Developmental scales Development

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. 

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... 

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... 

Additional assays have surfaced on both ends of the scale of complexity. Single end point assays such as those for a host of receptor binding and activation assays and enzyme activity modulation assays have been developed and applied to alternative developmental toxicity testing. These assays can be carried out in a... 

We are currently involved in a three phase developmental program to extend the process to other hydrogen containing streams. The program involves screening candidate streams to identify poisonous species for the metal hydrides, developing poison resistant processes for each stream, and demonstrating the process(es) on a pilot scale to establish process economics. 

The pilot program is defined as the scale-up operations conducted subsequent to the product and its process leaving the development laboratory and prior to its acceptance by the full scale manufacturing unit. For the pilot program to be successful, elements of process validation must be included and completed during the developmental or pilot laboratory phase of the work. 

As I indicated earlier, prospective validation is used when a new chapter in manufacturing is about to be established. As such, it requires a sound game plan to document the transition from one stage to another (e.g., process development to full-scale production, the inclusion of new equipment, or the inclusion of a modified or new facility). The generated data must support the fact that the new process or facility ought to be used routinely in production. The successful validation provides the documentation that the developmental quality standards for the procedures and operations are adequate to manufacture a quality product in production. Finally, it becomes the basis for the quality standards, which must be maintained throughout the product s lifetime. 

The major concern with document linking to validation is with master batch records and SOPs. The defined ranges for the operating parameters (as established in development) as defined in the master batch record are confirmed to be satisfactory during the validation effort. There is no requirement, nor should there be, to establish on a commercial scale that success is possible at the extremes of these ranges. That type of confirmation is ordinarily restricted to developmental trials, in which the financial impact is less significant. The only common exception to this practice is in the validation of sterilization processes, in which the performance qualification efforts will oftentimes use worst-case conditions at or below the routine sterilization parameters. 

The effects of prenatal cocaine exposure on information processing and developmental assessment have been studied in 108 infants aged 3 months, 61 of whom had been exposed to cocaine, and 47 controls using an infant-control habituation and novelty responsiveness procedure in a developmental assessment using the Bayley Scales of Infant Development (276). Infants exposed to cocaine prenatally were significantly more likely than controls to... 

Cognitive, motor, and behavior development, as measured by the Mullen Scales of Early Learning and the Bayley Scales of Infant Development-II, were compared in 56 prenatally cocaine-exposed infants and toddlers (aged 1-3 years) and 56 non-exposed matched controls (287). There were developmental problems in expressive and receptive language areas in those who had been exposed prenatally. 

A second report from the Maternal Lifestyle Study focused on motor development in 392 children prenatally exposed to cocaine and 776 non-exposed control infants who were identified by meconium assay and mothers self-reporting (327). Motor skills were assessed at 1 month with the NICU Network Neurobehavioral Scale (NNNS), at 4 months with the posture and fine motor assessment of infants (PFMAI), at 12 months with the Bayley Scales of Infant Development-2nd edition (BSID-II), and at 18 months with the Peabody Developmental Motor Scales (PDMS). The infants with prenatal cocaine exposure had motor skill deficits at 1 month, but normal function at 18 months. Heavy cocaine use was associated with poorer motor performance. Both lower and higher nicotine exposures related to poorer motor performance. 

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