This document discusses formulation of biotechnology based pharmaceuticals. It begins with an introduction to biotechnology and techniques used to produce biologic products like recombinant DNA technology, monoclonal antibodies, cell therapy, and gene therapy. It then discusses production methods including prokaryotic and eukaryotic systems, applications across various fields, analytical testing and regulations. Manufacturing challenges and safety concerns for cell and gene therapy products are also covered.
Biotechnology is the use of living organisms to develop products and technologies. Pharmaceutical biotechnology applies biotechnology principles to develop drugs. The majority of current drugs are biologics such as antibodies, nucleic acids, and vaccines. Biotechnology methods are important in drug research and development, with key applications in oncology, metabolic disorders, and musculoskeletal disorders. Examples of biotech drugs include insulin for diabetes, gene therapy to replace mutated genes, clotting factors for hemophilia, human serum albumin for burns treatment, and engineered enzymes for enzyme deficiencies.
Pharmaceutical biotechnology is the application of biotechnology principles to develop drugs. It aims to design drugs tailored to an individual's genetics for maximum therapeutic effect. Key applications include recombinant DNA vaccines, drugs, and proteins. Advantages include pharmacogenomics to customize medicine based on genetics. Recombinant DNA and monoclonal antibodies also provide opportunities for new drug development and delivery approaches. Common biotechnology products are antibodies, proteins, and recombinant DNA products. Therapeutic uses include detecting and treating genetic diseases, cancer, AIDS, and autoimmune diseases.
The document discusses drug design, development, and delivery. It covers rational drug design using molecular properties and receptor modeling. Computer-assisted drug design uses molecular docking and QSAR methods. Neural networks are also used in drug design. Drug discovery involves identifying candidates and screening for efficacy. Drug development evaluates ADME, toxicity, and safety through preclinical and clinical studies. Drug delivery methods aim to effectively administer pharmaceutical compounds and improve drug release profiles.
This document discusses targeted drug delivery systems. It defines targeted drug delivery as selectively delivering medication to its site of action to increase concentration in tissues of interest while reducing it in other tissues, improving efficacy and reducing side effects. The document outlines various strategies for targeted delivery including passive, active, ligand-mediated and physical targeting. It also describes several types of targeted delivery systems including liposomes, dendrimers, nanotubes, nanoshells and others. The goal is to achieve the desired pharmacological response at selected sites with minimal side effects.
Biotechnology with reference to pharmaceutical scienceAdarsh Patil
Biotechnology combines biology and technology to modify or make products. Karl Krkey is considered the father of biotechnology for describing using biological processes to boost agricultural production in 1919. Some early uses of biotechnology principles include making bread and curd 4000 BC and wine/beer 6000 BC. Major fields include animal, medical, industrial, and environmental biotechnology. Pharmaceutical biotechnology is the science of producing biological drugs using microorganisms, cells, or tissues and includes cytokines, enzymes, hormones, vaccines, monoclonal antibodies, and drug delivery applications.
The document discusses drug targeting and targeted drug delivery systems. It defines drug targeting as delivering a drug only to its site of action and not to non-target organs, tissues, or cells. It discusses various types, approaches, and levels of drug targeting. It also discusses factors that affect drug targeting and various targeted drug delivery systems including prodrugs, liposomes, niosomes, nanoparticles, and microparticles.
Biotechnology is the use of living organisms to develop products and technologies. Pharmaceutical biotechnology applies biotechnology principles to develop drugs. The majority of current drugs are biologics such as antibodies, nucleic acids, and vaccines. Biotechnology methods are important in drug research and development, with key applications in oncology, metabolic disorders, and musculoskeletal disorders. Examples of biotech drugs include insulin for diabetes, gene therapy to replace mutated genes, clotting factors for hemophilia, human serum albumin for burns treatment, and engineered enzymes for enzyme deficiencies.
Pharmaceutical biotechnology is the application of biotechnology principles to develop drugs. It aims to design drugs tailored to an individual's genetics for maximum therapeutic effect. Key applications include recombinant DNA vaccines, drugs, and proteins. Advantages include pharmacogenomics to customize medicine based on genetics. Recombinant DNA and monoclonal antibodies also provide opportunities for new drug development and delivery approaches. Common biotechnology products are antibodies, proteins, and recombinant DNA products. Therapeutic uses include detecting and treating genetic diseases, cancer, AIDS, and autoimmune diseases.
The document discusses drug design, development, and delivery. It covers rational drug design using molecular properties and receptor modeling. Computer-assisted drug design uses molecular docking and QSAR methods. Neural networks are also used in drug design. Drug discovery involves identifying candidates and screening for efficacy. Drug development evaluates ADME, toxicity, and safety through preclinical and clinical studies. Drug delivery methods aim to effectively administer pharmaceutical compounds and improve drug release profiles.
This document discusses targeted drug delivery systems. It defines targeted drug delivery as selectively delivering medication to its site of action to increase concentration in tissues of interest while reducing it in other tissues, improving efficacy and reducing side effects. The document outlines various strategies for targeted delivery including passive, active, ligand-mediated and physical targeting. It also describes several types of targeted delivery systems including liposomes, dendrimers, nanotubes, nanoshells and others. The goal is to achieve the desired pharmacological response at selected sites with minimal side effects.
Biotechnology with reference to pharmaceutical scienceAdarsh Patil
Biotechnology combines biology and technology to modify or make products. Karl Krkey is considered the father of biotechnology for describing using biological processes to boost agricultural production in 1919. Some early uses of biotechnology principles include making bread and curd 4000 BC and wine/beer 6000 BC. Major fields include animal, medical, industrial, and environmental biotechnology. Pharmaceutical biotechnology is the science of producing biological drugs using microorganisms, cells, or tissues and includes cytokines, enzymes, hormones, vaccines, monoclonal antibodies, and drug delivery applications.
The document discusses drug targeting and targeted drug delivery systems. It defines drug targeting as delivering a drug only to its site of action and not to non-target organs, tissues, or cells. It discusses various types, approaches, and levels of drug targeting. It also discusses factors that affect drug targeting and various targeted drug delivery systems including prodrugs, liposomes, niosomes, nanoparticles, and microparticles.
The document discusses protein engineering and techniques used for it. Protein engineering involves altering cloned DNA to modify protein properties. It merges molecular biology, protein chemistry, and other disciplines. Techniques include genetic modifications like site-directed mutagenesis and chemical modifications. Site-directed mutagenesis allows specific changes to the DNA base using methods like oligonucleotide primers and PCR. This allows investigation of protein function and commercial applications like creating detergent-stable enzymes. Protein engineering has applications in increasing stability, activity and investigating protein properties.
Use of microbes in industry. Production of enzymes-General consideration-Amyl...Steffi Thomas
Industrial uses of microbes, properties of useful industrial microbes, various industrial products, production of enzymes-general consideration-amylase, catalase, peroxidase, lipase, protease, penicillinase, procedure for culturing bacteria and inoculum preparation, submerged fermentation and solid state fermentation, uses of different enzymes
The document discusses the process of drug design and development. It begins by defining drugs and their targets at the molecular level. Historically, drugs came from plants and natural products, but now they can be designed rationally through understanding disease processes. The drug design process involves identifying a target, discovering leads, and optimizing candidates through computer modeling and testing before clinical trials. Modern techniques like molecular modeling, virtual screening, and computer-aided design have made drug discovery more efficient, but it remains a long, complex, and expensive process.
