Aseptic processing manufacturing activities

The manufacture of sterile products is universally acknowledged to be the most difficult of all pharmaceutical production activities to execute. When these products are manufactured using aseptic processing, poorly controlled processes can expose the patient to an unacceptable level of contamination. In rare instances contaminated products can lead to microbial infection resulting from products intended to hasten the patient s recovery. The production of sterile products requires fastidious design, operation, and maintenance of facilities and equipment. It also requires attention to detail in process development and validation to ensure success. This chapter will review the salient elements of sterile manufacturing necessary to provide acceptable levels of risk regarding sterility assurance. 

Media fill failures are investigated in accordance with manufacturing site SOPs. The investigation may include, but is not limited to, a review of the aseptic fill data, review of the environmental monitoring data, review of the component sterilization results, review of all intervention activities, and identification of the contaminants found. Also, additional media fills may be performed to demonstrate that the area and processes are under aseptic control. If the system cannot be shown to be under control, product produced subsequent to the media fill failure on that fill line will be placed under management review for final disposition. 

Some sterile powder formulations (these are predominantly, but not exclusively, antibiotics) may require sampling, mixing, milling, and subdivision activities similar to those found in oral powder manufacturing. The facilities and equipment utilized for these products is substantially different from that used for liquids, and the production area bears little resemblance to that utilized for liquids. These materials are received sterile and must be processed through sterilized equipment specifically intended for powder handling in a fully aseptic environment with ISO 5 protection over all open container activities. 

Validation is described as proof that the system performs as stated. As an engineering control, the LAF system must demonstrably support the intended aseptic or controlled process. Validation of the aseptic manufacturing process and the LAF systems that support terminal sterilization in pharmaceutical manufacturing applications should be carried out in accordance with industry standards. Such validation should be accomplished in three phases, consisting of installation qualification (IQ), operational qualification (OQ), and process qualification (PQ), with full and detailed documentation of all activities and... 

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