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The Practice of Tofflon Freeze-Drying System in API Production

Active Pharmaceutical Ingredient (API) is defined as a kind of active ingredient obtained by chemical synthesis, semi-synthesis, microbial fermentation or extracting from natural products. It experienced one or more chemical reactions and physical operations before applied to manufacture pharmaceutical preparation. Freeze-drying of APIs features large-scale bulk lyophilization, and the freeze-drying capacity of a single batch size ranging from 10 to 1000kg. API lyophilization systems can be applied for freeze-drying of sterile and non-sterile APIs, probiotics, food and health care products.

Usually, API lyophilization systems can be categorized by its loading methods: loading with Lyophilization trays, loading with PE membrane, loading with shelf as tray.

Conventional loading with Lyophilization trays and PE membrane have been processed manually, by which solutions are poured into tray or PE membrane directly and then transferred to the shelves of the freeze dryer. After lyophilization, freeze-dried APIs are collected manually. It is obvious that too much human intervention is involved in the whole freeze-drying process.

However,the advantages of these conventional loading methods feature low equipment cost in early stage, no need of special supporting equipment and easy cleaning and maintenance.And the disadvantages involves higher risks of contamination for non-sterile products, and not suitable for manufacturing product with toxic substance. These loading methods are widely used, especially for some products with relatively high viscosity and in small batches.

In recent years, with the increasingly request to auto loading systems for freeze dryers to meet increasing cGMP expectations, Tofflon has developed Auto LoadingSystems :Fixed Loading Systems, Flexible Loading Systems (AGV) and Mixed Loading Systems (Mixed) equipped with advanced isolation systems, which can reduce manual intervention in the critical area and minimize the cross contamination while protecting safety of operators as well as products.

Fixed Loading Systems:

It is applied to handle highly potent active pharmaceutical ingredient (HPAPI), high sterility and high value-added products, which is most suitable for small-scale freeze dryers.

Flexible Loading Systems:

It applies to the manufacture of multitudinous products.

Although the loading methods with tray is improved continuously, due to the door of freeze dryer keeps open in the loading process, the dispense of the sterilized API into the trays is exposed to the ambient and the risk of contamination no matter whether barrier systems and automatic metering and weighing device are integrated into the loading systems. Besides, the frictions between stainless steel trays and freeze-dryer shelves may generate insoluble particles, which pose contamination risks to products. During the lyophilization process, vacuuming or other operations and unloading of the trays may still generate insoluble particles, which may bring about the risks of the secondary contamination to products.

Shelf as tray in freeze dryer has replaced conventional one loading with tray. Freeze dryer is designed shelf as the tray with folded edges, which can be tipped at specific angles .And the API solution is charged into the shelf directly by the inlet pipe from the side of freeze dryer without opening the door or manual operations during the whole loading process, and freeze-dried API can be sucked by robot after lyophilization. The whole loading and unloading process is fully automated and unmanned.

Freeze dryers with shelf as tray are Tofflon patent products, which are installed and operated widely in the pharmaceutical companies’ worldwide. It can be customized according to individual output demands from customers , the freeze drying area ranges 2~40 ㎡, and the technical features as below :

? Shelves are designed as trays with 100% effective area. API solutions are directly dispensed into shelves where heat is transferred directly to products and production cycle is improved effectively

? Without the process of cleaning, sterilization and transportation of trays, it minimizes the risks of cross contamination, reduces functional rooms of the factory, improves productivity as well as reduces operating cost;

? The API solution is monitored by a mass flow meter to achieve precise feeding of each laye;

? The internal structure of the chamber is simple, which is easy to clean and sterilize;

? Shelf as tray lyophilizer systems load API in an enclosed space and can integrate with robot loading system ,which realizes full automation and unmanned management.

Freeze Dryer with shelf as tray can integrate with conventional loading and unloading system, such as auto-loading with robot and semi-automatic loading with peristaltic pump.

Unloading method can be alvacuum intake robot, pulverizing & vacuum absorption robot, or Automatic scraper vehicle- is available in tipping shelves lyophilizer system.