An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended.
In biosimilar development, analytical studies are undertaken to support the structural and functional similarity of the proposed product to the reference product and to evaluate the impact of any differences identified.
A method of tracking where compounds of interest travel in an experimental animal or human subject.
Biologics include a wide range of biologic products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and genetically engineered therapeutic proteins. In this guide, “biologics” refers to genetically engineered proteins produced by living cells.
Biosimilars are highly similar to the original biologics. Although it is impossible to produce an identical copy of any biologic medicine, a biosimilar must be proven to show no clinically meaningful differences in terms of safety and efficacy from an originator medicine.
A research study using human subjects to evaluate biomedical or health-related outcomes.
The process of making, growing, or building drugs and proteins to be used to treat conditions and diseases in humans and animals.
A scientific and regulatory principle that refers to the approval of a biosimilar for use in an indication held by the reference product but not directly studied in a comparative clinical trial with a biosimilar. Extrapolation of efficacy and safety data from one indication to another may be considered if biosimilarity to the reference product has been shown by a comprehensive comparability program including safety, efficacy, and immunogenicity, and there is sufficient scientific justification for extrapolation. Extrapolation is not automatic and is considered only after biosimilarity is established based on the totality of evidence.
A generic drug is the same as a brand-name drug in dosage, safety, strength, route of administration, quality, performance, and intended use. Before approving a generic drug product, the FDA requires many rigorous tests and procedures to ensure that the generic drug can be substituted for the brand-name drug. The FDA bases evaluations of substitutability, or “therapeutic equivalence,” of generic drugs on scientific evaluations. By law, 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.
A substance made by the body that functions to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy.
The ability of a substance to trigger an immune response or reaction (eg, development of specific antibodies, T-cell response, or allergic or anaphylactic reaction).
Interchangeability is defined by statute in the United States to mean that the product may be substituted for the reference product without the intervention of the physician who prescribed the reference product. The legal standard for interchangeability is an additional standard beyond demonstration of biosimilarity.
A type of protein made in the laboratory that can bind to substances in the body. There are many kinds of monoclonal antibodies. A monoclonal antibody is typically made so that it binds to only 1 substance.
Safety assessments for marketing approval of a pharmaceutical that usually include pharmacology studies, general toxicity studies, toxicokinetic and nonclinical pharmacokinetic studies, reproduction toxicity studies, genotoxicity studies, and, for drugs that have special cause for concern or are intended for a long duration of use, an assessment of carcinogenic potential.
The study of the biochemical, physiologic, and molecular effects of drugs on the body.
Studies that examine the relationship between dose, plasma concentrations, and therapeutic or toxic effects. Pharmacokinetic factors include absorption, distribution, metabolism, and elimination.
Science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem.
The practice of monitoring the safety of a marketed drug or biologic product.
Reference product means the single biologic product licensed under section 351(a) of the Public Health Service Act against which a biologic product is evaluated in a 351(k) application.
Small-molecule drugs are usually chemically synthesized with a fixed, known structure having a molecular weight of less than 1000 daltons, and typically between 300 and 700 daltons. For reference, aspirin is 180 daltons, and paclitaxel is 854 daltons.
A practice by which an “interchangeable” biologic is dispensed by a pharmacist to the patient without the prior informed consent of the treating physician or patient.
Considerations of both the quantity and quality of the evidence to support safety and effectiveness for drugs and biological products.
