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At least 1,441 records · Page 80Linked to original sources

PubMed1992

Philosophy and goals of validation for biotech products and the relevance of scale.

A model for validation of viral clearances in Biopharmaceutical processes is developed from an analysis of validation of terminal sterilization processes. The model develops the role for small-scale experiments in the validation of large-scale production processes. The steps for process validation are: identify or discover the basic general physical, chemical, or biological laws governing the process; identify the critical process control parameters for the specific application under investigation; and demonstrate the ability of the production equipment to maintain critical parameters with specified limits. For concurrent validation, this final step is seen as equivalent to demonstrating that a scaled-down model experiment is an appropriate representation of the production process.

Biological Products↗

PubMed1992

Experience in cell line testing.

For more than ten years Microbiological Associates, Inc. has provided testing services for cell lines, products and processes associated with the safety of recombinant biologics. The results of numerous cell line characterizations performed under the guidance of "Points to Consider" documents shed light on the incidence of contamination of production cell banks. The most common sources of compromise of production substrates are also identified. Findings from this short review, though necessarily general, permit attention to be focused on areas of cell line characterization where concern is warranted. Conversely, where an alternative technique of equal sensitivity to existing tests is available for specific cell substrates, these may be given consideration. The observations presented here support the overall safety of biopharmaceuticals produced from genetically engineered cell lines and the wisdom of a multifaceted approach to assure product safety.

Animals↗

PubMed2004

In vitro testing of drug absorption for drug 'developability' assessment: forming an interface between in vitro preclinical data and clinical outcome.

Drug 'developability' assessment has become an increasingly important addition to traditional drug efficacy and toxicity evaluations, as pharmaceutical scientists strive to accelerate drug discovery and development processes in a time- and cost-effective manner. The fraction of drug absorbed and the maximum absorbable dose (MAD) can be estimated from in vivo clinical pharmacokinetics, mass balance studies or in vivo drug permeability in humans by different calculation methods. Unfortunately, in vivo data are usually unavailable at the early stages of drug discovery and development, and in vitro screening for the permeability, solubility, activity and toxicity of a drug has become a routine measurement in drug discovery and development. These in vitro data could be used to predict drug 'developability' with different calculation methods before selecting candidates for clinical evaluation. The fraction of drug absorbed in human could be predicted by in vivo human permeability or in vitro Caco2 permeability. For example, if drug permeability in Caco2 cells reaches 13.3 to 18.1 x 10(-6) cm/s, its predicted in vivo permeability in humans would reach 2 x 10(-4) cm/s, and its predicted fraction of drug absorbed would be > 90%, which is defined as highly permeable. The MAD could also be predicted with in vitro permeability, or calculated absorption rate constant. In addition, in vitro solubility and permeability data can also be used for the biopharmaceutics classification system (BCS) and, subsequently, to direct formulation optimization strategies. If drug 'developability' becomes an obstacle for drug delivery based on these in vitro data and predictions at the early stages of drug discovery and development, options such as prodrug approaches could be explored to enhance drug 'developability', in addition to different formulation methods. Therefore, in vitro absorption testing is a highly valuable tool in the decision-making process to select candidates for in vivo clinical studies at early-stage drug discovery and development.

Biological Transport↗

PubMed2004

Blood on tap. Part 1. History in the making.

Emergency services around the United States are about to become part of the front lines in the race to bring to market the first blood substitute with oxygen-carrying capabilities. Take a look inside the high-tech world of biopharmaceuticals and the innovative pioneers who are chasing after a scientific holy grail; a synthetic substitute for blood. In the process, they have made and lost fortunes, advanced our understanding of the nature of blood and launched one of the biggest ethical controversies in modern medical history. As phase three clinical trials move to the prehospital arena, biotechnology firms are staking everything on the notion that they're about to change the way we treat trauma patients. They may be right.

Animals↗

PubMedDate not supplied

Study of insolubility problems of dexamethasone and digoxin: cyclodextrin complexation.

