Quality assurance functions

QA is an important aspect of any technical study. It is particularly crucial in an LSMBS, because several hundred participants, widely separated geographically, are involved. The analytical laboratories typically have standard provisions for QA inspections and reviews, and the field phase management organization is also likely to have standard provisions for QA inspection and review. Shoppers, however, are typically external to study management and analytical laboratories and, thus, are not directly covered by existing QA systems. The study design must include a means by which the field phase, i.e., sample collection and shipment by the shoppers, is made to comply with QA requirements. 

Each contract laboratory used in the QPMBS and the organization that coordinated the field phase already had in place a well-defined GLP-compliant quality assurance program. In addition to these existing quality assurance programs, an independent QA specialist was engaged to ensure compliance of all the aspects of the smdy with GLP requirements. 

The study QA specialist visited each laboratory, conferred with the local QA specialist, and reviewed local practices and record keeping, thereby establishing that personnel and practices at each laboratory were satisfactory. Each laboratory, of course, remained responsible for internal compliance with the protocol and with GLP requirements throughout the study. 

Thereafter, the primary functions of the study QA specialist fell into two main headings. First, GLP compliance during the collection and documentation of commodity samples had to be assured. This was done via observation of several collections for different shops (collection incidents) at various geographic locations. In these audits, the study QA specialist examined specific items, such as (1) did the shopper follow the written instructions, (2) were the correct types and numbers of samples collected, (3) was the documentation maintained as required, (4) were the samples labeled and packaged correctly, and (5) were the samples delivered to the shipper as required Findings were communicated to study management and used as appropriate in subsequent shops. 

The second main function of the study QA specialist was to review and validate the assembly of the final study report. As developed above, the workbooks containing the 

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Each process owner is required to work closely with his or her QA counterpart. This ensures design and operational issues are clearly reviewed and approved by a representative from the quality assurance function, a regulatory expectation. The quality assurance counterpart must be familiar with the process, understand documentation supporting the process, and able to convey what approval the Quality... 

Each procedure fully describes the purpose, responsibility, authority, and interrelationships of personnel for all quality activities. The responsibilities for personnel related to quality assurance functions are defined in the job description file. 

For computer systems that are an integral part of the operation of a manufacturing plant or process, the system PQ may be conducted in conjunction with process validation. The combined activities are generally led by the pharmaceutical manufacturer s quality assurance function and can be in the form of an extended process trial. 

Quality assurance functions primarily to monitor the fact that the quality function is being performed. Its role in PV is readily associated with its main functions. For example, it performs the tests that demonstrate the product s content uniformity. It may also perform the statistical evaluation of the test results to show that the process is reproducible. Quality assurance initiates the action to dispose of nonconforming product. It implements the inspection criteria and sets the specifications for product approval or rejection. It analyzes the product complaints to learn how effective its test program has been in preventing reject-able product from reaching the marketplace. 

As previously indicated, these GLP regulations and international guidelines were written to address the issue of the conduct of studies and assuring their quality. In order to address these issues, each of the regulations and the international guidelines calls for the establishment of a Quality Assurance Unit or "quality assurance function" within each laboratory. They also specify that certain tasks be carried out by this unit or function. These requirements have resulted in the creation of a new scientific, managerial professional - the quality assurance unit... 

All inspection, measuring or test equipment, whether mechanical, electrical, automatic, or mechanical in operation, which performs a quality assurance function must be validated for its intended use. This equipment must also be routinely calibrated according to a written procedure and the records that document these activities must be maintained. 

The investigation report should become a permanent part of the batch record(s) and stored appropriately under the auspices of quality assurance. It is the direct responsibility of the group generating the OOS or process deviation, as well as the quality assurance function, to ensure the corrective action described in the formal investigation report is carried out in its entirely and within the time frame committed to. 

Backup mechanisms for GxP functionality include an independent parallel or downstream component/device to detect any malfunction (e.g., independent monitoring systems). The focus for validation can then shift from the componenPdevice to the backup system, as illustrated in Figure 7.3. Where this implies implementing a backup system that is simpler to validate, the shift can relieve the burden of validating more complex components and devices. For a backup mechanism to be accepted as a validated alternative, it must be able to independently manage key quality assurance functions. Such functions include but are not necessarily limited to ... 

Several systems are used by the quality assurance unit to help carry out quality assurance functions. One such system helps the quality assurance function... 

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-... 

These various situations are graphically represented in figure 9. It lies in the responsibility of the test facility management to investigate the possible interrelations between the various test facility units and their common involvement in studies to select the most appropriate individuals for performing the respective Quality Assurance functions. 

Figure 9 Schematic representation of possibilities for the reciprocal performance of Quality Assurance functions in a company with two different test facilities.

This question of compatibility of various levels and functions within a GLP test facility has given rise to many questions. Not always is the situation as clearly delineated in the GLP Principles as it is with the requirement of absolute independence of Quality Assurance functions from study conduct. 

There are situations where one person may have multiple roles or positions in a test facility without violating neither letter nor spirit of the GLP Principles, while in other combinations of functions the compatibility with GLP may be questionable. But even the seemingly clear-cut requirement of absolute independence of Quality Assurance functions from study conduct may experience ambiguities, as there may be some situations where the case might not be quite obvious Would it be considered acceptable for a Quality Assurance manager to be also a member of an upper management level or to be married to a Study Director ... 

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 the context of inspections. Quality Assurance may face a number of additional problems when dealing with field studies, even if conducted at test sites within the same test facility. One of these is the number of staff needed for the correct execution of the Quality Assurance functions. While in a small test facility performing only a limited number of toxicity studies, and all of them in its own laboratories, one single person may be considered sufficient for the performance of Quality Assurance functions, a single individual will, on the other hand, probably not be able to perform all the necessary Quality... 

The key to the successful operation of Quality Assurance functions lies, as everywhere, in a good planning. Logically, prospective planning should concern not only Quality Assurance inspections, but it has to be applied to all of the various Quality Assurance activities. However, due to the special nature of study- and process-based inspections, and to the time restrictions connected with them, the need for proper instruments and procedures is very much obvious in this special area. Certain critical study activities may be performed in only a few minutes if the Quality Assurance inspector would wish to inspect exactly this specific phase of the study, he or she had better be present at the precise time, when this activity would be going on. Since this is a prerequisite for the required precision in the attendance at specific activities or study phases, a well developed communication network between Quality Assurance and study personnel can be seen as an obvious necessity. 

Umatilla Chemical Depot, OR Quality Assurance Function Range... 

Control Inadequacies The report says that DCMC approved an IV V process with incomplete coverage and that there was a software quality assurance function operating at DCMC, but it operated without a detailed understanding of the overall process or program and therefore was ineffective. 

A principal section of a safety report should be devoted to the description of the quality assurance programmes of the plant owner and of its contractors during the design, construction, testing and operation of the plant. The methods for the implementation of the quality assurance functions should also be described. 

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