PDA Technical Glossary

Synonym: Drug Substance. (TR14) (TR42) A substance or mixture of substances that, when delivered in a finished drug product, directly affects the structure or function of the body. (TR54-4) Any substance or mixture of substance intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body. Note: also known as Drug Substance. (TR29) (TR56) (TR41) (TR54-3) (TR60) Any substance or mixture of substances intended to be used in the compounding of a drug preparation, thereby becoming the active ingredient in that preparation and furnishing pharmacological activity o other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans and animals or affecting the structure and function of the body. (TR63) (TR70) Any substance or mixture of substances intended to be used in the manufacture of a drug product, and that when used in the production of a drug, becomes an active ingredient in the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure and function of the body. (TR74)

Manufactured biological active substances and medicinal products involving biological process­es and materials, such as cultivation of cells or extraction from living organisms. (TR56)

An application, filed with the US Food and Drug Administration (FDA), which contains specific information on the manufacturing processes, chemistry, pharmacology, clinical pharmacology and the medical effects of the biologic product (similar function as the Marketing Authorization Application in Europe). (TR56)

The body of information that defines the technical development, manufacturing facility and support utilities; the process equipment and materials used in manufacturing; the manufacturing process itself; the personnel involved in manufacturing and qual­ity; the chemistry of the product; QC in process and release testing, specifications, and stability of the product; all of the controls, documentation, and training necessary to ensure that all of these listed ac­tivities are properly and effectively carried out. (TR56)

Generally used to indicate Phase 1 and A clinical studies.(TR 56)

Formal or informal study performed to assess initial method performance prior to full ICH Q2 (R1) validation; assessment activity that cul­minates in a scientifically sound method that has an acceptable level of performance and is docu­mented to be suitable for its intended use. (TR56) Experimental studies performed to confirm the inherent performance capabilities of a test method for the material being analyzed and the intended use of the method. Method qualification can be performed during early development phases, prior to method validation. Specific method qualification characteristics (e.g., accuracy, specificity) should be confirmed based on the intended use of the analytical method and the relevant risk(s). (TR57)

A formal, archived demonstration of the analyti­cal capacity of an assay that provides justification for use of the assay for an intended purpose. (TR56) A formal, archived demonstration of the analytical capacity of an assay that provides justification for use of the assay for an intended purpose. Validations are conducted prospectively according to a written, approved plan that states acceptance criteria. (TR57) (TR57-2)

Studies designed to speed up the development of promising drugs by establishing early on whether the drug or agent behaves in human subjects as was expected from preclinical studies. May in­clude the administration of single subtherapeutic doses of the study drug to a small number of sub­jects (10 to 15) to gather preliminary data on the agent’s pharmacokinetics and pharmacodynam­ics. A Microdosing study gives no data on safety or efficacy, being by definition a dose too low to cause any therapeutic effect. (TR56)

An application filed with the FDA used for the regulation and control of new drugs in the Unit­ed States; the goal is to provide enough infor­mation to permit the FDA reviewer to reach the following key decisions: whether the drug is safe and effective in its proposed use(s), and wheth­er the benefits of the drug outweigh the risks; whether the drugs proposed labeling (package insert) is appropriate, and what it should con­tain; whether the methods used in manufactur­ing the drug, and the controls used to maintain the drug’s quality are adequate to preserve the drug’s identity, strength, quality, and purity. (TR56)

A statement of origin for a drug, active ingredi­ent, or other critical starting material that identi­fies the original source of the material and each sale, purchase, or trade prior to receipt by the user, including the dates, names, and addresses of all parties involved in such transactions. Note: Also called a “batch tree.” (TR56)

How the drug works in the body, the biochemical and physiological effects of drug and its mecha­nisms of their actions. (TR56)

Phase 1 trials are the first stage of testing in hu­man subjects. Often, a small (20-100) group of healthy volunteers will be selected. For life-threat­ening indications such as oncology, these can be patients that have the target disease but may not yet be the ideal target population. This Phase in­cludes trials designed to assess the safety (phar­macovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. These trials are often conducted in an inpatient clinic, where the subject can be observed by full-time staff. (TR56)

Once the initial safety of the study drug has been con­firmed in Phase 1 trials, Phase 2 trials are performed on larger groups (20-300) and are designed to assess efficacy, as well as to continue safety assessments in a larger group of volunteers and patients. Phase 2a is specifically designed to assess dosing requirements (how much drug should be given). Phase 2b trials are specifically designed to study efficacy (how well the drug works at the prescribed dose(s). (TR56)