Within the pharmaceutical industry, it is a regulatory requirement to ensure that pharmaceutical drug manufacturing equipment is clean prior to use. Cleaning processes of manufacturing equipment are performed using a "validated" process and subsequently verified since inadequate cleaning can result in a contaminated or adulterated product. Historically, cleanliness of equipment within Drug Substance/Product/Active Pharmaceutical Ingredient (API) manufacturing is validated and verified using direct swabbing of the equipment and subsequent analytical testing of the swab extract. In this study, a novel approach has been evaluated using a number of innovative technologies and techniques to develop and validate a methodology based on an in situ hand-held Process Analytical Technology (PAT) to verify manufacturing equipment cleanliness and eliminate swabbing and associated off-line laboratory testing. Specular reflectance Mid Infrared (Mid-IR) spectroscopy was used to detect and quantify surface residue. It is expected that this analytical technique will allow the elimination or reduction of the number of swabs and subsequent off-line analytical testing required during cleaning verification of manufacturing equipment in the pharmaceutical and biopharmaceutical industry. This study was focused on the development and validation of a Mid-IR based calibration model. The results indicate that surface a residue of 0.19 μg cm-2 for a specific molecule is detectable using a specular reflectance Mid-IR technique.