PCR is a technique that amplifies a specific DNA sequence. It involves repeated cycles of heating and cooling of the DNA sample in the presence of primers and a DNA polymerase. During each cycle, the DNA strands are separated by heating, then primers allow the polymerase to selectively copy the target sequence. This results in exponential amplification of the target DNA. PCR is used in a wide range of applications including pathogen detection, genetic testing, and forensic analysis due to its ability to rapidly produce large amounts of a specific DNA sequence from a small sample.
Drug targeting aims to selectively deliver drugs to target cells while avoiding non-target cells to maximize therapeutic effects and minimize toxicity. This can be achieved through passive targeting using carriers, active targeting using ligands, or physical targeting exploiting environmental differences between target and non-target sites. The ideal targeted drug delivery system releases drug in a controlled manner at the target site and is non-toxic, biocompatible, and eliminated from the body. Common approaches to drug targeting include carriers, prodrugs, magnetic targeting using magnetic carriers, and monoclonal antibody-based targeting of drug conjugates.
The document discusses various approaches used in drug design, including quantitative structure activity relationship (QSAR) analysis. QSAR uses physicochemical parameters like partition coefficient, electronic parameters, and steric parameters to develop mathematical models correlating a drug molecule's structure to its biological activity. The goal is to predict activity for new compounds and guide drug design. Parameters commonly used in QSAR include log P for hydrophobicity, Hammett constants for electronics, and Taft constants for sterics. Methods involve Hansch analysis, Free Wilson models, and other statistical techniques.
Biosensors working and application in pharmaceutical industryShivraj Jadhav
Biosensors convert biological responses into electrical signals and were pioneered by Professor Leland C. Clark. They should provide accurate, precise, reproducible results using cheap, small, portable devices operable by semi-skilled users. Biosensors contain bioreceptors, transducers, signal processors and displays. Depending on the transducer, examples include electrochemical, amperometric, potentiometric, conductometric, thermometric, optical and piezoelectric biosensors. Biosensors have wide applications in medicine such as glucose monitoring, infectious disease diagnosis, and detection of cardiac markers.
This document discusses targeted drug delivery systems. It begins by introducing the concept of targeted drug delivery as proposed by Paul Ehrlich in 1902 to deliver "magic bullets" of medicine exclusively to target cells. It then outlines several approaches to targeted drug delivery including controlling drug distribution, altering the drug's structure, and controlling drug input for a programmed bio-distribution. Finally, it describes various carrier systems that can be used for targeted drug delivery like liposomes, nanoparticles, antibodies, and ligands to actively target drugs to specific sites.
Microencapsulation techniques involve coating small particles of core materials with thin layers of coating materials to form microcapsules. Some common microencapsulation techniques described in the document include coacervation, interfacial polymerization, in situ polymerization, and solvent evaporation. Microencapsulation can be used to increase bioavailability, alter drug release profiles, mask tastes, and enable targeted drug delivery.
Protein engineering is the process of developing useful or valuable proteins. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles
Application of rDNA in the Production of Interferon, Hepatitis Vaccines & Ins...Theabhi.in
1) The document discusses the application of recombinant DNA technology in the production of interferon, hepatitis B vaccine, and insulin.
2) Interferon is produced through recombinant DNA by isolating the human interferon gene and inserting it into bacterial plasmids, allowing bacteria to express the gene and produce interferon protein.
3) Insulin is similarly produced by isolating the human insulin gene, inserting it into bacterial plasmids, and having bacteria express the gene to synthesize insulin protein.
Methods of enhancing Dissolution and bioavailability of poorly soluble drugsRam Kanth
Bioavailability refers to the amount of drug that reaches systemic circulation after administration. It is reduced when drugs are administered orally rather than intravenously due to incomplete absorption and first-pass metabolism. The document discusses several methods for enhancing bioavailability of orally administered drugs with poor solubility or permeability. These include micronization, use of surfactants, salt forms, altering pH, polymorphism, complexation, molecular encapsulation, and forming solid solutions, eutectic mixtures or solid dispersions to improve solubility and dissolution rate.
Computer aided drug design uses computational methods to facilitate the design and discovery of new therapeutic solutions. There are two main types of drug design - ligand-based which relies on knowledge of molecules that bind to the target, and structure-based which relies on the 3D structure of the target. The main steps in structure-based design are target selection, binding site identification, molecular docking to predict how ligands bind to the target, and scoring to evaluate interactions. Computational tools are used for databases, molecular modeling, docking, screening, and predicting absorption and toxicity properties. These tools help speed up the drug design process and make it more efficient.
Brief introduction to biotechnology with reference to pharmaceutical Biotechnology
General introduction to biotechnology, principle of biotechnology, history and application in different field.
Type of biotechnology
Traditional and modern biotechnology
Overview on genetic engineering
Role of Biotechnology in pharma and medicine sectors, products in pharmaceutical biotechnology
1. Drug absorption involves the movement of unchanged drug molecules from the site of administration into systemic circulation. It occurs primarily through the gastrointestinal (GI) tract and is influenced by factors like solubility, permeability, and transport mechanisms.
2. There are three main mechanisms of drug transport across the GI tract - transcellular, paracellular, and vesicular. Transcellular transport occurs across cells and includes passive diffusion, active transport, and carrier-mediated transport. Paracellular transport is between cell junctions. Vesicular transport involves endocytosis within cells.
3. The most common mechanism is passive diffusion, which does not require energy. Other mechanisms like active transport and carrier-mediated transport use
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is the study of factors influencing drug absorption, distribution, metabolism and excretion (ADME). There are three main mechanisms of drug absorption in the body: 1) transcellular/intracellular transport across epithelial cells, 2) paracellular/intercellular transport between epithelial cells, and 3) vesicular or corpuscular transport through endocytosis. Transcellular transport can occur passively through diffusion, pores or ion pairs, or actively through carriers or pumps. Paracellular transport is between tight cell junctions or through temporary openings. Vesicular transport involves pinocytosis or phagocytosis of substances into cells.
The document discusses the pH partition theory of drug absorption from the gastrointestinal tract. The theory states that a drug's absorption is governed by its dissociation constant (pKa), the lipid solubility of its unionized form, and the pH of the absorption site. According to the theory, only the unionized form of an acid or base drug can be absorbed if it is sufficiently lipid soluble. The fraction of a drug in its unionized form depends on the drug's pKa and the pH of the solution based on the Henderson-Hasselbalch equation. While the pH partition theory explains many observations, it has limitations such as not accounting for the presence of an unstirred water layer and virtual membrane pH at the absorption
This document provides an overview of antisense oligonucleotide therapy, including its definition as synthetic genetic material that binds to mRNA to prevent protein translation, mechanisms of action such as blocking ribosomes and activating RNase enzymes, applications in oncology and other therapeutic areas, examples of compounds in clinical trials, and its future potential as over 30 compounds are currently in clinical trials.
The document discusses protein-drug binding, including the two main classes of binding: intracellular and extracellular. It describes the reversible mechanisms of binding such as hydrogen bonds and hydrophobic bonds. Key factors that affect protein-drug binding are the physicochemical properties of the drug and protein, their concentrations, and the number of binding sites. The significance of protein binding is that the bound fraction of a drug is pharmacologically inactive.
This document discusses various methods for the production of pharmaceutical drugs through microbial biotechnology and genetic engineering. It covers topics like the production of antibiotics like penicillin and chlortetracycline through fermentation, the use of recombinant DNA technology to produce drugs in microorganisms, and the application of genetic manipulation techniques. It also summarizes strategies for producing drugs like human insulin through the transformation of E. coli or B. subtilis with human genes.
