Acuity Technology Management - Academia.edu (original) (raw)

Papers by Acuity Technology Management

The Chemical Engineering Journal, 1986

Attempts to scale up immunoaffinity separations have highlighted the limitations of the commonly ... more Attempts to scale up immunoaffinity separations have highlighted the limitations of the commonly employed CNBr-actiuated agarose gel supports. As an aid to the selection of an alternative configuration, we investigated the behaviour of a monoclonal antibody covalently immobilized to styrene, nylon and acrylic acid using several different chemical methods. The level of uptake of antibody was found to be dependent on the immobilization method used. The apparent antibody-antigen dissociation constant of the immobilized antibody averaged 1.5 X 1 OM6 M. This value was an order of magnitude lower than previously reported results for the same antibody in free solution and was not affected by either the immobilization method or the support polymer used. The different covalent bonds were subjected to commonly encountered eluting agents. Most were stable in at least one solution capable of breaking antibody-antigen bonds although all were highly labile in 4 M KI. The most stable bond in elutant was formed by glutaraldehyde-activated amino groups, followed by bonds formed through N-hydroxysuccinimide esters. Overall, the results suggest that immobilization through glutaraldehydeactivated amino groups, a simple procedure, results in a highly stable bond without adversely affecting antibody immunological reactivity.

Transactions - American Society for Artificial Internal Organs, 1981

Bioprocess Engineering, 1991

A perfusion system for production of monoclonal antibodies was developed using an externally-moun... more A perfusion system for production of monoclonal antibodies was developed using an externally-mounted, hollow-fibre cartridge. The experimental apparatus was operated for 420 h and demonstrated increased steady-state viable cell concentration with increase in perfusion rate. Antibody titres were up to three times those measured for batch cultures and specific antibody productivity was doubled. The procedure was successfully scaled to a 10 dm 3 system which produced antibody under conditions of Good Manufacturing Practice (GMP). A calculation of productivity between the scaled perfusion system and 260 dm 3 batch cultures resulted in comparable antibody production, whereas the perfusion allowed a halving in medium utilisation. Reactivity assays conducted on the purified antibody from both batch and perfusion cultures showed no evidence of proteolysis or altered antibody activity in the final perfusion product. This study provides additional support for the use of homogeneous perfusion cultures in production of monoclonal antibodies under GMP conditions.

Artificial Organs, 1982

In vitro and in vivo sieving coefficients (SC) have been determined for a spectrum of proteins ra... more In vitro and in vivo sieving coefficients (SC) have been determined for a spectrum of proteins ranging in molecular weight from 66,500 daltons (albumin) to 2.4 million (beta-lipoprotein) daltons for three commercially available membrane plasma separation devices: the Plasmaflo 0.1, Plasmaflo 02, and Plasmaflux. A model relating serum level of a protein to pretherapy level, plasma volume, plasma filtration rate, membrane SC, and duration of treatment has been used to investigate the influence of SC on exchange efficiency. Comparison of predicted and clinically obtained reductions in serum solute levels demonstrated the validity of the model. The results of the analysis suggest that all three plasma separators are capable of delivering equally acceptable therapy. The model further demonstrates the decreasing effectiveness, and increased cost in terms of replacement fluid per unit of solute removed, with prolonged treatment times.

Australian and New Zealand Journal of Medicine, 1980

The demand for large quantities of monoclonal antibodies has increased dramatically over the last... more The demand for large quantities of monoclonal antibodies has increased dramatically over the last few years to supply diagnostic kits for application areas with large markets, and for use in developing applications such as anti-tumour therapies and affinity chromatography. Scale-up from tissue and murine culture has not been a straightforward matter because of the special requirements of mammalian cells in culture. The sensitivity of hybridomas to their environment means that efficient mixing must be obtained at low shear rates, and that oxygen transfer must be adequate for high density cultures without aggressive sparging. The high fraction of serum required to satisfy undefined nutrient requirements needs to be reduced considerably in order to achieve economy of scale. This review discusses the technical barriers to scale-up and reports on successful attempts to produce large volumes of monoclonal antibodies.

