Large-scale crystallization as an intermediate processing step in insulin downstream process: explored advantages and identified tool for process intensification.

The rising global prevalence of diabetes and increasing demand for insulin, calls for an increase in accessibility and affordability of insulin drugs through efficient and cost-effective manufacturing processes. Often downstream operations become manufacturing bottlenecks while processing a high volume of product. Thus, process integration and intensification play an important role in reducing process steps and time, volume reduction, and lower equipment footprints, which brings additional process efficiencies and lowers the production cost. Manufacturers thrive to optimize existing unit operation to maximize its benefit replacing with simple but different efficient technologies. In this manuscript, the typical property of insulin in forming the pH-dependent zinc-insulin complex is explored. The benefit of zinc chloride precipitation/crystallization has been shown to increase the in-process product purity by reducing the product and process-related impurities. Incorporation of such unit operation in the insulin process has also a clear potential for replacing the high cost involved capture chromatography step. Same time, the reduction in volume of operation, buffer consumption, equipment footprint, and capabilities of product long time storage brings manufacturing flexibility and efficiencies. The data and capabilities of simple operation captured here would be significantly helpful for insulins and other biosimilar manufacturer to make progresses on cost-effective productions.

A rare case of rectal perforation from an accidentally swallowed foreign body.

Rectal foreign bodies are not an infrequent presentation and can cause a serious dilemma regarding extraction and management. Management is determined by the site of the injury, degree of fecal contamination, the hemodynamic status of the patient, and comorbidities. Intraperitoneal injuries require surgery in the form of either a primary repair or formal resection with or without diversion. Extraperitoneal perforations maybe managed with presacral drainage and antibiotics with or without diversion.