Applications of FTIR in identification of foreign materials for biopharmaceutical clinical manufacturing

Over the last two decades, the number of biopharmaceutical drug candidates entering clinical trials to treat various diseases has dramatically increased. During the manufacturing process of clinical drug candidates, foreign materials may be introduced into biopharmaceutical products and result in non-conformance incidents. The foreign materials could be accidentally brought in from raw materials, manufacturing equipment, manufacturing process or deviations introduced by contract manufacturers. All these potential sources could end up contributing to contaminants in the final product. The purpose of forensic analysis is to identify the foreign materials and find their root causes. Fourier Transform Infrared (FTIR) Microspectroscopy plays a key role in forensic analysis by providing information on the functional groups present. Furthermore, unknown materials could be identified by comparing their spectra with library standard spectra since almost every molecule has unique FTIR spectrum. Other microscopic techniques including Light Microscopy and SEM/EDS provide complementary information. Three cases where contaminants in the manufacturing facilities required forensic investigations are presented to illustrate the special challenges in application of FTIR for clinical manufacturing of biotherapeutics. The forensic identification results assisted engineers in finding the root causes and implementing corrective and preventative actions.