GLP and Other Laboratory Quality Systems

One of the misconceptions about GLP which has already been mentioned earlier is simply connected with the terminology The name, the Good Laboratory Practice , implies that any laboratory capable of faultless operation and quality work must conduct its activities under the auspices of Good Laboratory Practice. The name seems thus to have completely usurped the quality field with respect to work conducted in laboratories. In reality GLP has a strictly defined area of application, which includes only some types of laboratories, and some types of studies, as has been described earlier (see section 4, page 25). Other quality systems do exist, however, which may apply to those laboratories and the work conducted therein, which are falling outside the area of GLP. They will be better tailored not only to the needs of sponsors and laboratories alike, but indeed to the type and nature of the work conducted in those types of laboratories. 

When a physician, because of concerns about some risk factors for heart troubles, wants to have the blood sample of a patient analysed for the content of cholesterol, he or she will be interested in the precision of the result, because the decision to prescribe a lipid-lowering drug may critically depend on this information. Therefore the laboratory has to convince the physician of its technical expertise and of the precision and reproducibility with which it is 

In the first example, quality is determined in terms of precision and reproducibility of the result obtained, while in the second case, it is the reliability of the study that counts, because the results may not be challenged through a repetition of the study. In the first case, if the physician would have some reservations with regard of the precision of the reported values, he might send a second sample to another laboratory and compare the two sets of results. Either, they would correspond, in which case there would be no reason to mistrust the first laboratory, or they would not, in which case a third opinion might be sought. In the second example, as experience has shown, a repetition of the toxicology study will, in all probability, yield results which will quantitatively not be comparable to the results of the first one. Quite apart from considerations of animal protection which would anyway prohibit the repetition of studies just for the sake of corroboration, the repetition of such a study with the purpose of verification would therefore be scientifically objectionable. 

It has been stated already that the primary purpose of GLP is not to guarantee primarily the scientific or technical quality of studies, but to provide transparency in enabling third parties to follow in retrospect the whole course of a study to trace back all activities to procedural standards, to relate activities to the personnel that had performed them and decisions to the authorised individuals, in fact to reconstruct the whole study. While such a purpose of the quality system is valuable in situations where the outcome of a study may not be readily reproducible, and where repeating studies may be out of the question, other situations may require different approaches. 

if quality is established in terms of precision and reproducibility of the results obtained in the studies (i.e. in the respective sets of measurements or experiments), the need to provide for each of the studies a study plan, approved by the head of the laboratory before the experiments or measurements can be started, will not be an important consideration. Certainly, Standard Operating Procedures will have to be observed, and the acknowledged methods will have to be followed, with any deviations to be described and justified. Since it is the quality of the result which counts for the determination of the test facility s quality , and not the way on which it has been obtained, there is no need for a single point of study control in the person of the Study Director. Certainly, a laboratory head will have to be appointed, who has to ensure that the quality of the data obtained in the laboratory remains high, and who has to provide the necessary education and training for the technical personnel in order to enhance and update their technical expertise. If precision and reproducibility are the primary purpose of the test facility s quality concerns, then apparatus, instruments, equipment and computerised systems have to comply to the highest technical standards in terms of validation, maintenance and calibration. 

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The main similarities of GLP and other laboratory quality systems may be seen in their focus on apparatus and instrument suitability, maintenance and calibration, where the requirements of accreditation systems go beyond what GLP is regulating, since these issues are of the utmost importance for generating accurate, precise and reproducible results. Thus, it has to be possible in every case to trace back the calibrations to the respective national standards of measurement, and the quality control of the measurements has to ensure that trends to deviations form the precision required are detected already early on. 

The computerized systems, both hardware and software, that form part of the GLP study should comply with the requirements of the principles of GLP. This relates to the development, validation, operation and maintenance of the system. Validation means that tests have been carried out to demonstrate that the system is fit for its intended purpose. Like any other validation, this will be the use of objective evidence to confirm that the pre-set requirements for the system have been met. There will be a number of different types of computer system, ranging from personal computers and programmable analytical instruments to a laboratory information management system (LIMS). The extent of validation depends on the impact the system has on product quality, safety and record integrity. A risk-based approach can be used to assess the extent of validation required, focusing effort on critical areas. A computerized analytical system in a QC laboratory requires full validation (equipment qualification) with clear boundaries set on its range of operation because this has a high... 

Good science exists in research in academic institutions apart from the soon to be established Environmental Protection Agency s (EPA) Good Laboratory Practice (GLP) guidelines. However, this is not to say that GLP s are not advisable. Good science should be able to stand up to review as having been performed using appropriate and adequate laboratory practices. Scientists have had their work routinely scrutinized by their peers for its quality and will not resent careful analysis by others. For example, only a portion of the work produced by the scientific community is acceptable for publication in its various journals. The rate of acceptance in journals varies but it is apparent that the peer review system attempts to serve as a quality control mechanism in the scientific community. 

While it may thus be possible that in certain areas, the different quality systems may be similar to one another, it has nevertheless to be recognised that neither the adherence to an ISO or accreditation standard may replace GLP compliance (for this aspect see the respective OECD Position Paper), nor can a GLP compliant test facility claim the same technical competence as a laboratory operating under an accreditation scheme. However, the existing redundancies in the different sets of rules can make it possible to implement two such quality systems in one laboratory utilising the common points of the two systems to facilitate the tasks of personnel and quality management. The same can be true for the official compliance monitoring inspections and audits, where audit or inspection results of aspects that are fully covered by one system may be accepted by the other without further investigation. 

Ms. Snelham is the lead consultant for laboratory validation within Eutech. Previous experience includes validation within GLP and GMP arenas. Before joining Eutech, she was head of quality assurance for Ciba Pharmaceuticals. During her career at Ciba and at Medeva Pharmaceuticals, she gained experience in the validation of LIMS, Toxicology, MRP II and other computerized systems and led regulatory inspections from the UK, U.S. and Japanese authorities. 

In study-based quality management systems, such as good laboratory practice (GLP) and good clinical practice (GCP), the study number is considered as the main index variable and any other information along the meta-data model can be derived from it. With the help of the meta-data model (see Box Meta-Data Model), it can be checked easily if the information of the documented GxP-relevant process is complete. 

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