Cyclodextrins are able to form inclusion complexes with a number of drugs if their molecular dimensions correspond to those of the cyclodextrin cavity which leads to change of physicochemical and biopharmaceutical properties of drugs. 2-Hydroxypropyl beta cyclodextrin (HP beta CD) is suitable for parenteral application because of its considerable solubility in water and low hemolytic activity. Digoxin is insoluble in water, sensitive to light and is a subject of acidic hydrolysis, it is a challenge to the technologists of parenteral dosage forms. Dexamethasone (Dex) has a very small solubility in water (0.1 mg/ml), which caused troubles by preparing liquid medicine forms. The inclusion of hydroxy acids in CD-complexes in the necessary molar proportions leads to considerable increase in the solubility of a medicine and to several times decrease of the amount of CD used. Inclusion complexation was confirmed by the results from the studies of Differential Scanning Calorimetry. The present investigation demonstrated that Digoxin/CD complex shows stability in water medium and the optimum molar ratio Digoxin/HP beta CD is 1:6. The same results can be achieved through HP beta CD, by including Dex in a multicomponent composition containing HP beta CD and citric acid in a molar ratio of 1:4:1.

Anti-Arrhythmia Agents↗

PubMed2004

Hydrostatic pressure induced death of mammalian cells engages pathways related to apoptosis or necrosis.

We investigated the response to high hydrostatic pressure (HHP) of mammalian cells, since HHP is proposed to be suitable to inactivate mammalian cells in biopharmaceutics and patient's material. We observed that cells were not restricted in their viability by pressures up to 100 MPa. Mammalian cells die when treated with pressures of 200 MPa or more. But the effects of 200, 300 or 400 MPa do not follow the same pattem. At 200 MPa, cells die in a way that is related to apoptosis. Some apoptotic characteristics like phosphatidylserine (PS) exposure and morphological alterations appear very fast. Other features like a higher exposure of intracellular NPn ligands and pronounced degradation of DNA and lectin ligands are unique features of HHP induced apoptosis. Cells treated with 300 and 400 MPa die immediately following a unique necrotic pathway, since treated cells harbour high DNA and glycoprotein degrading activities.

Apoptosis↗

PubMed2003

[Plants as bioreactor for the production of pharmaceutical proteins].

Transgenic plant as bioreactor has been used to produce recombinant proteins for medicinal purposes, including mammalian antibodies, blood substitutes and vaccines. As the demand for biopharmaceuticals is expected to increase, transgenic plants have the potential to provide virtually unlimited quantities of proteins for use as tools in both human health care and the bioscience. This paper reviews the recent developments in this field and the prospect of commercial applications.

English Abstract↗

PubMed2004

Use of bacteriophages as surrogates for mammalian viruses.

The threat of viral contamination is common to all processes using biological products of animal or human origin. Therefore, demonstration of virus clearance (i.e. validation of virus removal and/or inactivation steps) is of utmost importance to the biopharmaceutical industries. Ultimately, virus clearance studies should show that any virus removal/inactivation stage incorporated into the manufacturing process not only removes or inactivates known viruses that may be conceivably present (e.g. from cell banks and source materials), but also other viruses that may be introduced adventitiously (e.g. by addition of supplements downstream of the manufacturing process). In this paper, we outline the shared properties of mammalian viruses and similar sized bacteriophages, and factors that may influence the virus clearance process. We also present test data from filtration studies, showing similar titre reductions for both types of virus. We propose that well-characterised bacteriophage, such as PP7 and PR772 can be used as models for mammalian viruses if the virus removal mechanism is based on size exclusion.

Animals↗

PubMed2005

[Fuzeon, first of the so-called "fusion inhibitor" drug in new class of AIDS treatments and its warnings].

