Good laboratory practice or GLP is a set of principles intended to assure the quality and integrity of non-clinical laboratory studies that are intended to support research or marketing permits for products regulated by government agencies. The term GLP is most commonly associated with the pharmaceutical industry and the required non-clinical animal testing that must be performed prior to approval of new drug products. However, GLP applies to many other non-pharmaceutical agents such as color additives, food additives, food contamination limits, food packaging, and medical devices.
The actual regulations in the United States can be found in 21CFR58 (link) and for the European Union via the Organization for Economic Co-operation and Development (OECD, link). This post is not intended to be a comprehensive review of GLP regulations; however, there are some key areas of interest that touch pharmacokineticists. The most important area is the scope of these regulations. Too often the GLP regulations are applied when they should not be used, creating confusion, extra work, and additional costs. Let’s take a look at the scope of GLPs from the FDA documents and the OECD (italics added for emphasis):
This part prescribes good laboratory practices for conducting
non-clinical laboratory studies … (FDA 21CFR58)
These Principles of Good Laboratory Practice should be applied to the non-clinical safety testing … (OECD, No.1)
GLP only applies to non-clinical studies and testing. It does not apply to clinical studies. This is extremely important because clinical studies are governed by Good Clinical Practices (GCP), the Declaration of Helsinki, and other regulations intended to protect human participant safety. Furthermore, much of the GLP structure depends on the roles and responsibilities of the Study Director, a single individual that is responsible for the oversight and execution of all aspects of the non-clinical study. Study Directors do not exist in the clinical study arena, thus GLP principles cannot be applied effectively in the clinical setting.
Beyond the scope, there are two other items I would like to discuss. First, GLP is a quality management system, not a scientific management system. Or, in other words, GLP defines a set of quality standards for study conduct, data collection, and results reporting. GLP does not define scientific standards. If a study follows GLP, then you can be reasonably sure that the reported results were collected as outlined in the study protocol; however, you cannot be sure that the study actually addresses the scientific hypothesis. In the world of cooking, GLP would ensure that someone follows the recipe exactly as written; however, it does not assure you that the recipe was good or that the resulting item will be tasty!
Second, a key component of the GLP system of quality standards is the idea of a Quality Assurance unit (QA). This QA unit is intended to be an independent group or individual that monitors the entire study conduct, analysis, and reporting. The purpose of QA is to verify that all written procedures are followed throughout the study. As an example, perhaps there is an SOP that says that a senior pharmacokineticist must review the results prior to finalization. The QA auditor will verify that this review occurred. Verification could be done by reviewing a signed document, reviewing an electronic signature, or even speaking directly with the reviewer. The QA auditor will ensure that the senior pharmacokineticist has adequate training (as defined by SOPs in the organization) to perform his or her duties. This quality audit permits confidence that procedures were followed. But again, this audit does not ensure that the procedures are of high quality, or that no errors are made in the analysis.
Here are a few examples of how I think GLPs are misinterpreted:
- Using GLP to perform bioanalysis for human clinical trials. As noted in the scope for both GLP and OECD GLP, the principles of GLP only apply to non-clinical studies. Therefore, following GLP, particularly with respect to QA reviews is an unnecessary cost. It is more important to follow analytical validation plans.
- Performing GLP as a single person. GLP work requires at minimum 2 or 3 individuals. These are the person performing the work (analyst), a person reviewing the work (management), and a quality assurance reviewer (QA). If SOPs are written well, the analyst and the management can be the same individual; however, QA must always be an independent person.
- Results of GLP studies are “right.” A statement that a study was conducted in conformance with GLP simply means that quality systems were followed, and that the results of the study accurately report the conduct of the study. It does not indicate that the conclusions drawn are accurate, scientifically robust, or even useful!
I hope you take some time to learn more about GLP and apply it correctly in your future work.
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