In recent years, the pharmaceutical industry is seeing a movement towards the implementation of more efficient continuous manufacturing. This shift requires the development of in-line process analytical technologies to monitor and control the process at any given time. However, extracting reliable information from these sensors is a challenge. Among the available technologies, in-line image analysis is quickly gaining importance. This work presents an image analysis framework developed to address one of the main challenges of in-line image analysis: the presence of out-of-focus particles. Through two relevant examples such as the characterisation of a system of microparticles of mixed shapes and the monitoring of a common operation in the pharmaceutical industry such as the wet milling process, the benefits of incorporating this technique are assessed. The real-time analysis of imaging data in combination with other simultaneously-acquired quantitative data streams enables the user to make informed decisions and implement enhanced control strategies.