Monoclonal antibodies are identical antibodies produced by a single clone of B cells that recognize a specific epitope on an antigen. They are produced through the fusion of B cells from an immunized animal with myeloma cells to form a hybridoma. This hybridoma will continuously secrete the same monoclonal antibody. Monoclonal antibodies have various diagnostic and therapeutic applications including use in biochemical assays, diagnostic imaging, cancer treatment, and protein purification due to their high specificity for targets.
The document discusses protein engineering and techniques used for it. Protein engineering involves altering cloned DNA to modify protein properties. It merges molecular biology, protein chemistry, and other disciplines. Techniques include genetic modifications like site-directed mutagenesis and chemical modifications. Site-directed mutagenesis allows specific changes to the DNA base using methods like oligonucleotide primers and PCR. This allows investigation of protein function and commercial applications like creating detergent-stable enzymes. Protein engineering has applications in increasing stability, activity and investigating protein properties.
Use of microbes in industry. Production of enzymes-General consideration-Amyl...Steffi Thomas
Industrial uses of microbes, properties of useful industrial microbes, various industrial products, production of enzymes-general consideration-amylase, catalase, peroxidase, lipase, protease, penicillinase, procedure for culturing bacteria and inoculum preparation, submerged fermentation and solid state fermentation, uses of different enzymes
The document discusses the process of drug design and development. It begins by defining drugs and their targets at the molecular level. Historically, drugs came from plants and natural products, but now they can be designed rationally through understanding disease processes. The drug design process involves identifying a target, discovering leads, and optimizing candidates through computer modeling and testing before clinical trials. Modern techniques like molecular modeling, virtual screening, and computer-aided design have made drug discovery more efficient, but it remains a long, complex, and expensive process.
PCR is a technique that amplifies a specific DNA sequence. It involves repeated cycles of heating and cooling of the DNA sample in the presence of primers and a DNA polymerase. During each cycle, the DNA strands are separated by heating, then primers allow the polymerase to selectively copy the target sequence. This results in exponential amplification of the target DNA. PCR is used in a wide range of applications including pathogen detection, genetic testing, and forensic analysis due to its ability to rapidly produce large amounts of a specific DNA sequence from a small sample.
Drug targeting aims to selectively deliver drugs to target cells while avoiding non-target cells to maximize therapeutic effects and minimize toxicity. This can be achieved through passive targeting using carriers, active targeting using ligands, or physical targeting exploiting environmental differences between target and non-target sites. The ideal targeted drug delivery system releases drug in a controlled manner at the target site and is non-toxic, biocompatible, and eliminated from the body. Common approaches to drug targeting include carriers, prodrugs, magnetic targeting using magnetic carriers, and monoclonal antibody-based targeting of drug conjugates.
The document discusses various approaches used in drug design, including quantitative structure activity relationship (QSAR) analysis. QSAR uses physicochemical parameters like partition coefficient, electronic parameters, and steric parameters to develop mathematical models correlating a drug molecule's structure to its biological activity. The goal is to predict activity for new compounds and guide drug design. Parameters commonly used in QSAR include log P for hydrophobicity, Hammett constants for electronics, and Taft constants for sterics. Methods involve Hansch analysis, Free Wilson models, and other statistical techniques.
Biosensors working and application in pharmaceutical industryShivraj Jadhav
Biosensors convert biological responses into electrical signals and were pioneered by Professor Leland C. Clark. They should provide accurate, precise, reproducible results using cheap, small, portable devices operable by semi-skilled users. Biosensors contain bioreceptors, transducers, signal processors and displays. Depending on the transducer, examples include electrochemical, amperometric, potentiometric, conductometric, thermometric, optical and piezoelectric biosensors. Biosensors have wide applications in medicine such as glucose monitoring, infectious disease diagnosis, and detection of cardiac markers.
This document discusses targeted drug delivery systems. It begins by introducing the concept of targeted drug delivery as proposed by Paul Ehrlich in 1902 to deliver "magic bullets" of medicine exclusively to target cells. It then outlines several approaches to targeted drug delivery including controlling drug distribution, altering the drug's structure, and controlling drug input for a programmed bio-distribution. Finally, it describes various carrier systems that can be used for targeted drug delivery like liposomes, nanoparticles, antibodies, and ligands to actively target drugs to specific sites.
Microencapsulation techniques involve coating small particles of core materials with thin layers of coating materials to form microcapsules. Some common microencapsulation techniques described in the document include coacervation, interfacial polymerization, in situ polymerization, and solvent evaporation. Microencapsulation can be used to increase bioavailability, alter drug release profiles, mask tastes, and enable targeted drug delivery.
Protein engineering is the process of developing useful or valuable proteins. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles
Application of rDNA in the Production of Interferon, Hepatitis Vaccines & Ins...Theabhi.in
1) The document discusses the application of recombinant DNA technology in the production of interferon, hepatitis B vaccine, and insulin.
2) Interferon is produced through recombinant DNA by isolating the human interferon gene and inserting it into bacterial plasmids, allowing bacteria to express the gene and produce interferon protein.
3) Insulin is similarly produced by isolating the human insulin gene, inserting it into bacterial plasmids, and having bacteria express the gene to synthesize insulin protein.
Methods of enhancing Dissolution and bioavailability of poorly soluble drugsRam Kanth
Bioavailability refers to the amount of drug that reaches systemic circulation after administration. It is reduced when drugs are administered orally rather than intravenously due to incomplete absorption and first-pass metabolism. The document discusses several methods for enhancing bioavailability of orally administered drugs with poor solubility or permeability. These include micronization, use of surfactants, salt forms, altering pH, polymorphism, complexation, molecular encapsulation, and forming solid solutions, eutectic mixtures or solid dispersions to improve solubility and dissolution rate.
Computer aided drug design uses computational methods to facilitate the design and discovery of new therapeutic solutions. There are two main types of drug design - ligand-based which relies on knowledge of molecules that bind to the target, and structure-based which relies on the 3D structure of the target. The main steps in structure-based design are target selection, binding site identification, molecular docking to predict how ligands bind to the target, and scoring to evaluate interactions. Computational tools are used for databases, molecular modeling, docking, screening, and predicting absorption and toxicity properties. These tools help speed up the drug design process and make it more efficient.
Brief introduction to biotechnology with reference to pharmaceutical Biotechnology
General introduction to biotechnology, principle of biotechnology, history and application in different field.
Type of biotechnology
Traditional and modern biotechnology
Overview on genetic engineering
Role of Biotechnology in pharma and medicine sectors, products in pharmaceutical biotechnology
1. Drug absorption involves the movement of unchanged drug molecules from the site of administration into systemic circulation. It occurs primarily through the gastrointestinal (GI) tract and is influenced by factors like solubility, permeability, and transport mechanisms.
2. There are three main mechanisms of drug transport across the GI tract - transcellular, paracellular, and vesicular. Transcellular transport occurs across cells and includes passive diffusion, active transport, and carrier-mediated transport. Paracellular transport is between cell junctions. Vesicular transport involves endocytosis within cells.
3. The most common mechanism is passive diffusion, which does not require energy. Other mechanisms like active transport and carrier-mediated transport use
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is the study of factors influencing drug absorption, distribution, metabolism and excretion (ADME). There are three main mechanisms of drug absorption in the body: 1) transcellular/intracellular transport across epithelial cells, 2) paracellular/intercellular transport between epithelial cells, and 3) vesicular or corpuscular transport through endocytosis. Transcellular transport can occur passively through diffusion, pores or ion pairs, or actively through carriers or pumps. Paracellular transport is between tight cell junctions or through temporary openings. Vesicular transport involves pinocytosis or phagocytosis of substances into cells.
