Aseptic Formulation and Filling Using Isolator Technology

www.pharmtech.com he number of parenteral products entering development and reaching the market has increased significantly during the past decade. By some estimates as many as half of all investigational new drug applications consist of biopharmaceuticals, the vast majority of which are manufactured aseptically. Most of these products are proteins and therefore highly susceptible to microbial contamination. In addition, regulatory agencies around the world are devising and enforcing increasingly stringent requirements for environmental and process control in aseptic processing. These factors are creating interest in advanced aseptic technologies that provide superior contamination control. Historically, the construction of an aseptic processing suite for small-scale or clinical-size batches has been a time consuming and expensive venture. Depending upon a facility’s starting point, construction can take 18–36 months. If an existing room or suite of rooms is to be remodeled, it may be possible to have a fully validated and functional facility in 18–24 months, depending upon the scope and complexity of the manufacturing requirements. However, if a facility must be built in a “green field,” or if a new construction is attached to an existing structure, the time to completion may be much longer, frequently on the order of 30–36 months. Validation of even a small-scale aseptic processing facility can take 3–6 months or more, depending on the size of the facility and the type of equipment required. It is not uncommon for a project that consists of building and validating a clinical or small-scale aseptic processing facility to cost more than $10 million, which does not include ancillary costs such as staffing and training a highly specialized cadre of operational, quality assurance, and compliance personnel. After completion, such facilities can be costly to operate because of several factors, not the least of which are high energy costs as a result of extensive air-handling requirements. Even though small-scale facilities are generally not in continuous use, most firms find that running air-handling systems continuously is necessary to maintain the exacting level of contamination control required by the regulations. In addition, monitoring the environment generally is required at all times, which requires expensive gowning supplies and consumables even when the facility is not in production. Aseptic Formulation and Filling Using Isolator Technology