Low-Risk Lyophilization

By Brian Bucur, Associate Director, Lyophilization & Sterilization and Timothy Smith, Director, Product & Process Development - Ben Venue Laboratories, Inc. An important consideration for the development stage of a lyophilized product is to consider selection of a stopper that has a coating or film which prevents it from sticking to the shelf above during stoppering. Historically, a silicone emulsion applied during stopper preparation has been used to facilitate machinability during filling as well as reducing stopper adherence to lyophilizer shelves. For some products, this may result in a perceptible haze or opalescence in the constituted liquid. Stoppers are available with a fluororesin film or polymerized silicone coating on the top (and other surfaces depending on the stopper). These can reduce or eliminate sticking, prevent silicone-related opalescence in the constituted liquid and make chamber unloading a smoother operation. Design, Training, and Technical Support There are several other keys to reduction of risk during formulation and lyophilization development. Above all, a clear set of design criteria are needed. Every opportunity should be taken to involve Quality and Manufacturing personnel in establishing product-specific expectations and design criteria to ensure success and reduce risk from the start of a project. There are times when the need to produce clinical products outweighs the objective of developing an optimized cycle. In this situation, non-optimal conditions that are introduced into the process may initially be tolerable but will clearly need to be addressed during the continued development of the product. If, for example, active ingredients or excipients are used that do not fully reflect the characteristics of later clinical or commercial materials, the possibility exists that formulation, lyophilization, constituted liquid characteristics or shelf-life stability will be altered. Non-optimal cycles may not only impact product cost, as a result of extended cycle time or unnecessary risk to batches,