The Process Body of Knowledge

In developing the process for a bulk drug, the need to gather and properly organize a process body of knowledge is compelling  

The dossier requires that the process foundation— chemistry, engineering, scale-up, bulk drug chemical and physicochemical attributes, environmental impact, process controls, preparative and developmental history, and bulk/ dosage issues— be readily available and well organized for the assembly of the various individual submissions. Increas- 

The technology transfer to manufacturing demands that the process be well documented. Most important, and as a coalescence of the process know-how, a comprehensive process document, written for the specific purpose of imparting knowledge, is a requisite for the tasks of  

of course, unacceptable to bind together all manner of development reports and send them over with a cover memorandum (part of what is aptly known as over the fence technology transfer). Attachments are very important, but a well-edited document that is rich in content and aimed at guiding the downstream practitioners is the indispensable first vehicle for the transfer of the know-how. Not even the most thorough collaboration between development and manufacturing can completely remedy the lack of the above comprehensive process document intended for imparting knowledge. 

There is no attempt here to gloss over the extraordinary effort and discipline required to turn out such documentation on a timely basis. The consolidation stage is intense, the gentle slope of the know-how curve notwithstanding. Yet, the quality of the technology transfer—on both the short and the long term—is very much enhanced if such a document is available soon enough. 

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The effort in setting down and organizing the process body of knowledge should not trail the acquisition of the raw inputs, as tardy heroic efforts to properly document accumulated knowledge are invariably not as good as the task deserves. Figure 18 outlines the body of knowledge task on the applied effort vs. know-how plane. 

Figure 18 The process body of knowledge in the know-how vs. applied effort plame.

Table 4 The Scope of the Process Body of Knowledge and Its Applications...

Figure 7 depicts a proven model for the flow of the process body of knowledge as it is applied to process design and first manufacture. 

Figure 7 A model for the flow of the process body of knowledge Successful first manufacture (timely, sufficient, and reliable) depends not only on the assembly of the requisite process body of knowledge, but also on its timely flow to the various downstream activities. The model shown above has worked well in each of numerous instances that the author has seen it applied.

The licensee should beware of accepting the licensor s production documents as the core of the process documentation, as such documents—operating procedures with the blanks filled in—are poor vehicles for imparting process knowledge. To the extent that it exists, the process body of knowledge should be well documented and provided by the licensor, along the lines described in Section V of Chapter 2. 

From our experience, further refinement to establish a suitable minimum under the three topics above appears best accomplished by doctoral faculty committees selected for the Individual, considering Individual needs. The basic body of knowledge might be conceived as an understanding of the environment, Its characteristics and processes, a knowledge of environment-related technology, an ability to use quantitative analytical techniques, and an appreciation for the social and Institutional framework of environmental policy. 

Despite the considerable body of knowledge now available on the extraction chemistry of ruthenium, it remains a problematic element for fuel reprocessors. A variety of means10 may be used to render the ruthenium less extractable. These include the addition of reagents such as oxalate or thiourea, the oxidation of Ru111 to inextractable RuIV or the addition of nitrogen dioxide to retain more Ru(NO) 3+ in the form of nitrito complexes of low DRu. However, such treatments may have undesirable effects on plant operation. It is possible to attain high decontamination factors for ruthenium over several process cycles, the penalty being that the ruthenium will appear in several waste streams, not just the HAW from the first decontamination cycle. 

The increasing importance of hydrotreating in oil refining is contrasted to the limited body of knowledge of its kinetics, especially of hydrodeni-trogenation (4, 95). Knowledge of the kinetics of a reaction is important for process operations. It may also yield information about the nature and density of catalytic sites, facilitating the interpretation of the influence of reaction conditions, the reaction mechanism, the properties of the catalyst, and its preparation. 

Conceptual validation addresses the question of whether the model contains all relevant processes underlying exposure in accordance with the present body of knowledge. Conceptual validation also applies to cases in which models aim at a reasonable worst-case prediction of exposure it should be validated whether the scenario as described by the model actually is a reasonable worst-case . In order to model exposure to a pesticide, all relevant routes of exposure should be included a first conceptual check of the model is to determine if the model contains all of these routes. If not, only part of the possible exposures will be modeled. The model can further be checked against physico-chemical laws and mass balances. For example, if the model describes inhalation exposure over a range of temperatures, they must be included in the model since temperature affects evaporation (Schenk et al, 1997). 

In the second system, the computer is programmed to follow very similar reasoning processes to the mass spectroscopist by making available to it the extensive body of knowledge currently known about mass spectral behaviour [60,61]. The reduction of the latter to a computer programme represents considerable effort and requires up-dating as further MS data becomes available. 

Despite the growing body of knowledge of process control theory most process plants are instrumented empirically today. Some useful empirical procedures are described in Section III, C, 3. 

Figure 13 Technology transfer in the outsourcing environment— the worst scenario, shown on the basis of a virtual company that licenses a compound that does not bring a sufficient process body of knowledge.

Da Vinci also correctly recognized the significance of mistakes for research and inquiry. Mistakes (called negative examples in computer science) are critically important in the process of both human and automated (computer-generated) knowledge acquisition because both are equally necessary to acquire decision rules, which are the basis for formal knowledge and which represent the specific body of knowledge contained in any subject matter. 

Along with a unique analytic treatment of coordination activity, the Project Design concept is built on our field experiences with ideas pulled from different lines of contemporary thinking, practices, and tools. We focused on improvements in the areas of representation, analytics of prediction, and social process. Why are these improvements necessary Because the established body of knowledge and... 

The direct dissociation of diatomic molecules is the most well studied process in gas-surface dynamics, the one for which the combination of surface science and molecular beam teclmiques allied to the computation of total energies and detailed and painstaking solution of the molecular dynamics has been most successful. The result is a substantial body of knowledge concerning the importance of the various degrees of freedom (e.g. molecular rotation) to the reaction dynamics, the details of which are contained in a number of review articles [2, 36, 37, 38, 39, 40 and 41]. 

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