A Multicompany Survey Study for Helium Leak Container Closure Integrity Test.

All products labeled as sterile are required to be free of microbial contamination throughout their shelf life (obligatory critical quality attribute). Container closure integrity (CCI) needs to be addressed with a holistic life cycle strategy comprising adequate primary packaging components selection and the assessment of critical unit operations and critical process parameters (CPPs) according to quality by design (QbD) principles. The helium leak method is currently the most sensitive CCI test method and preferably used for the initial container closure system (CCS) qualification and characterization studies. Currently, two different measuring principles are used in the pharmaceutical industry, and no data is available in the public domain for typical method performance parameters such as accuracy, precision, intermediate-precision, and limit of quantification of the method. Furthermore, the performance of different types and sizes of artificial leaks as well as certified helium leak standards have not yet been characterized across different test laboratories. In this multicompany study, we shared 17 artificially prepared leak samples using the most common types of artificial leaks in relevant nominal size ranges that are commercially available or can be easily prepared in a laboratory. Each participating company generated results according to their in-house methods, applying their established test parameters as the aim of the study was not to create a standard for helium leak measurements, but to compare real-world performance between different laboratories. Consequently, this study is not an interlaboratory study using the same test method across laboratories.

Spray congealed solid lipid microparticles as a sustained release delivery system for Gonadorelin [6-D-Phe]: Production, optimization and in vitro release behavior.

Sustained release lipid microparticles for a potential veterinary application were produced by the means of spray congealing using saturated triglycerides with respective surfactants. The spray congealing process was optimized using unloaded and loaded microparticles, revealing the highest impact of the spray flow on material loss. Yield could be optimized by increasing the spray flow as well as a reduction of the melt temperature from 90 to 75 °C. For the delivery system developed in this study, a release of around 15 days was targeted. The release profile was in first hand determined with the use of model substances (aspartame and tryptophan), before incorporating the decapeptide Gonadorelin [6-D-Phe]. Release could be controlled between 2 and 28 d, which was dependent on stability of microparticles upon incubation, type and concentration of emulsifier, as well as the used triglyceride. Differential scanning calorimetry and X-ray powder diffraction confirmed the crystallization behavior of C14 and C16-triglycerides in combination with various emulsifiers in different modification without impact on release.

Standardization of the Reconstitution Procedure of Protein Lyophilizates as a Key Parameter to Control Product Stability.

Lyophilization of protein formulations is an essential tool for stabilization and is becoming increasingly important for pharmaceutical development. Reconstitution of the lyophilized cakes is crucial to obtain an applicable product. Nowadays, manual reconstitution by patients or medical staff is the common method defined in instructions for marketed lyophilized drug products. Even though this step is influencing the quality of the final solution, it can represent a challenge to develop a standardized manual protocol and the performance is highly dependent on human factors. This study summarizes the implementation and performance of controlled reconstitution studies for protein lyophilizates applying a mechanical reconstitution device. Using automated and standardized protocols, reconstitution time of a bispecific antibody lyophilizate could be reduced effectively from 25 to below 5 min compared to the predeveloped manual protocol. It was shown that the reconstitution protocol is influencing the stability of sensitive proteins. Monomer content as well as formation of subvisible particles differed considerably between the tested protocols emphasizing the relevance of standardized procedures.