Method definition requirement

The outcome of planning should include the generation of a method definition requirement document (MDRD) in which all stake holders agree, prior to method development, on the critical attributes of the method. Considerations such as what impurities/degradation products should be monitored, requisite reporting thresholds, the need for an MS-compatible method, if identical methods for DP and DS are required, etc., should be clearly decided and agreed upon by all stakeholders. 

Current methods for DNA detection usually require enzymatic amplification of the target DNA sequence prior to analysis. For example, the PCR technique selectively increases the concentration of the target sequence relative to unrelated sequences. PCR methods, however, introduce ambiguities resulting from contamination by different DNA sequence. Therefore, a definitive method is required for the analysis of a single, original DNA sequence. To achieve this objective, the sensitivity and speed of the chemiluminescent enhancement techniques described in this chapter must be improved. 

Method development and optimization are started with review of the currently available methods within the company or in literature. Available methods are used as a starting point and evaluated against the method requirements set in the method definition. If necessary the method is optimized or redeveloped in order to fulfill the requirements. DOE tools (response surface design) are preferentially applied to obtain the best optimal conditions in terms of robustness. Application of DOE methodology is not new in chromatography and DOE is frequently applied also for enantiomeric separations in Especially in... 

All MADA methods require a definition and structuring of objectives, attributes and alternatives and the majority of methods also requires a definition of weights that reflect the importance of different sub-objectives. In... 

Some chemists feel that the mole is an unnecessary SI unit as they make measurements in mass/mass or mass/ volume units, using ratio methods. The definition and the importance of the mole has been discussed elsewhere [8], and the distinction has been made between its importance as a concept, the importance of the related atomic mass values, and the lesser role of the mole as a unit for actually reporting results. A distinctive feature of the mole is the need to define the entity . This is an extra dimension compared with other SI units. For example, it is not necessary to ask, is this a mass when measuring the mass of an object, in the way that it is critical to ask, is this lead before attempting to measure the amount of lead. A mole measurement thus requires two issues to be addressed, namely identity and amount. It follows therefore that traceability claims must show unbroken chains covering both of these issues. It is because of the existence of a vast number of chemical species that it is necessary to clearly specify and separate the specified chemical entities from all other possible chemical entities prior to measurement. This leads to complex chemical measurement processes, with considerable attention to validation of the measurement method being required. 

All interpretive optimization methods are by definition required to obtain the retention data of all sample components at each experimental location. If the sample components are known and available they may be injected separately (at the cost of a large increase in the required number of experiments). For unknown samples, for samples of which the individual components are not available, and in those situations in which we are not prepared to perform a very large number of experiments (as will usually be the case in the optimization of programmed analysis) we need to rely on the recognition of all the individual sample components in each chromatogram (see section 5.6). 

Based on the data in Table 6 4 3, it is apparent that none of the degradation methods currently in use is capable of providing a completely unequivocal characterization of lignin and hence use of a combination of methods is required to attain this objective However, as a single method, thioacidolysis has a definite advantage in that it may be used to characterize unambiguously typical and prominent lignin structures... 

While MD methods almost by definition require a full atomic model of the protein and detailed energy function, MC methods can be used both on detailed models or on simplified models of proteins. These latter can range from a very... 

These methods are subject to the difficulties inherent in all such chemical methods and require careful experimental control to establish definitive results. With adequate checks, however, they can be extremely valuable for establishing the nature of the intermediates in complex reactions and... 

The theoretical treatment of the Van der Waals interaction, on the other hand, definitely requires the application of more sophisticated, correlated methods such as perturbation theory (performed mostly in the form of Moller-Plesset perturbation theory, MP), coiffiguration interaction (Cl) or coupled cluster (CC) approaches (see below). 

Table A-2 in Appendix A displays disposition options for chemicals that are subject to abandonment or destruction (Section 4.7). Such non-t5 ical disposition methods, which require prior DOE authorization, may be appropriate for chemicals identified as High Risk property (see definition also Section 4.1.2) that have the potential to adversely impact national security interests, proliferation concerns, public health and safety, or the environment.

Measurements, and concepts with which they are associated, can contribute to a shift from experience-based knowledge acquisition to rule-based, engineering-like methods. This requires (1) a widely accepted conceptual framework (i.e., known to assistive device manufacturers, rehabilitation engineers, and other professionals within the rehabilitation community), (2) a more complete set of measurement tools that are at least standardized with regard to the definition of the quantity measured, (3) special analysis and assessment software (that removes the resistance to the application of more rigorous methods by enhancing the quality of decisions as well as the speed with which they can be reached), and (4) properly trained practitioners. Each is a necessary but not sufficient component. Thus balanced progress is required in each of these areas. 

---