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22 Pharmaceutical Technology Regulatory Sourcebook October 2020 P h a r mTe c h . c o m Process Development • Raw material controls (controls related to the excipients including supplier quality manage- ment, specification, and qualification) • In-process controls • Release testing • Stability testing. To ensure the product quality, the results of the control strategy must be within the limits (or accep- tance criteria) established according to the product knowledge that assures the quality of the product. Thus, this stage collects the results of the process design and is usually summarized using simple tables containing for each manufacturing step/unit opera- tion the identified critical process parameters (CPPs) and critical material attributes together with the CQA to be controlled, with the rationales that led to their identification. An example is given in Table V. Before starting process qualification activities, an integrated team must be defined that includes expertise from a variety of disciplines. The team members should belong to quality assurance unit, production department, engineering, qual- ity control, and development function. A team leader must be designated who will be responsible for process qualification activities execution. The team is in charge of the definition of the process qualification scope and extent, of the editing of qualification protocols and reports, and of the evaluation of the results. General prerequisites for process qualification have to also be considered by the team such as: • Approved and adequate standard operating procedures (SOPs) and working instructions are in place. Table IV. Key formulation development studies for a solid oral dosage form. Formulation attributes and study design Applicability Formulation step Manufacturing Step Packaging step Pre-formulation: Perform characterization of the API (differential scanning calorimetry, microscopic evaluation, etc.) and stability studies to verify the compatibility of the active substance with the other formulation ingredients X X Optimization of formulation: Excipients • Select excipients that are physically and chemically compatible with the active ingredient • Evaluate the need to include specific excipients to improve the formulation stability • Evaluate the need to include specific excipients to enhance or modulate the active ingredient bioavailability • Evaluate excipients that ensure product manufacturability X X Optimization of formulation: Development of the final formula • Evaluate different concentrations and addition rate of each raw material • Evaluate the need for overage • Perform studies to define final API content and tablet size • Evaluate the chemical, microbiological and physical properties of the formulation (water content, uniformity content, dissolution test....) X X Optimization of manufacturing process: • Evaluate and select the optimal manufacturing method (dry granulation, wet granulation, direct compression, etc...) • Evaluate the need to use organic solvents as granulating liquids • Evaluate appropriate equipment • Evaluate the influence of process parameters (e.g. mixing time, speed, drying temperature and time, etc.) on product quality to define critical process parameters (CPPs) X X Optimization of packaging process: • Evaluate the influence of different primary packaging materials • Evaluate the efficiency in temperature and humidity protection of different primary packaging materials • Evaluate the compatibility with the finished product • Evaluate the stability of the finished product • Evaluate the influence of CPPs X