A holistic approach to validation and quality assurance is essential.
Biologic drugs are highly valuable in treating diseases, and assurance of sterility and proper final product quality is essential. Appropriate testing must be conducted to ensure the filled vials, syringes, cartridges, etc. contain the correct quantity of sterile, contaminant-free product. Aseptic process simulations are crucial for the assessment of aseptic filling capabilities.
The best approach, agrees Maria Lacourt, director of manufacturing operations for Alcami, is to conduct a holistic assessment of all the controls for the process and work toward a facility design that ensures proper execution of the process. “Beyond meeting requirements for the relevant room classification, the right equipment must be identified that enables optimum performance within appropriate containment systems such as isolators, which ensure reduced intervention of operators during aseptic processing.”
In addition to proper training and qualification of staff executing the filling process, Lacourt also stresses the importance of managing the materials used in the process. “It is important to identify vendors, establish container closure integrity, and assess all of the properties of the materials that can impact product quality attributes,” she explains.
Media fill studies
Aseptic process simulations (APS), also referred to as media fill studies, are critical to qualification of an aseptic facility. They demonstrate the ability of the filling process to operate consistently all of the time due to the design of the process, facility, equipment, and the training of the personnel. “The goal is to determine the microbiological risk associated with the performance of specific interventions and to challenge the way those interventions are executed in a simulation to confirm that they do not in any case affect the sterility of any manufactured product,” she says. Media fill execution is also used to certify the personnel who will participate in the sterile manufacturing process.
The key to performing successful media fill studies is development of a validation master plan that includes the strategy that will be followed, the components that will be used, the aseptic process times to be challenged, and the validation approach. Personnel must also be trained to ensure proper execution of each step and appropriate documentation must be maintained.
Analytical aspects are equally important
During media fills (APS), microbiological testing should encompass all of the testing completed during the manufacturing process itself, according to Lacourt, including pre- and post-use filter testing and sterility testing. Sterility tests are critical to assessing the successful execution of aseptic processing, and procedures on sample collection and testing performance should be documented.
A holistic approach is best
For Lacourt, it is important that everyone involved in aseptic filling operations understands that aseptic processes rely heavily on process protocols, personnel practices, equipment utilization, and facility design and controls. “It is the combination of these elements that ensures the exclusion of microorganisms from sterile processes, components, and products. It isn’t sufficient to have the best techniques for intervention if the equipment is not properly designed or the facility is not qualified to ensure contamination control,” she concludes.
Vol. 44, No. 6
When referring to this article, please cite it as F. Thomas, “Reducing Risk with Abuse-Deterrent Formulations,” Pharmaceutical Technology 44 (6) 2020.
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