This abstract provides follow-up data of previously presented 6 months' data of stability of IGIV in glycine and L-proline. Immunoglobulin intravenous 10% solutions formulated in either 0.25M glycine or 0.25M L-proline at a target pH of 4.8 were now investigated for up to 18 months. Three lots of IGIV process intermediates were divided into two parts and further processed to the final IGIV 10% formulated either in 0.25M glycine or 0.25M L-proline. Products were stored at 25oC in 60% relative humidity for 18 months. Immunoglobulin monomers, dimers, aggregates and fragments were measured by high-performance size-exclusion chromatography. Anti-hepatitis B surface (anti-HBs) antigen antibodies were measured by an enzyme immunoassay. The data were analyzed using the “paired t-test”. There were no statistically significant differences in total “monomers+dimers” (97.5% vs. 97.1%, p=0.540), aggregates and fragment content (0.19% vs. 0.18%, p=0.921, 2.27% vs. 2.71%, p=0.481) or the protective anti-HBs antigen antibody level (4.52 IU/mL vs. 4.44 IU/mL, p=0.636) between the formulations in glycine and L-proline after 18 months' storage. Dimer level was found to be well below 10% (6.3% in glycine, 4.6% in L-proline), considered to be the upper limit for good tolerability, in both formulations. The results obtained from IGIVs formulated in 0.25M glycine or 0.25M L-proline after 18 months' storage at 25°C indicate that these amino acids provide similar stabilization of the IgG molecule in liquid formulations at low pH.

RATIONALE: This study compares the stability at 25°C of immunoglobulin intravenous 10% solutions formulated in either 0.25M glycine or 0.25M L-proline at a target pH of 4.8. Both amino acids are used in commercially available IGIVs as excipient, merely to prevent IgG aggregation and fragmentation, which may affect product tolerability. METHODS: Three lots of IGIV process intermediates were divided into two parts and further processed to the final IGIV 10% formulated either in 0.25M glycine or 0.25M L-proline. Products were stored at 25oC/60% relative humidity for 6 months. Immunoglobulin monomers, dimers, aggregates and fragments were measured by high-performance size-exclusion chromatography, anti-Hepatitis B surface (anti-HBs) antigen antibodies by an enzyme immunoassay. The data were analyzed using the "paired t-test". RESULTS: There were no statistical significant differences in total "monomers+dimers" (99.1% vs. 99.0%, p=0.568), in aggregates (0.12% vs. 0.14%, p=0.08), in fragment content (0.74% vs. 0.85%, p=0.506) and in the protective anti-HBs antigen antibody level (4.41 IU/mL vs. 4.51 IU/mL, p=0.441) between the formulations in glycine and L-proline after 6 months storage. Dimer level was found to be in both formulations well below 10% (6.92% in glycine, 5.10% in L-proline), considered to be the upper limit for good tolerability. CONCLUSIONS: The results obtained from IGIVs formulated in 0.25M glycine or 0.25M L-proline after 6 months storage at 25°C indicate that both amino acids provide a similar stabilization of the IgG molecule in liquid formulations at low pH.

CFD applications in the context of power plants illustrate the detailed three-dimensional studies in complex geometries that are possible today, with a special emphasis on the necessity of solving the time-dependent equations. These routine simulations give a much more detailed representation of many flow configurations than was possible with scale models in the design stage of the plants, thus increasing their safety and life span. Aside from these global simulations conducted with standard models, use of Second Moment Closures is shown to better represent the effects of body forces, such as buoyancy and rotation, encountered in sub components of the plant. Finally Large Eddy Simulation is introduced on unstructured meshes and the related needs concerning fluid/structure coupling and unsteady thermal loading in plant components are described.

The benefit of using unstructured meshes for industrial applications of Computational Fluid Dynamics is now well established. The main advantages of unstructured meshes are to enable an easy and fast (with the use of automatic mesh generator) treatment of complex boundaries and to allow local and automatic mesh refinement. Finite Element methods provide a rigorous mathematics formulation. Nevertheless, implementing complex modelization is more tricky than when using finite volume or finite difference methods on structured meshes, especially when dealing with complex sets of non linear equations such as those encountered in turbulence modelling. This paper presents recent works done at the Research and Development Division of Electricite de France on the implementation of various kinds of turbulence models in the finite element code N3S. First will be detailed the numerical procedure used for solving efficiently the Reynolds Averaged Navier-Stokes Equations (RANSE) coupled with a standard k-epsilon turbulence model. Then, improvement of the k-epsilon model will be presented. The extension of this algorithm to more complex turbulence models such as Reynolds Stress Transport Models (RSTM) will be discussed. The last part of the paper will be devoted to the discussion of Large Eddy Simulation (LES) on unstructured meshes.

Today combining supercomputer performances with algorithmic optimizations large linear systems are solved in a very short time. Consequently reduction of FE calculations time becomes crucial. This paper presents how these calculations can be efficiently speed-up by replacing them by analytical ones and by fully vectorizing their assembling. Moreover the simplicity of these calculations enables on efficient parallelization on CRAY YMP.

Some numerical results obtained by the code MELINA are given. This code has been designed for the solution of three-dimensional steady and transient flows past a floating or submerged body; the fundamental equations of dynamics are taken into account in the case where the body is freely floating. Only the case of an ocean ot infinite depth is addressed here. It is shown that convergence to a steady state is achieved in the case of a periodic forced motion if the history ot the motion is correctly taken into account. Also, the case of a freely floating sphere with initial vertical displacement from equilibrium is treated and compared with experiments.

L'influence de la houle sur le rayonnement acoustique tres basse frequence d'une structure sous-marine presente deux aspects decouples : la propagation acoustique dans un fluide en mouvement et la diffraction des ondes acoustiques due a la deformation de la surface libre par la houle. Nous etudions ce dernier aspect, plus typique de l'acoustique sous-marine : nous donnons la solution analytique pour le cas d'une structure reduite a une source ponctuelle, et nous proposons une methode numerique de resolution dans le cas general.