ADME CRO: An ADME lab that can provide absorption, distribution, metabolism, and excretion (ADME) evaluations of a drug or biologic in an in vivo model.
ADME Studies: A study that evaluates the absorption, distribution, metabolism, and excretion (ADME) of a drug or biologic in an in vivo model. ADME describes the disposition of a pharmaceutical compound within an organism. The four criteria all influence the drug levels and kinetics of drug exposure to the tissues and hence influence the performance and pharmacological activity of the compound as a drug.
Animal GLP CRO: A Contract Research Organization, also called a Clinical Research Organization, (CRO) is a service organization that provides support to the pharmaceutical/biotech industry. CROs offer clients a wide range of “outsourced” pharmaceutical research services to aid in the drug and medical device research & development process. In the Code of Federal Regulations (CFR), the U.S. Food and Drug Administration regulations state that a CRO is “a person [i.e., a legal person, which may be a corporation] that assumes, as an independent contractor with the sponsor, one or more of the obligations of a sponsor, e.g., design of a protocol, selection or monitoring of investigations, evaluation of reports, and preparation of materials to be submitted to the Food and Drug Administration.” [21 CFR 312.3(b)]
Carcinogenicity CRO: A Carcinogenicity Lab that can provide chronic toxicology evaluations of a drug or biologic in an in vivo model.
Carcinogenicity Studies: A study that provides chronic toxicology evaluations of a drug or biologic in vivo. The objectives of carcinogenicity studies are to identify a tumorigenic potential in animals and to assess the relevant risk in humans. Any cause for concern derived from laboratory investigations, animal toxicology studies, and data in humans may lead to a need for carcinogenicity studies. The practice of requiring carcinogenicity studies in rodents was instituted for pharmaceuticals that were expected to be administered regularly over a substantial part of a patient’s lifetime. The design and interpretation of the results from these studies preceded much of the available current technology to test for genotoxic potential and the more recent advances in technologies to assess systemic exposure. These studies also preceded our current understanding of tumorigenesis with nongenotoxic agents. Results from genotoxicity studies, toxicokinetics, and mechanistic studies can now be routinely applied in preclinical safety assessment. These additional data are important not only in considering whether to perform carcinogenicity studies but for interpreting study outcomes with respect to relevance for human safety. Since carcinogenicity studies are time consuming and resource intensive, they should be performed only when human exposure warrants the need for information from life-time studies in animals in order to assess carcinogenic potential.
CRO (Contract Research Organization): A Contract Research Organization, also called a Clinical Research Organization, (CRO) is a service organization that provides support to the pharmaceutical/biotech industry. CROs offer clients a wide range of “outsourced” pharmaceutical research services to aid in the drug and medical device research & development process.[1] In the Code of Federal Regulations (CFR), the U.S. Food and Drug Administration regulations state that a CRO is “a person [i.e., a legal person, which may be a corporation] that assumes, as an independent contractor with the sponsor, one or more of the obligations of a sponsor, e.g., design of a protocol, selection or monitoring of investigations, evaluation of reports, and preparation of materials to be submitted to the Food and Drug Administration.”
Services offered by CROs include: product development, formulation and manufacturing; clinical trial management (preclinical through phase IV); clinical, medical and safety monitoring; preclinical, toxicology, and clinical laboratory services for processing trial samples; data management, biostatistics and medical writing services for preparation of an FDA New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Biologics License Application (BLA); regulatory affairs support; and many other complementary services. CROs range from large, international full service organizations to small, niche specialty groups and can offer their clients the experience of moving a new drug or device from its conception to FDA marketing approval without the drug sponsor having to maintain a staff for these services.
DART CRO: A DART Lab that provides developmental and reproduction toxicity evaluations of a drug or biologic in vivo.
DART Studies: A study that provides developmental and reproduction toxicity evaluations of a drug or biologic in vivo. Reproductive toxicity studies are designed to investigate the affect of a test article on male and female fertility and reproductive performance, estrous, spermatogenesis, implantation, embryo-fetal survival and development, gestation length, parturition, lactation, pup survival and development (including potential functional and behavioral effects), and the ability of offspring from the exposed parental generation to reproduce normally. Non-GLP pilot studies are conducted to provide data needed to determine dose levels for definitive studies. Pilot and embryo-fetal development studies are usually conducted in rats and rabbits. Fertility and reproductive performance, and pre and postnatal development studies are usually conducted in rats or mice. Mice or dogs can also be used when necessary for embryo-fetal development studies.
IND Preclinical Studies: Under FDA requirements, a sponsor must first submit data showing that the drug is reasonably safe for use in initial, small-scale clinical studies. Depending on whether the compound has been studied or marketed previously, the sponsor may have several options for fulfilling this requirement: (1) compiling existing nonclinical data from past in vitro laboratory or animal studies on the compound; (2) compiling data from previous clinical testing or marketing of the drug in the United States or another country whose population is relevant to the U.S. population; or (3) undertaking new preclinical studies designed to provide the evidence necessary to support the safety of administering the compound to humans.