The Food and Drug Administration (FDA) approved a new type of drug to treat advanced HIV-1 infection in adults and children six and older. The drug is called Fuzeon and it's the first of the so-called 'fusion inhibitor' drugs to be approved anywhere in the world. Fusion inhibitors work by inhibiting the fusion of viral and target cellular membranes, thus blocking the HIV ability to infect cells. Fuzeon's generic name is efuvirtide and it will be distributed by Roche Pharmaceuticals and Trimeris. Fuzeon is the first new class of AIDS treatment approved by the FDA in seven years. But Fuzeon will be expensive, maker sets a price of 20,000 US dollars a year, topping experts' estimated of 10,000 US dollars to 15,000 US dollars. In addition, the medication will come with a warning, its label will advise doctors to carefully monitor patients for signs of pneumonia. During the trial, more patients using Fuzeon can also cause severe allergic reactions, and skin reactions at the injection site occurred in almost all patients. Co-developed by Roche and Trimeris, a biopharmaceutical company, Fuzeon is expected to provide new hope to AIDS patients who have developed a resistance to existing medications.

Animals↗

PubMed2005

Biochip platforms as functional genomics tools for drug discovery.

Improvements in DNA microarray technology have resulted in the generation of data on a scale that, for the first time, permits detailed scrutiny of the human genome. These data provide the foundation for understanding not only the connections between genes and the purpose of genes in the human genome, but also the molecular basis of genetic defects. These advances have the potential to significantly improve healthcare management by improving disease diagnosis and specifically targeting molecular therapy. Herein, the current state of the technology is reviewed, the commercial platforms used by the biopharmaceutical industry are compared and contrasted, and recent efforts in cross-platform data integration are explored.

Animals↗

PubMed2005

Multiplexed serum measurement of IgG, IgA, IgM, and IgE antibody responses to therapeutic biologicals.

Analytical methods characterizing the immunogenicity of therapeutic proteins are useful for monitoring, characterizing and predicting reactions to biopharmaceuticals. A multiplexed assay capable of isotyping the specific IgG, IgA, IgM and IgE (IgGAME) antibody responses against a biotherapeutic was demonstrated in a hyper-immunized cynomolgus monkey, over a 15-month period. The quantitative range of the antibody measurements was determined to be 15 ng/ml to 50 ng/ml in 10% serum. By the use of any biotinylated or fluorescently tagged therapeutic as a detector, this multiplexed isotyping assay can be broadly applied to human and non-human primate IgG, IgA, IgM and IgE immunogenicity studies.

Animals↗

PubMed2001

Engineered antibodies accelerating drug discovery and development.

This meeting, organized by the Strategic Research Institute, reviewed advances in both engineering technologies and clinical development of antibody products. A panel of speakers, mainly from the biotechnology and pharmaceutical industries, covered several important issues in the development of antibody therapeutics, including new display technologies, human antibody generation, high-level expression of antibodies in both mammalian cells and in transgenic plants, and the latest data from ongoing clinical trials of antibody products. In the case of human antibody generation, Abgenix Inc's XenoMax technology combines the powers of the transgenic XenoMouse and in vitro B cell culture and selection to enable the robust identification of antibodies with rare properties and very high affinity. MAbstract from Crucell NV provides a unique approach to the identification of human antibodies directed against tumor-specific glycosylation variants and activation epitopes of otherwise normal cellular molecules. Regarding antibody production, the use of transgenic plants is gaining more interest among biopharmaceutical industrials. Promising results were also reported on several antibody-based therapeutic, including antibody-drug conjugates and prodrugs.

Journal Article↗

PubMed2001

Pseudotyped retrovectors for tumor-specific delivery of toxic suicide genes.

Tumor-targeted gene transfer of the suicide gene, herpes simplex virus thymidine kinase (HSV-TK) is an extremely powerful biopharmaceutical approach for the treatment of cancer. However, no substantive clinical benefit has been reported since this concept was first developed more than a decade ago. This review summarizes the current status of human clinical trials employing viral-vector based delivery of HSV-TK as well as novel means being developed by which killing of tumor cells could be enhanced. In particular, we discuss of the use of VSV-G pseudotyped retrovectors in successfully achieving high tumor-restricted gene transfer efficiency in preclinical studies and the challenges still to be overcome to bring cancer gene therapy safely to the clinic.

Journal Article↗

PubMed2005

Biomarker World Congress 2005.

This report covers some of the many excellent talks, and a selected number of posters, that were presented at this conference. It includes several emerging issues in biomarker development and the question of how biomarker science can drive targeted drug discovery and development and form a scientific basis for personalized medicine. Although relatively small, the meeting provided a good opportunity for business networking, particularly for those involved in the development and regulation of medical diagnostics and biopharmaceuticals.

