Validity, content-related

Audit instruments can be evaluated on the basis of three different types of validity when linking the audit to safety performance. These are content-related, criterion-related, and construct-related procedures for accumulating evidence of validity (Anastasi 1988, 139). Content-related validity involves the examination of the audit content to determine whether it covers a representative sample of the behaviors to be measured. Criterion-related validity procedures indicate the effectiveness of an audit in predicting performance in specified activities. The performance on the audit is checked against a criterion that is considered a direct and independent measure of what the audit was intended to measure. The third type of validity, construct validity, is the extent to which the audit is said to be measuring a theoretical construct or trait. Construct validation requires accumulation of information from a variety of sources. 

Content-Related Validity of Incident-Based Measures... 

Accident rates have obvious face vahdity as a measure of the safety process. After all, most recordable accidents are instances of something we are attempting to prevent At the same time, a cut finger, on its face, is very different from the release of a large cloud of toxic gas. To the extent that we are concerned more about the toxic cloud than about the cut, the cut finger may have little content-related validity. If the release does not result in an... 

Content-related evidence of validity refers to the content and format of the... 

Validity relates to whether you are measuring what you want to measure. When we measure the width of a room, the question of validity usually does not arise. When we are measuring a complex process, such as aptitude to perform well in college or the ability of the safety-management system in a plant to prevent future loss, validity becomes a serious question. Scientists (Chronbach and Meeh 1955) generally define three categories of validity content-related, criterion-related, and construct-related validity. 

The maimer in which the list of critical behaviors is developed ensures a degree of content-based validity. These are behaviors that are related to incidents or that safety professionals believe to involve risk. Krause argues that behavior is the final common path for accidents. Although this is easy to demonstrate when people faU, catch their hand in a machine, or are struck by a falling object, the connection is often much more complicated when a plane crashes or a refinery catches fire. There are undoubtedly acts and failures to act involved in each of these, but an analysis of individual behavior is a rather inefficient way to understand the root causes of these events. 

Because the rates of chemical reactions are controlled by the free energy of the transition state, information about the stmcture of transition states is crucial to understanding reaction mechanism. However, because transition states have only transitory existence, it is not possible to make experimental measurements that provide direct information about their structure.. Hammond has discussed the circumstances under which it is valid to relate transition-state stmcture to the stmcture of reactants, intermediates, and products. His statements concerning transition-state stmcture are known as Hammond s postulate. Discussing individual steps in a reaction mechanism, Hammond s postulate states if two states, as, for example, a transition state and an unstable intermediate, occur consecutively during a reaction process and have neariy the same energy content, their interconversion will involve only a small reorganization of molecular stmcture. ... 

The content of a curriculum must be functional when dealing with societal activities necessary chemical concepts, skills and attitudes with respect to macro-micro thinking must be included. This can be derived from representative authentic tasks. The content of the curriculum should be considered as a chemical toolbox. The traditional content of the present chemistry curriculum, such as the stmcture of atoms, ionic theoiy, fundamental acid-base calculations, are not necessarily part of the chemical toolbox when addressing chemical and technological tasks. The validity of the toolbox (philosophical substmcture) is determined by the representative practices and tasks related to chemistry (cf need-to-know principle in context-based approaches). 

Non-specific absolute assay methods, e.g. volumetric titration, can be applied to avoid the establishment of a reference substance. This is only appropriate, however, when the monograph describes a separation test for related substances. This approach is certainly valid for the determination of the content of pharmaceutical raw materials but less acceptable for the assay of content of pharmaceutical preparations where the employment of specific assay methods is recommended (ICH Guideline 1994) to take account of decomposition of the active ingredient during the shelf life of the product and to avoid possible interference from excipients. 

The reader may wonder why process validation is included. This is simply a matter of consideration of the content of guidelines issued in the past that relate to development pharmaceutics. The first such pan-European guideline, adopted by the Committee for Proprietary Medicinal Products (CPMP) in 1988, included advice on both development pharmaceutics and process development. Later versions of the guidelines on development pharmaceutics and on process development have addressed these topics separately, but the historical and practical perspectives suggests that both need to be discussed here. 

Part—I has three chapters that exclusively deal with General Aspects of pharmaceutical analysis. Chapter 1 focuses on the pharmaceutical chemicals and their respective purity and management. Critical information with regard to description of the finished product, sampling procedures, bioavailability, identification tests, physical constants and miscellaneous characteristics, such as ash values, loss on drying, clarity and color of solution, specific tests, limit tests of metallic and non-metallic impurities, limits of moisture content, volatile and non-volatile matter and lastly residue on ignition have also been dealt with. Each section provides adequate procedural details supported by ample typical examples from the Official Compendia. Chapter 2 embraces the theory and technique of quantitative analysis with specific emphasis on volumetric analysis, volumetric apparatus, their specifications, standardization and utility. It also includes biomedical analytical chemistry, colorimetric assays, theory and assay of biochemicals, such as urea, bilirubin, cholesterol and enzymatic assays, such as alkaline phosphatase, lactate dehydrogenase, salient features of radioimmunoassay and automated methods of chemical analysis. Chapter 3 provides special emphasis on errors in pharmaceutical analysis and their statistical validation. The first aspect is related to errors in pharmaceutical analysis and embodies classification of errors, accuracy, precision and makes... 

CO2, a blank compost inoculum without an additional carbon source (polymer sample) is simultaneously tested under the same conditions. The CO2 content of the exhaust air of both vessels is compared. After subtracting the CO2 evolution of the blank inoculum, the CO2 evolution related to the test polymer is monitored and plotted as a biodegradation curve (see Fig. 1). Finally, the activity of the compost inoculum in the controlled composting test is validated using a cellulose reference instead of the polymer. In Fig. 1, the biodegradation curve of Ecoflex is depicted. After 80 days, 90% of the theoretical CO2 evolution is reached. Thus, Ecoflex is ultimately biodegradable according to the ISO standard for compostable polymers (ISO 17088), which requires 90% of the theoretical CO2 evolution within 180 days. 

Once the analytical method is validated for accuracy at the laboratory scale, it can be used to obtain extensive information on process performance (blend homogeneity, granulation particle size distribution, and moisture content) under various conditions (blender speed, mixing time, drying air temperature, humidity, volume, etc.). Statistical models can then be used to relate the observable variables to other performance attributes (e.g., tablet hardness, content uniformity, and dissolution) in order to determine ranges of measured values that are predictive of acceptable performance. 

Analytical Development of API and Drug Products. Early methods to support synthetic and formulation developments are often developed in the form of potency assay, impurities/related substance assay, dissolution, Karl Fischer, identity, chiral method, and content uniformity. These analytical methods are developed and validated in a fast and timely manner to support all phase II studies. 

---