IND Animal Toxicology Studies: During preclinical drug development, a sponsor evaluates the drug’s toxic and pharmacologic effects through in vitro and in vivo laboratory animal testing. Genotoxicity screening is performed, as well as investigations on drug absorption and metabolism, the toxicity of the drug’s metabolites, and the speed with which the drug and its metabolites are excreted from the body. At the preclinical stage, the FDA will generally ask, at a minimum, that sponsors: (1) develop a pharmacological profile of the drug; (2) determine the acute toxicity of the drug in at least two species of animals, and (3) conduct short-term toxicity studies ranging from 2 weeks to 3 months, depending on the proposed duration of use of the substance in the proposed clinical studies.
GLP Animal Studies: In vivo studies performed under GLP guidelines are required to file an IND. These studies follow the guidelines in CFR 21 Part 58. Please see GLP Preclinical Studies for more information.
GLP CRO: A GLP Contract Research Organization, also called a GLP Clinical Research Organization, (CRO) is a service organization that provides support to the pharmaceutical/biotech industry. CROs offer clients a wide range of “outsourced” pharmaceutical research services to aid in the drug and medical device research & development process. In the Code of Federal Regulations (CFR), the U.S. Food and Drug Administration regulations state that a CRO is “a person [i.e., a legal person, which may be a corporation] that assumes, as an independent contractor with the sponsor, one or more of the obligations of a sponsor, e.g., design of a protocol, selection or monitoring of investigations, evaluation of reports, and preparation of materials to be submitted to the Food and Drug Administration.” [21 CFR 312.3(b)]
Services offered by CROs include: product development, formulation and manufacturing; clinical trial management (preclinical through phase IV); clinical, medical and safety monitoring; preclinical, toxicology, and clinical laboratory services for processing trial samples; data management, biostatistics and medical writing services for preparation of an FDA New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Biologics License Application (BLA); regulatory affairs support; and many other complementary services. CROs range from large, international full service organizations to small, niche specialty groups and can offer their clients the experience of moving a new drug or device from its conception to FDA marketing approval without the drug sponsor having to maintain a staff for these services.
GLP Preclinical Studies: The pre-clinical development is a stage of research that begins before clinical trials (testing in humans) can begin, and during which important feasibility, iterative testing and safety (also known as Good Laboratory Practice or “GLP”) data is collected.
The main goals of pre-clinical studies (also named preclinical studies and nonclinical studies) are to determine a product’s ultimate safety profile. Products may include new or iterated or like-kind medical devices, drugs, gene therapy solutions, etc. Each class of product may undergo different types of preclinical research. For instance, drugs may undergo pharmacodynamics (PD), pharmacokinetics (PK), ADME, and toxicity testing through animal testing. This data allows researchers to allometrically estimate a safe starting dose of the drug for clinical trials in humans. Medical devices that do not have drug attached will not undergo these additional tests and may go directly to GLP testing for safety of the device and its components. Some medical devices will also undergo biocompatibility testing which helps to show whether a component of the device or all components are sustainable in a living model. Most pre-clinical studies must adhere to Good Laboratory Practices (GLP) in ICH Guidelines to be acceptable for submission to regulatory agencies such as the Food & Drug Administration in the United States.
Typically, both in vitro and in vivo tests will be performed. Studies of a drug’s toxicity include which organs are targeted by that drug, as well as if there are any long-term carcinogenic effects or toxic effects on mammalian reproduction.
GLP Toxicology: All safety studies providing primary safety support for IND, NDA, and BLA submissions should be performed under GLP guidelines (21 CFR Part 58). This includes the acute (single dose), repeated dose (7, 14, 28, 90 days, 6, 9, 12 months), chronic and/or carcinogenicity, genetic toxicology (in vitro/in vivo), reproductive and developmental toxicity (DART), specialized studies (inhalation, phototoxicity, arthropathy, allergenicity), and safety pharmacology.
GLP Animal Toxicology Research: Scientists use whole living systems (i.e. animal models) in experiments to understand the relationships between exposure and effect, and to use them appropriately, responsibly and humanely. Data from these studies provide the essential foundation to distinguish and recommend which level of exposure is safe and which is harmful to people, animals and the environment.
Histopath CRO: A histopath lab is one that provides histopathological evaluations of the effects of a drug or biologic in vivo within specified tissues. Histopathology, the microscopic study of diseased tissue, is an important tool in anatomical pathology, since accurate diagnosis of cancer and other diseases usually requires histopathological examination of samples. Trained medical doctors, frequently board-certified as Pathologists, are the personnel who perform histopathological examination and provide diagnostic information based on their observations. These observations are performed under GLP regulations and included in toxicological evaluations.
