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Nonclinical Laboratory Studies |
FDA (58.2 (d)): Nonclinical laboratory studies are in vivo or in vitro experiments in which test articles are studied prospectively in test systems under laboratory conditions to determine their safety; are exclusive of studies which utilize human subjects or clinical field trials in animals; exclusive of exploratory studies for efficacy; and are exclusive of studies to determine physical or chemical characteristics of a test article.
EPA (792.3): Study means any experiment at one or more test sites, in which a test substance is studied in a test system under laboratory conditions or in the environment to determine or help predict its effects, metabolism, product performance (efficacy studies only as required by 40 CFR 158.640), environmental and chemical fate, persistence and residue, or other characteristics in humans, other living organisms, or media. The term “study” does not include basic exploratory studies carried out to determine whether a test substance or a test method has any potential utility.
OECD (Section I, 2.3.1.): Non-clinical health and environmental safety study, henceforth referred to simply as “study”, means an experiment or set of experiments in which a test item is examined under laboratory conditions or in the environment to obtain data on its properties and/or its safety, intended for submission to appropriate regulatory authorities. |
| PK Studies |
A study of how a medicine is handled by the body, usually involving measurement of blood concentrations of drug and its metabolite(s) (sometimes concentrations in urine or tissues) as a function of time. Pharmacokinetic (PK) studies are used to characterize absorption, distribution, metabolism and excretion of a drug, either in blood or in other pertinent locations. When combined with pharmacodynamic measures (a PK/PD study) it can characterize the relation of blood concentrations to the extent and timing of pharmacodynamic effects. |
| TK Studies |
Drug safety evaluations consisting of standard animal toxicology studies for the assessment of drug exposure: hazard screens or systemic toxicology. |
| CHMP |
The Committee for Medicinal Products is the EMEA’s committee responsible for elaborating the agency’s opinions on all issues regarding medicinal products for human use. |
| FDA |
FDA regulation (21 CFR Part 58) for studies regulated under the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act.
FDA regulations apply to nonclinical laboratory studies conducted for test articles studies in test systems under laboratory conditions to determine their safety. |
| OECD |
Organization for Economic Cooperation and Development (OECD) GLPs Section 8(8.1) regulation (ENV/MC/CHEM(98)17) the OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring, Number 1.
OECD regulations apply to non-clinical safety studies to obtain data on the properties and/or safety with respect to human health and/or the environment of the pharmaceutical products, pesticide products, cosmetic products, veterinary drugs, food and feed additives, industrial chemicals, environmental safety studies conducted in the laboratory, greenhouses or in the field. |
| EPA |
Environmental Protection Agency (EPA) GLPs 40CFR160, Subpart G, Section 160.120(2).
Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) and Part 792 Toxic Substances Control Act (TSCA). |
| MHRA |
Medicines and Healthcare products Regulatory Agency, UK (Statutory Instrument 1999/3106)
MHRA (UK GLPs) is an executive agency of the Department of Health in the UK that regulates medicines and medical devices as well as blood and therapeutic products/services derived from tissue engineering. |
| Test Article/Item/Substance |
FDA (58.3(b)): Test article means any food additive, color additive, drug, biological product, electronic product, medical device for human use, or any other article subject to regulation under the act or under sections 351 and 354- 360F of the Public Health Service Act.
EPA (792.3): Test substance means a substance or mixture administered or added to a test system in a study, which substance or mixture: 1) Is the subject of an application for a research or marketing permit supported by the study, or is the contemplated subject of such an application; or 2) Is an ingredient, impurity, degradation product, metabolite, or radioactive isotope of a substance described by paragraph (1) of this definition, or some other substance related to a substance described by that paragraph, which is used in the study to assist in characterizing the toxicity, metabolism, or other characteristics of a substance described by that paragraph.
OECD (Section I, 2.4.1.): Test item means an article that is the subject of a study.
UK GLPs: Test item means an article that is the subject of a regulatory study.
