Non-procedure related factors

In the second approach non-procedure related factors are considered. Factors such as e.g. different laboratories, different analysts, different instruments, different lots of reagents, different days, different columns for HPLC methods or different plates for TLC methods are then examined. 

In the literature, ruggedness tests concern mainly procedure related factors, but occasionally one of the other factors, e.g. a column factor in HPLC, is examined. This will be discussed further in more detail (see Sections 3.4.2 and 3.4.4.4). The examination of the non-procedure related factors in ruggedness testing is described less frequently and requires another approach than the examination of procedure related factors. 

RUGGEDNESS TESTING OF NON-PROCEDURE RELATED FACTORS THE USE OF NESTED DESIGNS... 

The examination of more than one of the non-procedure related factors (e.g. different laboratories, analysts, instruments, columns or batches of reagents, days) by Plackett-Burman and fractional factorial designs causes problems. These designs require combinations that are impossible to... 

Ferric ion was immobilized on a Chelating Sepharose Fast Flow column preparatory to the separation of seven enkephalin-related phosphopep-tides.17 Non-phosphorylated peptides flowed through the column, and the bound fraction contained the product. The capacity of the column was found to be 23 pmol/mL by frontal elution analysis. Cupric ion was immobilized on Chelating Superose for the isolation of bovine serum albumin.18 Cupric ion was immobilized on a Pharmacia HiTrap column for the separation of Protein C from prothrombin, a separation that was used to model the subsequent apparently successful separation of Factor IX from prothrombin Factor IX activity of the eluate was, however, not checked.19 Imidazole was used as the displacement agent to recover p-galactosidase from unclarified homogenates injected onto a nickel-loaded IMAC column.20 Pretreatment with nucleases and cleaning in place between injections were required procedures. A sixfold purification factor was observed. 

The second difference relates to the definition of a cutoff time point for the evaluation of the difference factor and the Rescigno index. When cumulative data are available, evaluation of the difference factor or the Rescigno index usually requires a reference data set in order to define the cutoff time point for index evaluation (30). For the evaluation of fl and the , i.e., when the difference factor and the Rescigno index are evaluated from non-cumulative data, this difficulty does not exist, provided that the release process has been monitored up to the end (i.e., until dissolution of the drug is complete). At this point, it is worth mentioning that a similar conclusion cannot be drawn for the similarity factor (31) because application of this index to non-cumulative data is set apart by the careful scaling procedure required, in addition to the existence of a reference data set. The reason is that this index can continue to change even after dissolution of both products is complete. 

Unfortunately, the relations between the electron density, the restraints we have discussed here, and the structure factors are non-linear. Thus, the only strategy we can adopt is to use the approximate phases we start out with and improve these iteratively. Even this is not straightforward, mainly because Eq. 1 is expensive to compute. However, there exists a powerful and straightforward procedure that is used in virtually all phase refinement programs Eourier cycling. 

All of these procedures involve heating T1203 in non-sealed systems, and all are typified by superconducting product stoichiometries far different from the starting compositions. Again, in addition to safety concerns, little control of superconducting-phase composition and reproducibility of synthetic conditions is afforded by use of non-hermetically sealed reaction containers. The problem appears to be more complex than simply thallium reactant loss factors related to reaction kinetics are most likely quite important for the preparation of these metastable phases. 

The measured storage capacities at 77 K ranged from less than 1.6 wt% for a low surface area MOF-5 sample (BET SSA = 572 m g ) [88,89] prepared by the so-called Huang s synthesis [90] to 7 wt% when the sample was prepared in an inert atmosphere with complete absence of water and moisture, leading to a material with a B ET specific surface area of 3800m g [91]. These discrepancies were attributed to different factors related to the synthesis procedure, such as (i) the decomposition of MOE-5 and formation of a non-porous second phase in the presence of moisture [91],... 

The development of an ADI is essentially the same in the NAS procedures, the EPA Food Tolerance procedures, and the NACA proposal for groundwater. An ADI is determined by dividing the NOEL in the most sensitive species by a suitable Safety Factor (SF). Safety Factors for subchronic or repeat administration are usually 1,000 for chronic or lifetime studies, 100 is used. Species conversions can be based upon mg/kg, ppm in the food, or body surface area conversion [29]. Currently, non-oncogenic effects are considered on an mg/kg basis without attempts to correct for species differences. Risk assessment procedures for oncogenic risk employed by the EPA are based upon surface area extrapolations in an attempt to relate to man [30]. 

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