Development Assurance process advantages

At the same time, however, considerable research was being done, especially in Germany, on a novel process called emulsion polymerization, in which the monomer was polymerized as an emulsion in the presence of water and soap. This seemed advantageous since the product appeared as a latex, just like natural mbber, leading to low viscosity even at high soHds content, while the presence of the water assured better temperature control. The final result, based mainly on work at the LG. Farbenindustrie (IGF) (10), was the development of a butadiene—styrene copolymer prepared by emulsion polymerization, the foremnner of the present-day leading synthetic mbber, SBR. 

However, compared with the traditional analytical methods, the adoption of chromatographic methods represented a signihcant improvement in pharmaceutical analysis. This was because chromatographic methods had the advantages of method specihcity, the ability to separate and detect low-level impurities. Specihcity is especially important for methods intended for early-phase drug development when the chemical and physical properties of the active pharmaceutical ingredient (API) are not fully understood and the synthetic processes are not fully developed. Therefore the assurance of safety in clinical trials of an API relies heavily on the ability of analytical methods to detect and quantitate unknown impurities that may pose safety concerns. This task was not easily performed or simply could not be carried out by classic wet chemistry methods. Therefore, slowly, HPLC and GC established their places as the mainstream analytical methods in pharmaceutical analysis. 

Host-cell protein ELISA have the advantage of quantitating host protein impurities. The disadvantage, however, is that the quantitation is of a group of impurities. Western blot analysis, on the other hand, provides the analyst with a relative level of an individual impurity compared to other impurities. If the level of one or more host protein impurities appears to be excessive based on the intended use of the drug product then it may be necessary to identify those impurities. This can provide assurance that the impurity is innocuous and it can also define the physicochemical properties of the impurity such that the process can be modified to reduce its presence in future production lots. The identification can also lead to the development of a quantitative assay for monitoring the individual impurity in every lot. 

Chemical manufacturers who license their competitors can of course expect to meet them in the marketplace. The more conservative attitude of old-line companies in the past was based on a desire to maintain the advantages of their novel advances at least until their research and development costs had been recouped, and this is, of course, the principle behind the seventeen-year monopoly inherent in a U.S. patent. The recent change of view towards licensing can be attributed first to the increased availability and attractiveness of the opportunities, but also to an appreciation of the constant threat of process obsolescence. Modern enlightened self-interest, with its emphasis on the time value of money, tends to choose the course with the assured payout and let the salesman handle the market problems as they occur. 

ECM can offer substantial advantages in a wide range of cavity-sinking and shaped hole production operation. The technique nowadays is also utilized for very specific microapplications. The advent of new technologies for controlling the ECM process and the development of new and improved metal alloys, which are difficult to machine by conventional means, will assure the future of ECM. 

However, styrene is the simplest vinyl aromatic with the fewest production and purification problems and an adequate supply of benzene was soon assured by the development of a new process to convert toluene to benzene (9). Construction of larger scale plants and growing production experience accelerated the cost advantage of styrene over its rivals, and, as a result, styrene/poly-styrene became the dominant vinyl aromatic monomer/polymer in the marketplace For three decades that situation has remained virtually unchallenged by a substituted styrene. 

Despite the obvious advantages of the formal equivalence checking approach, there are limitations. Formal tools appear to provide the ultimate assurance of design correctness. At the end of a run, the program provides counter-examples for each specified property specified by developer which were found not valid. Every property is 100% covered. But the Achilles heel of the process is determining how completely the set of properties covers the design intent. This requires human-in-the-loop - the skill of experienced designers. 

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