Finite element analysis of EBM manufactured bespoke implants: A probabilistic study.

This study analyses three additively manufactured canine implants designed for angular limb deformity correction procedure through probabilistic numerical analysis. These implants have produced excellent results in-vivo and are operational to-date. Therefore, this study uses finite element analysis in conjunction with statistical analysis in order to further validate these implants from a numerical perspective. Due to uncertainties associated with boundary conditions for a bespoke implant geometry, the analyses in this study were conducted on a range of input values. An interrogation of these parameters through sensitivity analysis enabled in identifying the vital inputs. These inputs were then employed to conduct robustness analysis in order to determine the mean value of stress on which these implants ideally operate. These mean values were then compared with the associated safety and failure limit to obtain the probability of reaching these limits through different reliability techniques. A low probability of failure computed from numerical analysis in combination with the continued performance of these implants, suggests a successful integration of the methodology in the design phase of bespoke implants.

A novel approach to sterile pharmaceutical freeze-drying.

A novel approach has been developed that enables sterile pharmaceutical products to be freeze-dried in the open laboratory without specialist facilities. The product is filled into vials, semi-stoppered and sealed inside one, followed by a second, sterilization pouch under class 100 conditions. The product is then freeze-dried in the laboratory where the vials are shelf-stoppered before being returned to class 100, unwrapped and crimped. The sterilization pouches increased the resistance to water vapor movement during sublimation, thereby increasing the sublimation time and product temperature. Ovine immunoglobulins were double wrapped and lyophilized (as above) adjusting the primary drying time and shelf temperature for increased product temperature and, therefore, prevention of collapse. Ovine immunoglobulin G formulations freeze-dried to ≤ 1.1% residual moisture with no effect on protein aggregation or biological activity. The process was simulated with tryptone soya broth and no growth of contaminating microbial cells was observed after incubation at 35 °C for 2 weeks. Although increasing lyophilization time, this approach offers significant plant and validation cost savings when sterile freeze-drying small numbers of vials thereby making the manufacture of treatments for neglected and orphan diseases more viable economically.