MTD CRO: A CRO that provides Maximum Tolerated Dose evaluations of a drug or biologic in vivo.
MTD Studies: A CRO that provides Maximum Tolerated Dose evaluations of a drug or biologic in vivo. The MTD is operationally defined in toxicology as the highest daily dose of a chemical that does not cause overt toxicity in specified period of time in laboratory mice or rats. This dose is then used for longer-term safety assessment in the same species, usually lasting two years or a lifetime. The rationale for using the MTD is to maximize the likelihood of detecting any chronic disease effects of a chemical, including cancer. Using higher doses also increases the statistical likelihood of detecting the intrinsic hazards of chemicals.
Nonclinical Toxicology Services: These services are utilized to perform the GLP toxicology studies required to file an IND.
Pharmacokinetics CRO: A pharmacokinetic (PK) lab that provides PK evaluations of a drug or biologic in vitro or in vivo.
PK Studies: A study that focuses on pharmacokinetic evaluations of a drug or biologic in vitro or in vivo. Pharmacokinetics is often studied in conjunction with pharmacodynamics. Pharmacodynamics explores what a drug does to the body, whereas pharmacokinetics explores what the body does to the drug. Pharmacokinetics includes the study of the mechanisms of absorption and distribution of an administered drug, the rate at which a drug action begins and the duration of the effect, the chemical changes of the substance in the body (e.g. by enzymes) and the effects and routes of excretion of the metabolites of the drug.
Preclinical CRO – A Contract Research Organization, also called a Clinical Research Organization, (CRO) is a service organization that provides support to the pharmaceutical/biotech industry. CROs offer clients a wide range of “outsourced” pharmaceutical research services to aid in the drug and medical device research & development process. In the Code of Federal Regulations (CFR), the U.S. Food and Drug Administration regulations state that a CRO is “a person [i.e., a legal person, which may be a corporation] that assumes, as an independent contractor with the sponsor, one or more of the obligations of a sponsor, e.g., design of a protocol, selection or monitoring of investigations, evaluation of reports, and preparation of materials to be submitted to the Food and Drug Administration.” [21 CFR 312.3(b)]
Preclinical Toxicology – All safety studies providing primary safety support for INDs should be GLP (21 CFR Part 58). This includes the acute (single dose), repeated dose (7, 14, 28, 90 days), genetic toxicology (in vitro/in vivo), specialized studies (inhalation, phototoxicity, arthropathy, allergenicity), and safety pharmacology.
Reproductive CRO – A CRO that provides developmental and reproduction toxicity evaluations of a drug or biologic in vivo.
Reproductive Studies – A CRO that provides developmental and reproduction toxicity evaluations of a drug or biologic in vivo. Reproductive toxicity studies are designed to investigate the affect of a test article on male and female fertility and reproductive performance, estrous, spermatogenesis, implantation, embryo-fetal survival and development, gestation length, parturition, lactation, pup survival and development (including potential functional and behavioral effects), and the ability of offspring from the exposed parental generation to reproduce normally. Non-GLP pilot studies are conducted to provide data needed to determine dose levels for definitive studies. Pilot and embryo-fetal development studies are usually conducted in rats and rabbits. Fertility and reproductive performance, and pre and postnatal development studies are usually conducted in rats or mice. Mice or dogs can also be used when necessary for embryo-fetal development studies.
Safety Pharmacology CRO – A CRO that provides safety pharmacology evaluations of a drug or biologic in vivo.
Safety Pharmacology Studies – A study that provides safety pharmacology evaluations of a drug or biologic in vivo. The safety pharmacology studies are defined as those studies which investigate the potential undesirable pharmacodynamic effects of a substance on the functions in relation to the exposure in the therapeutic range and above. In particular, for the medicinal products targeting the immune system, the potential unintended effects should be investigated, e.g. using the in-vitro studies, including the human material. The animal models that are thought to be similar to the human disease may provide further insight in the pharmacological action, the pharmacokinetics, and dosing in the patients. They may also help the determination of the safety.
Toxicology Drug Development In Rats – The rat is the primary species used for testing the safety of new drugs and selecting an appropriate starting dose for Phase I clinical trials. They are particularly useful as a toxicology model; also particularly useful as a neurological model and source of primary cell cultures, owing to the larger size of organs and suborganellar structures relative to the mouse.
Toxicology Drug Development In Mice – The mouse is the second most commonly used species used for testing the safety of new drugs and selecting an appropriate starting dose for Phase I clinical trials. Dose transformations from mice to humans are per formed by using body surface area. Usually, one-tenth of the LD10 is taken as a safe starting point, and dose escalation is performed according to a modified Fibonacci scheme.