I‑MR Control Chart: A Tool for Judging the Health of the Current Manufacturing Process of an API and for Setting the Trial Control Limits in Phase I of the Process Improvement

It has been observed that the main focus during the process development and manufacturing of an API is to meet the customer’s specifications (LSL and USL) rather than estimating and improving the natural control limits (LCL and UCL) of the process. It results in the overlap of the natural control limit and customer’s specification, which in turn increases the chance of failure with respect to the customer’s specifications. A better approach is to work on decreasing the variability of the process so that natural control limits become much tighter than customer’s specification. The statistical control charts not only help in estimating these internal/natural control limits but also raises an alert when the process goes out of control. These alerts trigger the investigation through root cause analysis leading to the process improvements which in turn lead to the decrease in variability of the process. This process continues till inherent variability of the process is due to common causes only and cannot be attributed to assignable causes. At this point, the natural control limits of the process can be taken as internal specification for an output quality parameter

Development of a Chemoenzymatic Process for Dehydroepiandrosterone Acetate Synthesis

Dehydroepiandrosterone (DHEA, <b>2</b>) is an important endogenous steroid hormone in mammals used in the treatment of a variety of dysfunctions in female and male health, as well as an intermediate in the synthesis of steroidal drugs, such as abiraterone acetate which is used for the treatment of prostate cancer.− In this manuscript we describe a novel, concise, and cost-efficient route toward DHEA (<b>2</b>) and DHEA acetate (<b>3</b>) from 4-androstene-3,17-dione (4-AD, <b>1</b>). Crucial to success was the identification of a ketoreductase from <i>Sphingomonas wittichii</i> for the highly regio- and stereoselective reduction of the C3-carbonyl group of 5-androstene-3,17-dione (<b>5</b>) to the required 3β-alcohol (<b>2</b>, >99% de). The enzyme displayed excellent robustness and solvent stability under high substrate concentrations (up to 150 g/L)