Research, Development, and

The research and development of new drugs includes four phases  

The preclinical research and development starts after the discovery and the isolation of a promising compound in the laboratory. The biological activity and safety is extensively studied in the laboratory and tested on animals. This phase is usually completed in 6 years. 

The clinical research and development is typically conducted in three phases, with each phase involving progressively more people. The aim of the first phase is to establish the safety of the drug. It involves a small number of healthy volunteers and lasts about 1 year. The effectiveness of the drug is determined in the second phase, which lasts about 2 years. In the third phase, the drug is used in clinics and hospitals to confirm the results of the earlier tests. The clinical research and development phase takes about 6 years. 

Finally, the pharmaceutical company files a new drug application (NDA) for approval. The NDA should contain comprehensive data including the safety of the drug and its effectiveness. The regulations worldwide require specific and detailed information about the NDA  

For the purposes of research and development involving the placing on the market of an unauthorised biocidal product or a new active substance intended exclusively for the use in a biocidal product, derogations from the authorisation rules are possible  

This information shall only be made available to the competent authority on request. 

For the protection of commercially sensitive information the applicant may indicate that which he wishes to be kept confidential from all persons other than the competent authorities and the Commission. 

Full justification is required of why disclosure of the information might harm the applicant industrially or commercially. Information accepted as confidential by the receiving competent authority shall be treated as confidential by the other competent authorities. Member States and the Commission. 

Biocidal products have to be classified, packaged and labelled according to the provisions of Directive 88/379/ EEC [5]. Additionally the label of each biocidal product must show  

The extent to which plastics are used in any industry in the future will depend in part upon the continued total R D activity carried on by materials producers, processors, fabricators, and users in their desire to broaden the scope of plastic applications. An R D example is the rail car hopper, called the Grasshopper (10,14). It is literally all plastic that provides improved load and operating performances over metals (Fig. 10-11).  

The bulk of such research expenditure is done by the materials producers themselves and the rest by the additive and equipment industries who do more than the processors and fabricators whose share is very small. Important to plastic growth have been government projects in basic research and new applications, particularly the military. Their work in turn expands into the industrial industry. 

The project of communicating new technology to processors and users is the subject of much discussion in the industry. The lag time from laboratory discovery to end user benefits is generally three years or more. 

The R D for Monju covered system design, core and fuel, heat transfer and fluid dynamics, structures and materials, instrumentation and safety. Research projects were started in the early years, in concert with design studies, so that the results could be applied to Monju. The R D aimed to  

Reactor physics PNC developed a nuclear design analyds method which consists of nuclear data and reactor constants, calculation models, computer codes and methods for interpolation and extrapolation (Bondarenko-type 26 group constants, computer codes for 2D or 3D diffusion calculations, etc.). In addition, PNC performed a fiill size mockup test (the MOZART project) in the ZEBRA t critical test fa ty at Winfidth in the UK, and a partial mockup test at the FCA (JAERI) in Japan, to help understand the nuclear characteristics of the Monju core and confirm the validity and accuracy of the nuclear dedgn. 

Fuel deveh ment The aim of the fuel development for Monju was to develop core materials which would guarantee performance to 130,000 MWd/t bum-up (pellet peak) and to 

PNC also developed a type of 316 stainless steel with significantly increased high temperature creep strength and low swelling properties by adding small amounts of phosphorus, boron, titanium and niobium to conventional SUS 316 stainless steel. The low-swelling PNC 316 steel used in Monju will be applicable to 90,000 MWd/t in the initial core and 130,000 MWd/t in a high bum-up core. It is a top performer compared with similar materials that have been developed around the world. A fuel pin behavior analysis code (CEDAR) was also developed by PNC to evaluate the behavior of the fuel pins in Monju. 

Initial fuel irradiation tests (accelerated fuel bum-up) were conducted in PFR (UK) and Rapsodie (France). Subsequently Joyo and EBR-II (USA) were used for various irradiation tests. These facilitated understanding of the behaviour of Monju fuel at high bum-up. In addition, irradiation tests to confirm high bura-up properties were performed on full-scale fuel assemblies in FFTF and Phenix (France). The results showed that Monju fuel can meet the specified requirements with both high reliability and safety. 

Special care must be taken with notes regarding development work that could lead to a future patent. A patent attorney should be contacted about such matters and his recommendations followed to the letter. In general, all details must be recorded, including experiments that did not work out. There are many cases where exciting developments have come as a result of something 

In one such case, the author was saddled with the job of reviving an old project because the person in charge of it no longer worked at the laboratory. However, he had left behind volumes of notes, complete with a sprinkling of profanity indicating where things had not worked out. With such information, the project was quickly completed. 

Laboratories working on products that eventually will need approval by a government agency, such as FDA, would do well to consult the agency in question about its latest requirements. If the request is made in writing, this can be of great help in case of an argument later on. 

