Study Directors processing

Persons responsible for the GxP processes/activities/studies (e.g., preclinical study director, process owner, clinical project leader or sponsor/investigator)... 

Applications to and harvest of major crops such as coffee, bananas, and pineapples frequently involve procedures and equipment for which standard operating procedures have not been written. These must be identified in the planning stage, so that the Study Director or Principal Investigator can write these procedures with sufficient time to allow for review and approval. If a procedure is specific to the trial at hand, the process may be described in an addition or amendment to the protocol, but this still requires QA and management approval. In some cases, SOPs specific to a local crop are maintained at a regional site. SOPs must also be available at the site at which the raw data are archived. 

The protocol will provide important date and time requirements. Estimated start and completion dates for the study are required by regulation. In addition, the Study Director may specify a maximum storage time of the RAC prior to processing if the chemical in question or its metabolites degrade rapidly. A maximum time after generation of a processed fraction before that fraction is placed into frozen storage may also be specified. A maximum storage time prior to shipment may also be specified. 

The Study Director is the pivotal person in any GLP study. The sponsor initiates the study and assigns a Study Director to act as the primary control point for all aspects of the study. The Processing Principle Investigator (PPI) acts as an agent of the Study Director and handles the processing phase of the study. The PPI reports directly to the Study Director, and quality assurance (QA) documents resulting from the processing phase are sent to the Study Director for approval. The Study Director has final say in all questions of compliance with GLP and interpretations of the protocol. The... 

PPI acts as a resource to the Study Director with specific expertise in the area of food processing and acts as an extension of the Study Director in supervising of the processing phase of the study. 

The Field Principal Investigator (FPI) provides the same services to the Study Director as the PPI except that the FPFs services are provided in the area of growing crops and application of pesticides. The FPI and the PPI must interact so that information on application timing and its impact on harvest date and subsequent delivery of the RAC to the processing facility is communicated in a timely fashion. Delivery method, RAC condition, and timing are all important aspects of the processing phase that are actually controlled by the FPI. 

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. 

The integration of different forms of study information from various locations and sources is possible with electronic information. Both study management and quality assurance are addressing critical issues associated with this process. Study Directors must now keep track of more data and study reports than ever before. Quality assurance (QA) departments must have systems in place to audit electronic data. 

Regardless of the objective, the study director and advisory staff will need to determine the scope of validation prior to use of the method in specimen analyses. Criteria for acceptance of the method or for establishment of laboratory capability should also be established and documented prior to the validation process. 

The EPA and FDA audit is a formal process involving advance notice, planning and scheduling (Figure 8.2), and a follow-up report, as well as the actual on-site observations and interviews. The advance notice includes an announcement of what specifically is to be audited. When the auditors arrive, the study director and lab workers are interviewed as a group, in what may be called an "opening conference," and the audit plan is laid out for everyone s full understanding. Included here would be a review of the purpose... 

Records are kept of when a sample was collected, the method of collection, who collected the sample, what the elapsed time was between harvest and freezing, the conditions under which it was stored, how it was shipped to the laboratory, and when it was shipped. When a sample arrives at the laboratory, the condition of the sample is checked and recorded. Then the information on the sample bag (sample number, application rate, preharvest interval, etc.) is compared to the trial information sheets which are submitted along with the samples. Any omissions or discrepancies are corrected at that time. If there is an omission or discrepancy that cannot be easily corrected by a telephone call from the sample processing laboratory to the field scientist, the study director is notified. The study director must make the decision about the validity of the sample and put a note in the data file explaining how the problem was corrected or that the problem could not be corrected and the trial is to be abandoned. If the trial is dropped, Quality Assurance is notified, the trial is deleted from the active Master Schedule, and an explanation is put in the study file. 

The purpose of the qualification/audit is for the sponsor to investigate the standard practices of the contractor. Quality as well as technical capabilities should be evaluated. One should determine where the test article will actually be stored, the department that will conduct the in-life portion, make an assessment of procedures (SOPs) for dosing, identify differences between the sponsor s general practices and the facilities operating procedures (proto-col/study-specific procedures (SSPs), and assess the process of interim data exchange and the method of reporting of SOP and protocol deviations to the study director and the sponsor. 

In the nonclinical laboratory, it is primarily the role of the study director and the QAU to set up these document control processes and monitor the documents and records produced throughout the study to make sure GLP regulations are being followed. 

The writing of some such kind of a study plan before initiating the respective investigations would not only improve the reconstructability of the studies conducted. Already the process itself of writing-up the various aspects of the premeditated study would serve the Study Director to clarify in his or her mind the relative value of the different ways to achieve the purpose of the research project and thus to set out in a logical manner all the possibilities for proceeding to this end. 

While thus the term and the use of process-based inspections have been defined, the applicability of this inspection type with regard to study types may seem less clear. Therefore it is of utmost importance to define clearly and unequivocally those study types which would qualify for this facilitation of the Quality Assurance function. To this end, the Quality Assurance has to develop SQPs which should primarily define the circumstances under which process-based inspections may be performed and which should also present a final list of the respective study types. It probably needs not to be especially mentioned that it would certainly be advisable to develop these SQPs in collaboration with the respective Study Directors and on the basis of historical data regarding study frequencies. 

In manual calculations, such problems could easily be spotted by an independent, critical observer, as one of the points made in the Study Director s statement shown in figure 34 (see page 271) will demonstrate. In an electronic system only an expert programmer, however, could be expected to deal with such issues, and furthermore only so, if he had full access to the source code. Therefore, the basic process for ensuring GLP compliance of an IT application is to demonstrate that the respective application does indeed perform the intended task in a correct way, and that it does so in the actual working environment of computer hardware and connected peripheral components and apparatus. This demonstration of the suitability for its intended purpose is obviously of fundamental importance, and this process is referred to as computer validation . In essence, such validation should provide a high degree of assurance that the system will meet its predetermined specifications. 

While the formulation of the scientific rationale for the studies should pose no problems to the Study Directors - if there were problems with this topic, then the respective individual should not be allowed to act as Study Director - and while the observations, measurements and data to be collected are prescribed either by international guidelines (as in toxicology studies), or by the declared purpose of the study, the whole timing and organisation of the process will have to be looked at. A flow chart of study conduct, like the one already shown in figure 38, will certainly help very much in delineating the chronological order of activities to be performed. 

Polyvinyl chloride (PVC) is produced by a batch process. Since it is usually cheaper to produce chemicals if a flow process is used, the development department proposes a new process and has a process engineer assigned to design it and estimate its cost. If it is only slightly less expensive than the batch process, the new method will be dropped. If it appears that substantial savings can be realized by using the continuous process, further research and pilot-plant studies will be. insfituted to make certain it will work before the board of directors is asked to authorize the construction of the plant. 

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