Biologics Flashcards
What are biologics, and how are they produced?
Biologics, also known as biopharmaceuticals, are medicinal products derived from living organisms. They are produced by transfecting a human gene into a cell line that generates the biologic protein. The first generation of biologics are replicas of human hormones, while the second generation involves engineered proteins where the genes are altered to modify the structure of the biologic protein.
How do monoclonal antibodies function in the immune system?
Monoclonal antibodies are large proteins that bind to a pathogen’s antigen. They flag the pathogen for destruction by immune cells or directly inhibit the pathogen’s protein. Unlike the original antibody therapies, which were derived from animal or human blood, monoclonal antibodies are genetically produced and can be chimeric, humanized, or fully human molecules.
What is the difference between fusion proteins and monoclonal antibodies?
Fusion proteins are created by linking two or more genes to produce a combined protein. Some monoclonal antibodies are a type of fusion protein, using part of an antibody and another protein. These fusion proteins can target specific cells or proteins, like in cancer treatments.
Why do biologics have a different absorption process compared to small molecule drugs?
Biologics are significantly larger than conventional small molecule drugs, with monoclonal antibodies averaging 150 kDa compared to the 1 kDa of small molecule drugs. Because of their large molecular size, biologics cannot be absorbed through the capillaries and instead are absorbed via the lymphatic system. As a result, biologics are administered via intravenous, subcutaneous, or intramuscular routes.
What is the primary route of distribution for monoclonal antibodies?
Monoclonal antibodies have a small volume of distribution, typically between 2 to 4 L. This limited distribution is due to their size, charge (they are polar), and tight target binding.
How are biologics eliminated from the body?
Unlike small molecule drugs, which are eliminated primarily through hepatic metabolism or excretion in urine or bile, biologics are cleared via processes such as endocytosis, proteolysis, Fc receptor-mediated clearance, and target-mediated clearance. These processes are influenced by the formation of immune complexes.
What role do anti-drug antibodies (ADAs) play in the effectiveness of biologics?
Anti-drug antibodies (ADAs) can be induced by biologics, leading to the formation of immune complexes. These complexes may be cleared more quickly from the body, which can reduce the efficacy of the biologic over time, potentially leading to a decrease in treatment effectiveness.
What does the nomenclature of monoclonal antibodies indicate?
The nomenclature of monoclonal antibodies typically ends with “-mab.” The third segment of the name indicates the source of the antibody (e.g., -o- for mouse, -u- for human, -xi- for chimeric, -z- for humanized). The second segment indicates the target of the antibody (e.g., -b(ac)- for bacteria, -l(im)- for immune system, -t(u)- for tumors).
How do biologics differ from small molecule drugs in terms of production?
Biologics are produced using biological processes, whereas small molecule drugs are chemically synthesized, making the latter more homogeneous. Biologics have a complex physicochemical structure and are typically more immunogenic, whereas small molecule drugs are simpler and less likely to provoke an immune response.
What is the significance of the drug Adalimumab, and what does its name signify?
Adalimumab is a human monoclonal antibody that targets TNF-alpha, a protein involved in the pathogenesis of autoimmune inflammatory arthritis, such as rheumatoid arthritis. Its name follows the typical monoclonal antibody nomenclature, where “mab” indicates it’s a monoclonal antibody, and the “u” signifies it is human in origin. It is administered subcutaneously and has a half-life of 2 weeks.
What are some key differences between biologics and small molecule drugs?
Biologics are larger, with a complex structure, while small molecule drugs are smaller and simpler.
Biologics are produced biologically, while small molecules are chemically synthesized.
Biologics have a complex pharmacokinetic (PK) profile, while small molecule drugs tend to have a more predictable PK.
Biologics have limited distribution, while small molecule drugs’ distribution varies greatly.
Biologics are inherently immunogenic, potentially causing immune responses, whereas small molecule drugs are generally not immunogenic.
Biologics are highly selective for their targets, while small molecule drugs tend to be less selective.
What are the two main generations of biologics, and how do they differ?
The two main generations of biologics are:
First generation: These are replicas of human hormones produced by transfecting a human gene into a cell line to produce the biologic protein.
Second generation: These biologics are engineered proteins where the genes are altered to change the structure of the biologic protein.
How does the size of biologics affect their absorption and distribution in the body?
The large size of biologics prevents them from being absorbed through capillaries and requires absorption via the lymphatic system. Their size also contributes to a small volume of distribution, typically between 2 to 4 L for monoclonal antibodies, due to tight target binding and their polar nature.
Why are drug interactions rare with biologics compared to small molecule drugs?
Drug interactions are rare with biologics because of their large size, complex structure, and highly selective target binding. This contrasts with small molecule drugs, which are more chemically reactive and may interact with a wider range of other drugs.
What is the typical route of administration for biologics, and why?
Biologics are typically administered intravenously, subcutaneously, or intramuscularly due to their large molecular size. This prevents them from being absorbed through the digestive system, making alternative routes like the lymphatic system the most effective for their absorption.
What does the segment “-cept” in biologic nomenclature indicate?
The segment “-cept” in the nomenclature of biologics indicates that the molecule is a receptor molecule. These molecules typically mimic natural receptors and can interfere with disease processes by blocking specific proteins or signals.
How do monoclonal antibodies differ in terms of structure compared to traditional antibodies?
Traditional antibodies are typically polyclonal, meaning they consist of a mix of antibodies from various immune cells that target different parts of an antigen. Monoclonal antibodies, on the other hand, are genetically engineered to be identical, targeting a specific epitope or antigen, which allows for more precise treatment.
What does the suffix “-nib” indicate in the nomenclature of biologic drugs?
The suffix “-nib” indicates that the biologic is a small molecule inhibitor, often targeting specific enzymes or pathways involved in disease processes. These drugs are commonly used in cancer treatment and work by blocking key proteins that promote tumor growth.
