Vendor qualification: Utilization of solid state characterization “Toolbox” to assess material variability for active pharmaceutical ingredient

ABSTRACT

One of the credos for a successful product development, early clinical trial supplies, achieving full-scalemanufacturability and speed to the market is the vendor qualification. The focus of this paper is to employ a systematicapproach to qualify different active pharmaceutical ingredient (API) suppliers. In this context, API sourced from twodifferent vendors used in product development, where prototype formulations manufactured with identical componentsand specifications demonstrated significant variations in drug product performance attributable to vendor-to-vendorvariability. Prototype prepared using API (Vendor 1) showed disintegration of tablets in 4.5 minutes which compliedwith in-house specifications, whereas it was >15 minutes for the prototype prepared from API (Vendor 2). In orderto understand these differences, a vast array of solid state techniques were employed to compare the critical materialattributes of API (GDCS1902) from two different Vendors. Furthermore, these tools were orthogonally applied tounderstand whether API from two Vendors demonstrated any process-induced transformations, such as processinduced polymorphism, process-induced crystal disorder, and process-induced fragmentation. The results of thesemeasurements indicated the presence of fine particles of varied morphology with API (Vendor 1), while API (Vendor2) showed more medium-sized uniform particles. Formulation process modification to induce API fragmentation insitu was carried out for the API from Vendor 2. This modification produced desired granule properties which were thensubjected to drug performance tests and was found to match the specification. This study demonstrates the importanceof understanding the critical material attributes to match the final product performance when multiple vendors wereselected.