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 Freeze Drying System can be applied for freeze-drying of sterile and non-sterile APIs, probiotics, food and health care products. Usually, API Freeze Drying System can be categorized by its loading methods: loading with lyo trays, loading with PE membrane, loading with shelf as tray.
Conventional loading with lyo 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 freeze dryers. 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 in 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 demand for auto loading systems for freeze dryers to meet increasing cGMP expectations, Tofflon has developed API Auto Loading Systems equipped with advanced barrier systems, which can reduce manual intervention in the critical area and minimize the cross contamination while protecting safety of operators as well as products.
Although the loading method with trays is improved continuously, due to the door of freeze dryers keeps open in the loading process, the dispense of the sterile 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 shelf loading with tray. Freeze dryer is designed with shelf as 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 automatic without personnel intervention.
The freeze dryers with shelf as tray are Tofflon’s patent products, which are installed and operated widely in the pharmaceutical plants 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 tray 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 transfer of trays, it minimizes the risks of cross contamination, reduces tray stroage room, improves productivity as well as reduces operating cost.
The API solution is monitored by a mass flow meter to achieve precise feeding of each layer.
The internal structure of the chamber is simple, which is easy to clean and sterilize.
Today sterile API manufactuirng demands automated handling system solutions for aseptic applications to meet increasing cGMP expectation, especially for generic API large-sclae manufacturing with aim to export to regulated markets. Meanwhile the solution should keep cost competitveness and production efficiency as well. The above API Auto Loading Systems, espeiclaly with shelf as tray design, work for these requirements. It offers package solution from aseptic process to package proces and meet both aseptic requirements and operator protection for potent products. The installed systems have been successfully approved by international regulatory authority.