Product development optimization

According to an older German study, the time-to-market of new chemical products, besides optimizing the internal research and development as outlined above, could profit from faster administrative approval by the public authorities [138]. For example, the phase of getting the concession has a share of about 20% of the overall time for process development, amounting on average to 7.5 years in Germany. Process development in other countries is faster, e.g. 5.0 and 5.7 years in Japan and the USA, respectively. 

In contrast to the biopharmaceuticals discussed thus far (recombinant proteins and gene therapy products), antisense oligonucleotides are manufactured by direct chemical synthesis. Organic synthetic pathways have been developed, optimized and commercialized for some time, as oligonucleotides are widely used reagents in molecular biology. They are required as primers, probes and for the purposes of site-directed mutagenesis. 

An MEKC method for the determination of ibuprofen, codeine phosphate hemihydrate, their nine potential degradation products, and impurities in a commercial tablet formulation was developed, optimized, and fully validated according to ICH guidelines and submitted to the regulatory authorities. The optimized system containing ACN as organic modifier allowed baseline separation of ibuprofen, codeine, and nine related substances within 12 min. 

Beyond perfonnance optimization, issues relative to packaging and the need for compliance with certain safety and electronics regulatory codes are cited as reasons for a customized solution. In the latter case, a systems approach is required, especially when attempting to meet the code or performance requirements for compliance with European Certification (CE) mark or electrical and fire safety codes such as National Eire Prevention Association (NFPA) and CENELEC (European Committee for Electrotechiucal Standardization). Off-the-shelf electronics may provide the necessary performance characteristics for generic applications, and their use eliminates large expenses related to product development, plus the associated time delays. Photonics-related components are solely addressed in this section because they are used to customize instruments for application-specific systems. 

As it is imperative that the plant-derived hiopharmaceutical product must be obtained repeatedly and on a consistent basis, a master cell culture bank, seed bank for transgenic plants, or virus seed stock for transient expression systems must be constantly maintained. Storage conditions must therefore he optimized to prevent contamination and ensure viability. Both transgene stability (e.g., reversion to wild type or sequence drift of plant virus expression vectors) and protein expression levels must be monitored in a representative plant of a given bank or stock to minimize any possible variation in expression levels that may affect safety and consistency of the hnal product. A program that monitors lot-to-lot consistency of the hiochemical and biological properties by comparing the product with appropriate in-house reference standards could he implemented as a fundamental component of product development. 

Product yield optimization is a continuous process. It continues through preclini-cal and clinical development because it ultimately translates into the profit margin of the product when it is approved for marketing. 

In the author s opinion, the situation just described is not an unavoidable consequence of the intrinsic complexity of pharmaceutical products. In fact, other industries with products that are equally complex (e.g., microelectronics) have developed and implemented predictive methods for product and process development, optimization, and control, capable of much higher quality standards (as defined by allowed variability in product functionality) than the pharmaceutical industry. Rather, current practices in the industry... 

Arguably, given its immediate and direct impact on public health, the pharmaceutical industry has additional reasons to achieve a higher level of technological execution where product quality is assured by effective automated systems and where variability sources are understood and minimized. Even removing this motivation, this industry should embrace model-based optimization enthusiastically, since it has reduced cost and accelerated product development across many other industries. 

A pilot production is at about a lOOx level in general, the full scale-batch and the technology transfer at this stage should comprise preformulation information, product development report, and product stability and analytical methods reports. This is the time to finalize the batch production documentation for the lOOx level. The objectives of prevalidation trials at this stage are to qualify and optimize the process in full-scale production equipment and facilities. 

Standardization of the milk fat and total solids contents of milk is accomplished by blending cream or skim milk with separated milk. Modern technology has developed continuous standardization processes that use turbidity or infrared absorption measuring devices to monitor and adjust the composition of the product as it leaves the separator. It is important that milk be accurately standardized to meet governmental legal requirements and to manufacture dairy products with optimal functional and quality attributes. 

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