Pharmaceutical Technology - May 2018

Pharmaceutical Technology eBook - Biologics and Sterile Drug Manufacturing

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Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 61 processes validation studies are finalized, and ul- timately continuous process monitoring and veri- fication programs are implemented. It stands to reason, however, that at the time of regulatory approval not all sources of process or product variability may be fully understood. Process monitoring and capability studies are used to predict the ability of a process to produce a prod- uct meeting pre-established quality attributes. An adequately designed and controlled process is able to reliably produce high-quality products as intended, re- duces process and product variability, and provides a basis for continuous process improvement. Change management Validation studies and data serve as the basis for modifications to the implemented manufacturing process and associated equipment, materials, pro- cedures, and the operating environment. Without detailed knowledge of the current process and how it functions, it is impossible to assess the potential impact of any change. Therefore, it is important that the validation records and reports are compre- hensive, detailed, and available to serve as the basis for any change. These data must include process and piping drawings, full equipment identification, specifications and parts lists, process operating pa- rameters, and written procedures. Once the process has been validated, routine pro- cess control records, measurements of critical pro- cess parameters, and CQAs will serve as a basis for deciding whether changes are necessary. Multivari- ate analysis and evaluations of interactions among various process parameters, for example drying time, temperature, and particle size, can also show whether the process is operating within its design space. ICH Q8(R2) discusses pharmaceutical devel- opment and can provide helpful information with respect to change management and design space (10). A formal change control system must be in place, and any proposed change must be evaluated, re- viewed, and approved prior to implementation. Change records must be current, up to date, sup- plement the original records, and be available to support future changes. Conclusion Validation links the process to the product. Even the best validation efforts still leave room for variability that may be impossible to eliminate because it is inherent in the process itself (i.e., normal variation). Process validation aims to identify and eliminate the special, or abnormal, variation that may be due to improper process design, lack of important in- formation concerning process inputs, and limited knowledge of processing equipment, its operation, and maintenance requirements. W. Edwards Dem- ing pointed out the foolishness of trying to control normal process variation; it is special variation that should attract our concern (21). A process is inputs working through a process- ing system resulting in outputs. The outputs of one process can be inputs to other processes, or they can be a finished product intended for the patient. Inputs and outputs are influenced by people, mate- rial, equipment, procedures, and the environment. Validation does a reasonably good job with material, equipment, procedures, and the environment, but people—who are the keys to the entire process—are

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