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3. Compliance with GLP regulations is NOT required for these studies: l Discovery l Basic research l Screening l Any other in vitro studies in which the safety of the product is not being assessed
Mixed messages for drug interaction and reaction phenotyping While non-GLP studies do not need to fulfill GLP requirements, they must still produce high-quality, reviewed and reliable data. In particular, multiple nations’ regulatory agen-
cies and the pharma industry have singled out in vitro drug interaction studies (such as CYP inhibi- tion, induction or reaction phenotyping data, or transporter inhibition or substrate potential) as especially important in assessing drug safety – even though these are technically non-GLP studies. Moreover, the pharmaceutical industry states that
drug interaction studies must be “performed with high quality and consistency, particularly when the studies ultimately influence the design of clinical tri- als”2. Furthermore, the US FDA recommended that these studies be carried out “in the spirit of GLP”3, with the investigator “taking necessary steps to assure the quality and integrity of the data”. In light of these statements, sponsors often feel
they must deliver the same level of data integrity and validity for in vitro drug interaction studies as
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they would for non-clinical safety studies. To achieve this, when outsourcing, they frequently request GLP-compliant studies as a matter of course. But is GLP truly the only way to be certain these non-GLP studies meet the guidelines above? Depending upon the rigour of the non-GLP study conduct, perhaps not.
Waste not, want not: scrutinise your options Unnecessary GLP studies squander both time and money. Before you decide on GLP or non-GLP enzyme inhibition, enzyme induction, drug trans- port or drug metabolism studies, analyse your pro- posed CRO’s study options for in vitro and ex vivo test systems. Once you consider the exact differ- ences between the GLP and non-GLP studies, you will be able to decide whether the CRO’s non-GLP conduct will fulfill the research objectives of your particular project. In the end, you may decide on non-GLP studies – or those in compliance with US FDA GLP regulations, Japan MHLW GLP regula- tions or OECD GLP guidance.
Considerations when evaluating how your prospective CRO applies GLP regulations to in vitro and ex vivo studies Most elements of the GLP regulations are constant, regardless of test system. For in vitro studies, though, a few points require interpretation in view of intent and applicability. It’s useful to compare:
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