The R D process is benefitting from the expanding knowledge base, and from the increasing contributions from robotics and automation, informatics and bioinformatics, equipment development, and tire outsourcing of key processes and consolidation of the regulatory environment. 

Scientific research on noise affecting the environment, methods for noise-level reductions, low-noise techniques, and development of special low-noise products are 

Emission standards Emission standards are defined by governments and determine emission limit values applied to individual sources and included in the type of approval procedures to identify whether new products are in compliance with the noise limits at the time of production. 

Immission standards Immission standards are based on the qualitative criteria or guide values for noise exposure that are to be applied at a specific location and are generally included in the planning processes. 

A Steam cooled fast reactor is defined as one in which the core inlet coolant is steam , not water. Blowers are required for steam cooled reactors instead of reactor coolant pumps. The pumping power of blowers is huge. Some supercritical pressure water cooled reactors have adopted pressure tubes instead of the RPV and have separate moderator and coolant. Indirect cycle reactors with a RPV are also found. 

No detailed calculations and analyses have been given in the reports on the past concepts, including their safety systems and safety analysis. 

The Super LWR and Super FR are new concepts based on the experiences with LWRs and fast reactors as well as supercritical FPPs. The concepts have been developed with full numerical analyses. 

The conceptual design study made at the University of Tokyo for the Super LWR and Super FR was described in Sect. 1.3. The early designs carried other names such as SCLWR, SCLWR-H, SCm, SCTTl-H, SCFBR-H, SWFR etc. Publications are found on the home page [125]. 

Heat transfer experiments and material research studies have been carried out at Kyushu University, IAEA, the University of Tokyo and elsewhere. Comparison of heat transfer coefficients predicted by different correlations is shown in Fig. 1.60. Accuracy above 500°C is important for the calculation of MCST. Calculated MCSTs with different correlations are compared in Table 1.16 [122]. The largest difference is 44°C. Current heat transfer correlations were developed based on experiments using smooth circular tubes. Experiments on fuel bundle geometry are necessary. The effect of grid spacers on the heat transfer correlation should be included in the prediction of MCST. The correlation of downward flow is necessary for the design. Downward flow is adopted in the low temperature region below the pseudo-critical temperature. 

There continues to be much work done in imiversities and educational institutions to imderstand the mixing process, much of which is totally ignored by the industry at large, except where they are directly involved. An example of this latter case is the EU-funded pan-European research project on tangential rotors for masterbatch compounding, mentioned earlier. 

Deutsches Institut fur Kautschuktechnologie in Hanover has been carrying out interesting work on the continuous mixing of both curable rubbers and thermoplastic vulcanisates, with published papers comparing different screw designs, for example (39). 

Akron University continues to publish many papers on mixing and blending, more particularly using batch mixers and with a developing interest in intercalation and exfoliation of nanofillers in rubbery materials (41). Osaka City University is also carrying out work on mixing techniques as reported recently (24). 

Many other institutions are also concerned with polymer-polymer and polymer-filler interactions (including silane coupling of fillers) and the morphology of filled compounds. A list of institutions taken from recent journals submitted to the Rapra library includes  

Universite Pierre et Marie Curie in Paris under Jean LeBlanc (42) 

Concern over the negative environmental impact of accumulating nondegradable plastic films and containers has been increasing. Replacement of these petroleum-based plastics with biodegradable plastics maybe inevitable within the next 50 years. Lactic acid based bioplastics will play an important role in future potential products (see section O Areas of Research and Development in this chapter). 

The major commercial producers of lactic acid are listed in O Table 1.10. The worldwide market for lactic acid and lactic acid esters was estimated at 60-65,000 t/year (54.5-59 10 kg/year) (Litchfield 1996). Producers of synthetic and fermentation lactic acid are both included, considering they share the market about equally. The United States consumes almost 40 % of annual production (Bigelis and Tsai 1995). The major producer of fermentation lactic acid in the United States is Archer 

Main producers of lactic acid and lactic acid esters 

Ecological Chemical Co., Conagra/DuPont, Adell, Wisconsin 

Chemie Combinatie Amsterdam CCA/PURAC, Gorinchem, the Netherlands 

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Connolly, J. F., Kandalic, G. A., Research and Development Dept., Amoco Oil Co., Naperville, 111., personal communication (1976)... 

The partition coefficient and aqueous solubility are properties important for the study of the adsorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) of drugs. The prediction of the ADME-Tox properties of drug candidates has recently attracted much interest because these properties account for the failure of about 60 % of all drug candidates in the clinical phases. The prediction of these properties in an early phase of the drug development process could therefore lead to significant savings in research and development costs. 

