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20 Pharmaceutical Technology Regulatory Sourcebook October 2020 P h a r mTe c h . c o m Process Development tail in subsequent formulation and process devel- opment studies. Even for solid oral forms, cause-and-effect dia- grams are a simple and useful tool to identify the input variables that can impact the desired quality attributes. These diagrams can be easily found in the literature, for example in (5). This information represents the basis for the initial risk assessment of the impact of each operation on the identified CQAs (i.e., to define the high-risk steps that may affect the CQAs of the final drug product). This ex- ercise, which is based on previous knowledge and experience with related formulations, is to be made on a product-by-product basis and represents the Table III. Potentially critical process parameters and response for a tablet. Granulation (high shear) Response (test)* Impeller speed, time Chopper speed/time Appearance Fluid feed rate Solvent content Atomizing pressure (if any) Amount granulation fluid Loading Process Analytical Technology (PAT) option: granulation end point monitored by using a process analyzer. Wet sizing (if any) Response (test) Screen size Appearance Speed Feed rate Granulation and drying (fluid) Response (test) Air IN (volume/time, temperature, humidity) Particle size distribution Air OUT (temperature, exhaust humidity) Loss on drying Product temperature Bulk density Atomizing pressure Assay Spray rate Degradation products Amount granulation fluid Loading PAT option: drying end point monitored by using a process analyzer. Drying (static) Response (test) Air IN (volume/time, T, humidity) Particle size distribution Air OUT (T, Exhaust humidity) Loss on drying Product temperature Bulk density Loading (number of trays and amount for tray) Assay Degradation products Milling Response (test) Screen size Particle size distribution Speed Loss on drying Feed rate Bulk density/Tapped density Powder blending Response (test) Time Content uniformity Speed Assay Loading Particle size distribution Flowability, bulk density, tapped density