Isolation Technology for Research and Development Applications: From Concept to Production

Abstract

A prototype parenteral manufacturing facility based on isolation technology was designed, constructed, and commissioned at Warner-Lambert Co., Morris Plains, NJ, with emphasis on its application to research and development (R&D) settings. The facility contains closed isolators for holding, transferring, and manufacturing sterile products. Vaporized hydrogen peroxide (VHP) was used for sanitization of the isolators. Various factors were evaluated to ensure complete distribution of VHP inside the isolators. VHP sanitization validation of the isolators was performed using chemical and biological indicators, and by swab testing the inside surfaces of the isolators. On the basis of these studies, operating conditions for routine VHP sanitization of the various isolators were established. Performance qualification of the manufacturing facility was conducted via media fills, which demonstrated sterile integrity of the manufacturing process. The media fills revealed certain deficiencies in handling procedures of filled product, which were subsequently corrected. The Warner-Lambert isolation technology-based parenteral facility proved to be a reliable and cost-effective alternative to standard clean room technology. The facility is ideally suited for manufacturing small batches. Closed isolator technology has its limitations when used for production-size batches involving automated processing.

Decontamination assessment of Bacillus anthracis, Bacillus subtilis, and Geobacillus stearothermophilus spores on indoor surfaces using a hydrogen peroxide gas generator

“…Therefore, gaseous hydrogen peroxide has been used as a decontaminant for treating laboratory and medical equipment, pharmaceutical facilities, hospital rooms and animal holding rooms (Klapes and Vesley 1990; Heckert et al. 1997; McDonnell and Russell 1999; Krishna et al. 2000; Krause et al.…”

“…Hydrogen peroxide is considered less toxic than other fumigants such as chlorine dioxide, ethylene oxide and formaldehyde, and breaks down into water and oxygen. Therefore, gaseous hydrogen peroxide has been used as a decontaminant for treating laboratory and medical equipment, pharmaceutical facilities, hospital rooms and animal holding rooms (Klapes and Vesley 1990;Heckert et al 1997;McDonnell and Russell 1999;Krishna et al 2000;Krause et al 2001;Fichet et al 2004;French et al 2004;Hillman 2004;Wagenaar and Snijders 2004).…”

GMP-Grade Manufacturing and Quality Control of a Non-Virally Engineered Advanced Therapy Medicinal Product for Personalized Treatment of Age-Related Macular Degeneration

“…To ensure sterility during delivery of tIPE from the manufacturing to the surgical site, a customized bioconfined container for transportation of tIPE was designed to be a simple, economical and commercially competitive product, manufactured using 3D injection printing [ 41 ]. The material was chosen to make it autoclavable and therefore reusable [ 42 ] with a disposable internal syringe holder. An enhanced version with a spring in which the syringe will be clamped to “close” the syringe during transport is in development and will further improve safety.…”

Large-Scale Inactivation ofBacillus AnthracisAmes, Vollum, and Sterne Spores Using Vaporous Hydrogen Peroxide

“…Hydrogen peroxide is considered less toxic to humans than other fumigants (e.g., formaldehyde, chlorine dioxide); therefore, it has been widely used to treat laboratory and medical equipment, pharmaceutical facilities, hospital rooms, ambulances, animal holding rooms, and air ducts (Anderson et al, 2006;Dryden et al, 2008;Fichet et al, 2004;French et al, 2004;Heckert et al, 1997;Hillman, 2004;Johnston et al, 2005;Klapes & Vesley, 1990;Krause et al, 2001;;Krishna et al, 2000;Verce et al, 2008;Wagenaar & Snijders, 2004). The use of hydrogen peroxide as a fumigant, dry mist, or an aqueous solution promotes decontamination efficacy against a wide range of microorganisms, including bacterial spores, vegetative bacteria, fungi, viruses, and bacteriophages (French et al, 2004;Grare et al, 2008;Hall et al, 2007;Hall et al, 2008;Heckert et al, 1997;Hillman, 2004;Johnston et al, 2005;Klapes & Vesley, 1990;Melley et al, 2002;Otter & Dudde-Niekiel, 2009;Rastogi et al, 2009;Rogers et al, 2005;Rogers et al, 2008b;Rogers & Choi, 2008).…”