The document discusses the pH partition theory of drug absorption from the gastrointestinal tract. The theory states that a drug's absorption is governed by its dissociation constant (pKa), the lipid solubility of its unionized form, and the pH of the absorption site. According to the theory, only the unionized form of an acid or base drug can be absorbed if it is sufficiently lipid soluble. The fraction of a drug in its unionized form depends on the drug's pKa and the pH of the solution based on the Henderson-Hasselbalch equation. While the pH partition theory explains many observations, it has limitations such as not accounting for the presence of an unstirred water layer and virtual membrane pH at the absorption
This document provides an overview of antisense oligonucleotide therapy, including its definition as synthetic genetic material that binds to mRNA to prevent protein translation, mechanisms of action such as blocking ribosomes and activating RNase enzymes, applications in oncology and other therapeutic areas, examples of compounds in clinical trials, and its future potential as over 30 compounds are currently in clinical trials.
The document discusses protein-drug binding, including the two main classes of binding: intracellular and extracellular. It describes the reversible mechanisms of binding such as hydrogen bonds and hydrophobic bonds. Key factors that affect protein-drug binding are the physicochemical properties of the drug and protein, their concentrations, and the number of binding sites. The significance of protein binding is that the bound fraction of a drug is pharmacologically inactive.
This document discusses various methods for the production of pharmaceutical drugs through microbial biotechnology and genetic engineering. It covers topics like the production of antibiotics like penicillin and chlortetracycline through fermentation, the use of recombinant DNA technology to produce drugs in microorganisms, and the application of genetic manipulation techniques. It also summarizes strategies for producing drugs like human insulin through the transformation of E. coli or B. subtilis with human genes.
Monoclonal antibodies are identical antibodies produced by a single clone of B cells that recognize a specific epitope on an antigen. They are produced through the fusion of B cells from an immunized animal with myeloma cells to form a hybridoma. This hybridoma will continuously secrete the same monoclonal antibody. Monoclonal antibodies have various diagnostic and therapeutic applications including use in biochemical assays, diagnostic imaging, cancer treatment, and protein purification due to their high specificity for targets.
Monoclonal antibodies are produced through the hybridoma technology developed by Kohler and Milstein in 1975. This involves fusing B cells from an immunized animal with myeloma cells to produce hybridomas that secrete a single antibody specific to the target antigen. The antibodies can be screened and a clone selected to mass produce monoclonal antibodies that recognize a single epitope. Monoclonal antibodies have various applications including disease diagnosis, immunotherapy, and immunosuppression for organ transplants. While powerful tools, limitations include potential immunogenicity and high production costs.
This document discusses monoclonal antibodies (mAb), including their production through hybridoma technology. Some key points:
- mAb are identical antibodies produced by identical immune cells cloned from a single parent cell. They were first produced in 1975 using cell fusions.
- The hybridoma technique involves immunizing an animal, fusing spleen cells that produce antibodies with myeloma cells to form a hybridoma, and using HAT medium to select antibody-producing hybridomas.
- Applications of mAb include research, diagnostics, and therapies for cancer, autoimmune disorders, and more. Variants like chimeric and humanized mAb reduce immunogenicity.
Biotechnology uses living organisms to produce useful materials. It has both traditional and innovative forms. Recombinant DNA technology allows genes to be transferred between organisms. This has led to important medical advances like producing insulin in bacteria. However, there are also concerns about GMOs, including possible allergic reactions in humans and the risk of transgenic genes escaping into the wild. Overall, biotechnology presents both opportunities and risks that require careful consideration.
This document provides information about the production of biopharmaceutical products. It begins with an introduction to biotechnology and defines it. It then discusses the development and fields of biotechnology. Specific biotech products like insulin and vaccines are described in detail, outlining their production processes which involve recombinant DNA technology. The document also discusses monoclonal antibodies, their uses as diagnostic tools, and the ELISA test method. It provides information on the production of monoclonal antibodies through hybridoma technology.
This document discusses therapeutic proteins and their production using recombinant DNA technology. It begins by defining therapeutic proteins as proteins engineered for pharmaceutical use to treat illnesses where certain proteins are low or absent. The four main sections discuss: 1) different protein expression systems including bacterial, yeast, insect and mammalian cells; 2) optimizing gene expression and production of recombinant proteins; 3) examples of therapeutic proteins produced including insulin, growth hormone, and interferons; and 4) the use of enzymes like DNase and alginate lyase as therapeutic agents.
The document discusses how monoclonal antibodies are produced by fusing B lymphocytes from immunized mice with myeloma cells, screening the resulting hybridomas for the desired antibody specificity using tests like ELISA, and identifying the hybridomas that produce homogenous and specific monoclonal antibodies targeting the antigen of interest.
Monoclonal antibody production by hybridoma technologyHasnat Tariq
Monoclonal antibodies are identical antibodies produced by a single clone of B cells that recognize a specific epitope. They are produced through the hybridoma technology which involves fusing antibody producing B cells with myeloma cells to form a hybridoma cell line. This allows for the mass production of antibodies that recognize a single epitope. Monoclonal antibodies have various applications including use in biochemical analysis through techniques like ELISA and RIA. They can also be used for diagnostic imaging by labeling them with radioisotopes.
The document discusses biotechnological product development, concepts, and technologies. It begins with definitions of biotechnology and biotechnological drugs. It then covers the history of biotechnology, examples of biotechnological drugs, routes of administration, and the process of developing biotechnological drugs. This includes techniques such as isolating genes of interest, transferring genes to expression vectors, growing host cells, purifying and formulating proteins. The document also discusses monoclonal antibody production, gene therapy, issues with biotech products, and applications of biotechnological drugs.
Students of medical and allied subjects must be exposed to the concept of monoclonal antibodies for the efficient practice of clinical and laboratory medicine.
Hybridoma technology for production of monoclonal antibodies.pdfsoniaangeline
The document discusses hybridoma technology for producing monoclonal antibodies. It describes the process which involves fusing antibody-producing B cells from immunized mice with myeloma tumor cells, using a chemical or electrical method. The resulting hybridoma cells are selected and cultured, retaining the antibody-producing ability of B cells and indefinite lifespan of tumor cells. The monoclonal antibodies produced can be extracted and purified for therapeutic and research applications.
Monoclonal antibodies (MAbs) are antibodies that are identical and bind to the same epitope. The document discusses the history and development of MAb technology, including the hybridoma technique developed by Kohler and Milstein. It describes how MAbs are produced through cell fusion, screening, and cloning. The document outlines applications of MAbs in diagnostics, such as cancer detection and imaging, and therapeutics, including cancer treatment. MAbs provide advantages over polyclonal antibodies in being highly specific and reproducible.
BIOTECHNOLOGY IS
CHALLENGING SUBJECT TO TEACH AND UNDERSTAND ......
ITS A VERY INTERESTING TO LEARN ABOUT HYBRIDOMA TECHNOLOGY .. THEIR PRODUCTION AND
APPLICATION ALSO ....
