The Quality Assurance Statement

The Principles of GLP require Quality Assurance to prepare and sign a statement, to be included with the final report, which specifies types of inspections and their dates, including the phase(s) of the study inspected, and the dates inspection results were reported to management and the Study Director and Principal Investigator(s), if applicable . Thus, after having audited the final report of the study, and after having been satisfied with the way the raw data have been recorded and represented in the final report. Quality Assurance has to look at its own records to identify the respective activities performed in connection with the study in question. Quality Assurance has then to draw up a list of such activities with their dates and to include this list in the Quality Assurance statement. 

Quality assurance inspections of Study were made and 

This study was conducted in accordance with Good Laboratory Practice 

There is another point that has to be taken into account by Quality Assurance when writing (or by the Regulatory Authority when reading) a Quality Assurance statement. The format of the Quality Assurance statement will be specific to the nature of the study and thus of the final study report. While it is required for all studies that the statement include on the one hand the full study identification and on the other the dates of relevant Quality Assurance monitoring activities, these latter may be of a variable nature with respect to their connection to the study. For example in the case of short-term studies, where single or repeated inspections for each study are inefficient or impractical, where thus individual study-based inspections have not been part of the Quality Assurance activities, and where therefore the Quality Assurance statement is referring to process-based inspections only, details of the monitoring inspections that did take place must be included. These should demonstrate that Quality Assurance did in fact monitor the critical phases of 

SINGLE DOSE TOXICITY STUDY OF IN MICE AND EATS 

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There are many more questions involved in these instances of splitting studies into various, practically independent parts. The question of, e.g., the various problems of Quality Assurance involvement with regard to the Quality Assurance statement in such fragmented studies will be investigated in more detail in section 4.5 (see page 163). The existence of such a great number of more or less unresolved issues within the conduct of multi-site studies finally led to their broad discussion and resolution in an OECD Consensus Document (OECD, 2002). A further problem, which cannot be resolved in the context of GLP, is the question of confidentiality and of various shades of competitor relationships. These issues have to be dealt with in the context of the contractual provisions and need not be considered further in the context of this book. 

It is a self-evident truth and should not need to be specially mentioned that, of course, the Quality Assurance Statement in the final study report will have to reflect this and that the relevant inspections will be clearly labelled as process-based inspections , as is shown below in the example of figure 10. 

The problematic area of study fragmentation which has already been discussed at various places in this book has its reverberations also in the question of the Quality Assurance statement. Especially for multi-site studies, where more than one Quality Assurance unit might have been active, or for subcontracted parts of studies conducted at test sites not connected with the Study Director s facility, the question may arise whether there should be multiple Quality Assurance statements appended to the final report, each of them reflecting the involvement of the different Quality Assurance units with the respective, specific parts of the study. 

Another such case may involve the treatment of areas of non-compliance. There may be differences in opinion between sponsor and Quality Assurance of the test facility with regard to certain exceptions to be addressed in the Quality Assurance statement. There may even be divergences arising between Study Director and Quality Assurance in their respective judgement of compliance issues here, again, test facility management would be summoned to arbitrate the case and to decide on the action to be taken with respect to the Quality Assurance statement. 

The Quality Assurance statement has a two-fold function. It firstly serves to demonstrate that Quality Assurance has adequately monitored the conduct and progress of the study, from the first check of the study plan for GLP conformity to the audit of the final report as a second opinion on the completeness of the reporting and the adequacy of raw data coverage. It secondly provides the study with the seal of approval by attesting to the GLP compliant conduct. In this sense the Quality Assurance statement carries as much weight for the assessment of the study s integrity and validity as the Study Director s signature. 

The format of the final report from a study is closely defined and the Study Director is responsible for its production. The test item and name of the study must be clearly identified, along with the start and end date. It has to be accompanied by a statement from the Quality Assurance unit that the study and any critical aspects of the work have been conducted to the requirements of GLP principles. It will contain the names of all those involved with the study and their address this includes the Study Director, the Principal Investigator, and all the scientists... 

A quality assurance statement listing the details (types of inspections, dates, phase(s), results, reporting date to management and study director)... 

For the sake of accumulation of expertise and in order to ensure consistent interpretation of the GLP Principles with regard to the test facility s activities, continuity in the Quality Assurance staff is certainly desirable. In such a case, the individual (or individuals) charged with the duties of Quality Assurance may, for the remaining part of the job, also be involved in some of the test facilities other study activities. From the viewpoint of GLP this can be tolerated, if this person is not involved directly in the study which he or she is going to assure. There is a pitfall in this statement, however It is acceptable for an individual involved in GLP studies to perform the Quality Assurance function for other GLP studies conducted in the test facility, but these supervised studies need to be performed in another department within the test facility. Thus, the specialist for HPLC analysis may not act as Quality Assurance per-... 

Figure lo Quality Assurance Statement for a study, the experimental part of which had been inspected in a process-based manner. 

Figure i6 This study had not been in need to be conducted to the GLP Principles, therefore the Quality Assurance issued a statement to this effect. 

Figure 17 Completely uninformative Quality Assurance Statement, where it is not possible to establish what kind of activities within the study had been the subject of the inspections.

One such case may be the question of report amendments. If a report should have to be amended, because either further data from other studies may have invalidated some of the conclusions drawn in the original report, or because an error has been detected which had escaped earlier on the attention of the Study Director and the Quality Assurance, then this amendment to the report will again have to be audited by the Quality Assurance, which will furthermore have to prepare an amendment to the former Quality Assurance statement. 

Obviously no final report would be written, and no Quality Assurance statement could be issued, and the unfinished study would thus not be in compliance with GLP. 

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