Protocol deviations

The second perspective is closer to the mark Measurements that apparently do not fit model or experience should always be investigated in the light of all available information. While there is the distinct possibility of a discovery about to be made, the other outcome of a sober analysis of the circumstances is more probable a deviation from the experimental protocol. If this is documented, all the better the probable outlier can, in good conscience, be rejected and replaced by a reliable repeat result. 

Accuracy is the term used to describe the degree of deviation (bias) between the (often unknown) true value and what is found by means of a given analytical method. Accuracy cannot be determined by statistical means the test protocol must be devised to include the necessary comparisons (blanks, other methods). 

The study protocol determines the quantities of raw materials to be processed. The protocol should state the quantity of each fraction sample to be provided and whether multiple samples are to be drawn from each fraction sample. The wording of the protocol should allow for a range of quantities that is to be provided for each processes commodity to avoid having to prepare protocol deviations. For example, stating that a minimum of 1 lb of pur6e is to be provided avoids a protocol deviation if the processor provides 1.1 lb of purde. 

The GLP standards identify three types of deviations there are deviations from GLP standards, from the protocol, and from SOPs. Any deviation must be reported to the Study Director and documented in the raw data notebook. There are differences in the reporting process for the types of deviations. 

Protocol deviations in the processing phase of the study must be reported to the Study Director without delay. The Study Director will determine any potential impact upon the study that would result from the protocol deviation and will advise the PPI how to proceed with the study. Regardless of the form of communication by which the Study Director is notified of the protocol deviation, a formal description of the protocol deviation must be written by the PPI and submitted to the Smdy Director for an assessment of impact on the study. The assessment of impact by the Study Director should address any scientific and GLP compliance issues. A signed copy of the deviation report is included with the raw data notebook. 

If the PPI determines that there may be an impact on the study, the Study Director must be consulted promptly to determine the proper course of action. Any impact on the scientific aspect of the study resulting from an SOP deviation may generate a protocol deviation. Any impact on the GLP compliance of the study resulting from an SOP or GLP deviation will at the very least need to be addressed in the GLP compliance statement from the processing facility which is included in the raw data notebook. 

An adequate measurement technique is not sufficient for good analytical results. Analyses are operated under ISO 9001 and carried out according to validated analytical protocols. Deviations from such protocols are to be given as amendments (a priori) or as deviations (a... 

It is recommended that the protocol itself contain language that allows for minor modifications of an analytical method or procedure without necessitating an amendment (or a deviation) for example, "Minor modifications in instrumental parameters and/or adjustments in technique may be made in the method during specimen analysis to enhance overall efficiency or the sensitivity, specificity, or selectivity of analyte response."... 

Figure 3.3 Comparison of array CGH among DNA extracted from fresh tissue, FFPE tissue by heating protocol or nonheating protocol for two human tissue samples of metastatic carcinoma in lymph node (a-c), and undifferentiated non-small cell carcinoma (d-f). Array CGH hybridization genomic profiles show ratio values representing relative copy number of single BACs. A good result is scored as 1.0 that indicates a low standard deviation for gains (>0.2), normal (0.0), or losses (<-0.2). In these two cases, fresh samples show best score as 2, both FFPE tissue samples show identical score of 3. Each spot represents the average of three replicates. Clones are ordered by chromosomal position as numbers at the bottom (x axis) of each picture. The y axis is the log2 ratio of test reference intensity. Provided by Sandy DeVries from Dr. Frederic Waldman s Lab at UCSF.

Enzyme containing Nation membranes prepared according to the proposed protocol have shown high specific activity and stability of immobilized glucose oxidase. As expected, the simplicity of preparation provided high reproducibility. When the same casting solution is used, the maximum deviation in membrane activity is <2%. This, however, is also the precision limit for kinetic investigations. 

A Study Director must be appointed, with overall responsibility for the study and for approving the study plan and any amendments to the study. The Study Director has the responsibility to oversee the technical aspects of the study and so must have appropriate qualifications and experience to be able to supervise the work carried out. The Study Director must ensure that the agreed protocols are followed and that any unavoidable deviations from the protocol are justified and fully documented. The Study Director is also responsible for the following ... 

To verify the developed concepts underlying the structured 7-stage protocol in a reactive way, they were applied to an analysis of recent accidents in the Dutch chemical process industry. Despite the limitations in the information available from the accident database, it could be deduced that all accidents were preceded by precursors, and even that similar precursors had led to similar accidents, implying that companies had failed to learn from these re-occurring deviations which were in fact pre-warning signs of impeding accidents. 

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