Issue link: https://www.e-digitaleditions.com/i/1302985
Pharmaceutical Technology Regulatory Sourcebook October 2020 11 Suitable statistical tools for traditional PPQ data analysis are summarized in Table VI. Continued process verification (CPV) Aim of this stage (stage 3) is to assure the control of CPP and CQA through the entire lifecycle. Several aspects must be assessed (and possibly documented in a protocol) to establish an ap- propriate level of process control and detect un- planned deviations from the process as designed. CQA and CPP (including relevant process trends and quality of incoming materials or components, in-process material, and finished products) must be controlled and periodically reviewed. The col- lection of these data will allow detection of unde- sired process variability. If supported by appropriate IT tools (8,9), the review may be executed before releasing any batch; however, as this opportunity is not generally pos- sible, criteria for frequency of the review must be established (e.g., production volumes, process criti- cality). Moreover, the frequency criteria must as- Table IV. Potentially critical process parameters and response for a freeze-dried product Compounding and filling Response (test)* Order of addition of components Appearance Stirrer type and speed Particulate matter Temperature Assay Time Degradation products Irregular filling Content uniformity pH Freezing Response (test) Vial loading shelf temperature Appearance Ramp rate to final shelf temperature Porosity Final shelf temperature Solid state Hold time at final temperature Reconstitution time Annealing (Y/N) Assay (proteins) Degradation products (proteins) pH Particulate matter Primary drying Response (test) Ramp rate to final shelf temperature Appearance Shelf temperature Solid state Chamber pressure Reconstitution time Hold at final shelf temperature Assay Degradation products Particulate matter Process analytical technology (PAT) option: primary drying end-point monitored by using a process analyzer. Secondary drying Response (test) Ramp rate to final shelf temperature Appearance Final shelf temperature Assay Hold at final shelf temperature Degradation products Chamber pressure Residual moisture Residual solvent (if relevant) PAT option: residual moisture monitored by using a process analyzer. * The term response (test) refers to the potential impact of the process stage on drug product characteristics.