Commercial process validation

In summary, the problem this book addresses is how to select a catalyst in laboratory experiments that will be the best for commercial processes and how to develop kinetic expressions both valid in production units and useful in maximizing profits in safe operations. 

The CCT program involves a number of projects that achieve reduction of SO, NO, and particulate emissions in a single processing unit. The technologies described arc uniquely combined to achieve project goals and, at the same time, to provide commercial-scale validation of technologies for utilities to consider in order to meet environmental standards. 

Process validation, in commercial-scale pharmaceutical operations, 18 735 Process water... 

A process or facility fit assessment needs to be performed and involves translating the transferring site s process into a fit-for-purpose process within the manufacturing facility (Worsham, 2010). A comprehensive appraisal of the process requirements versus facility capabilities should be performed. This can help avoid unanticipated issues, which could lead to either unexpected delays and/or hidden costs at a later stage. Any changes to the process to accommodate the needs of the facility could result in additional process validation requirements. Therefore, changes should be constrained to the absolute minimum, but may be still required to facilitate a commercially viable process. 

FDA inspectors are instructed to look for any differences between the process filed in the application and the process used to manufacturer the bio/clinical batch. Furthermore, one of the main requirements of a manufacturing process is that the process will yield a product that is equivalent to the substance on which the biostudy or pivotal clinical study was conducted. Validation of the process development and scale-up should include sufficient documentation so that a link between the bio/clinical batches and the commercial process can be established. If the process is different after scale-up, the company has to demonstrate that the product produced by a modified process will be equivalent, using data such as granulation studies, finished product test results, and dissolution profiles. 

In prospective process validation, an experimental plan called the validation protocol is executed (following completion of the qualification trials) before the process is put into commercial use. Most validation efforts require some degree of prospective experimentation to generate validation support data. This particular type of process validation is normally carried out in connection with the introduction of new drug products and their manufacturing processes. The formalized process validation program should never be undertaken unless and until the following operations and procedures have been completed satisfactorily ... 

Of course these pieces or steps begin in development with initial process-development activities and conclude with product commercialization. All pre-process validation activities—from the initial ranging studies to the process-specific validations—can be dubbed as PQ activities, since they create a certain level of comfort with the process. These activities typically involve more than three full-scale runs—the number usually associated with validation. How exactly does this work How can a qualification require more runs than a validation The answer is very simple validation includes qualification, which means... 

As we know, a critical step within the development cycle of any new product or process is the scale-up step. At this particular point, it is very important that adequate communications have occurred between the group responsible for the product development and the group charged with process validation. Actually, in many organizations, the process/product development department shoulders the responsibility for product scale-up and then transfers the technology to manufacturing for product commercialization [6],... 

Process validation embraces an entire life cycle beginning in R D, including IQ, OQ, and PQ (installation, operational, and performance qualifications), and ending only when the related product is no longer commercial [6], (An older, now outdated, perception is that process validation starts after IQ and OQ.)... 

Some current publications address process validation from an almost exclusively statistical approach. The effect of such articles on nonstatisticians usually ranges from dismay to panic and, unfortunately drives them away, instead of toward use of statistics. Statistical process control (SPC) can be especially valuable when applied to process validation, both before and after the validated process enters commercial use. By statistically analyzing critical process parameter data throughout a batch or continuous process, SPC provides the opportunity to predict problems (trend analysis) and even take corrective action (trend control), before the problems occur, yet relatively few firms appear to be actually implementing SPC universally across all processing today, probably because SPC... 

During 1983 and 1984, representatives of FDA and industry debated at length over the value of positioning three consecutive commercial-sized lots as pivotal evidence of process validation. Industry agreed that FDA s argument for three lots might be suitable for medical devices, but argued successfully that it was not appropriate for pharmaceutical processes, for several reasons. 

In 1990, when FDA launched its preapproval inspections (PAI) program, the three-lot issue again arose. The PAI s chief architects (Richard Davis and Joseph Phillips, FDA Newark district directors) announced they would require evidence of three consecutive successful lots of commercial size prior to shipment of a new product across state lines as final evidence of process validation, even when the firm had already received its NDA approvable letter. 

Across the industry, there is a clear impression that since process validation is a regulatory requirement the possibility of any financial return has been eliminated. As a consequence, it has taken the industry a long time to recognize that there is a commercial advantage and tangible financial benefit to validation activities. 

In order to assess the state of SPC, a sufficient number of pilot- or commercial-scale batches should be manufactured (at least 10% of anticipated commercial scale) using the same process anticipated for the scaled-up product. When the formulation is finalized, the critical in-process and final product control specifications will be challenged through process validation studies on at least three full- or pilot-scale batches. 

Describe the logic behind all pertinent activities that occurred during technology transfer from phase III clinical production to the commercial process (determination of full-scale commercial processes, specifications, lot size, etc.). Discuss problems, failures, and so on. Justify the absence of equivalency concerns despite the differences in process parameters. Reference the report that indicates successful technology transfer (e.g., validation report, verification report). 

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