A

  • adverse event
    An adverse event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment.
  • amino acid
    One of several molecules that join together to form proteins. There are 20 common amino acids found in proteins.
  • analytical testing
    Tests performed by chemist or biochemists to determine a medicine’s physical, chemical, and certain biological properties, typically those biological properties which can be measured using reagents or cloned cells.
  • antibody (pl: antibodies)
    Antibodies (also known as immunoglobulins, abbreviated to Ig) are proteins that are found in blood or other bodily fluids. Antibodies are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses.
  • antibody dependent cell-mediated cytotoxicity (ADCC)
    This is a biological process through which an antibody activates the body’s immune system to kill a cell with particular characteristics recognized by the antibody, often a cancer cell that overexpresses the antibody’s target.
  • assay
    The determination of the amount of a particular constituent of a mixture or of the biological or pharmacological potency of a drug.1
  • automatic substitution and substitution
    The practice by which a product other than the one specified on the prescription is dispensed to the patient, without the prior informed consent of the treating physician. A variation of substitution is practiced in some countries where, if the physician prescribes by international non-proprietary name (INN), the pharmacist may dispense any product with the same active ingredient.

    B

  • bioassay
    Bioassay or biological standardization is a type of scientific experiment. Bioassays are typically conducted to measure the effects of a substance on a living organism and are essential in the development of new drugs and in monitoring environmental pollutants. Both are procedures by which the potency (pharmacology) or the nature of a substance is estimated by studying its effects on living matter.2
  • biologic
    A product derived from a living organism (from animal products or other biological sources) that is used in the diagnosis, prevention or treatment of disease. Examples of biologic medicines include recombinant proteins, allergy shots, vaccines and hematopoietic growth factors.
  • Biologic License Application (BLA)
    An application submitted to the FDA seeking approval to market a biologic in the United States. The application contains a description of the trials and results, formulation, dosage, drug shelf life, manufacturing protocols, packaging information, etc. There are two different types of BLAs: full, stand-alone BLAs filed for approval of an originator biological product, and abbreviated BLAs filed for approval of a biosimilar product.
  • Biologic Qualifier (BQ)
    A BQ is intended to be an alphabetic code assigned at random to a biological active substance manufactured at a specified site as proposed by the WHO. The scheme will be applicable to all biological active substances to which INNs are assigned and is applicable retrospectively. It is intended to provide a unique identification code (Biological Qualifier), distinct from the INN, for all biological substances that are assigned INNs in accordance with information given in the Bioreview.  The BQ code will not be part of the INN, whose selection by the usual procedure will remain unchanged. Where use of a BQ is considered by an authority to be desirable, availability of a single global scheme will avoid proliferation of separate and distinct national qualifier systems. The scheme will be overseen by the WHO INN Expert Group and administered by the WHO INN Secretariat and the BQ proposal is currently under review. 3
  • biosimilar
    DEFINING BIOSIMILARS:

    The World Health Organization: A biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product.4

    The European Medicines Agency: A biological medicine that is developed to be similar to an existing biological medicine (the ‘reference medicine’). When approved, a biosimilar’s variability and any differences between it and its reference medicine will have been shown not to affect safety or effectiveness.5

    The U.S. Food and Drug Administration: A biological product that is highly similar to a
    U.S. licensed reference biological product notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity and potency of the product.6

  • biotechnology
    Technology based on biology, especially when used in agriculture, food science and medicine. The United Nations Convention on Biological Diversity defines biotechnology as “any technological application that uses biological systems, living organisms, or derivatives thereof, to make or modify products or processes for specific use.”

