Method transfer data evaluation

Fig. 9 gives an example of how to determine the charge transfer current density. The plotted lines were evaluated according to the least squares method. The data were taken from the stationary potentiostatic current-potential curves at five different rotating electrode disk speeds. 

The primary objective of this chapter is to highlight current industry best practices in effecting successful method transfers for those carrying out ligandbinding assays in biological matrices, usually plasma or serum. In most instances, the data generated support pharmacokinetic and/or pharmacodynamic evaluations as part of the chug development process. However, the procedures and processes are applicable to any GXP environment only the acceptance criteria will vary. 

Since a quasi-steady-state analysis was used, it was necessary to choose a point in time to establish an empirical method for the evaluation of (5). The point in time chosen was at the time when the frost formation acquired a maximum resistance to heat transfer, or when the experimental heat-leak data (from test section boil-off) showed a minimum value. At this point, analysis of heat transfer data indicated that Ts approaches a maximum value (see Fig. 4) and one may observe glazed patches on the frost surface and, on some tests, liquid droplets. Since Ts remains relatively constant from this time on, q will vary primarily with frost surface area and, at this point, will show a minimum value because all subsequent areas will be larger. This point in time is called the < min point and is used as a reference point in subsequent discussions. 

The comparative testing type of technical transfer generates results that need to be compared using one or more statistical tools. Although data can be evaluated subjectively, the use of statistics will build objectivity into the data analysis and allow unbiased comparison of the data sets. Because comparative testing involves destructive testing of individual samples, a successful transfer involves proving mathematically that the data sets are equivalent. The complexity of the data treatment is directly related to that of the method transfer ... 

This chapter highlights the important aspects of the analytical transfer processes as they relate to process, compliance, analytical data, and documentation. Types of method transfers and the timeline of transfer activities are discussed. The risk assessment prior to initiation of transfer activities is also described. The chapter describes content and utility of the transfer protocol and final report, as well as documents that govern analytical method transfers (i.e., SOPs and master plan). The importance of selecting appropriate method transfer acceptance criteria and use of statistical methods to evaluate results are described. The significance of the inclusion of an adequate level of detail in the methods, protocol(s), and other documents cannot be overly stressed. Last of all, the process for transfer of technical ownership of the analytical methods is discussed. Other chapters in this text should be consulted for elaboration on the various important facets of technical transfer, including method development, method validation, documentation, and stability. 

The smooth and efficient method transfer between the two platforms will remain important within the transition period between UHPLC and HPLC. The column dimension, particle size, stationary phase chemistry, mobile phase flow rate and gradient profile, dwell volume, injection volume, and data acquisition are key factors to be carefully evaluated to ensure improved or maintained performance of transferred methods. Other factors including regulatory requirements should also be considered for a successful method transfer to quality control labs. The extra-column volume effects such as increased retention factors and decreased efficiency and high pressure effects (e.g., frictional heating and changes in retention factors) should be considered when various methods are compared and transferred. 

It was shown later that a mass transfer rate sufficiently high to measure the rate constant of potassium transfer [reaction (10a)] under steady-state conditions can be obtained using nanometer-sized pipettes (r < 250 nm) [8a]. Assuming uniform accessibility of the ITIES, the standard rate constant (k°) and transfer coefficient (a) were found by fitting the experimental data to Eq. (7) (Fig. 8). (Alternatively, the kinetic parameters of the interfacial reaction can be evaluated by the three-point method, i.e., the half-wave potential, iii/2, and two quartile potentials, and ii3/4 [8a,27].) A number of voltam-mograms obtained at 5-250 nm pipettes yielded similar values of kinetic parameters, = 1.3 0.6 cm/s, and a = 0.4 0.1. Importantly, no apparent correlation was found between the measured rate constant and the pipette size. The mass transfer coefficient for a 10 nm-radius pipette is > 10 cm/s (assuming D = 10 cm /s). Thus the upper limit for the determinable heterogeneous rate constant is at least 50 cm/s. 

Critically evaluated experimental data covering the densities of organic compounds is essential for both scientific and industrial applications. Knowledge of densities is important in many areas, including custody transfer of materials, product specification, development of various predictive methods, and for characterizing compounds and estimating their purity. 

The third principle relates to the set of equations which describe the potential energy surface of the molecule. These potential energy equations, derived primarily from classical physics, contain parameters optimized to obtain the best match between experimental data and/or theoretical results for a training set of compounds. Once the parameters are evaluated for a set of structures (as diverse as possible), they are fixed and then used unmodified for other similar (and usually larger) compounds. As a first approximation, these parameters must be transferable from one structure to another for this method to work and be generally applicable. 

---