Following Good Laboratory Practice (GLP) guidelines is a compliance need today in the U.S. for any pharmaceutical company to submit an investigational new drug application (INDA) or a new drug application (NDA). GLP standards aim to ensure that the reported safety data of the potential; drug candidate is sturdy enough.
Denmark and New Zealand first adopted Good Laboratory Practice (GLP) standards in 1972. The U.S. adopted GLP guidelines in 1979 in the aftermath of the Industrial Bio-Test (IBT) Laboratories scandal.
The IBT Lab, a major testing laboratory in the U.S. carried out safety tests for chemical manufacturers, pharmaceutical companies, and other industries needing such tests. IBT Lab carried out 35-40% of all toxicological testings in the U.S., informs an undated essay in Westgard QC,the University of Maryland’s journal.
In a routine audit in 1976, the Food and Drug Administration (FDA) found out that 618 among the 867 audited IBT results were invalid. A 2016 article mentions five major gaps that the FDA had identified:
- Faulty study execution due to insufficient planning.
- Unsatisfactory documentation of methods and results, allowing fraudulent data to be furnished.
- The use of hematological data from other studies as a control group.
- Excluding macroscopic observational data (necropsy).
- Changing raw data to get the desired final results.
The FDA recommended the adoption of GLP standards to regulate such unscientific practices with serious adverse ramifications for drug safety. The guidelines got finalized in 1978 and became operational in 1979.
The FDA brought in GLP guidelines to ensure the sturdiness of safety data in terms of quality and integrity. Good Laboratory Practice (GLP) standards allow all experiments to be accurately reconstructed to demonstrate that they have been carried out in compliance with the relevant regulations.
The GLP provides Standard Operating Procedures (SOPs) that must be followed for every assay. The SOPs refer to all the aspects involved in testing. From the required qualification and number of personnel to instrumentation and documentation. The management of every laboratory is responsible for maintaining the GLP SOPs.
GLP SOPs stress maintaining four basic principles of thorough scientific research:
- Experts must design and guide the study
- Standardized tests with validated techniques get used to the extent possible
- The appropriate calibration and accuracy of instruments must be ascertained
- All records, including initial lab reports, must remain available for an independent audit
Applicability of GLP Standards
Non-compliance with GLP guidelines results in diluting the scientific rigor of assays during the drug development process. Application of GLP standards become particularly critical from the non-clinical phase of animal studies.
The early stages of drug discovery, popularly known as the go/no go stage, also involve a number of assays. Regulatory needs of GLP compliance usually do not apply to many of these early studies.
Studies during the early stages involve pharmacokinetic (PK) studies, ADME studies, as also preliminary safety studies such as general toxicology, and safety pharmacology. These studies aim at gaining basic safety information about a potential drug candidate to decide on the feasibility of proceeding further.
However, there are other safety studies that need to be conducted before INDA. Genotoxicity and repeated dose toxicity are two such studies that must be conducted following GLP standards.