Business
l Specific, relevant GLP regulations from 21 CFR Part 58 l How the CRO interprets these regulations in FDA GLP-compliant studies l How the CRO handles these regulations in non- GLP studies
In vitro and ex vivo drug metabolism and drug
interaction studies are critical to evaluate the safety of existing drugs or drug candidates and to assess the risk of toxicity and adverse drug-drug reactions in vivo. Nonetheless, they are not considered safety studies. In the end, the sponsor must choose whether to conduct them in GLP-compliant or non-GLP-compliant fashion. The degree to which your chosen CRO conducts
GLP and non-GLP studies identically will affect the likelihood that you will be able to utilise non-GLP drug metabolism and interaction studies. Specific aspects of GLP versus non-GLP study conduct you may want to compare are listed below:
l Personnel roles and functions m Planning m Training m Performance m Monitoring m Documentation m Archiving m Quality assurance
l Laboratory space l Standard operating procedures l Protocol and study conduct and documentation l Equipment l Hard copy and electronic records storage, retrieval and retention l Bioanalytical method validation
Selecting a CRO that conducts GLP and non-
GLP studies similarly will enable you to find new efficiencies by choosing non-GLP services for some of your drug interaction studies. When in doubt, seek technical assistance to help you decide – the result may be significant savings.
A few definitions In vitro non-clinical laboratory study: A test article is applied to tissue or tissue-derived material (such as subcellular fractions) in a test tube, plate, etc. l Examples: enzyme induction studies in cultured human hepatocytes, enzyme inhibition studies with human liver microsomes or recombinant enzymes, and reaction phenotyping (enzyme mapping) with human hepatocytes, human liver microsomes and recombinant enzymes
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Control article: Any food additive, colour additive, drug, biological product, electronic product, medi- cal 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 non-clinical labo- ratory study for the purpose of establishing a basis for comparison with the test article. l Note: Positive and negative controls used to show that the test system is responsive under the actual conditions of the assay may not necessarily be categorised as control articles per GLP regula- tions.
Specimen: Any material derived from a test system for examination or analysis. l Example: microsomes isolated from cultured hepatocytes treated with a test or control article.
Additional definitions and requirements for GLP Studies Organisation and personnel l Specific responsibilities are assigned as per GLP regulations for non-clinical studies to: m Study personnel m Study director m Facility management m Quality assurance unit (QAU) m Archivist
Ex vivo non-clinical laboratory study: A test article is administered to a laboratory animal in vivo, after which organs or tissues are removed and analysed in vitro for enzyme induction, etc. l Examples: enzyme induction studies in mice, rats, dogs or monkeys, often conducted as part of a 14-day toxicity study
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