Electron sterilization validation techniques using the controlled depth of sterilization process

Many pharmaceutical products, especially parenteral drugs, cannot be sterilized with gamma rays or high energy electrons due to the concomitant product degradation. In view of the well-controlled electron energy spectrum available in modern electron processors, it is practical to deliver sterilizing doses over depths considerably less than those defining the thickness of blister-pack constructions or pharmaceutical containers. Because bremsstrahlung and X-ray production are minimized at these low electron energies and in these low Z materials, very high electron: penetrating X-ray dose ratios are possible for the application of the technique. Thin film dosimetric techniques have been developed utilizing radiochromic film in the 10-60 g/m2 range for determining the surface dose distribution in occluded surface areas where direct electron illumination is not possible. Procedures for validation of the process using dried spore inoculum on the product as well as in good geometry are employed to determine the process lethality and its dependence on product surface geometry. Applications of the process to labile pharmaceuticals in glass and polystyrene syringes are reviewed. It has been applied to the sterilization of commercial sterile products since 1987, and the advantages and the natural limitations of the technique are discussed. (author)