Test item application

A large range of equipment and types of application procedures are used in the agrochemical industry, and field trial techniques, where possible, should mimic these practices as closely and as accurately as possible. 

The rate of product to be applied is the critical factor affecting all residue studies. The rate should be the highest recommended rate for that particular crop and should be applied at the limit of the GAP for the specific crop. The test item should ideally be pre-weighed in a laboratory prior to making the application. In most cases, this procedure results in easier accountability of test items, more accurate measurement of required doses, and more accurate application in the field since only the correct amount of water is required to be added by the field operator. This procedure also reduces the quantity of test item required and hence reduces the waste, which has to be disposed of. An additional spare sample, which is weighed at the same time in case of mishap with the original sample may be prepared. 

Application rates in protocols can be expressed in various ways, and the field staff should be aware of these types of expressions and understand their meanings, e.g., 

The list can be extended for each and every situation where plant protection products are used. There is an ongoing debate as to how to treat three-dimensional crops such as trees. The first approach is to estimate the number of trees in a given area, e.g., number per hectare. Having estimated the number of trees, the required water volume, e.g., 1000 L ha can be divided by the number of trees to ascertain the quantity of solution that each tree should receive. Knowing the calibrated output of the equipment, the required time to spray the required output per tree can be calculated. The disadvantage of this method is that each tree, whatever the size, receives the same amount of solution. 

The second approach is to use a specified concenfration of solution. This concentration is normally expressed as a hectolitre concentration and is the grams or milliliters of formulated product per 100 L of water. Here the trees are sprayed until run-off (the point at which the droplets coalesce and start to drip from the leaves). Once this point has been reached, the trees cannot be overdosed, since any additional solution will fall from the trees. This method, therefore, gives the advantages of (a) not overdosing, (b) tree size is irrelevant, and (c) no calculation of tree numbers is required. 

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Consider the statements that an experiment starts at "the date on which the first study specific data are collected. and is completed on the last date on which data are collected from the study. Could these dates not be defined in a more straightforward way Why, for instance, should the experimental starting date not be the date on which the test item is first applied to the test system, as it is stated in the GLP Regulations of the Environmental Protection Agency (40 CFR 160 and 792, resp., see Appendix II.III, page 329) And, conversely, why should the experimental completion date not be the date on which the test item is last applied to the test system The answer to these questions is, however, not as simple as it would seem at the first glimpse. It may be true that in the majority of cases, test item application can best define the experimental phase, i.e. its beginning and end. However, consider two situations, one of which has been already used to elucidate another point. 

Where a significant part of the consumable crop is present during the application, half of the trials reported should include data on the residue level present over time (residue decline studies). The number of decline trials may be reduced if it can be shown that the edible part of the crop is not affected or present at the time of application of the test item and no movement of the active ingredient or its metabolite occurs. 

Experience has shown that confirmatory data relating to the amount of test item applied can be gained by the collection of samples immediately following the final application. 

Any portion of the study that is a "field study" may also be audited. A field study auditor would inspect many of the same items already mentioned, but at the field site location. These include the training and experience of the field personnel, the calibration and maintenance of equipment, the field management and operations, the test substance application, and the sampling. Special problems are sometimes encountered in the field because the site is physically displaced from the main site of the study. Despite the physical displacement, the equipment must still be calibrated and maintained, the protocols and SOPs must be followed, there must be proper record-keeping, and there must be regular inspections by the QAU. 

Studies for pesticide risk assessment focus on the situation in a water body near the field edge, with the peak of exposure soon after application due to drift, runoff, or drainage. In most cases, endpoints are related to the initial concentration of the test item (which can encompass multiple applications). In contrast to this, the focus of EQS derivation is mostly on protection against effects of long-term exposure. 

The role of Performance Qualification, which entails challenging the application within the scope of business processes, is harder to distinguish. As a consequence PQ for databases may be combined with User Acceptance testing. Items for consideration within a PQ include verification of data management within the application (actually checking manipulated data sets to determine they are correct), and examining the role of the application within the wider process flow. 

What does suitability for its intended purpose mean Basically, suitability is determined by the specification limits (or the aim of the analytical investigation) and the design of the given test item. For some applications, the requirements are explicitly defined in the ICH guidelines. For example, the reporting level for unknown impurities in drug substances is set to 0.05% or 0.03% thus the corresponding test procedure must be able to quantify impurities at this concentration... 