PPT ON MONOCLONAL ANTIBODIES.saurabh punia.ppt.pptxSAURABH PUNIA
This document discusses monoclonal antibodies, including their production, structure, and applications. Monoclonal antibodies are produced through hybridoma technology, which involves fusing antibody-producing B cells with myeloma cells to create immortal cell lines. They have identical binding sites since they are clones of a single parent cell. The production process involves immunizing an animal, harvesting spleen cells, fusing them with myeloma cells, selecting hybridomas that produce the desired antibody, and propagating these cells to produce large amounts of monoclonal antibodies. Monoclonal antibodies have various medical applications, such as targeted delivery of cancer drugs and treatment of diseases.
Production and applications of monoclonal antibodiesKaayathri Devi
production and applications of monoclonal antibodies, monoclonal antibodies ,applications of monoclonal antibodies, production of monoclonal antibodies,
This document discusses monoclonal antibody production and applications. It begins by defining monoclonal and polyclonal antibodies, noting that monoclonal antibodies are identical because they are derived from a single parent cell. It then covers the history of monoclonal antibody development, the monoclonal antibody production method involving mouse immunization and cell fusion, and the types and uses of monoclonal antibodies including diagnostic and cancer treatment applications. Potential side effects of monoclonal antibody therapy are also mentioned.
- Georges Köhler and Cesar Milstein developed hybridoma technology in 1975 for which they received the Nobel Prize in 1984. Hybridoma technology involves fusing myeloma cells with antibody-producing immune cells to create immortal cell lines that produce monoclonal antibodies.
- Monoclonal antibodies are identical antibodies produced by a single clone and recognize a specific antigen, whereas polyclonal antibodies are derived from different cell lines.
- Hybridoma technology involves immunizing an animal, fusing its immune cells with myeloma cells, selecting and cloning hybridoma cells that produce the desired antibody, and characterizing and storing the monoclonal antibody produced. Monoclonal antibodies have important applications in diagnostics and treatment of diseases like cancer.
This document provides an overview of common instrumental analytical techniques used in chromatography and spectroscopy. It describes various chromatographic techniques including thin layer chromatography, column chromatography, gas chromatography, and high performance liquid chromatography. It also outlines several spectroscopic techniques such as atomic absorption spectroscopy, colorimetry, and UV-visible spectroscopy. The document explains the basic principles, components, and applications of these analytical methods for separating and analyzing mixtures.
The document discusses Investigational New Drug Applications (INDs), which are required for clinical trials of new drugs. It outlines the key components of an IND, including an introductory statement, investigator's brochure, protocols, chemistry/manufacturing information, and previous human experience. It also describes IND amendments, annual reports, and the roles of the sponsor and investigator. The overall purpose of an IND is to provide information to the FDA on a new drug's safety before it can be tested in humans.
Fractional factorial designs (FFDs) are used to efficiently study many factors using fewer experimental runs than a full factorial design. FFDs exploit redundancy in estimating interactions to select a subset of runs. Regular FFDs have desirable properties like balance and orthogonality. Resolution indicates how interactions are aliased, with higher resolutions preferred. FFDs are useful in screening experiments to identify important factors efficiently before further optimization. Software helps select appropriate FFDs based on desired resolution and aliasing.
This document discusses herbal medicines and their use in the pharmaceutical industry. It provides information on patient use of herbal remedies, why herbal products are in demand, approaches to developing herbal formulations, standardizing herbs, guidelines for using herbs safely, and interacting with other medications. The document addresses issues like herbal products not being well-tested, lacking quality control, and having imprecise potency, while also noting two sides to herbs in terms of benefits and risks.
Herbal medicine involves the use of whole plants to promote health and treat disease, drawing on a tradition of human use for over 60,000 years. It views disease more broadly by addressing underlying causes and individual expression rather than just symptoms. Herbal medicines are prescribed to restore homeostasis and promote optimal cellular nutrition and elimination. Around 1 in 5 people in the UK regularly use herbal medicine, and it is regulated through organizations like the National Institute of Medical Herbalists. Herbal medicines are prescribed individually based on a comprehensive medical history and clinical examination.
The document discusses Investigational New Drug Applications (INDs), which are required for clinical testing of new drugs. It describes the key components of an IND including an introductory statement, investigator's brochure, protocols, chemistry and manufacturing information, and annual reports. It also defines important terms like sponsor and investigator and outlines the regulatory requirements for INDs.
This document provides an introduction to water systems for pharmaceutical use. It discusses the importance of water quality for pharmaceutical processes and products. It outlines various water types like purified water, highly purified water, and water for injections. It emphasizes that water systems must be properly designed, installed, operated and maintained according to GMP to ensure consistent production of water meeting quality specifications. It also discusses common water contaminants and the need to monitor water sources and treat water appropriately based on its chemistry and contaminants.
Good Manufacturing Practices (GMPs) establish minimum standards for methods, facilities, and controls used in manufacturing drugs to ensure they are safe, have the appropriate identity and strength, and meet quality and purity standards. GMP violations can result in severe consequences for drug manufacturers such as product seizures, recalls, shutdown of facilities, and large financial penalties. Current trends in GMPs include a risk-based approach, international harmonization of quality standards, and proposed amendments regarding validation and cross-contamination prevention.
GMP (good manufacturing practices) and cGMP (current good manufacturing practices) are quality standards for the manufacture of pharmaceutical products and medical devices. They help ensure that products are consistently produced and controlled according to quality standards for safety and efficacy. Key aspects of GMP include establishing processes and procedures for production, cleaning, maintenance, personnel training, and quality testing of products. Following GMP guidelines helps manufacturers produce pharmaceuticals that meet the necessary quality standards.
The document discusses the FDA's Inactive Ingredient Guide (IIG), which lists inactive ingredients that are present in approved drug products. It provides information on obtaining the IIG and describes the contents and purpose of the guide. The IIG is intended to help identify inactive ingredients that may require less extensive review if they are already present in approved drug products for a particular route of administration. It lists ingredients alphabetically and provides information like routes of administration, CAS numbers, number of NDAs, and potency ranges.
The document discusses Drug Master Files (DMFs), which provide confidential detailed information to the FDA in support of applications. It defines 5 types of DMFs and outlines their typical contents. These include manufacturing processes and facilities, active pharmaceutical ingredients, packaging materials, excipients, and reference information. The summary provides guidelines on submitting DMFs, required content for each type, quality controls, stability testing, and the FDA review process. Holders must adhere to good manufacturing practices and be willing to allow inspections.
This document outlines the history of drug development and approval processes in the United States from 1820 to 1997. It describes key milestones and legislation that established regulations for new drug applications (NDAs). NDAs were first required in 1938 to show drug safety, and in 1962 were amended to require proof of efficacy. The FDA now reviews NDAs to ensure the benefits of new drugs outweigh the risks based on clinical trial data.
The EMEA (European Medicines Agency) is a decentralized body of the European Union headquartered in London. It was established in 1995 and coordinates the evaluation and supervision of medicines for human and veterinary use throughout the EU. It is composed of various committees including the CHMP (Committee for Medicinal Products for Human Use) and CVMP (Committee for Medicinal Products for Veterinary Use) which are responsible for assessment and authorization of medicines. The EMEA ensures that medicines are evaluated based on quality, safety and efficacy with the goal of protecting public health.
This document discusses key considerations for dosage form design and formulation. It explains that pharmaceutical formulation involves selecting excipients to solubilize, thicken, stabilize, flavor, and otherwise modify drug substances for patient delivery. Proper dosage form design requires considering the physical and chemical properties of drug substances and ensuring compatibility with excipients. Preformulation studies characterize the drug's properties including solubility, dissolution rate, and stability. Understanding these properties helps determine the appropriate dosage form and formulation to provide stable, effective delivery of the active drug to patients.
