Standards Born From Scandals Help Ensure Reliable Drug Data
A wave of scandals in the 1970s involving toxicology labs falsifying safety data forced regulators to create Good Laboratory Practice (GLP) standards that still guide how laboratories document, design, and validate preclinical studies.
By the mid-1970s, federal regulators were faced with a troubling pattern. Toxicology studies submitted to the US FDA, which are essential for safety evaluations for new drugs and medical products, contained serious problems.1 Agency inspectors encountered animal facilities where research animals were kept in poor conditions and scientific documentation was so thin or deeply flawed that the validity of the studies was called into question. Tips from whistleblowers alleged scientific misconduct that spanned inadequate animal care, intentional omissions of safety data, and statistical manipulations that minimized adverse findings.
When the FDA investigated, it uncovered a systemic problem: there were no consistent standards for how nonclinical toxicology studies should be designed, conducted, or reported. Investigators documented a litany of issues, including insufficient training of personnel, deviations from study protocols, undocumented changes to data, and discrepancies suggesting that results had been altered. A summary of these early inquiries painted a stark picture. The absence of quality control mechanisms had created an environment where poor practices could flourish, undermining scientific integrity and threatening public health.
From Scandals to Standards
In response, the US Congress enacted Good Laboratory Practice (GLP) regulations, formalized in Title 21 Part 58 of the Code of Federal Regulations.2 GLP established the minimum operational standards required for conducting preclinical laboratory studies intended to support applications for research or marketing authorization for FDA-regulated products. The objective was straightforward but critical: ensure that the safety data underpinning decisions about human exposure to new products are reliable, reproducible, and collected under defined, auditable conditions.
The regulations cover not only human drugs and biological products but also medical devices. Parallel frameworks have also been adopted internationally, most notably the Organisation for Economic Co-operation and Development’s Principles of GLP, which enable greater harmonization across global regulatory systems.
Studies that require GLP conditions include definitive pharmacokinetics studies, Investigational New Drug (IND)-enabling toxicology studies, and those establishing the no-observed-adverse-effect level (NOAEL). However, not all preclinical work falls under GLP requirements. Early pharmacokinetic experiments, efficacy studies, and dose range-finding assessments may be conducted under non-GLP conditions, but they should still be scientifically rigorous and reproducible.
Regulatory agencies scrutinize GLP-compliant nonclinical safety packages closely when reviewing IND applications. These studies assess whether an investigational product’s formulation, dosage, and route of administration are sufficiently safe to justify initial human testing. Because GLP studies are significantly more rigorous, expensive, and time-consuming than non-GLP work, many academic groups and small biotechnology companies rely on specialized contract research organizations to conduct them. The meticulous documentation required at every procedural step necessitates highly structured workflows and dedicated quality assurance units. To maintain confidence in the data generated by these organizations, the FDA conducts regular inspections of GLP facilities, assessing not only procedural adherence but also data integrity.
Planning Backward From the Clinic
Given the cost and complexity of GLP studies, experienced developers stress the importance of strategic planning, starting with the end product and outcome in mind and working backward. A well-defined Target Product Profile helps pinpoint the safety questions that GLP studies must address. Before initiating these expensive studies, sponsors typically outline their proposed clinical trial design, as GLP studies should directly support the planned human testing. For instance, the duration of GLP toxicology studies must match the expected dosing period in early clinical trials. Many sponsors also request a pre-IND meeting with the FDA to confirm that their proposed program aligns with regulatory expectations and to avoid unnecessary effort or expense. Bringing preliminary efficacy data and results from non-GLP toxicology or dose range-finding studies helps make this discussion more meaningful and productive.
Nearly 50 years after their implementation, GLP regulations remain a cornerstone of drug development. By enforcing transparency, traceability, and consistency, they protect not only the scientific enterprise but also the patients who ultimately rely on safe, well-vetted medical products.
References
- Baldeshwiler AM. History of FDA Good Laboratory Practices. Qual Assur J. 2003;7:157-161.
- Code of Federal Regulations, Title 21. “Part 58—Good Laboratory Practice for Nonclinical Laboratory Studies.”
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