    C

  • The Center for Drug Evaluation and Research (CDER)
    As part of the US Food and Drug Administration (FDA), CDER regulates over-the-counter and prescription drugs, including biologic therapeutics and generic drugs.
  • chemical drug or chemical medicine
    Refers to medicines that are manufactured without the involvement of living organisms.7
  • chemical synthesis
    The production of a more complex chemical compound by combining two or simpler chemical entities or precursors.8
  • chemistry, manufacturing and control (CMC)
    The CMC stage of product development focuses on how a drug was created. It should be demonstrated that the manufacturing method is proper and valid on a technological level and that quality is ensured through consistent production in accordance with Good Manufacturing Procedure. Many aspects of both the active ingredients and the product as a whole will be reviewed, including characterization, control and stability.
  • chromatography
    A process in which a chemical mixture carried by a liquid or gas is separated into components as a result of differential distribution of the solutes as they flow around or over a stationary liquid or solid phase.9
  • clinical pharmacology
    The study of drugs in healthy volunteers and patients and defining the relationships between dose, drug exposure, and response in populations.  Drug dose refer to an amount of drug administered via a particular dose route (e.g., intravenous, oral, subcutaneous).  Drug exposure is a function of the concentration of drug in the body, and usually levels in the blood/plasma/serum serve as a surrogate, with respect to time.  Response is a measure of effect and can relate to both advantageous (efficacy) and untoward (toxic) reactions.10
  • clinical trial
    A test in which a drug or biologic is given to humans to establish how it works in the body and measure the nature and extent of any intended or unintended consequences.
  • clone
    A cell or group of cells, or organism that is genetically identical to an original cell.
  • Committee for Medicinal Products for Human Use (CHMP)
    The CHMP is the scientific committee responsible for formulating the opinion of the European Medicines Agency on any question concerning the evaluation of human medicinal products.
  • comparability exercise
    The head-to-head comparison of a biotherapeutic product with a licensed originator product, with the goal of establishing similarity in quality, safety, and efficacy. Products should be compared in the same study using the same procedures.
  • Critical Quality Attributes (CQA)
    Some attributes are important to the different ways the body can recognize proteins and are therefore critical to the safety, efficacy and pharmacokinetics of the drug.  Features important to these functions are known as “critical quality attributes.” These critical quality attributes include structures that are determined both by the DNA used and by the cell line and manufacturing process. An understanding of which attributes are important to each function for each product is important in order to obtain the best possible match between a biosimilar and the reference product.

    D

  • data exclusivity
    The period of time during which the clinical testing data that supported approval of the innovator medicine is protected, so that the prior approval of that originator based on those data may not be relied upon by another applicant to help approve a copy of that product.
  • DNA (Deoxyribonucleic Acid)
    DNA is a nucleic acid that contains the genetic information used in the development and functioning of all cellular organisms. Molecular systems interpret the sequence of these nucleic acids to produce proteins.

    E

  • efficacy
    The desired impact that a medicine or treatment has when administered to a human.
  • Epidermal Growth Factor Receptor (EGFR)
    A protein found on the surface of cells to which epidermal growth factor (EGF) binds. When EGF attaches to EGFR, it activates the enzyme tyrosine kinase, triggering reactions that cause the cells to grow and multiply. EGFR is found at abnormally high levels on the surface of many types of cancer cells, which may divide excessively in the presence of EGF.11
  • Erythropoiesis-Stimulating agent (ESA)
    Endogenous erythropoietin (EPO) is a glycoprotein hematopoietic growth factor that regulates hemoglobin levels in response to changes in the blood oxygen concentration. Erythropoiesis-stimulating agents (ESAs) are produced using recombinant DNA technologies and have pharmacologic properties similar to endogenous EPO. The primary clinical use of ESAs is to produce red blood cells in patients with chronic anemia.12
  • European Medicines Agency (EMA)
    The EMA is responsible for evaluating marketing applications for medicinal products to be approved in the European Union.
  • extrapolation
    For biosimilars, extrapolation is using analytical and clinical data in one disease indication to acquire regulatory approval for use in other disease indications for which the reference biologic has been approved previously.

    F

  • Federal Food, Drug and Cosmetic Act
    The federal law that regulates FDA’s licensing of drugs but not the majority of biologic medicines. Instead, most biologic medicines are licensed by FDA under the Public Health Service Act. Once licensed by FDA, however, most of the other provisions set forth in the Federal Food, Drug and Cosmetic Act concerning the marketing and other regulatory requirements are applicable to both drugs and biologic medicines.
  • fusion protein
    A protein made from a fusion gene, which is created by joining parts of two different genes. Fusion genes may occur naturally in the body by transfer of DNA between chromosomes.
  • U.S. Food and Drug Administration
    The federal agency responsible for evaluating marketing applications and/or otherwise regulating the U.S. marketing of medicinal products, medical devices, food and cosmetics to be approved in the United States.