Animals↗

PubMed2002

Manipulation of ginsenoside heterogeneity in cell cultures of Panax notoginseng by addition of jasmonates.

Manipulation of the heterogeneity of ginsenosides with different pharmacological activities was attempted by adding methyl jasmonate (MJA) or dihydro-methyl jasmonate (HMJA) to suspension cultures of a high-saponin-producing cell line of Panax notoginseng. Compared with HMJA, MJA not only increased ginsenoside content to a large degree but also significantly altered the ratio of Rb to Rg groups of ginsenosides. The ginsenoside Rd was not detected in either control cultures (without MJA addition) or when HMJA was added, but interestingly was detected upon supplementation of MJA. By increasing the concentration of MJA added from 0 to 500 microM, the ratio of Rb to Rg groups also increased from 0.49+/-0.06 to 2.49+/-0.06 (on day 15). The cells exhibited their maximal ginsenoside content when 200 microM MJA was added. The maximal Rb1 content was 3.15+/-0.08 mg/100 mg DW (day 15), which was about ninefold that of the control. The maximal Rg1 and Re contents were 0.90+/-0.01 (day 12) and 0.80+/-0.01 (day 15) mg/100 mg DW, respectively, which were about twofold that of the control. The information obtained will be useful for the exploitation of the diversity of biopharmaceutical molecules and for the large-scale bioprocessing of heterogeneous products.

Journal Article↗

PubMed2005

Antibody engineering for the development of therapeutic antibodies.

Therapeutic antibodies represent one of the fastest growing areas of the pharmaceutical industry. There are currently 19 monoclonal antibodies in the market that have been approved by the FDA and over 150 in clinical developments. Driven by innovation and technological developments, therapeutic antibodies are the second largest biopharmaceutical product category after vaccines. Antibodies have been engineered by a variety of methods to suit a particular therapeutic use. This review describes the structural and functional characteristics of antibody and the antibody engineering for the generation and optimization of therapeutic antibodies.

Animals↗

PubMed2005

[Surface active agents in drug forms and biological systems].

The application areas of surface active agents in the pharmaceutical technology are surveyed. Three topics are summarized: (i) application of surfactant as traditional additives, (ii) the role of surfactant in modern drug delivery systems, and (iii) biopharmaceutical use of surfactants in different dosage forms. The team dealing with colloid carriers at the Pharmaceutical-Technological Department in Szeged has worked out several relationships in mathematical form. These relationships establish the formulation and give an exact character to it. Exponential functions were found between contact angle of wetting and the consistency parameters of water free coherent ointment-systems. There is an exponential relationship between contact angle and structure solidification of ointments measured during storage, between contact angle and structure-forming constant of coherent emulsions, and between contact angle and activation energy of thermostability. There is a linear relation between the contact angle of wetting and water uptake ability of absorbing ointments. On the investigation of emulsions a relationship was evaluated between the surfactant amount accumulated of the interface of oil and water phase and the viscosity and stability of emulsions. The amount of surfactant accumulated on the interface can determine the formation of multiple emulsions. On the area of solubilization there is a reciprocal relationship between the surface tension of surfactant solution and the solubilized amount of drugs. On the area of drug liberation a relationship characterized with a maximum curve can be described between the concentration of surfactant and the released drug. These functions can help the formulation of compositions having a suitable bioavailability.

Dosage Forms↗

PubMed2005

[Surfactants in dosage forms and biological systems. Part II].

The 2nd parts of publications are summarized the modern drug delivery systems contained surface active agents and the role of surfactants in the formation and stability of drug delivery systems. This paper reviews the structure and stability of multiple emulsions, and the different associates forming from surfactants. The solubilization is characterized and some mathematic functions between surface tension of surfactants and their solubilization capacity are introduced. Surfactants represent as important components of coherent emulsions, different vesicles and liposomes. The tensids have an important biopharmaceutical role. They can influenced the bioavailability by increase of thermodynamic activity of active substance and by change of permeability of cellular membranes.

Dosage Forms↗