...Clarkson Pharmaceuticals Upstream Process Design for a Monoclonal Antibody Production Facility 1 1 Marie Rogers 2 2 Executive Summary This report will discuss the design and material requirements for the upstream process of a large scale monoclonal antibody production plant. • • • Medium preparation Seed train Production reactor 3 3 4 4 Table of Contents Executive Summary Background Medium Preparation Cell Growth Seed Train 20 L WaveTM Perfusion Bioreactor 200 L Xcellerex Disposable Stirred Tank Reactor TM 3 6 9 13 16 17 19 21 22 2,000 L Xcellerex Disposable Stirred Tank Reactor TM 12,000 L Fermenter Medium Storage Material Transportation pumps References Appendix A: Project Guidelines 26 27 28 31 Appendix B:Calculations Exponential Cell Growth Production of MAb per Batch Carbon Balance for Glucose Consumption _ Carbon from MAb Produced Carbon from Lactic Acid Produced Carbon from Carbon Dioxide Produced 33 33 33 34 34 35 35 Total Glucose Consumption 36 Number of Reactor Lines Appendix C: MATLAB Code 36 37 5 5 Background Biopharmaceutical companies producing monoclonal antibodies perpetually investigate novel approaches for manufacturing their products. Process development investigates innovative methods to attain the goals of optimizing efficacy and preserving the product’s desirable qualities. Optimizing parameters in manufacturing has the potential to...
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...because A, B antigens are strongly immunogenic and upon stimulation elicit a strong antibody response and their alloantibody can cause destruction of transfused red cells (Enosolease & Bazuaye, 2008). The ABO blood group system is considered to be safe and cost effective in most transfusion except in case of multiple transfusions where extensive cross matching is required even for minor antigen to prevent alloimmunization (Hassan et al., 2004). ABO antigen is the integral part of cell membrane and has different biochemical composition despite similar basic antigen (Dean, 2005). B phenotype is most common...
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...IgG and how might such an understanding influence the choice of IgG subclass in potential antibody-based therapies? Our body is under constant attack whether from external with viruses, bacteria and parasites or from the internal; with the development of tumour cells in cancer. We have a number of ways to prevent organisms from entering our body and surviving. This includes our skin, mucous membranes and the low pH of our stomach acids. However, if an organisms pass this barriers, the body have specific self defence mechanisms to act on these invasions. Humans have an intricate network of highly specialised cells known collectively as leukocytes or more commonly as white blood cells. Each cells is highly specialised and plays a critical role in the human response. One example is the HIV virus which infects and kills one particular type of immune cell which cause devastating consequences to the entire immune system. When the human body immune system invasion can lead to severe harm, the importance of understanding the structure and functions of this system may be seen as a vital role in combating the effect of these foreign substances. This essay will give some insight into the human IgG class structures and functions which is highly important in human defence system studies and show how these understanding can help in the development of potential antibody-based therapies. Antibodies is a group of protein which is involved in the immune response against foreign substance such...
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...TCGF is required for growth and development of T cells followed by antigen encounters and to maintain them in long-term cultures. The expression of the human immune system reaction involves both the in take of TCGF synthesis and the development of particular TCGF membrane receptors (Leonard 1982). Monoclonal antibodies attached to TCGF have been assemble within the immune system. In contrast, antibodies particular for the TCGF membrane receptor have not been known, nor has the receptor been distinguished (Leonard 1982). A monoclonal antibody named anti-Tac, appears to attach to the human membrane receptor for TCGF (Leonard 1982). As a matter of fact, anti-Tac suppressors demonstrate that TCGF prompt growth of T cells and prevent attachment of TCGF to cells from a copied human T-cell lines (Leonard 1982). Also, TCGF receptor have been refined and...
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...Indirect ELISA The term "indirect ELISA" refers to an ELISA in which the antigen is bound by the primary antibody, which then is detected by an enzyme labeled secondary antibody. The Secondary antibodies were raised against the primary antibody in other species of animal by immunization. The indirect ELISA has advantages over the direct ELISA. 1) The Indirect ELISA consist mainly two antigen – antibody reactions; the first reaction is between coated antigen and primary antibody and a second reaction between the primary antibody and the enzyme-labeled secondary antibody (with reference to secondary antibody the primary antibody is an antigen). Therefore, when the secondary antibody is enzyme tagged instead of primary antibody the amplified...
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...medicinal compounds derived from animals In modern medication, monoclonal antibody has been used to treat various kinds of disease. For cancer therapy, monoclonal antibody is extremely success. Monoclonal antibody, an immune protein with specific binding site and purified from mouse, can bind with target protein (Campbell NA, 1996). Such as: Specific antigen, growth factor and so on. As tumor cell always avoid immune system and even try to suppress the immune response, they always avoid immune defense. However, if monoclonal antibody is presented, they will bind with the target protein and immune system can recognize. Finally, immune response will be triggered. Tumor cell can be killed by B-cell or Phagocyte. Over a hundred years ago, target drug idea has been proposed. If a drug can be delivery to the target site precisely, the adverse effect of the drug can be minimized. “Delivery the drug to the target site” became a challenge the scientist. In the 1970s, B-cell has been discovered and played essential role (Biotech Resources, 1995-7). Anyways, as the technology, antibody cannot be cloned directly. For this reason, mouse antibody is used. In the beginning, some antigen was injected into the mouse and induced B-cell proliferation. Then, purified the antibody from the mouse. Compare with traditional drug, monoclonal antibody has a relatively low adverse effect. However, as murine monoclonal antibody is not a human protein. It only has a short half- life and causes an...
