Sterility assurance level pharmaceutical products

In pharmaceutical technology, to define an item as sterile, one must be able to demonstrate that on a statistical basis related to the processing conditions, no more than 1 in 10 units subjected to sterilization may be non-sterile. Therefore, the SAL (Sterility Assurance Level) of the product must be greater than (or equal to) 10 . The obvious consequence of this situation is that although the word sterile expresses an absolute concept, the word sterilized, understood as the result of an adequate sterilization process, has a probabilistic meaning. 

Photochemical reactivity of drug formulations is an important aspect to consider during development, production, storage, and use of pharmaceutical preparations. However, photochemical stability of drug substances is rarely as well documented as thermal stability of the compounds. For instance, in order to obtain a high sterility assurance level of the product, a parenteral preparation is sterilized in its final container if possible. Steam sterilization at minimum temperature of 121°C for... 

In making this proposal, the FDA recognizes that a dual standard of sterility a iunmee has been in operation. Terminal sterilization processes for parenteral pharmaceutical products are currently required to be validated to sterility assurance levels of 10 aseptic processes can only be demonstrated to achieve sterility assurance levels of 10. This is clearly an example of dual standards. Fuithefmore, to the FDA it appears to be fundamentally wrong for products that are quite capable of tolerating terminal sterilization to be manufactured asepti-cally. 

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. 

Aseptic pharmaceutical BFS technology for the manufacture of sterile liquid products demonstrates high levels of sterility assurance when correctly operated and configured. The technology is continually improving as more expertise is developed. 

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