Good Laboratory Practice (GLP) is a formal regulatory quality system (defined by 21 CFR Part 58 and OECD GLP principles) that governs how nonclinical safety studies are planned, performed, monitored, recorded, archived, and reported.
Whether an assay is GLP-compliant depends on the assay category, its execution environment, and its regulatory purpose:
GLP Compliance Status by Domain
1. In Silico Tools (QSAR & Computational Models)
Status: Non-GLP / GLP Principles Apply
Explanation: GLP regulations were originally written for physical laboratory environments with tangible test systems (animals, cells, chemicals). Computer models (like Derek Nexus, Leadscope, or GastroPlus) do not fall directly under traditional 21 CFR Part 58 wet-lab GLP inspections.
Regulatory Acceptance: For IND submissions (e.g., ICH M7 mutagenicity impurity reports), regulatory agencies accept in silico results as long as the software is validated according to OECD QSAR principles and executed by a qualified computational toxicologist following formal Quality Assurance (QA) audit procedures.
2. In Chemico Assays (e.g., DPRA, GSH Trapping)
Status: Both Non-GLP (Screening) and Full GLP (Regulatory)
Explanation:
Hit-to-Lead Phase: Run as fast, low-cost non-GLP screening assays to eliminate reactive candidates early.
Regulatory Submissions: Standardized in chemico assays—such as the Direct Peptide Reactivity Assay (DPRA – OECD TG 442C)—can be run in GLP-certified CRO labs using validated equipment, analytical standards, and QA oversight for inclusion in official regulatory dossiers (e.g., EU REACH, ISO 10993, or FDA submissions).
3. In Vitro Assays (e.g., Ames, hERG, Transporters, Off-Target Panels)
Status: Both Non-GLP (Screening) and Full GLP (Regulatory)
Explanation: Most wet-lab in vitro assays exist in two distinct formats:
Screening / Miniaturized Versions (Non-GLP): Micro-Ames (Ames MPF), high-throughput automated patch-clamp (QPatch), and 10 uM single-concentration off-target panels are typically performed under non-GLP conditions. This keeps costs low and turnaround times fast during early lead selection.
Definitive Regulatory Studies (GLP): When submitting data for an Investigational New Drug (IND) application or OECD test guideline compliance (e.g., standard GLP Ames Test under OECD TG 471, GLP In Vitro Micronucleus under OECD TG 487, or GLP hERG assay), the exact same biological system is run under full GLP conditions. This requires certified facilities, chain-of-custody tracking, validated software, and QA auditing.
Summary Checklist for R&D Teams
| Stage | Goal | GLP Required? | Example Assays Used |
| Virtual Design | Screen libraries for toxic alerts | No (Software validation only) | Derek Nexus, Leadscope, GastroPlus |
| Hit-to-Lead | Rank candidates & drop reactive leads | No (Non-GLP screening) | DPRA screening, GSH Trapping, Micro-Ames |
| Lead Optimization | Establish safety margins & secondary targets | No (Non-GLP exploratory) | QPatch hERG, Caco-2, Safety44 Panel |
| IND-Enabling Package | Formal filing to FDA, EMA, or PMDA | YES (Definitive Safety Studies) | Full Standard GLP Ames Test, GLP hERG, GLP Skin Sensitization |
