Chemical Engineering @ChemengFiles.Com

Inherently safer process design – the elimination or substantial reduction of hazards from a manufacturing process, rather than the application of engineering and procedural controls to manage hazards – has the greatest benefits early in process development. However, there are opportunities for application of inherently safer design principles throughout the process life cycle.

The term “inherently safer design” is relatively recent, but many of its principles have been a part of good engineering design for many years. In this paper we will describe an early example of the application of inherently safer design principles, and then focus on opportunities for enhancing the inherent safety of chemical plants during detailed design. In particular, we will emphasize the relationship between plant reliability and inherent safety. A reliable plant is inherently safer, and
design features, which enhance reliability, will generally also enhance safety.

Inherently safer process design – the elimination or substantial reduction of hazards from a manufacturing process, rather than the application of engineering and procedural controls to manage hazards – has the greatest benefits early in process development. However, there are opportunities for application of inherently safer design principles throughout the process life cycle.

The term “inherently safer design” is relatively recent, but many of its principles have been a part of good engineering design for many years. In this paper we will describe an early example of the application of inherently safer design principles, and then focus on opportunities for enhancing the inherent safety of chemical plants during detailed design. In particular, we will emphasize the relationship between plant reliability and inherent safety. A reliable plant is inherently safer, and
design features, which enhance reliability, will generally also enhance safety.

Armed with the complete sequence of the human genome and an ever-increasing array of biological techniques, researchers continue to learn more about the genetic basis of diseases. For two decades, scientists and physicians have been developing therapeutic strategies for treating many diseases at the genetic level, creating the field of "gene therapy." For those diseases caused by loss-of-function mutations in a specific gene, delivery of a wild-type copy of that gene to affected cells can reduce or eliminate the disease phenotype. Viruses, having evolved to be extremely effective at delivering nucleic acids (i.e., their own genes for viral production) to cells, have been modified to include therapeutic genes of interest. While such viral gene therapy vectors are the most efficient vectors developed, concerns about their safety and immunogenicity have prompted many to investigate non-viral vector alternatives. Cationic polymers and lipids have emerged as leading non-viral vector materials. Our laboratory has developed a class of cyclodextrin-containing polycations (CDPs) that condense DNA into complexes that can be endocytosed by cells, achieve expression of their genetic payload in those cells, and may be modified to target particular cell types within an animal.

In the past five years, scientists have discovered a new mechanism for the reduction of gene expression in mammalian cells via sequence-specific cleavage of a particular messenger RNA (mRNA); this phenomenon is known as RNA interference (RNAi). Since RNAi is triggered by nucleic acids (small interfering RNA (siRNA) duplexes), I hypothesized that CDPs may be suitable vectors for the delivery of siRNA. In my thesis work, the safety of synthetic siRNA duplexes is examined both in cultured cells and in vivo. Using a number of different siRNA sequences, two different strains of mice, and three different methods of administration, I fail to observe any cytokine (IL-12 or IFN-a) responses, morphological changes, or alterations in complete blood counts (CBCs) or liver enzyme levels.

Armed with the complete sequence of the human genome and an ever-increasing array of biological techniques, researchers continue to learn more about the genetic basis of diseases. For two decades, scientists and physicians have been developing therapeutic strategies for treating many diseases at the genetic level, creating the field of "gene therapy." For those diseases caused by loss-of-function mutations in a specific gene, delivery of a wild-type copy of that gene to affected cells can reduce or eliminate the disease phenotype. Viruses, having evolved to be extremely effective at delivering nucleic acids (i.e., their own genes for viral production) to cells, have been modified to include therapeutic genes of interest. While such viral gene therapy vectors are the most efficient vectors developed, concerns about their safety and immunogenicity have prompted many to investigate non-viral vector alternatives. Cationic polymers and lipids have emerged as leading non-viral vector materials. Our laboratory has developed a class of cyclodextrin-containing polycations (CDPs) that condense DNA into complexes that can be endocytosed by cells, achieve expression of their genetic payload in those cells, and may be modified to target particular cell types within an animal.

In the past five years, scientists have discovered a new mechanism for the reduction of gene expression in mammalian cells via sequence-specific cleavage of a particular messenger RNA (mRNA); this phenomenon is known as RNA interference (RNAi). Since RNAi is triggered by nucleic acids (small interfering RNA (siRNA) duplexes), I hypothesized that CDPs may be suitable vectors for the delivery of siRNA. In my thesis work, the safety of synthetic siRNA duplexes is examined both in cultured cells and in vivo. Using a number of different siRNA sequences, two different strains of mice, and three different methods of administration, I fail to observe any cytokine (IL-12 or IFN-a) responses, morphological changes, or alterations in complete blood counts (CBCs) or liver enzyme levels.

Cambridge Laboratories Limited has announced that its main product, Tetrabenazine, (known as NITOMAN (R) in Germany and other key territories in Europe and XENAZINE (R) in the UK, U.S. and other markets) has received the approval of the market in Spain through the Spanish Agency of Medicines and Health Products.

The company has also announced that it has recently signed distribution agreements for Tetrabenazine in Finland and Taiwan, in addition to renewing existing agreements enAustraliay New Zealand.

Cambridge Laboratories Limited has announced that its main product, Tetrabenazine, (known as NITOMAN (R) in Germany and other key territories in Europe and XENAZINE (R) in the UK, U.S. and other markets) has received the approval of the market in Spain through the Spanish Agency of Medicines and Health Products.

The company has also announced that it has recently signed distribution agreements for Tetrabenazine in Finland and Taiwan, in addition to renewing existing agreements enAustraliay New Zealand.