Extraneous material, such as micro-particles, found in the manufacturing stream of biopharmaceuticals must be identified and the root cause must be determined to take corrective actions. Biopharmaceuticals differ significantly from conventional pharmaceutics in manufacturing and delivery. They are typically manufactured after molecular cloning by cell culture fermentation, purification by multiple chromatography and filtration steps, and formulated as injectable to bypass the digestive system. Different extraneous material may appear during the many steps of the manufacturing processes. For instance, the presence of extraneous material in the in-coming raw materials, manufacturing equipment, drug delivery devices will result in the quarantine of materials, production slow down and even loss of product. Extraneous material in cell culture media may stop cell growth and production. For final products to be delivered in liquid formulation, any visible particles are not allowed. In our lab, we employed multiple microspectroscopic techniques to investigate and identify the unknown visible particulate materials that are involved in the contaminant incidents. They include but are not limited to optical microscopy, FTIR-microscopy, and scanning electron microscopy (SEM) with energy dispersive x-ray spectrometry (EDS). In this presentation, we will report a few archetypical incident investigations to demonstrate the challenges and the diversity of the manufacturing incidents and the capability and the flexibility of the combination of micro-spectroscopic techniques to the biopharmaceutical manufacturing industry.