In this paper: we will refer to the ”analyte” (active pharmaceutical ingredient / drug substance / test article / control article / reference substance / test item). |
| Test System |
FDA (58.3, (i)): Test system means any animal, plant, microorganism, or subparts thereof to which the test or control article is administered or added for study. Test system also includes appropriate groups or components of the system not treated with the test or control articles.
EPA (792.3): Test system means any animal, plant, microorganism, chemical or physical matrix, including but not limited to soil or water, or subparts thereof, to which the test, control, or reference substance is administered or added for study. "Test system" also includes appropriate groups or components of the system not treated with the test, control, or reference substance.
OECD (Section I, 2.3.6.): Test system means any biological, chemical or physical system or a combination thereof used in a study.
UK GLPs: Test System means any biological, chemical or physical system or a combination thereof used in a regulatory study. |
| Carrier/Excipients/Vehicle |
OECD (2.4, 4.): Vehicle means any agent which serves as a carrier used to mix, disperse, or solubilize the test item or reference item to facilitate the administration/application to the test system.
UK GLPs: Vehicle means any agent which serves as a carrier used to mix, disperse, or solubilize the test or reference item to facilitate the administration or application to the test system.
EPA Parts 160 and 792: Carrier means any material, including but limited to, feed, water, soil, and nutrient media, with which the test substance is combined for administration to a test system.
EPA Parts 160 and 792: Vehicle means any agent which facilitates the mixture, dispersion, or solubilization of a test substance with a carrier. |
| Mixtures/Formulations |
FDA (58.113): For each test or control article that is mixed with a carrier, tests by appropriate analytical methods shall be conducted: To determine the uniformity of the mixture and to determine, periodically, the concentration of the test or control article in the mixture. To determine the stability of the test and control articles in the mixture as required by the conditions of the study either before study initiation, or concomitantly according to written standard operating procedures which provide for periodic analysis of the test and control articles in the mixture. Where any of the components of the test or control article carrier mixture has an expiration date, that date shall be clearly shown on the container. If more than one component has an expiration date, the earliest date shall be shown.
EPA (792.113) For each test, control, or reference substance that is mixed with a carrier, tests by appropriate analytical methods shall be conducted: To determine the uniformity of the mixture and to determine, periodically, the concentration of the test, control, or reference substance in the mixture. To determine the stability of the test, control or reference substance in the mixture before the experimental start date or concomitantly according to written standard operating procedures, which provide for periodic analysis of each batch. Solubility and Interference of vehicle with article is also required. Where any of the components of the test, control, or reference substance carrier mixture has an expiration date, that date shall be clearly shown on the container. I f more than one component has an expiration date; the earliest date shall be shown.
OECD (Section II): 6.2.5. If the test item is administered or applied in a vehicle, the homogeneity, concentration and stability of the test item in that vehicle should be determined. For test items used in field studies (e.g., tank mixes), these may be determined through separate laboratory experiments. |
| Reference Item / Control Substance |
FDA (58.3, (c)): Control Article means any food additive, color additive, drug, biological product, electronic product, medical device for human use, or any article other than a test article, feed, or water that is administered to the test system in the course of a nonclinical laboratory study for the purpose of establishing a basis for comparison with the test article.
OECD (2.4, 2.): Reference item (“control item”) means any article used to provide a basis for comparison with the test item.
UK GLPs: Reference item means any article used to provide a basis for comparison with a test item.
EPA Parts 160 and 792: Control Substance means any chemical substance or mixture, or any other material other than a test substance, feed, or water, that is administered to the test system in the course of a study for the purpose of establishing a basis for comparison with the test substance for known chemical or biological measurements.
EPA Parts 160 and 792: Reference Substance means any chemical substance or mixture, or analytical standard, or any material other than a test substance, feed, or water, that is administered to or used in analyzing the test system in the course of a study for the purpose of establishing a basis for comparison with the test substance for known chemical or biological measurements. |
Note: The pertinent references used to prepare this table are numbers 1-13. |