps.