Development of a process using electron beam for a terminal sterilization for parenteral formulations of pharmaceuticals

Matagne, Daniel; Delbar, N; Hartmann, HJ; Gray, M; Stickelmeyer, Mary P.

doi:10.1016/j.radphyschem.2004.03.041

Cited by 7 publications

(2 citation statements)

References 2 publications

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“…The necessity for the sterility of parenteral products is mandated by multiple regulatory agencies (1). Although there are a number of alternative methods for product sterilization for pharmaceutical products, including irradiation, heat sterilization, and lyophylization (2–4), by far the most common method for the sterilization of biological products is filtration through a membrane with a pore size of 0.22 μm or less and collection in a sterile environment (5).…”

Section: Introductionmentioning

confidence: 99%

Sterilizing Filtration of Plasmid DNA: Effects of Plasmid Concentration, Molecular Weight, and Conformation

Watson¹,

Winters²,

Sagar³

et al. 2006

Biotechnol. Prog.

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Plasmid DNA purification development has been driven by the increased need for large quantities of highly purified, sterile plasmid DNA for clinical studies. Detailed characterization and development of the terminal sterile filtration process step is often limited due to time constraints and the scarcity of sufficient quantities of purified plasmid. However, the large size of the plasmid molecule and variations in conformation can lead to significant yield losses if this process step is not optimized. In this work, the gradual pore-plugging model of flow decay was found to be valid for plasmid DNA by using an ultra scaledown apparatus (1-4 cm(2) filter area). Filtration capacity was found to be insensitive to pressure. Multiple filter types were screened and both source and composition of materials were found to affect filter capacity dramatically. The filter capacity for plasmid was improved by increasing plasmid concentrations as well as by modifying buffer conditions to reduce the apparent size of the plasmid. Filtration capacities varied over a greater than 2 log range when plasmids with sizes ranging from 5.5 to 11 kb and supercoiled plasmid content of 55-95% were explored. Larger plasmids and feeds with lower supercoiled contents led to reduced capacities. These results can be used to define conditions for scale-up of plasmid sterile filtration, as evidenced by processing a 30 g lot using a filtration area of 1,000 cm(2), with a 96% yield, based on filtration capacity data from 4 cm(2) test filters.

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Section: Introductionmentioning

confidence: 99%

Sterilizing Filtration of Plasmid DNA: Effects of Plasmid Concentration, Molecular Weight, and Conformation

Watson¹,

Winters²,

Sagar³

et al. 2006

Biotechnol. Prog.

View full text Add to dashboard Cite

show abstract

“…It is known that use of an aluminum or stainless-steel tray helps to scatter the beam and thus obtain excellent dose uniformity ratio (DUR) across all dose monitoring positions within vials and throughout the tray [9]. Hence this may be attempted in further studies to test inactivation of larger populations of a wider range of micro-organisms in this machine.…”

Section: Candida Albicansmentioning

confidence: 99%