Good Manufacturing, Good Laboratory or Good Clinical Practice regulations all apply to laboratory testing, but they each serve different purposes with responsibilities being handled by different people.  In the second of three articles we explore GLP.

Good Laboratory Practice (GLP)
GLP regulations are designed to protect the integrity of scientific data and provide regulators with a robust audit trail of how a research study was carried out.  

The formal concept of “Good Laboratory Practice” came about in the USA, during the 1970s as the result of FDA laboratory inspections which revealed poor study planning and execution, insufficient documentation, questionable animal welfare practices and fraudulent reporting.  The FDA, and later the OECD, formulated GLP principles to ensure regulatory submissions fully and reliably reflected the experimental work conducted.

Today we generally associate GLPs with the pharmaceutical industry and non-clinical safety and efficacy testing prior to new drug approval.  But there is often confusion about when GLP regulations should be applied and this can create unnecessary and costly additional work.  

The process of drug development, for example, involves both non-clinical and clinical studies, with GLPs applying to non-clinical studies and testing, including animal studies.  By contrast, clinical studies are governed by Good Clinical Practices (GCP) which are intended to protect the safety of human participants in clinical trials.

In early-stage drug development, a candidate compound or chemical passes through several steps.  Preliminary “go/no-go” non-clinical studies – which collect early information about toxicological and pharmacokinetic tolerability in different animal systems - are relevant for further decision-making but do not need to comply with GLP regulations.  Other studies are mandatory for determining safe exposure to humans and should be performed according to GLP standards.  These include repeated dose toxicity, genotoxicity and safety pharmacology testing that provide the toxicological information needed for the safe transposition of drugs from animals to humans and must be conducted before Investigational New Drug (IND) application.  After IND approval, other GLP experiments may be carried out depending on the clinical application and purpose of the new drug.

GLP is defined as "a quality program related to organizational processes and conditions where non-clinical health and environmental safety are planned, performed, monitored, recorded, reported and archived." The GLP system is built on three main pillars – Testing Facility Management (TFM), Quality Assurance Unit (QAU), and Study Director (SD).

The TFM is responsible for designating a qualified SD, ensuring there is an independent QAU separate from the personnel engaged in the study, and that the facilities, equipment and personnel are made available with written GLP-compliant Standard Operating Procedures (SOPs).

An independent QAU is the defining component of the GLP system.  It monitors the conduct, analysis and reporting of the entire study to verify that written procedures and approved protocols are followed.  As an example, if an SOP requires a senior toxicologist to review results, the QAU auditor will verify that this happened by reviewing documentation or speaking directly with the senior toxicologist.  The QA auditor will also ensure that this person is qualified to perform his or her duties.  

Much of the GLP structure centres on the responsibilities of the SD as the individual appointed by the TFM responsible for all aspects of the non-clinical study.  SDs do not exist in the clinical study arena, thus GLP principles cannot be applied effectively in the clinical setting.

At its core, GLP is a quality management system that defines standards for study conduct, data collection, and results reporting.  GLP does not define scientific standards or address the underlying scientific hypothesis of a research project.  If it were applied to the world of cooking, GLP would ensure that the chef and his teams have followed the recipe exactly as written; however, it does not assure you that the recipe itself is a good one, or that the resulting dish will be tasty!

Originally developed to combat fraud, GLPs have become much broader than a control mechanism for regulators to judge the integrity of a study.  Three central ideas can be summarized into “common sense” points:

Reproducibility: The ability to reconstruct a study assures that the experiments were conducted as described in the report submitted to the regulatory agency; for example, that all animals received the correct dose of the test article during the duration of the study, the correct samples were collected and analysed, and the compilation of results faithfully reflects the data collected.

Responsibility: GLP-compliant study documentation records who did what, who can be held responsible for likely errors and, in questionable cases, identify those culpable.

Awareness: SDs who perform GLP studies in an orderly manner help to raise awareness of the need for quality and transparency in small routine tasks - such as accurate archiving - enabling full recovery of information whenever necessary. 

Hoeford is GMP-certified can assist with pre-clinical non-GLP toxicology and batch release testing.  Contact us to find out more.