    G

  • generic medicine
    A generic drug is the same as a brand name drug in dosage, safety, strength, how it is taken, quality, performance, and intended use. A generic drug product must contain the identical amounts of the same active ingredient(s) as the brand name product. Drug products evaluated as “therapeutically equivalent” can be expected to have equal effect and no difference when substituted for the brand name product.
  • genetic engineering
    The direct manipulation of an organism’s genes by introducing, eliminating or rearranging specific genes using the methods of modern molecular biology, particularly those techniques referred to as recombinant DNA techniques. These techniques entail producing a piece of DNA (the recombinant DNA or synthetic rDNA construct) and introducing it into an organism so that new or altered traits can be imparted to that organism.
  • glycan
    Also known as polysaccharides. Compounds consisting of a large number of monosaccharides linked glycosidically. This term is commonly used only for those containing more than ten monosaccharide residues.13
  • Granulocyte Colony Stimulating Factor (GCSF)
    A colony-stimulating factor produced by macrophages, endothelial cells, and fibroblasts that stimulates the production of neutrophils (a type of white blood cell). G-CSF is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents.14
  • guidance
    A document issued by a regulatory agency to provide interpretation of a law that the regulatory agency is responsible for administering and/or enforcing and recommendations as to how to proceed with particular issues.

    I

  • immune system
    The collection of mechanisms within the body that protect against disease by identifying and attacking foreign substances in the body.
  • immunogenicity
    The ability of a substance to trigger an immune response or reaction (e.g., development of specific antibodies, T-cell response, allergic or anaphylactic reaction).
  • inflammatory disorders
    Inflammation refers to a biological response to stimuli interpreted by the body to have a potentially harmful effect. While after injury or in certain conditions inflammation is a normal, healthy response, inflammatory disorders that result in the immune system attacking the body’s own cells or tissues may cause abnormal inflammation, which results in chronic pain, redness, swelling, stiffness, and damage to normal tissues.  Common inflammatory disorders include rheumatoid arthritis, lupus, ankylosing spondylitis, psoriasis etc.15
  • intended biosimilars
    See Non-comparable biologics
  • INN (International non-proprietary name)
    Allocated by the World Health Organization, an INN identifies pharmaceutical substances or active pharmaceutical ingredients. Each INN is a unique name that is globally recognized and is public property. A non-proprietary name is also known as a generic name.
  • innovator
    Describes a company that invested considerably in research and development to develop a new medicine through innovative technologies, such as biotechnology.
  • innovator product
    Original approved biologic medicine.
  • insulin
    A hormone that affects metabolism and causes the body’s cells to take up glucose (sugar) from the blood and store it as glycogen in the liver and muscles.
  • interchangeability
    An “interchangeable” biological product is biosimilar to the reference product, and can be expected to produce the same clinical result as the reference product in any given patient.  If administered more than once to an individual (as many biological products are), the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the reference product without such alternation or switch.16

    L

  • large molecule drugs
    Are therapeutic proteins – also known as biologic medicines. Essentially, these are copies or optimized versions of endogenous human proteins.

    M

  • mechanism of action
    The specific way by which a medicine achieves the desired outcome.
  • Medicines and Healthcare products Regulatory Agency (MHRA)
    UK government agency that is responsible for ensuring that medicines and medical devices work and are acceptably safe.
  • metastasis
    The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor.17
  • molecule
    The smallest physical unit of an element or compound, consisting of one or more like atoms in an element and two or more different atoms in a compound. A molecule is also a quantity of a substance, the weight of which, measured in any chosen unit, is numerically equal to the molecular weight; gram molecule.18
  • monoclonal antibody
    An antibody produced in the laboratory by a single clone of cells or a cell line and consisting of identical antibody molecules.

    N

  • non-comparable biologic
    A non-comparable biologic is intended to function like a known biologic medicine, but has not undergone strict quality product development and when analytically tested is found to have important differences compared to the intended reference product. Unlike biosimilars in highly regulated environments, non-comparable biologics are developed independent of the reference product, may or may not have comparative safety and efficacy data against the reference product and are approved by less established local regulatory pathways.