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...AS Biology Unit 1 Key Terms and Definitions Make sure you use these terms when answering exam questions! Chapter 1 – Causes of Disease Book Ref | Key Term | Definition | 1.1 | Pathogen | A micro-organism that causes disease | 1.1 | Transmission | Passing a pathogen from one individual to another | 1.2 | Correlation | A change in one variable is reflected by a change in another e.g. incidence of cancer increases as number of cigarettes increases | 1.2 | Cause | There is experimental evidence to prove that one factor causes another | 1.3 | Risk | A measure of the probability that damage to health will occur as a result of a given hazard | 1.3 | Lifestyle Factors | Factors to do with how we live that contribute to suffering a disease. These are in our power to change. | Chapter 2 – Enzymes and the Digestive System Book Ref | Key Term | Definition | 2.1 | Digestion | Physical and chemical breakdown of food | 2.1 | Hydrolysis | Splitting up of molecules by adding water to them. Enzymes do this to help break down molecules. | 2.1 | Assimilation | Incorporating broken down molecules into body tissues/using them in processes | 2.2 | Monomer | One of many small molecules that combine to form a larger one | 2.2 | Polymer | Larger molecule made up of repeating smaller molecules | 2.3 | Condensation Reaction | When 2 monosaccharides combine, water is removed | 2.3 | Glycosidic Bond | The bond in a disaccharide | 2.5 | Peptide Bond | The bond between 2...
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...The immune system is your body's defense. It is comprised of organs, cells and other substances that work together to help the body fight any outside or abnormal organisms. This could include germs that could lead to infection or the abnormal cells that make up a cancer. The immune system attacks and destroys the invaders that are not normally in the body. Immunotherapy is when the body uses certain parts of the immune system to fight cancer. This can be achieved in two ways; by making the immune system work harder and smarter, and/or by giving the patient synthetic immune system proteins. Immunotherapy can also be called biotherapy or biologic therapy. Immunotherapy can be used to specifically attack cancer cells or to help boost the body’s...
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...MART-1 DESCRIPTION: Protein MelanA (Melanoma Antigen), also known as MART-1 (Melanocytic Antigen Recognized by cytotoxic T lymphocytes) is a common biomarker used to identify malignant melanoma (MM) in patients, it falls under the MHC (major histocompatability complex) I class. MART-1 is encoded by the MLANA gene in humans and is present normally on the surface of benign nevi (beauty marks), as well as on melanocytes, the pigment-producing cells of your skin that become abnormal and grow out of control if malignant melanoma has developed. Approximately 76,000 new cases of melanoma are diagnosed annually in the Unites States, which accounts for about 2% of the total skin cancer diagnosis in United States annually; however 75% of skin cancer related deaths are the result of MM which exhibits how devastating this form of cancer is. With early detection of melanoma being correlated highly to improved prognosis of patients, it is necessary to create a point of care device that can measure the presence of MART-1 antigen in peripheral blood as a screening technique during annual examinations and upon identification of suspicious skin lesions Protein melan-A is a protein that in humans is encoded by the MLANA gene . A fragment of the protein, usually consisting of the nine amino acids 27 to 35, is bound byMHC class I complexes which present it to T cells of the immune system. These complexes can be found on the surface of melanoma cells. Decameric...
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...“Rhesus (RH) Incompatibility Disease” Sharon C. Clatterbuck Ottawa University In partial fulfillment of the requirements for the Proseminar Class Dr. Richard Kimberly. November 9, 2004 All the technology of our medical institutions and doctors do no good unless each female who becomes pregnant takes advantage of the prenatal care that is offered to them. According to the article titled “Routine ABO and RH Typing: An Introduction”, Phillip Levine and R.E. Stetson were the first scientists to discover the rhesus blood groups in 1939. Soon after their amazing discovery, Karl Landsteiner and A.S. Weiner discovered the ABO blood typing system in the late 1940’s, which ultimately lead to discovery of the Rh differences. Several medical studies and journals have concluded that the father is the basis of all fetal blood typing. The problem arises when the father’s blood type is positive and the mother’s blood type is negative, thus causes a condition called Rhesus (RH) Incompatibility or the RH Incompatibility Disease. (Mark-Maris) Women who receive proper treatment and testing during their first prenatal visit and subsequent visits can avoid most complications in their pregnancy, including the Rhesus Incompatibility. John M Bowman of the Canadian Medical Association states “the condition was first described as a medical problem in pregnancies in 1609, during the birth of a set of twins by a French midwife. The first twin had a severe case of Rh Incompatibility...