The Chemical Engineering Journal, 1986

Attempts to scale up immunoaffinity separations have highlighted the limitations of the commonly ... more Attempts to scale up immunoaffinity separations have highlighted the limitations of the commonly employed CNBr-actiuated agarose gel supports. As an aid to the selection of an alternative configuration, we investigated the behaviour of a monoclonal antibody covalently immobilized to styrene, nylon and acrylic acid using several different chemical methods. The level of uptake of antibody was found to be dependent on the immobilization method used. The apparent antibody-antigen dissociation constant of the immobilized antibody averaged 1.5 X 1 OM6 M. This value was an order of magnitude lower than previously reported results for the same antibody in free solution and was not affected by either the immobilization method or the support polymer used. The different covalent bonds were subjected to commonly encountered eluting agents. Most were stable in at least one solution capable of breaking antibody-antigen bonds although all were highly labile in 4 M KI. The most stable bond in elutant was formed by glutaraldehyde-activated amino groups, followed by bonds formed through N-hydroxysuccinimide esters. Overall, the results suggest that immobilization through glutaraldehydeactivated amino groups, a simple procedure, results in a highly stable bond without adversely affecting antibody immunological reactivity.

Transactions - American Society for Artificial Internal Organs, 1981

Bioprocess Engineering, 1991

A perfusion system for production of monoclonal antibodies was developed using an externally-moun... more A perfusion system for production of monoclonal antibodies was developed using an externally-mounted, hollow-fibre cartridge. The experimental apparatus was operated for 420 h and demonstrated increased steady-state viable cell concentration with increase in perfusion rate. Antibody titres were up to three times those measured for batch cultures and specific antibody productivity was doubled. The procedure was successfully scaled to a 10 dm 3 system which produced antibody under conditions of Good Manufacturing Practice (GMP). A calculation of productivity between the scaled perfusion system and 260 dm 3 batch cultures resulted in comparable antibody production, whereas the perfusion allowed a halving in medium utilisation. Reactivity assays conducted on the purified antibody from both batch and perfusion cultures showed no evidence of proteolysis or altered antibody activity in the final perfusion product. This study provides additional support for the use of homogeneous perfusion cultures in production of monoclonal antibodies under GMP conditions.

Artificial Organs, 1982

In vitro and in vivo sieving coefficients (SC) have been determined for a spectrum of proteins ra... more In vitro and in vivo sieving coefficients (SC) have been determined for a spectrum of proteins ranging in molecular weight from 66,500 daltons (albumin) to 2.4 million (beta-lipoprotein) daltons for three commercially available membrane plasma separation devices: the Plasmaflo 0.1, Plasmaflo 02, and Plasmaflux. A model relating serum level of a protein to pretherapy level, plasma volume, plasma filtration rate, membrane SC, and duration of treatment has been used to investigate the influence of SC on exchange efficiency. Comparison of predicted and clinically obtained reductions in serum solute levels demonstrated the validity of the model. The results of the analysis suggest that all three plasma separators are capable of delivering equally acceptable therapy. The model further demonstrates the decreasing effectiveness, and increased cost in terms of replacement fluid per unit of solute removed, with prolonged treatment times.

Australian and New Zealand Journal of Medicine, 1980

The demand for large quantities of monoclonal antibodies has increased dramatically over the last... more The demand for large quantities of monoclonal antibodies has increased dramatically over the last few years to supply diagnostic kits for application areas with large markets, and for use in developing applications such as anti-tumour therapies and affinity chromatography. Scale-up from tissue and murine culture has not been a straightforward matter because of the special requirements of mammalian cells in culture. The sensitivity of hybridomas to their environment means that efficient mixing must be obtained at low shear rates, and that oxygen transfer must be adequate for high density cultures without aggressive sparging. The high fraction of serum required to satisfy undefined nutrient requirements needs to be reduced considerably in order to achieve economy of scale. This review discusses the technical barriers to scale-up and reports on successful attempts to produce large volumes of monoclonal antibodies.