Pharmaceutical Technology - May 2018

Pharmaceutical Technology eBook - Biologics and Sterile Drug Manufacturing

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58 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 P h a r mTe c h . c o m Quality cleaning must also be available. Processing settings and conditions must be checked and calibration of water temperature, f low rate controls, and timers must be accomplished and documented. Cleaning procedures must be performed and evaluated for effectiveness and any problems corrected. The installed and qualified equipment may then be used in start-up and training exercises to ensure everything, including coffee shop staff, is ready for a successful opening day. Validation of the coffee brewing process may take place during the operational phase of equip- ment qualification, although the validation stud- ies extend backward and forward in time. Earlier activities include vendor qualification of the cof- fee supplier and roaster, qualification and valida- tion of the water supply system, validation of the equipment cleaning processes, and any calibration programs and maintenance procedures. Later ac- tivities include periodic evaluations to ensure the brewing process is functioning as intended, evalu- ation of cleaning and maintenance procedures to ensure adequate frequency and effectiveness, and a review to determine whether any operational issues or employee training programs need to be adjusted. This good-tasting coffee example is intended to stimulate thinking about the important points to consider when developing and marketing a prod- uct that consistently meets customer expectations. Although the product in question, good-tasting cof- fee, is not a biopharmaceutical, the same validation principles apply. The validated process must be ro- bust, consistent, and do what it is intended to do. Non-traditional process validation The following example of production of cells used in autologous cellular immunotherapies for per- sonalized medicine demonstrates how some con- ventional validation approaches may not be appli- cable due to the inherent process variability and because of the low numbers of units produced. In this example, the patient's blood is passed through a device where cells are separated and segregated, and the remainder is returned to the patient. The cells of interest are isolated from the apheresis unit by a gradient/centrifugation process. Then the cells are modified. Sometimes the cells are incubated with an antigen. Other processes infect cells with viral vectors. In any case, there is an incubation period where the cells grow in a me- dium that changes depending on the process. The incubation period is also variable depending on the process. Then the cells are collected, washed, and resuspended in a f luid such as lactated Ringer's. Depending on the process, intermediates may be frozen or refrigerated prior to onward processing. There are variable time limits on production and expiration periods as short as 18 hours for infusion of the packaged cells at the end of the process. A good way to approach this process is in stages. Each patient is different, as will be the collected and isolated cells, but the cell collection process can—and should—be standardized. For exam- ple, the apheresis unit and operating procedures should be specified based on studies that demon- strate the suitability of the equipment and operat- ing procedures for the intended use. Any clean- ing and sterilization procedures can likewise be specified and validated. The cell isolation process can be validated for the particular type of cells that are collected, in- cluding studies to ensure the cells are not damaged during the process and impurities are removed to acceptable levels. System operating parameters and

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