Good Laboratory Practices (GLP) provide regulations and the standard by which drug safety studies are conducted in nonclinical animal studies. In addition to ensuring the ethical treatment and welfare of animals, adhering to GLP regulations gives sound evidence of the validity, integrity, and reliability of nonclinical safety data. This nonclinical safety data will ultimately be submitted to and evaluated by regulatory agencies for approval to use in clinical studies in humans.
History of GLP
GLP regulations have become an ingrained part of maintaining quality in drug development for many years, however these regulations are younger than one may think. The FDA issued the Guidance for Industry Good Laboratory Practices Regulations in 1978 in response to an observed lack of quality as well as scientific integrity in nonclinical toxicology studies in the mid-1970s. The most notable instance being a scandal involving Industrial Bio-Test Laboratories in which former executives were accused of providing false data to chemical companies that were then submitted to the government to prove their products were safe. Before the FDA implemented these regulations, New Zealand and Denmark released their own GLP regulations years earlier in 1972. The Organization for Economic Co-operation and Development (OECD) adopted these principles in 1992 to promote compliance on a larger scale. Both sets of regulations cover a vast array of sectors including:
- General provisions
- Organization and personnel
- Facilities and equipment
- Testing facilities operation
- Test and control animals
- Protocol for conduct of a nonclinical laboratory study
- Records and reports
- Disqualification of testing facilities
When is GLP Compliance Required?
Generally, most nonclinical studies will fall under the GLP regulation requirements. However, there are some instances or stages in the early pre-clinical phase where adherence to GLP is not required. Examples of studies that could be exempt from GLP include exploratory genotoxicity, mutagenicity, safety pharmacology, and general in-vitro toxicology studies. Sponsors may decide to conduct this stage of studies outside of GLP requirements if the goal is solely to investigate preliminary drug safety by analyzing the drug’s absorption, distribution, metabolism, and elimination (ADME) properties. The objective of these studies would be to test the initial tolerability of the drug in various systems. This will then lead to further investigation that is conducted in a study where compliance with GLP is required. Examples of studies that require GLP compliance include standard repeated dose toxicity, genotoxicity, and safety pharmacology studies. Ultimately, all nonclinical trial results that will be submitted with an IND, must be conducted in accordance with GLP requirements.
GLP and Quality Assurance Unit Requirements
A vital aspect of GLP regulations is the requirement that the Quality Assurance Unit (QAU) remain independent of operations. GLP Part 58.35 states that the QAU must monitor the conduct of each study to “assure management that all facilities, equipment, personnel, methods, practices, records, and controls are in conformance with the regulations.” The QAU typically conducts an audit for each nonclinical laboratory GLP study. The goal of the audit is to ensure that the GLPs, standard operating procedures (SOPs), and protocols are being followed and that the data summarized in the final report accurately reflect the results of the study. The QAU audit can include:
- Reviewing the source data against the data imported into the analysis software
- Confirming that all routine quality control (QC) steps have been performed
- Reviewing the analysis, tables/listings/figures, and the report against the protocol/amendments, SOPs, and regulatory requirements
Benefits of CROs for GLP Compliance
A contract research organization (CRO) can provide subject matter experts in specific processes who can provide different perspectives. Being independent from the sponsor allows CROs to have an unbiased approach as the focus is on the service being provided rather than the success of the drug. Per the regulations, CROs must be current on their GLPs and any updates as they are released. In order to maintain compliance, CROs can monitor various metrics such as:
- Tracking the number of deviations
- What they are deviating from as well as the version
- Who submitted the deviation
- Planned vs unplanned deviations
- Deviations per year or quarter
All of the metrics listed above can help gain a better understanding of why deviations are occurring and how processes can be improved to prevent them. Metrics are a great way to see how the organization is currently doing when it comes to GLP compliance and overall quality and areas where improvements could be made.
Conclusions
In the pharmaceutical industry, GLP regulations are the standard used to assure the quality and integrity of nonclinical drug safety studies conducted in animals. GLP regulations were first introduced by the FDA in 1978 and have become an integral part of nonclinical drug development. A key component of GLP is an independent quality assurance unit intended to monitor study conduct, analysis, and reporting of nonclinical studies. Allucent’s nonclinical TK analysis and reporting experience covers every route of administration, type of toxicity study, and expertise in complex nonclinical study designs for GLP and non-GLP studies. In addition, our QA team is committed to providing the highest level of quality assurance possible. Contact an expert today for direct access to some of the most experienced TK scientists in the industry.