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...DESCRIPTION Herceptin (trastuzumab) is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2. Trastuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture containing the antibiotic gentamicin. Gentamicin is not detectable in the final product. Herceptin is a sterile, white to pale yellow, preservative-free lyophilized powder for intravenous administration. Each multi-use vial of Herceptin contains 440 mg trastuzumab, 400 mg α, α-trehalose dihydrate, 9.9 mg L-histidine HCl, 6.4 mg L-histidine, and 1.8 mg polysorbate 20, USP. Reconstitution with 20 mL of the appropriate diluent...
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...Outline and evaluate research into the relationship between the immune system and Stress-related illness. (12marks) It is suggested that stress can result in immunosuppression which can lead to stress-related illnesses such as Coronary Heart Disease and high blood pressure. Kiecolt and Glaser conducted an experiment to see the effects of stress on the immune system. This was achieved by taking blood samples of 75 medical students one month before and during their examination period. They then compared the two blood samples and found decreased leucocyte activity in the sample taken during high levels of stress (during their exams). This shows that stress reduces the activity of the immune system, making them more susceptible to becoming ill. Advantages of the study are that blood tests are objective measurements, so there was no social desirability or experimenter bias when analysing the results. The participants were also compared to themselves which removes participant variables on how they perceive stressors. The experiment was a field experiment so there was no manipulating of the independant variable to deliberately cause stress to the participants which makes it ethical. It also means the research has ecological validity and can be applied to the wider world. However, a field experiment may have extraneous variables which impact the results. For example, the student lifestyle of having little sleep and poor accomidation may have been an alternative source of stress. Another...
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...Physiological Changes: When understanding the relationship between stress and disease as they pertain to the body’s weakness and state the body is in, we must understand that the body is builds up a defense to keep out as much as it can of the bad diseases. The body uses its natural defenses to help keep out the bad infections. Stress can weaken the immune system which can bring on an increase of diseases such as arthritis, cancer, diabetes, and other serious diseases. Certain diseases attack the white blood cells which also make the immune system weak and hard for a person’s body to kick the disease or virus. Stress can cause not only emotional but physical damage as well. When a person’s body is under stress it can weaken the immune system and cause their body to become less capable to fighting off a disease. Organ Functions/Body Chemistry: Over time, stress can be seen as a weakening of the body. After a while the walls of our body start to break down and crumble, although there may be medication that will help slow down the process it never fully repairs the walls of the body. Stress can bring on a decrease in being able to fight of disease; increasing blood pressure, heart problems, anxiety, and the most common side effect are migraines. Certain diseases such as cancer, attack different parts of the body and its organ function. Most of the time it limits the ability of what the organ was supposed to be doing. This can cause stress on other organs and cause them to wear...
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...Hyperimmunoglobulin E syndrome (HIES) (also known as Job's syndrome or Buckley syndrome) Impact on the immune system: HIES leads to abnormal neutrophil chemotaxis (how it directs its movement depending on chemicals in its environment). Decreased production of interferon gamma (IFN-γ) by T lymphocytes is believed to be the cause of the disease. There are two types of inheritance for this disease: - autosomal dominant: The disease was linked to mutations in the STAT3 gene after cytokine profiles indicated alterations in the STAT3 pathway. - autosomal recessive: DOCK8 mutations. This type of HIES was only recently discovered, and is a small percentage of cases. Specific immune response: People with this disease have a higher-than-normal level of IgE. Despite this, patients are vulnerable to infection and disease because other important immune cells do not function properly. HIES patients are born with abnormal T cells that are unable to produce enough interferon gamma, which stimulates white blood cells called macrophages to engulf foreign invaders. Consequently, the immune system's response to antigens is delayed. Symptoms: Common symptoms of HIES include persistent skin abscesses and infections, recurrent pus in the sinuses, eczema, itchy skin, and painless skin abscesses (infections). These abscesses are why the disease was at first termed Job's syndrome, as these abscesses were similar to the ones Job suffered in the Bible. In addition to this, patients often suffer...
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...Ebola Kelly Minefield SCI/163 December 7, 2015 Bryn Van Patten Ebola The Ebola epidemic is the largest in history affecting multiple countries in West Africa. Two imported cases including one death and two locally acquired cases in healthcare workers have been reported in the United States. The risk of an Ebola outbreak affecting a large number of people in the U.S is very low. It is important to be educated about Ebola and other epidemics so that we can take every step to lessen the chances of an outbreak. Infectious Agents Ebola is an elongated filamentous virus, which can vary between 800 - 1000 nm in length, and can reach up to 14000 nm long ("Pathogen Safety Data Sheet - Infectious Substances", 2014).. The pleomorphic viral fragment may take on several distinct shapes, and are contained within a lipid membrane. Each virion contains a single-strand of non-segmented, negative-sense viral genomic RNA ("Pathogen Safety Data Sheet - Infectious Substances", 2014).. Ebola virions enter host cells through endocytosis and replication occurs in the cytoplasm. When infected, the virus affects the host blood coagulative and immune defence system and leads to severe immunosuppression ("Pathogen Safety Data Sheet - Infectious Substances", 2014).. Early signs that you are infected are flu-like. Transmission ...
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