    O

  • oncology
    A branch of medicine that specializes in the diagnosis and treatment of cancer. It includes medical oncology (the use of chemotherapy, hormone therapy, and other drugs to treat cancer), radiation oncology (the use of radiation therapy to treat cancer), and surgical oncology (the use of surgery and other procedures to treat cancer).19
  • originator
    See above for innovator.
  • originator product
    See above for innovator product.

    P

  • pharmaceutical medicine
    Also referred to as medicine or medication – any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.
  • pharmacodynamics
    Studies performed to determine what a drug does to the body.
  • pharmacokinetics
    Studies performed to determine what the body does to a drug.
  • pharmacovigilance
    Procedures that monitor the safety of medicines to detect, assess, understand, and prevent adverse effects or any other safety-related issue.
  • post-translational modifications
    The enzymatic processing and differentiation of a polypeptide chain after translation from messenger RNA by, for example, methylation, acylation, phosphorylation, glycosylation, sulfation, disulfide bonding, and other processes.20
  • preclinical toxicology
    Studies of the toxicology of a substance on animals and cells to prepare parameters for Phase I human subject clinical studies. These include determination of acute, sub-acute, and chronic toxicity, carcinogenicity, mutagenicity, teratogenicity, and effects on the reproductive system.21
  • preclinical trials (or studies)
    Tests that take place in a scientifically-controlled setting using cell culture and/or animals as disease models.
  • proteins
    Compounds (chains of amino acids) constituting the ultimate expression product of a gene. Created through the synthesis performed by ribosomes, proteins are the workhorses of living systems, causing chemical processes and changing as their environment changes.

    Q

  • Quality by Design (QbD)
    A proactive approach to product design which further integrates quality control into the manufacturing process.  For QbD, a set of principles are utilized throughout the design process.  The product and process knowledge base muct include an understanding of variability in raw materials, the relationship between a process and product’s critical quality attributes (CQAs), and the association between CQAs and a product’s clinical properties.22

    R

  • recombinant
    In genetics, recombinant means DNA, proteins, cells, or organisms that are made by combining genetic material from two different sources. Recombinant substances are made in living cells and are being studied in the treatment of cancer and for many other uses.
  • reference product
    The innovator/originator product that the biosimilar product is intended to copy.
  • RNA
    Ribonucleic acid is a nucleic acid which is central to the synthesis of proteins.

    S

  • Similar biotherapeutic product (SBP)
    A biotherapeutic product which is similar in terms of quality, safety and efficacy to an already-licensed, reference biotherapeutic product.
  • small molecule drugs
    Chemical compounds that have a defined structure and characteristics.
  • switching
    The decision of a physician to change a patient from one drug to another drug with the same therapeutic intent, in order to optimize therapy and reduce adverse effects. Also see 'interchangeability.'

    T

  • therapeutic substitution
    Therapeutic substitution happens when a pharmacist dispenses drugs alternative to those that have been specifically prescribed. These alternative drugs may be either generic drugs (identical to the brand name drug) or drugs that are similar (similar to the reference brand name drug), albeit not identical. These drugs may also be chemically different with different pharmacokinetic properties but which are believed to be therapeutically similar.23
  • totality of evidence
    FDA’s approach to assess biosimilars for US regulatory approval.  It is a stepwise approach to evidence development, ensuring that development includes only those elements necessary to address residual uncertainty.  This approach introduces the concept that only after a thorough review of data from structural and functional analyses can FDA provide meaningful advice on scope and extent of necessary animal and human testing.  It also explains general expectations for human clinical trials -
    − At least one study will be expected (immunogenicity/PK-PD)
    − Comparative safety and effectiveness data may be necessary if residual uncertainty exists24
  • toxicology
    See Preclinical Toxicology

    V

  • vaccine
    A biological preparation which is used to establish or improve immunity to a particular disease.

    W

  • World Health Organization (WHO)
    An agency of the United Nations, established in 1948, concerned with improving the health of the world's people and preventing or controlling communicable diseases on a worldwide basis through various technical projects and programs.25