Good Laboratory Practices (GLP) in Preclinical Research: Principles, Compliance, and Impact on Drug Safety

During the 1970s, the robustness of the non-clinical safety data submitted to the Food and Drug Administration (FDA) for New Drug Applications (NDA) was constantly questioned. Studies were inadequately planned, methods were not documented, and even raw data were changed to adjust the results for the final report. 

In 1979, the concept of “Good Laboratory Practice” (GLP) emerged, and the first GLP rules were published to ensure that FDA reports reflected the supporting experimental work. The Organization for Economic Co-operation and Development (OECD) also joined the initiative, and an initial proposal was adopted in 1981. 

What Are Good Laboratory Practices (GLP) and Why Are They Essential in Preclinical Research?

Good Laboratory Practice is a set of guidelines and quality systems designed to ensure the reliability, integrity, and reproducibility of non-clinical safety studies intended to support regulatory submissions. In the context of preclinical research, GLP serves as the foundation for generating credible data that regulators can use to assess the safety profile of drug candidates. Nevertheless, animal health products and medicated feed, food additives, cosmetics, medical devices, industrial chemicals, and food packaging are also governed by GLP. 

GLP adds a level of formal rigor to study design, data collection, reporting, and archiving, thereby building confidence in the findings. This becomes critical when decisions about human exposure and safety risks are on the line.

However, not all preclinical studies require GLP compliance. Early-stage toxicology, preliminary drug safety (absorption, distribution, metabolism, and elimination (ADME) properties), and non-regulatory research may not need to follow GLP protocols. Research in the discovery or lead optimization phases can be more flexible and faster without GLP, as long as data quality and integrity are still ensured. That said, once a candidate compound is selected for regulatory toxicology studies, adherence to GLP becomes essential for data acceptance by agencies such as the FDA, the European Medicines Agency (EMA), and others.

Core Principles of GLP: Ensuring Data Integrity, Traceability, and Reproducibility

At its core, GLP was born to build confidence in data. It mandates stringent processes to ensure that all study results are attributable, original, and verifiable: 

• Traceability ensures that every step of a study, from sample collection to final report, can be reconstructed and audited. This includes detailed standard operating procedures (SOPs), instrument calibration logs, sample tracking, and personnel training records.
• Data integrity is foundational. This means every result must be traceable to a source, whether an instrument, analyst, or sample, and documented in real time without alteration. But not only that, every result must also be traceable to a member of the personnel, the one who performed the task. Raw data must be preserved, and any amendments logged and justified.
• Reproducibility requires that a study be repeatable under the same conditions by independent parties. This is only possible when every detail of the methodology and environment is carefully documented.

To uphold Good Laboratory Practice principles, laboratories must implement a well-structured system that ensures consistency, accountability, and data reliability. This includes clearly defined and regularly updated SOPs to guide all tasks, a dedicated Quality Assurance (QA) unit that audits processes and reports independently, and personnel who are properly trained and continuously updated in both technical skills and GLP requirements. All equipment must be validated and maintained to guarantee accurate results, while secure archiving systems ensure that data remains intact, accessible, traceable, and protected over time. Regular internal audits complete the system, allowing for early detection of issues and reinforcing a culture of ongoing quality and compliance.

GLP Compliance and Regulatory Oversight: FDA, OECD, and Global Standards

GLP guidelines were first introduced by the FDA in the 1970s to combat scientific fraud and inconsistencies in toxicology data submitted for drug approvals. Today, GLP compliance is governed by a framework of international standards, including the FDA regulations (21 CFR Part 58) and the OECD Principles of GLP, which are accepted in over 30 member countries.

The FDA conducts periodic inspections of facilities conducting GLP studies to verify compliance. Violations may lead to warning letters, data rejection, or, in severe cases, suspension of studies. Companies submitting Investigational New Drug (IND) or New Drug Application (NDA) dossiers must demonstrate that their supporting data meet GLP requirements.

In Europe, the principles elaborated by the OECD are incorporated into EU law through GLP directives 2004/9/EC and 2004/10/EC. Directive 2004/9/EC obliges EU countries to designate the authorities responsible for GLP inspections in their territory. The EMA has a coordinating role in the inspections, but the responsibility for carrying them out is with each country's competent authority. In the case of Spain, the Spanish Agency of Medicines and Medical Devices (AEMPS) is responsible for medicinal products, whilst the competence over all other products falls under the National Accreditation Body (ENAC). 

Differences Between GLP and GMP in the Context of Drug Development

Good Laboratory Practices and Good Manufacturing Practices (GMP) are often mentioned together in pharmaceutical discussions, but they serve distinct purposes and apply to different phases of drug development.

GLP governs the preclinical, non-clinical testing phase, particularly safety studies in animals. Its primary concern is the quality and integrity of study data. GLP in the pharma industry ensures that toxicology, pharmacokinetics, and other non-clinical studies are performed in a reliable and traceable manner, ready for regulatory review.

GMP, on the other hand, applies to the manufacturing of medicinal products. It focuses on ensuring that products are consistently produced and controlled according to quality standards for their intended use. 

Another key difference is the subject of the regulation: GLP is about how studies are conducted and documented, while GMP is about how products are made. Where GLP emphasizes traceability of data, GMP emphasizes traceability of product batches and quality systems.

In conclusion, GLP ensures the credibility and transparency of preclinical research. Although it’s not mandatory during early exploratory phases, it becomes crucial once studies move into regulatory toxicology. When applied alongside GMP, GLP enables research institutions to produce data that regulatory agencies can trust, facilitating faster, more reliable progress through the drug development pipeline.

References

Andrade EL, Bento AF, Cavalli J, Oliveira SK, Schwanke RC, Siqueira JM, Freitas CS, Marcon R, Calixto JB. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies. Braz J Med Biol Res. 2016 Dec 12;49(12):e5646. doi: 10.1590/1414-431X20165646. 

European Medicines Agency. Good Laboratory Practice compliance [Internet]. EMA; [cited 2025 Jul 7]. Available from: https://www.ema.europa.eu/en/human-regulatory-overview/research-development/compliance-research-development/good-laboratory-practice-compliance#:~:text=The%20Standard%20operating%20procedure%20for,the%20development%20of%20collaborative%20projects.

Organisation for Economic Co‑operation and Development. Revised Guides for Compliance Monitoring Procedures for Good Laboratory Practice. OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring, No. 2. Paris: OECD; 1995. Available from: https://doi.org/10.1787/9789264078550-en

Robinson K. GLPs and the Importance of Standard Operating Procedures. BioPharm International. 1 Aug 2003. Available from: https://www.biopharminternational.com/view/glps-and-importance-standard-operating-procedures

By Miriam Martínez

Miriam is a Human Biologist with a strong background in neuropharmacology and a passion for bridging science and innovation. After earning a master’s degree in the Pharmaceutical and Biotech Industry, she completed her PhD in Biomedicine at Pompeu Fabra University (Barcelona), where her research focused on the behavioral analysis of animal models for neurophenotypical characterization. Following her doctoral studies, Miriam transitioned into the healthcare marketing and communication sector, where she played a key role in developing impactful marketing strategies and educational campaigns for leading pharmaceutical brands. She now leverages her scientific expertise, strategic thinking, and creative communication skills in her current role at ZeClinics.