Good Laboratory Practice (GLP) toxicology requirements vary according to the stage of drug development and the regulatory purpose of non-clinical safety studies. While early exploratory research is generally conducted without GLP compliance, studies intended to support clinical trials and marketing authorisation are typically required to follow internationally recognised standards.
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Understanding when these requirements apply is essential for planning non-clinical safety programmes in line with the anticipated clinical development pathway. Careful coordination of study timelines helps ensure that the necessary evidence is available at each regulatory milestone, reducing the risk of delays when progressing towards human trials and, ultimately, marketing authorisation.
GLP vs non-GLP toxicology studies: what is the difference?
The distinction between GLP and non-GLP toxicology studies is primarily determined by the intended use of their findings and the corresponding requirements for study planning, conduct, documentation and quality oversight:
- Non-GLP studies: primarily conducted during exploratory research to assess preliminary safety, investigate potential toxic effects and inform candidate selection. They allow greater flexibility in experimental design and execution;
- GLP studies: conducted under internationally recognised quality standards when non-clinical safety data are intended to support regulatory decisions. They follow defined requirements for study planning, execution, documentation and auditing.
The OECD Principles on Good Laboratory Practice establish the internationally recognised framework underpinning GLP toxicology requirements. Compliance with these principles supports the reliability and traceability of non-clinical safety data, facilitating their acceptance by regulatory authorities, including the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).
When are GLP toxicology studies required?
The transition from exploratory research to regulatory development determines when GLP compliance becomes necessary. The timing and scope of these studies depend on the candidate medicine and its planned clinical development.
Discovery and early optimisation
During discovery and early optimisation, researchers investigate multiple compounds to assess their potential and preliminary safety profiles.
Exploratory toxicology studies help identify tolerated doses, detect potentially sensitive organs and eliminate less promising compounds. Since their findings primarily inform internal research decisions, these investigations are generally conducted without GLP compliance, allowing greater flexibility in experimental design and execution.
Advanced preclinical development
Once a candidate molecule, its formulation and intended route of administration have been selected, GLP toxicology requirements become central to regulatory planning. Before clinical trials can begin, authorities generally require safety data from GLP-compliant studies conducted in rodents and, usually, another animal species.
The non-clinical safety assessment may include:
- Single-dose and repeated-dose toxicity studies: evaluating potential adverse effects following one or multiple administrations of a compound;
- Toxicokinetic assessments: characterising systemic exposure to the compound during toxicity studies;
- Studies of different durations: four-week toxicity studies may be sufficient to support initial human trials, although certain programmes require 90-day, chronic or reproductive toxicity studies before human exposure.
The duration and scope of these evaluations must be considered in relation to the planned clinical programme, in accordance with the applicable regulatory requirements.
Clinical development and marketing authorisation
GLP toxicology requirements continue to evolve as clinical development progresses. Longer treatment periods in humans may require additional non-clinical studies to characterise the safety of prolonged exposure.
As a general principle, the duration of repeated-dose toxicity studies in animals should equal or exceed the planned duration of human exposure, subject to the limits and exceptions established by ICH M3(R2). These studies contribute to the evidence required to support the continuation of clinical trials and subsequent marketing authorisation.
Their timing must therefore be considered throughout the development programme to ensure that the appropriate safety data are available for regulatory submissions.
GLP toxicology studies in rodents at VectorB2B
VectorB2B Drug Development is the only institution in Portugal with GLP certification for in vivo toxicology studies in rodents. Operating through a multifacility structure supported by highly qualified partner organisations, VectorB2B provides acute, subacute (up to 28 days), subchronic (up to 90 days), chronic and toxicokinetic studies.
These services can be adapted to small molecules, biologics, Advanced Therapy Medicinal Products (ATMPs) and oligonucleotides.
VectorB2B also provides regulatory advisory services, helping sponsors address GLP toxicology requirements by defining appropriate study programmes from initial planning through to submission to the competent authorities.
Contact our team to discuss the non-clinical safety requirements of your development programme.
Frequently asked questions (FAQ)
1. Are GLP studies always required before first-in-human trials?
Non-clinical safety studies intended to support first-in-human clinical trials are generally expected to comply with GLP. Earlier exploratory studies may be conducted without GLP compliance, as their primary purpose is to inform internal research decisions. GLP toxicology requirements depend on the development programme and planned clinical exposure.
2. How does the duration of GLP toxicology studies relate to clinical trials?
The duration of toxicology studies is determined in relation to the anticipated duration of treatment in humans. Four-week studies may support certain initial clinical trials, while longer treatment periods can require 90-day or chronic toxicity assessments. Depending on the programme, additional studies may also be necessary before human testing begins.
