JAN HALLER, OLIVER PLIETZSCH
Dynamit Nobel GmbH Explosivstoff- und Systemtechnik, an Axplora company Kalkstr., Leverkusen, Germany

Abstract

The demand for active substances for pharmaceutical and agrochemical applications is constantly increasing. Many chemical structures used in innovative active ingredients may be successfully synthesized using hazardous chemistry. Although such reactions require process safety methodology, trained employees, specialized equipment, and precautions during development and manufacturing, they can have significant advantages in terms of the number of synthesis steps, impurity formation, operating costs, and environmental impact. To develop safe and robust commercial production processes using hazardous chemistry it is crucial to assess and manage the risks and hazards from project start.
In this article, we will speak about highly energetic azide chemistry in the development of a commercial scale process to manufacture a tetrazole bearing API. We will focus on managing the risks evaluation and controls to develop safe and efficient processes on commercial scale. The description is based on a real-life example of a tetrazole formation involved in a commercial API – Oteseconazole/VT-1161.

Introduction
Hazardous chemistry can be a key element in the development of commercial scale processes to manufacture APIs. We focus on managing the risks of hazardous chemistry for developing safe and efficient processes on commercial scale. Based on an established pharmaceutical product – Oteseconazole/VT-1161 – we walk you through the project phases from development to scale-up and commercial production, showcasing a process safety methodology and tests. This example will focus on azide chemistry, involving in-situ generated hydrazoic acid as reactive species to introduce a tetrazole moiety. We show that optimized and robust large-scale commercial processes can be developed even though hazardous chemistry is involved or even thanks to the involvement of hazardous chemistry. (1, 2, 3).

Main contents
Oteseconazole is the active pharmaceutical ingredient (API) of VivjoaTM introduced to the market by Mycovia Pharmaceuticals Inc. in April 2022. VivjoaTM is an azole antifungal indicated to reduce the incidence of recurrent vulvovaginal candidiasis (RVCC) in females with a history of RVCC. RVCC (also known as ...