In terms of the number of scientists and engi neers involved research and development in polymer chemistry is the principal activity of the chemical in dustry The initial goal of making synthetic materials that are the equal of natural fibers has been more than met it has been far exceeded What is also im... 

In 1957 Standard Oil of Ohio (Sohio) discovered bismuth molybdate catalysts capable of producing high yields of acrolein at high propylene conversions (>90%) and at low pressures (12). Over the next 30 years much industrial and academic research and development was devoted to improving these catalysts, which are used in the production processes for acrolein, acryUc acid, and acrylonitrile. AH commercial acrolein manufacturing processes known today are based on propylene oxidation and use bismuth molybdate based catalysts. 

T. Morse, Handbook of Organic Additivesfor Use in Ceramic Bocf Formulation, Montana Energy and MHD Research and Development Institute, Inc., Butte, Mont., 1979. 

G. R. Walker and co-workers. Manual of Sensitivity Tests, The Technical Cooperation Program, TICP Panel 0-2C Canadian Armament Research and Development Establishment, Quebec, Canada, 1966. 

D. Burrows, Eiterature Eeview of the Toxicity ofEDX and HMX, U.S. Army Medical and Bioengineering Research and Development Lab., Washington, D.C., 1973. 

R. C. Elderfteld, Study of the British Continuous Tety/Process, Rpt. 661, Office of Scientific Research and Development (OSRD), Washington, D.C., 1942. 

Propellants," under "Explosives and Propellants," in ECT3rd ed., Vol. 9, pp. 620—671, by V. Lindner, U.S. Army Armament Research and Development Command. 

R. Stenson, Tactors Governing the Storage Tfe of Solid Propellant Pocket Motors, report no. TN047, Explosive Research and Development Establishment, Waltham Abbey, UK, 1972. 

T. L. Boggs and R. L. Derr, eds., Ha ard Studiesfor Solid Propellant Pocket Motors, NATO Advisory Group for Aerospace Research and Development, Agardograph 316, Technical Press, London, Sept. 1990. 

Although a tremendous number of fermentation processes have been researched and developed to various extents, only a couple of hundred ate used commercially. Fermentation industries have continued to expand in terms of the number of new products on the market, the total volume (capacity), and the total sales value of the products. The early 1990s U.S. market for fermentation products was estimated to be in the 9-10 x 10 range. The total world market is probably three times that figure, and antibiotics continue to comprise a primary share of the industry. Other principal product categories are enzymes, several organic acids, baker s yeast, ethanol (qv), vitamins (qv), and steroid hormones (qv). 

ISMA Technical Conference (Seville), Institute for Research and Development, Israel, Nov. 20,1972. 

Because of the rapid capital investment in acryUcs that occurred in the early 1970s, there is a large excess capacity. In 1981 worldwide demand was 2.1 X 10 kg whereas worldwide capacity was 2.6 X 10 kg. Prices have consequendy been soft since 1977. Since that time there has been only rninimal investment in plants or equipment and a curtailment ia research and development work. 

Boric acid/alkaU spinning has been commercialized in Kuraray Co. and Unitika Co. in Japan, and is reportedly under research and development also in the People s RepubHc of China as a process for producing high strength PVA fiber to be used for replacing asbestos (9). 

Product innovation absorbs considerable resources in the fine chemicals industry, in part because of the shorter life cycles of fine chemicals as compared to commodities. Consequently, research and development (R D) plays an important role. The main task of R D in fine chemicals is scaling-up lab processes, as described, eg, in the ORAC data bank or as provided by the customers, so that the processes can be transferred to pilot plants (see Pilot PLANTS AND microplants) and subsequently to industrial-scale production. Thus the R D department of a fine chemicals manufacturer typically is divided into a laboratory or process research section and a development section, the latter absorbing the Hon s share of the R D budget, which typically accounts for 5 to 10% of sales. Support functions include the analytical services, engineering, maintenance, and Hbrary. 

Trends in the research and development of phosphoms flame retardants have been in the direction of less volatile, less toxic, more stable compounds, and where feasible, in the direction of built-in phosphoms stmctures. At the same time, there have been an increasing number of regulatory delays in new compounds, and the existent materials are finding increased exploitation in the form of mixtures. Some interest is also noted in encapsulation. 

C. B. Willingham and R. T. Newbeig, Exploratory development of Fusion Cost Calcium Fluoridefor 1.06 Micrometer PulsedLaserOptics Piogiess Repoit, Sept. 25 to Dec. 25, 1976, NTIS Document COO-4029-2, Raytheon Co., foi U.S. Eneigy Research and Development Administiation, Jan. 1977. 

D. R. James, Technical Note No. 1, Cooperative Research and Development Agreement (CRADA), Investigation of S2p Q Production and Mitigation in... 

As of this writing, the primary focus of research and development in PEFC technology is a fuel-ceU system for terrestrial transportation appHcations... 

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