This document defines various microbiology terms related to sterilization and disinfection. It discusses sterilization techniques like heat, filtration, and radiation. It also covers chemical disinfectants including phenols, bisphenols, biguanides, halogens, and chlorine. Physical methods like heat, filtration, refrigeration, and radiation can kill microbes. Chemical disinfectants have varying mechanisms of action, with phenols and halogens damaging cell membranes and bisphenols inhibiting fatty acid synthesis. Proper evaluation of disinfectant efficacy involves tests against standard microbes.
This document provides an overview of computer validation and compliance with regulatory guidance. It discusses the need for computer validation and outlines key principles from guidance documents such as software validation, use of off-the-shelf software in medical devices, and validation of electronic records and signatures. Validation approaches for different systems and software are covered, including spreadsheets. The document provides references to FDA and international regulatory guidance on these topics.
This document discusses designing around patents from the perspectives of both patent holders and competitors. It notes that patent holders seek broad patent protection to maximize monopoly profits and minimize successful design around efforts, while competitors aim to create non-infringing alternative products without bearing the monopoly costs of the patent. The document outlines strategies for patent holders to draft claims to make designing around more difficult and for competitors to develop design around approaches in light of legal precedents like Festo v. Shoketsu, which impacted the doctrine of equivalents.
Clinical trials are conducted in phases to evaluate the safety and efficacy of new drugs. Phase 1 trials involve 10-20 healthy volunteers to determine toxicity and pharmacokinetics. Phase 2 trials involve 100-200 patients to identify effective doses and further evaluate safety. Phase 3 trials involve up to 1000 volunteers to study less common side effects, compare to standard treatments, and evaluate long-term safety and effectiveness. Phase 4 trials monitor drugs after approval in 5000-10,000 patients to identify rare or long-term issues.
Clinical trials progress through phases (preclinical, I-IV) to evaluate treatments safely in humans. Preclinical testing occurs in labs and animals. Phase I studies evaluate safety in 20-80 healthy volunteers. Phase II expands to 100-300 patient volunteers to assess efficacy. Phase III further tests efficacy in 1,000-3,000 patients. FDA approval requires compliance with Good Clinical Practice guidelines to protect subject rights and ensure credible data. Key elements include oversight by independent review boards, informed consent, qualified investigators and sponsors, adherence to protocols, and comprehensive record keeping.
Clinical research in India is growing rapidly due to several factors:
- India has a large population with a growing disease burden similar to developed countries. This provides opportunities for clinical trial recruitment.
- Regulatory reforms have made the approval process for clinical trials much faster, within 6-8 weeks for some applications.
- Costs for conducting clinical trials are around half of Western countries, providing significant cost savings for sponsors.
- There is an increasing pool of experienced investigators and staff familiar with Good Clinical Practice who can conduct trials to international standards.
- The pharmaceutical industry and contract research organizations see India as an important location for outsourcing various stages of drug development to take advantage of the opportunities.
How to Setup Warehouse & Location in Odoo 17 InventoryCeline George
In this slide, we'll explore how to set up warehouses and locations in Odoo 17 Inventory. This will help us manage our stock effectively, track inventory levels, and streamline warehouse operations.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
This document provides an overview of wound healing, its functions, stages, mechanisms, factors affecting it, and complications.
A wound is a break in the integrity of the skin or tissues, which may be associated with disruption of the structure and function.
Healing is the body’s response to injury in an attempt to restore normal structure and functions.
Healing can occur in two ways: Regeneration and Repair
There are 4 phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. This document also describes the mechanism of wound healing. Factors that affect healing include infection, uncontrolled diabetes, poor nutrition, age, anemia, the presence of foreign bodies, etc.
Complications of wound healing like infection, hyperpigmentation of scar, contractures, and keloid formation.
How to Make a Field Mandatory in Odoo 17Celine George
In Odoo, making a field required can be done through both Python code and XML views. When you set the required attribute to True in Python code, it makes the field required across all views where it's used. Conversely, when you set the required attribute in XML views, it makes the field required only in the context of that particular view.
How to Fix the Import Error in the Odoo 17Celine George
An import error occurs when a program fails to import a module or library, disrupting its execution. In languages like Python, this issue arises when the specified module cannot be found or accessed, hindering the program's functionality. Resolving import errors is crucial for maintaining smooth software operation and uninterrupted development processes.
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it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
Chapter wise All Notes of First year Basic Civil Engineering.pptxDenish Jangid
Chapter wise All Notes of First year Basic Civil Engineering
Syllabus
Chapter-1
Introduction to objective, scope and outcome the subject
Chapter 2
Introduction: Scope and Specialization of Civil Engineering, Role of civil Engineer in Society, Impact of infrastructural development on economy of country.
Chapter 3
Surveying: Object Principles & Types of Surveying; Site Plans, Plans & Maps; Scales & Unit of different Measurements.
Linear Measurements: Instruments used. Linear Measurement by Tape, Ranging out Survey Lines and overcoming Obstructions; Measurements on sloping ground; Tape corrections, conventional symbols. Angular Measurements: Instruments used; Introduction to Compass Surveying, Bearings and Longitude & Latitude of a Line, Introduction to total station.
Levelling: Instrument used Object of levelling, Methods of levelling in brief, and Contour maps.
Chapter 4
Buildings: Selection of site for Buildings, Layout of Building Plan, Types of buildings, Plinth area, carpet area, floor space index, Introduction to building byelaws, concept of sun light & ventilation. Components of Buildings & their functions, Basic concept of R.C.C., Introduction to types of foundation
Chapter 5
Transportation: Introduction to Transportation Engineering; Traffic and Road Safety: Types and Characteristics of Various Modes of Transportation; Various Road Traffic Signs, Causes of Accidents and Road Safety Measures.
Chapter 6
Environmental Engineering: Environmental Pollution, Environmental Acts and Regulations, Functional Concepts of Ecology, Basics of Species, Biodiversity, Ecosystem, Hydrological Cycle; Chemical Cycles: Carbon, Nitrogen & Phosphorus; Energy Flow in Ecosystems.
Water Pollution: Water Quality standards, Introduction to Treatment & Disposal of Waste Water. Reuse and Saving of Water, Rain Water Harvesting. Solid Waste Management: Classification of Solid Waste, Collection, Transportation and Disposal of Solid. Recycling of Solid Waste: Energy Recovery, Sanitary Landfill, On-Site Sanitation. Air & Noise Pollution: Primary and Secondary air pollutants, Harmful effects of Air Pollution, Control of Air Pollution. . Noise Pollution Harmful Effects of noise pollution, control of noise pollution, Global warming & Climate Change, Ozone depletion, Greenhouse effect
Text Books:
1. Palancharmy, Basic Civil Engineering, McGraw Hill publishers.
2. Satheesh Gopi, Basic Civil Engineering, Pearson Publishers.
3. Ketki Rangwala Dalal, Essentials of Civil Engineering, Charotar Publishing House.
4. BCP, Surveying volume 1
2. Introduction to biotechnology
Common features for production of biotechnological
material
Applications in Various fields
Techniques used to produce biotechnologic products
Recombinant DNA (rDNA) technology
Monoclonal antibodies
Cell therapy
Gene therapy
Equipments for Mfg.
Analytical Testing
Major Impurities
Regulations
References
2
3. Biotechnology encompasses any
techniques that use living organisms like
micro-organisms, isolated mammalian
cells in the production of products having
beneficial use.
