Part II: Matrix based scaffold lyophilization facilitates processing as a prerequisite for an innovative packaging system.

On large manufacturing lines, the fill finish process of drugs is generally accomplished by filling vials and syringes with their respective deliverable doses. Glass as a final container provides excellent protection of the drug product because of its chemical inertia, gas impermeability and relative robustness. However, due to potential needle stitch issues, diluent mix ups, or the required use of complex closed system transfer devices, lyophilizate vials present a significant challenge for healthcare professionals during the correct preparation of intravenous (IV) infusions. A more suitable container could potentially minimize such shortfalls during the preparation of IV infusions. Our investigations aimed at assessing if a novel medication system, consisting of an infusion bag separated into individual dry product and liquid diluent chambers, could facilitate the storage of a lyophilized product equivalently to the current standard, a vial. By incorporating an intermediate process container into two different dual chamber bags (DCB), the stability of a model monoclonal antibody formulation (mAb) was studied. The DCBs were evaluated over a 24-week period against their liquid and lyophilized dosage form equivalents in glass vials. Their stability was assessed through investigations into protein stability, residual moisture uptake of the dry products and permeability of the foil and film materials. It could be demonstrated that the stability of the incorporated drug is highly dependent on the container configuration. Ultimately it could be shown that the storage of lyophilizates is equally possible in DCBs as it is in vials, while being stored next to the diluent within the administration device.

Near-Infrared Spectroscopy to Determine Residual Moisture in Freeze-Dried Products: Model Generation by Statistical Design of Experiments.

Moisture content (MC) is a critical quality attribute of lyophilized biopharmaceuticals and can be determined by near-infrared (NIR) spectroscopy as nondestructive alternative to Karl-Fischer titration. In this study, we create NIR models to determine MC in mAb lyophilisates by use of statistical design of experiments (DoE) and multivariate data analysis. We varied the composition of the formulation as well as lyophilization parameters covering a large range of representative conditions, which is commonly referred to as "robustness testing" according to quality-by-design concepts. We applied principles of chemometrics with partial least squares and principal component analysis. The NIR model excluded samples with complete collapse and MC > 6%. The 2 main components in the principal component analysis were MC (91%) and protein:sugar ratio (6%). The third component amounted to only 3% and remained unspecified but may include variations in process parameters and cake structure. In contrast to traditional approaches for NIR model creation, the DoE-based model can be used to monitor MC during drug product development work including scale-up, and transfer without the need to update the NIR model if protein:sugar ratio and MC stays within the tested limits and cake structure remains macroscopically intact. The use of the DoE approach and multivariate data analysis ensures product consistency and improves understanding of the manufacturing process.

A review of near infrared spectroscopy and chemometrics in pharmaceutical technologies.

Near-infrared spectroscopy (NIRS) is a fast and non-destructive analytical method. Associated with chemometrics, it becomes a powerful tool for the pharmaceutical industry. Indeed, NIRS is suitable for analysis of solid, liquid and biotechnological pharmaceutical forms. Moreover, NIRS can be implemented during pharmaceutical development, in production for process monitoring or in quality control laboratories. This review focuses on chemometric techniques and pharmaceutical NIRS applications. The following topics are covered: qualitative analyses, quantitative methods and on-line applications. Theoretical and practical aspects are described with pharmaceutical examples of NIRS applications.