The area of application of an accreditation or scope of accreditation must be clearly defined by reference to one or more tests or types of tests and, if applicable, test items (NBN-ENA-5002 [12]). Accreditation takes into account only precise individual tests as described with reference to the particular products analyzed, to determinate parameters, according to the test method that is prescribed, and also with reference to the technical procedure for carrying out a test or for implementing a particular standard (NBN-EN 45001). 

First of all, there is the scope of GLP as it is defined in the OECD Principles, and which states that GLP encompasses the non-clinical safety testing of test items contained in pharmaceutical products, pesticide products, cosmetic products, veterinary drugs as well as food additives, feed additives, and industrial chemicals. These test items are frequently synthetic chemicals, but may be of natural or biological origin and, in some circumstances, may be living organisms. The purpose of testing these test items is to obtain data on their properties and/or their safety with respect to human health and/or the environment. (OECD, 1998). GLP is thus applicable to safety studies in two major areas Effects on human health and on the environment. These two areas may share some types of studies that have to be conducted in order to test the safety of the respective test item, but other study types may exclusively be required for one or the other area. 

GLP because the sponsor did not ask for a GLP compliant study. Where there is no obvious need for the application of the full requirements of GLP, e.g. no need for a formal Quality Assurance audit of the final report, it would seem to make no sense to apply these special regulations and thus to add to the administrative burden with no rewards whatsoever. However, in such a test facility, it would be of the utmost importance that in all other respects studies would be performed as if they were conducted under GLP Apparatus should be maintained and calibrated according to the respective SOPs, test systems should be properly located and identified, test items should be characterised and labelled, SOPs should be available for all activities performed at this test facility, the studies should be conducted to the applicable SOPs, the respective raw data should be treated in a manner analogous to those in a GLP study, and all these activities should be properly documented and recorded. Only if the personnel of this test facility were not allowed to apply two different standards in doing their work will it be ensured that a real GLP study, if one is to be performed, will truly be in compliance with the GLP Principles. 

Consider the two-year lysimeter study which has been described above, and in which there is just one application of the test item. Could this be the experimental starting as well as already the experimental completion date For the experimental starting date, this may well be correct but is it equally true for the completion date Certainly not, because the main experimental effort in such a study is the analytical determination of the test item concentration in the effluents and its distribution within the core of the lysimeter. Therefore, it is completely out of the question to set the experimental completion date as the date on which the test item has last been applied to the test system. 

These are the more or less straightforward cases, but there can be more contentious ones. In a field study, the exact date of the application of the test item can in most cases not be predicted with sufficient accuracy, since the time point of application depends on a good number of variables that cannot be influenced by the Study Director or the Principal Investigator, such as weather conditions and growth stage of the crop to be treated. It is therefore customary for field studies not to specify an exact date for the spraying of the crop, but to... 

It has to be recognised on the other hand that even in study-based inspections there is some element of process-based inspecting, since activities of a repetitive nature, like the application of the test item to the test animals in a chronic toxicity study, will only be inspected on a random basis once or a few times during the conduct of the study. While it is thus customary to assume that, for the purpose of covering phases which occur with a very high frequency within a single study, a limited number of inspections will be suffi-... 

The first of these two points deals with an important consideration in the whole area of test item documentation, namely the accountability of test item and its usage. The GLP Principles are not only concerned about the possibility for checking back the identity of the test item, i.e. that the correct test item had been applied to the test system, but also that it should be possible to reconstruct the probability that the test item had been applied in the correct amounts, concentrations and/or doses at all times. Since with its application the test item disappears in the test system, there is no immediate and direct means of ascertaining in retrospect that the correct amount had been applied. Obviously, it would provide for the highest degree of confidence in the assertion that indeed the target doses had been applied to the test system, if each and every preparation were to be analysed. It is, however, as obvious that such an effort would be stretching the analytical (and financial ) resources to the unbearable, and therefore some compromise will have to be reached. On the whole, it is considered sufficient, if periodic analyses are performed which, in connection with the full documentation of the actual preparation activities,... 

With this train of information available, it may be possible to exclude calculation and weighing errors at least to a certain extent, if the records of the test item logistics, compared to the application records, would show no discrepancies between these two data sets. The side-by-side comparison of the progressive diminution of test item remaining, with the records for the amounts weighed out for the application, will enable the reconstruction of the day-to-day procedures of test item preparation. 

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