The classic example of biotechnological
drugs was proteins obtained from
recombinant DNA technology.
Biotechnology now encompasses the use
of tissue culture, living cells or cell
enzymes to make a defined product. 3
4. Cloning of specific gene into a laboratory.
Construction of synthetic gene.
Insertion into the host cell and subcloning in micro-organism or cell culture.
Development of pilot scale to optimize the yield and quality.
Large scale fermentation or cell culture process.
Purification of macromolecular compounds.
Animal testing, clinical testing, regulatory approval and marketing. 4
7. It facilitates production of selective DNA
fragments from larger and complex DNA
molecule, in larger quantities
DNA from two or more sources is
incorporated into a single recombinant
molecule
7
9. Critical steps in application of rDNA technology for
production of desired protein….
1. Identification of protein that is to be produced.
2. DNA sequence coding for the desired protein is done.
3. Fully characterized gene is isolated using restriction enzymes
4. This gene is inserted into a suitable vector like plasmid
(circular extrachromosomal segment of DNA found in certain
bacteria) with DNA ligase.
5. The plasmid is then inserted into the host cell (eukaryotic of
prokaryotic cells) (transformation process)
6. Clones of the transformed host cells are isolated and those
producing protein of interest in desired quantity are preserved
under suitable conditions as a cell bank.
7. As the manufacturing need arise, the cloned cells can be scaled
up in a fermentation or cell culture process to produce the
protein product.
9
12. Prokaryotic (Bacterial) production
Advantages
Biology of bacteria is well understood.
Safe and effective use of E. coli as a host
organism is well documented.
The expression of new protein is easier to
accomplish than in other more theoretically
suitable system.
12
13. Prokaryotic (Bacterial) production
Disadvantages
It produces proteins in a chemically reduced form.
E. coli protein begin their sequence with N-formyle
methionine residue and thus yields methionine
derivative of desired natural protein.
Potential for product degradation because of trace
protease impurity.
Requires endotoxin removal during purification.
Expressed protein product may cause cellular
toxicity or it is extremely difficult to purify as it is
sequestered into bacterial inclusion body as large
aggregates.
13
14. Prokaryotic (Bacterial) production
Recent advancement
Exploration of E. coli molecular biology have lead
to the ability to express protein in periplasmic
space, allowing the removal of unwanted
terminal N-methionine group leading to more
rapidly purified proteins.
14
15. Eucaryotic (mammalian cell and yeast) production
The use of yeast strain Sachharomyces cerevisiae
for production has been explored.
15
16. Eucaryotic Production
Advantages
Can produce large proteins or glycoproteins
Secrete proteins that are properly folded and
identical in their primary, secondary and tertiary
structure to natural human protein
16
18. Eucaryotic Production
Recent advancement
Large scale culture using Chinese Hamster Ovary
(CHO) cells and formulation of highly defined growth
media have improve the economic feasibility of
eukaryotic cell substrate
18
19. Application
Techniques used in research for
developing and generating new drugs
Study and develop treatments for some
genetic diseases.
To produce molecules naturally present
in human body in large quantities
previously difficult to obtain from
human sources. (hormones like insulin
and growth hormone)
Continued…
19
20. Application
DNA probe technology for diagnosis of
disease. In this process…
Specific strand of DNA is synthesized with
sequence of nucleotide matches with the gene
under investigation.
Now tag the synthetic gene with dye or
radioactive isotop.
When introduced into a specimen, the
synthetic strand of DNA acts as a probe
searching for complementary strand.
When one is found, two are hybridized and
dye/radio isotop reveals the location of
synthetic strand. 20
21. Category Generic Name of Drugs
Anti coagulants Lepirudin
Systemic Antihemophilic factors
Clotting Factors
Recombinant factor VIII
Granulocyte CSF
Colony Stimulating
G-CSF + Monomethoxy PEG
Factors
Granulocyte Macrophase CSF
Epoetin Alfa
Erythropoietins Darbepoetin Alfa
Drotrecogin Alfa
Growth Factor Becaplermin
Human Growth 21
System Growth Hormon
Factor (hGH)
22. Category Generic Name of Drugs
Interferon beta 1-b
Interferon
Interferon beta 1-a
Aldesleukin
Interleukins Anakinra
Oprelvekin
Recombinant Alteplase
Tissue Plasminogen
Recombinant Reteplase
Activator
Recombinant Tenecteplase
Tyrosine Kinase
Imatinib Mesylated
Inhibitor
Hepatitis B vaccine Recombinant 22
Vaccine
Hemophilus B Conjugate Vaccine
23. Antibodies are proteins produced by differentiated B
lymphocytes.
Antibodies produced in immunized animals are formed
from different clones of B lymphocytes (polyclonal).
Polyclonal means they all are not specific to only that
antigen, and specific are less in number.
Antibodies that are produced by immortalized cell lines
(hybridoma) derived from single B cells are monoclonal
antibodies. MAb – Monoclonal Antibody are Specific to
only one Antigen.
23
24. Lower part of
Variable
antibody is called a Region
constant region,
identical in all
immunoglobulin of
specific class (e.g.,
IgG, IgM)
The variable domain
is highly hetrogenous
and gives antibody its
binding specificity
and affinity. Constant
Region
24
25. F(ab’)2 Fab’ sFv
Smaller fragments containing intact variable region like F(ab’)2, Fab’ and
sFv have following advantages:
• Do not contain the lower binding domain (constant region). Smaller
molecule leads to less immunogenic effect and have a greater
penetration capacity than larger molecule.
• In case of diagnostic imaging application, smaller fragments have
greater renal, biliary or colonic uptake.
• All three smaller antibody forms have had success in detecting smaller
(<2cm) lesions not seen on Computed tomography. 25
27. Mouse Origin
Chemical induced fusion of mouse sleen cell with
mouse myeloma cell.
The resultant mouse-mouse hybridoma cell
inherits the replication ability from myeloma cell
and ability to produce the desired monoclonal
antibody from spleen cell.
Limitation: production of human Antimouse
antibody responses against the MAbs – allergic
reaction.
27
28. Human Origin
Human B lymphocytes can be clonally selected for
hepten binding specificity of their product antibodies.
These selected cell are then immortalized by infection
with virus.
28
29. Cell banks of hybridoma cell (fused or transformed cell)
lines can be used to produce a continuous supply of
monoclonal antibody by two ways:
In-vivo : by injection into mice and subsequent collection
of the ascetic fluid.
In-vitro : by conventional cell culture techniques.
Antibody is produced as directed by the chromosomal
information in cell and is secreted into the medium from
which it can be easily purified.
29
30. Application
Diagnostic as well as therapeutic.
MAb can be coupled with other agents e.g., oncolytic
agent, radio nuclide, toxins, etc. with the resultant
antibody conjugate being final product of interest
30
31. Recent innovation
Development of transfectomas, E. coli and
bactriophage based production scheme which
may offer advantages for future production of
monoclonal antibodies.
Super Antigen + MAb technology:
(staphylococcal enterotoxin A) – toxin is attached
to MAb. Thus, Super Antigen binds to
macrophages and activates them. e.g., if super
antigen is linked to antibody having specificity for
tumor associated antigen, it targets activated
macrophages to the tumor cell. This is very Novel
approach, and it is under Phase I trials.
