Target acceptance criteria, for

Table 2 contains an example of validation target acceptance criteria for a stability-indicating HPLC method for the assay of an active drug substance and its related compounds. These criteria or others cited in the literature 22>23 can be used as a general guideline when considering acceptance criteria for a validation protocol. 

The conference report from the Crystal City III Workshop outlines the documentation requirements in detail [10]. The degree of documentation should be sufficient to recreate the validation. Prior to initiating a prestudy validation, an appropriate standard operating procedure or a detailed validation plan should be written. This plan can be a stand-alone document or can be contained in a laboratory notebook or some comparable format. The documentation should clearly state the intended use of the method and a summary of the performance parameters to be validated. The plan should include a summary of the proposed experiments and the target acceptance criteria for each performance parameter evaluated. 

The goal of the development phase for immunoassays is to establish a method that can consistently produce a reliable result culminating in a validation plan with established target acceptance criteria for accuracy and precision. The following recommended parameters are assessed critically during early development, evaluated in late development, and finally, confirmed during validation. 

Analytical completeness is the number of valid measurements as a percentage of the total number of measurements. One measurement is defined as an analytical result for one target analyte. A measurement is valid if it meets the quantitative acceptance criteria for accuracy and precision and the qualitative criteria for representativeness that have been established in the SAP. The total number of measurements can be defined in two different ways as follows ... 

During prestudy validation, the performance of the assay with respect to specificity and selectivity is confirmed with the most relevant compounds and matrices. Selectivity is expressed as acceptable recovery, using the same criteria that are applied during the assessment of accuracy. The recommended target acceptance criterion for selectivity is that acceptable recovery (e.g., 80 120% relative to buffer control) is obtained in at least 80% of the matrices evaluated. 

During development, preliminary assessments are conducted to predict not only the QC concentration values to be used but also the target acceptance criteria. In this case, it is prudent to include more QC levels than will finally be used during validation. For instance, three levels prepared at the LLQQ will likely provide a clear indication of which QC is acceptable and where the assay cannot support the target acceptance. The same can be performed for the ULOQ. At least three levels between the two asymptotes are necessary because these will be used during sample analysis. For the validation process, five QC levels should be selected for testing, based on the accurate and precise readout the final LLQQ to be confirmed the LQC less than three times the LLQQ the MQC, placed about the middle of the curve and the FIQC, placed no more than 75% below the ULOQ and the ULOQ. 

For each in-study run, the standard curve must satisfy criteria described in the standard-curve section however, run acceptance is based primarily on the performance of the QC samples. When using total error for ligand binding assays of macromolecules, the run acceptance criteria recommended in the precision and accuracy section requires that at least four of six (67%) QC results must be within 30% of their nominal values, with at least 50% of the values for each QC level satisfying the 30% limit. The recommended 4-6-30 rule imposes limits simultaneously on the allowable random error (imprecision) and systematic error (mean bias). If the application of an assay requires a QC target acceptance limit different than the 30% deviation from the nominal value, then prestudy acceptance criteria for precision and accuracy should be adjusted so that the limit for the sum of the interbatch imprecision and absolute mean RE is equal to the revised QC acceptance limit. 

The validation process is used to support acceptance criteria used for study sample analysis. The targeted acceptance criteria to be used for sample analysis will be dictated by the analytical requirement, sponsor, or regulatory guidelines but ultimately, the final criteria that will be used for... 

The acceptance criteria used to accept or reject the run based on the curve and QCs are estabhshed during method validation (Section 10.3.3d) and must be documented in the method or appropriate laboratory SOP. As previously discussed, the targeted acceptance criteria to be used for... 

The purpose of a scoping analysis is to determine, under worst case assumptions, if there is a risk that can cause injury, death or financial impact to the public, workers, company, or environment. The PSA begins by identifying the hazards, their physical and chemical properties, the confinement, conditions and distance for transport to a target, estimating the effects on the target, and comparing these effects with accepted criteria. 

The acceptance criterion for recovery data is 98-102% or 95-105% for drug preparations. In biological samples, the recovery should be 10%, and the range of the investigated concentrations is 20% of the target concentrations. For trace level analysis, the acceptance criteria are 70-120% (for below 1 ppm), 80-120% (for above 100 ppb), and 60-100% (for below 100 ppb) [2]. For impurities, the acceptance criteria are 20% (for impurity levels <0.5%) and 10% (for impurity levels >0.5%) [30], The AOAC (cited in Ref. [11]) described the recovery acceptance criteria at different concentrations, as detailed in Table 2. A statistically valid test, such as a /-test, the Doerffel-test, or the Wilcoxon-test, can be used to prove whether there is no significant difference between the result of accuracy study with the true value [29],... 

The next step is to set performance and cost criteria for the system in order to be able to determine whether the new greener design is acceptable. Chelants are often one of the hidden components in a formulation whose value is only found when the system fails. So, what is the cost of batch failure, product spoilage, laundry not being cleaned, reworking in a pulp mill, and so on Also, what is the target cost per dose for the chelant and related chemicals It is important to set acceptable limits on performance - for example, the formulated product needs to be stable for 6 months or show bleach stability >80% over the 30 min wash cycle. 

Accuracy, in general, is assessed using a minimum of nine determinations over a minimum of three concentration levels covering a range of 50-150% of the target concentration (e.g., three concentration levels with three replicates each). The criteria for acceptable accuracy of the assay results cannot be generalized because accuracy depends on the concentrations of the analytes being evaluated and the acceptable criteria depend on the purpose of the analysis (23). 

Sa becomes the maximum acceptable sample standard deviation to meet the acceptance criteria. If the sample standard deviation sn is less than scr, then we are guaranteed, with a minimum assurance of 100(1 - a)%, that the upper prediction bound for a future sample of size 10 will not be greater than 6.0% of the target concentration. 

The RSD for each target analyte in the calibration curve must meet the method acceptance criteria before analysis may start. 

The CCV response (calibration) factor has the acceptance criteria that must be met for each target analyte before the analysis may proceed. 

A series of analyzed samples must be bracketed by acceptable CCVs for the analysis to be valid. If any of the CCVs for the target analytes do not meet the acceptance criteria, the laboratory must take corrective action, reconfirm the initial calibration validity, and reanalyze the samples. 

At this step, the chemist will again make a distinction between the method target analytes and the project contaminants of concern. Proper calibration is critical for the contaminants of concern, especially for those detected in the samples. Deviations from calibration acceptance criteria may invalidate these concentrations or turn them into estimated values. These deviations may also turn the PQLs for undetected contaminants of concern into estimated values. 

The chemist may give a special consideration to the so-called poor performers, the target analytes of the VOC and SVOC analyses method lists with poor chromatographic behavior. Table 5.3 lists the common poor performers, which are well known for deviations from method-specified requirements for response factors and calibration acceptance criteria. 

For most products, a properly structured PQ protocol will require rigorous acceptance criteria, whether employed concurrently or prospectively. A protocol with vague requirements will provide very little information about a process or system. The application of targeted sampling approach methods in conjunction with 3 x or higher sample sizes will result in the strongest support to process reliability. Concurrent validation can be used... 

The presentation of results in graphical formats is state of the art (USEPA, 2000). Although we do not have uniformly accepted recommendations for the presentation formats, the targets of the visualization approaches seem to be in accordance with the following criteria to describe the expected variability in the target population ... 

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