Protocol statistical process

Concurrent validation is conducted under a protocol during the course of normal production. The first three production-scale batches must be monitored as comprehensively as possible. The evaluation of the results is used in establishing the acceptance criteria and specifications of subsequent in-process control and final product testing. Some form of concurrent validation, using statistical process control techniques (quality control charting), may be used throughout the product manufacturing life cycle. 

The statistical process sets up a sampling protocol that is constructed to provide an unbiased estimate of the summary statistic that defines the standard, say the annual mean or annual 95th percentile. The statistical methods provide an estimate of the standard error about this estimate of the summary statistic. Usually, the sampling regime... 

In order to reduce unnecessary data queries, the statistics group should be consulted early in the clinical database development process to identify variables critical for data analysis. Optimally, the statistical analysis plan would already be written by the time of database development so that the queries could be designed based on the critical variables indicated in the analysis plan. However, at the database development stage, usually only the clinical protocol exists to guide the statistics and clinical data management departments in developing the query or data management plan. 

All proficiency testing schemes should have a statistical protocol which states clearly how the data will be processed and how laboratory performance will be evaluated. This protocol should also describe how the assigned value for any parameter in a test sample is estimated. This is an important consideration, as the performance of individual laboratories is gauged by comparison with the assigned value. 

Protocol analysis. Protocol analysis is the process of capturing, decoding, and interpreting electronic traffic. The protocol analysis method of network intrusion detection involves the analysis of data captured during transactions between two or more systems or devices, and the evaluation of these data to identify unusual activity and potential problems. Once a problem is isolated and recorded, problems or potential threats can be linked to pieces of hardware or software. Sophisticated protocol analysis will also provide statistics and trend information on the captured traffic. 

Clinical trials generate vast quantities of data, most of which are processed by the sponsor. Assessments should be kept to the minimum that is compatible with the safety and comfort of the subject. Highest priority needs to be given to assessment and recording of primary endpoints, as these will determine the main outcome of the study. The power calculation for sample size should be based on the primary critical endpoint. Quite frequently, trials have two or more evaluable endpoints. It must be stated clearly in the protocol whether the secondary endpoints are to be statistically evaluated, in which case power statements will need to be given, or are simply... 

During the assessment process, there is a documented interactive dialogue between each assessor and the applicant to clarify points that are complex or ambiguous or to enable the applicant to provide additional raw data, statistical appendices and detailed protocols to facilitate the assessment process. However, none of the various parts of the dossier is self-standing or independent of others. There are areas within each, which are intricately linked to the others. In preparing a comprehensive and integrated regulatory assessment report, it is important that these areas of common interest are appropriately addressed. 

The design of the validation testing and the composition of the protocol reflect the circumstances under which the study is conducted. For retrospective validation the test may be statistical analysis of batch release data, such as assay, pH, physical appearance, residual moisture, reconstitution time, and constituted solution appearance. This retrospective process validation would be intended to demonstrate that the product is of consistent quality. A critical review of the processing conditions in a retrospective validation may consist of a test comparing actual processing conditions during lyophilization with ideal parameters. This not only shows adherence to the defined processing conditions, but also demonstrates process reproducibility. 

Statistically evaluate the data from the validation effort. Compare the data with the specification limits listed in the protocol. Conformance to these limits is essential, because this effort must also include the determination of whether failure signifies a missing link in the scientists s understanding of the process. This exercise is especially important when the size of the validation batch is significantly larger than the largest development batch made to date. 

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