31
32. FDA approved MAb products
Name Indication
Adalimumab Rheumatoid arthritis
Basiliximab IL-2 Antagonist –
Immunosuppresive
Daclizumab IL-2 Antagonist –
Immunosuppresive
Gemtuzumab Ozogamicin Acute Myeloid Leukemia
Ibritumomab Tiuxetan Radiolabeled for cancer
Infliximab Crohn’s disease
Murononab CD3 Block T-cell activity –
Immunosuppresive 32
33. Recent advances in biotechnology have
resulted in two new categories of product:
Cell therapy product and gene therapy
product.
Cell therapy products contain living
mammalian cells as one of their active
ingredient while gene therapy products
contain piece of nucleic acid, usually DNA
as their active ingredients.
Some of the products combine both
categories, resulting in therapy that uses
cells that express new gene product.
33
34. These are the products with live cells
that replace, augment or modify the
function of patient’s cells that are
diseased or dysfunctional or missing.
e.g., transplantation of bone marrow
to replace marrow that has been
destroyed by chemotherapy and
radiation is an example of cell- therapy
product.
These therapy products are referred to
as somatic cell therapy products as
non germ cells are used in the product.
34
35. Sources of donor for cell therapy products
1. The patient’s own cell (autologous cell product)
2. The cells from another human being
( allogeneic cell product)
3. Cells derived from animals such as pigs,
primates or cows (xenogenic cell products)
35
36. Autologous cells are not rejected by patient but they are not
available for many treatments as they are missing, dysfunctional
or diseased.
In such situations, allogenic or xenogenic cells are used.
The advantage of allogenic cells is that, they do not trigger a
rejection reaction as strong as xenogenic cells.
Xenogenic cells are used when human cells with desired
characteristics are not available or supply of human donor is too
limited.
Cell therapy products are sometimes encapsulated in a device
that prevents patients cells and antibodies from killing
xenogenic cells.
However, use of xenogenic cells in humans have potential to
cause zoonoses
Continued…
36
37. Much research is focused on identifying and
propagating stem cells regardless of the source as
stem cells can be manipulated to differentiate either
during manufacturing or after administration.
37
38. Manufacturing challenges
They cannot be terminally sterilized or filtered. So
removal or inactivation of micro-organisms or virus
without killing the cells in a problem.
Every raw material in manufacturing have potential
of remaining associated with the cells. So
quantification of these raw materials is critical to
produce a safe and effective product.
Storage of these products is a challenge as freezing
is the main mode for long term storage while some
of the cell therapy products cannot be frozen
without changing the basic characteristics. So,
these products have to be administered within
hours or days at most after manufacturing process.
Some products consist of a batch size as small as
one dose. 38
39. Indication Product
Bone marrow Devices and reagents to propagate stem and progenitor
transplantation cells or remove diseased cell
Cancer T cells or macrophages exposed to cancer specific
peptides to elicit immune response
Pain Cells secreting endorphins or chatecholamines
Diabetes Encapsulated β-islet cells secreting insulin in response to
glucose level
Tissue repair Autologus or allogenic chondrocytes in a biocompatible
matrix
Neurodegenerative Allogenic or xenogenic neuronal cells
diseases
Liver assist Allogenic or xenogenic hepatocytes
Infectious disease Activated T cell 39
40. These are the products in which nucleic
acids are used to modify the genetic material
of cells.
E.g., a retroviral vector used to deliver gene
for factor IX to cells of patients with
hemophilia B
40
41. These products can be classified broadly
on the bases of their delivery system.
1. Viral vector: viruses with genes of interest but
usually without the mechanism of self
replication in vivo.
2. Nucleic acid in a simple formulation (nacked
DNA)
3. Nucleic acids formulated with agents (such as
liposomes to enhance penetration)
4. Antisense oligonucleotide (complementory to
naturally occurring RNA and block its
expression.
Most of the clinical work is done using viral
vector. The most common viruses used till
date include murine retrovirus, human adeno 41
virus and human adeno associated virus
42. Manufacturing challenges
Analytical methodology for viruses are still
being developed.
Manufacturing of large batches of viral
vectors with no or minimal amount of
replication component viruses (RCV) is
challenging.
Detecting of small number of RCV particles
in the presence of large amount of
replication-defective vector is difficult.
Sourcing of raw material is difficult.
Defining purity is an issue for enveloped viral
vector such as retro viruses or herpes viruses 42
as they incorporate cellular proteins in their
43. Safety concerns related to therapy
Integration of gene therapy products into somatic cell
DNA carries a theoretical risk of mutation which could
lead to modified gene expression and deregulation of cell.
Patients need to be monitored in case of viral gene therapy
for presence of RCV.
To address risk associated with specific products,
preclinical studies, QC and patient monitoring strategies
need to be developed in accordance with applicable
regulations and guidance documents.
43
44. Categories Indication Product
Gene replacement CVS disease Growth factor vector
Sort term Cystic fibrosis Transmembrane conductance
Long term regulatory vector
Immuno therapy Cancer Autologous tumor cells
Arthritis Autologous lymphocytes
Conditionally lethal genes Cancer solid tumor Thymidine kinase (TK) or
Cytocine Deaminase (CD)
vector
Antisense Cancer Anti- oncogene vector
Cytomegalovirys Antiviral vector
retinitis
Ribozymes HIV Antiviral ribozyme vector into
autologous lymphocytes 44
47. Endotoxins
Host cell Protein
From Media
DNA
Protein mutants
Formyl Methionine
Oxidised Methionine
Protelytic Clevage residues
Aggregated Protein
MAb
Amino Acids
Bacteria, yeast, fungi, virus
47
48. In 1976, RAC Guidelines - Recombinant DNA
Advisory Committee by the US National Institute of
Health (NIH).
To ensure compliance with RAC Guidelines,
Institutional Biosafety Committees (IBCs) were set.
48
49. USA
Food and Drug Administration (FDA) – CBER
National Center for Toxicological Research - NCTR
United States Department of Agriculture (USDA)
Environmental Protection Agency (EPA)
WHO
Specific Guideline on Biological’s Manufacturing.
Expert Committee on Biological Standardization (ECBS) – directly
under Executive Board.
49
50. European Union - EMEA
Biological Working Party (BWP)
Biosimilar Medicinal products Working Party (BMWP)
Vaccine Expert Group (VEG)
UK – MHRA
Biological Sub-Committee under Advisory Body
Australia – TGA
ANNEX 2 : Manufacturing of Biological Medical Products for
Human Use
50
51. Ansel’s Pharmaceutical Dosage Form and
Drug Delivery Systems, L. V. Allen, N. C.
Popovich, H. C. Ansel; Lippincott Williams
& Wilkins publication, 8th edition, 600-650.
United State Pharmacopoeia – 26, NF-21,
2003, page no. 2247 – 2318.
Biotechnology : The Biological Principle, M.
D. Trevan, S. Boffey, K. H. Goulding, P.
Stanbury, Tata McGraw Hill publication,
2nd edition, 1990.
Comprehensive Biotechnology – The
Principles, Application and Regulation of
Biotechnology in Industry, Agriculture and
Medicine; Murray Moo-young, Pergamon 51
52. www.forfas.ie/icsti - ICSTI = Irish Council for
Science, Technology and Innovation
www.ualberta.ca/~csps – F.M.Steinberg, J.Raso;
Journal of Pharmacy and Pharmaceutical
Science; Volume 1 (2):48-59, 1998
www.expresspharmapulse.com Issue dated 28th
April 2005, by Dr. Krishan Maggon.
www.pharmacytimes.com Issue on uptake of
Biotech, by Stainly Schenidlin
52