Developmental scales

In some environments, scale-up is handled jointly by development and departments proficient in full-scale manufacture, such as technical services and process engineering and in some cases manufacturing. If a process has been well developed in development on subcommercial-scale development equipment, how does one assure that this same process is delivered on full-scale commercial equipment What affect does equipment scale have on the process Is it safe to assume that since developmental-scale equipment delivered acceptable performance it will perform likewise at commercial scale Probably not. This is the reason most progressive companies perform what is termed demonstrations on full-scale equipment. 

After a cursory review, the NDA/ANDA submission should be fully received, checking for contradicting information in the various sections of the submission. The FDA correspondence file should be reviewed and assessed as to whether all FDA questions have been adequately addressed. The summary section should be examined for inclusion of all batches used in developmental scale-up and stability studies. 

Figure 12.15 is a photograph of the installed demo reactor section. The demo reactors are sufficiently large and proportioned to allow for reliable scale-up. As such, each demo reactor represents a core of a much larger reactor and provides for the necessary hydrodynamic similarity (e.g., equivalent superficial velocities) to a full commercial-scale reactor system. Equally important, these reactors use AlkyClean catalyst produced in commercial manufacturing trials, not developmental-scale catalyst with characteristics that may not be fully duplicable under commercial-scale production conditions. 

Patients are divided into two groups on the basis of current thyroid status euthyroid (TSH < 5 mlU/L) or hypothyroid (TSH > 5 mlU/L). Total serum thyroxine (T4) was also measured. An Intelligence Quotient was derived for each patient using the Hiskey Nebraska Test of Learning Ability and the Griffiths Mental Developmental Scales. The details of the endocrine, psychological and neurophysiological studies are the subject of separate communications. 

Despite these severe restrictions the polymer has been available on a developmental scale from the Thiokol Corporation and has found speciality uses in the United States space programme and in protective clothing because of its non-inflammability and chemical resistance. 

Applications. These materials are stiU in developmental infancy. Current production is limited to one commercial process in Europe and a demonstration-scale process in North America. The lignins produced in these processes have potential appHcation in wood adhesives, as flame retardants (qv), as slow-release agents for agricultural and pharmaceutical products, as surfactants (qv), as antioxidants (qv), as asphalt extenders, and as a raw material source for lignin-derived chemicals. 

Process validation can be done in different ways, viz. prospectively, by carrying out a planned program of experiments, before routine production is started concurrently, during routine production retrospectively, by statistical analysis of historical data and during scale-up studies (developmental validation). 

G. M. Berntson, Topological scaling and plant root system architecture developmental and functional hierarchies, New Pliytol. I35 62 (1997). 

Chasnoff et al. (1984) have reported on the developmental outcome of three groups of children, from birth until 2 years of age. The methadone, polydrug, and control groups demonstrated a downward trend in scores in the Bayley Scales of Infant Development. Their interpretation is that the infants environment and subsequent lack of stimulation has a more direct influence on long-term development than does maternal use of drugs during pregnancy. 

The factors necessary to achieve quality in a product during the developmental stage have been discussed. The formulator of a new product must consider the manufacturing process to be used for full-scale production of the product. Many new product failures or deficiencies occur because of inability to resolve or foresee production-related problems, rather than to poor product development per se. Therefore, the... 

The disparity between plant costs obtained before 1963 (Rims 1 and 2 in Table 9-5 and Fig. 9-1, with m = 0.88) and those obtained after 1966 (other runs and Fig. 9-1 with m = 0.70) can be explained by advances in technology. This was discussed in Chapter 3. The use of an exponential factor to scale up size assumes that a similar plant will be built. This was not true for ammonia plants. In fact, if a company is doing developmental research it should never be true. Each plant should be better than the last. 

A later analysis (Emhart et al. 1987) related PbB levels obtained at delivery (maternal and cord blood) and at 6 months, 2 years, and 3 years of age to developmental tests (MDI, PDI, Kent Infant Development Scale [KID], and Stanford-Binet IQ) administered at 6 months, 1 year, 2 years, and 3 years of age, as appropriate. After controlling for covariates and confounding risk factors, the only significant associations of blood lead with concurrent or later development were an inverse association between maternal (but not cord) blood lead and MDI, PDI, and KID at 6 months, and a positive association between 6-month PbB and 6-month KID. The investigators concluded that, taken as a whole, the results of the 21 analyses of correlation between blood lead and developmental test scores were "reasonably consistent with what might be expected on the basis of sampling variability," that any association of blood lead level with measures of development was likely to be due to the dependence of both PbB and... 

Key technical issues facing gasifier technologies on the whole evolve around economies of scale and the fact that most technologies are not suitable for low-rank coals. The primary developmental needs are ... 

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