That is the question. . . Knowing the answer may save you time and money
Good Laboratory Practices (GLP) are federal regulations that require implementation of a robust quality management system to ensure the validity, integrity and reliability of non-clinical safety data submitted for regulatory evaluation and approval. SEKISUI XenoTech laboratories are in Kansas City, Kan., USA and therefore follow the US Food and Drug Administration (FDA) GLPs (21 CFR parts 11 and part 58). GLP regulations were first issued by the US in 1978. At that time, safety data was mainly obtained from in vivo animal test systems. Since then, researchers have continued to develop alternative ways to assess drug safety, and GLP regulations can be applied to all nonclinical laboratory safety studies, including in vitro and ex vivo test systems.
In short, GLP-compliant studies require documentation (e.g., standard operating procedures – SOPs) and are overseen by a quality assurance unit that performs process-, facility- and study-based inspections. Here, we provide an overview of which studies require GLP compliance, which do not, and why in some cases the choice is unclear. We also detail SEKISUI XenoTech’s approach to applying the US FDA GLP regulations to in vitro and ex vivo studies. And lastly, we provide an easy reference outlining our GLP-compliant and non-GLP compliant conduct of such studies. Once you know exactly what to expect, you can select the level of study you need to achieve your project’s objectives.
Which studies require GLP?
With formal regulations in place, you’d think the answer to this question would be simple. It is, and it isn’t. In summary, the FDA guidelines for GLP compliance are as follows:
1. Sponsors of nonclinical laboratory studies submitted to support the safety of:—
- Food and color additives
- Animal food additives
- Animal drugs
- Human drugs and biological products
- Medical devices for human use
- Electronic products
— must submit evidence that their products are safe in research and/or marketing applications. (21 CFR 58.1)
2. Non-clinical laboratory studies that must comply with FDA GLP regulations include:
- Toxicity profiles
- Observed no adverse effect levels
- Risks of clinical studies involving humans or animals
- Potential teratogenic, carcinogenic or other adverse effects
- Safe levels of use
3. Compliance with GLP regulations is NOT required for these studies:
- Basic research
- 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 agencies and the pharma industry have singled out in vitro drug interaction studies (such as CYP inhibition, 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 trials” (Bjornsson et al., 2003). Furthermore, the US FDA recommended that these studies be carried out “in the spirit of GLP” (Tucker, Houston, Huang, 2001), 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 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 rigor of the non-GLP study conduct, perhaps not. In addition, it is possible to outsource a study that is 100% compliant with GLP regulations but that is not scientifically valid or draws incorrect conclusions from the data that were collected.
Waste not, want not: scrutinize your options
Unnecessary GLP studies squander both time and money. Before you decide on GLP or non-GLP enzyme inhibition, enzyme induction, drug transport or drug metabolism studies, analyze SEKISUI XenoTech’s study options for in vitro and ex vivo test systems. Once you consider the exact differences between our GLP and non-GLP studies, you will be able to decide whether our non-GLP conduct will fulfill the research objectives of your particular project.
We offer these drug interaction studies as either non-GLP or in compliance with US FDA GLP regulations, Japan MHLW GLP regulations or OECD GLP guidance.
How SEKISUI XenoTech 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. In detail, Table 1 in our 2013 technical paper compares:
- Specific, relevant GLP regulations from 21 CFR Part 58
- How SEKISUI XenoTech interprets these regulations in FDA GLP-compliant studies
- How SEKISUI XenoTech 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.
At SEKISUI XenoTech, in many regards, we conduct GLP and non-GLP studies identically. Both levels of study are performed with the same:
- Personnel roles and functions
- Laboratory space
- Laboratory procedures and processes
Nevertheless, there are a few differences between GLP-compliant and non-GLP studies at SEKISUI XenoTech. Our non-GLP studies differ in that:
- Test and control article/mixture characterization is not included
- Quality assurance unit (QAU) inspection is not included (unless requested by sponsor)
- Archived records storage cabinets are not necessarily fire-resistant
- In method validation, the same quality control criteria are not necessarily applied to every batch
Please examine the SEKISUI XenoTech guide to our GLP and non-GLP services. Once you see how similar they are, we believe you will be able to find new efficiencies by choosing SEKISUI XenoTech’s non-GLP services for some of your drug interaction studies.
Learn more about:
Bjornsson et al., The Conduct of in vitro Drug-Dru1g Interaction Studies: A Pharmaceutical Research and Manufacturers of America (PhRMA) Perspective, p815-831, 2003
Tucker, Geoffrey T., J. Brian Houston, and Shiew-Mei Huang, Optimizing Drug Development: Strategies to Assess Drug Metabolism/Transporter Interaction Potential — Toward a Consensus. Br J Clin Pharmacol. 2001 Jul; 52(1): 107–117.
U.S. Food and Drug Administration’s Good Laboratory Practice for Nonclinical Laboratory Studies, Title 21, Vol. 1, Part 58.
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