The rapid advancement of technology has led to an increase in drug research and development. Ensuring that newly developed medications are safe, effective, and properly approved for human use is critical. One fundamental way to achieve this is by following Good Laboratory Practice (GLP).
GLP establishes a framework for conducting non-clinical laboratory studies with accuracy, reliability, and integrity. This ensures that data generated in research is credible and meets regulatory standards.
In this article, we will explore the definition of GLP, its core principles, and the compliance requirements that govern its application.
Introduction to good laboratory practice
In the world of experimental (non-clinical) research, GLP represents a comprehensive quality management system for research laboratories and organizations. Its primary goal is to guarantee the uniformity, consistency, reliability, reproducibility, quality, and integrity of products developed for human or animal health, encompassing pharmaceuticals.
GLP extends its application from physio-chemical properties to a range of safety tests, spanning from acute to chronic toxicity studies and tests. This quality system is important for studies that aren’t about treating patients directly but focus on ensuring that new health products are safe and effective for people.
It is essential to clarify that GLP, functioning as a data and operational quality system, differs from laboratory safety standards concerning protective equipment like gloves and glasses. The main ideas behind GLP are to ensure safety, consistency, high quality, and reliability in lab tests that aren’t directly related to patient care.
Notably, GLP’s scope is not confined to chemicals but extends to medical devices, food additives, packaging, color additives, animal food additives, non-pharmaceutical products, biological products, and electronic products.
The history of GLP
GLP was first implemented in New Zealand and Denmark in 1972. (1) It gained prominence in the United States after cases of fraud emerged, where toxicology labs submitted unreliable data to the Food and Drug Administration (FDA) on behalf of pharmaceutical companies.
The notorious case of Industrial BioTest Labs (IBT) revealed widespread falsification or poor execution of safety tests, causing public scrutiny and congressional hearings. In 1976, the FDA responded with proposed regulations on GLP, leading to the establishment of the final rule in June 1979 (21 CFR 58) (1).
The Environmental Protection Agency (EPA), encountering similar issues, formulated its own draft GLP regulations in 1979 and 1980, culminating in the publication of final rules in 1983 (40 CFR 160 and 40 CFR 792).
GLP was created to monitor and support the development of human drugs, biological products, cosmetics, medical devices for human use, electronic products, food and color additives, veterinary drugs, feed additives, and tobacco products (2).
There are, of course, studies that are not meant to be under the scope of GLP.
These include:
- Human clinical studies;
- Nonclinical PK (pharmacokinetics) evaluation that is not part of a GLP study;
- Bioanalysis of samples for clinical trials;
- Basic research (nonclinical pharmacology studies for mechanisms of action, efficacy);
- Discovery toxicology studies.
Global harmonization of GLP standards
The FDA and EMA (European Medicines Agency) play pivotal roles in regulating and ensuring compliance with GLP standards. These regulatory agencies create rules and guidelines that research labs must follow. They oversee non-clinical safety tests for medicines to ensure that the products are of high quality, reliable, and trustworthy for use in both human and animal health.
Both the FDA and EMA emphasize the importance of GLP in maintaining patient safety, data reliability, and ethical standards throughout the various phases of the clinical trial process. They mandate GLP compliance for studies on animal health products, overdosage studies, safety studies in the target species, and more.
The Organisation for Economic Co-operation and Development (OECD) plays a central role in developing and promoting global standards for GLP. Its guidelines ensure the quality of non-clinical safety studies, fostering international harmonization.
Collaborating with regulatory bodies, including the FDA and EMA, the OECD council contributes to consistent GLP standards worldwide. The organization also supports training initiatives for effective GLP implementation.
These agencies work with national competent authorities to ensure that clinical trials follow rigorous scientific and ethical standards across all phases, from preclinical research to Phase 4 trials. Following GLP guidelines, which are monitored and enforced by regulatory bodies, is crucial for getting approval to sell treatments in different markets.
The way to keep GLP standards and practices updated to the modern state of the healthcare industry is through constant communication between the different regulatory and inspection agencies. The main goal is to have an all-encompassing standard of procedures that evaluate medical research efficiently and fairly.
GMP compliance: purpose and challenges
GLP compliance is mandated for specific studies, including:
- Those related to overdosage;
- Animal safety
- Tissue residue;
- Udder irritation in animal health products.
Additionally, safety studies assessing the drug-abuse potential, submitted to the FDA for research or marketing permits, fall under the compliance requirement. Chemical procedures characterizing the test article, ensuring stability, and determining homogeneity are also included.
Conversely, GLP compliance is not required for certain activities, such as:
- Validation trials confirming analytical methods;
- Safety studies on cosmetic products;
- Organoleptic evaluation of processed foods;
- Work related to developing chemical methods or establishing specifications for a test article;
- Analyzing specimens through chemical procedures, like clinical chemistry and urinalysis.
It’s crucial to note that GLP is not obligatory during early development stages, encompassing discovery, screening, basic research, and concept assessment, aligning with the World Health Within the organizational process, the recommended GLP compliance typically applies from Stage 2 onward in the drug development process.
Maintaining good laboratory practice compliance presents challenges in understanding complex regulations, adapting to frequent changes, and allocating resources effectively. To ensure everyone follows the same practices and to avoid problems from not following rules, it’s important to have a strong culture of compliance and continuous training.
It’s also crucial to balance spending on infrastructure and quality control with other operational needs. The principles we’re discussing need to be implemented carefully, so having control and supervision over how they’re put into practice is essential.
Key principles of GLP
GLP guidelines encompass key elements to ensure the integrity and reliability of studies in a test facility.
Personnel
At the commencement of a study, a designated study director must be appointed by the testing facility manager to oversee overall conduct and GLP compliance.
The presence of an independent Quality Assurance Unit (QAU) is crucial, ensuring separation from the testing facility’s organizational management.
Characterization
Personnel conducting the study must possess knowledge about each test and control article.
This includes information about:
- Identity;
- Purity;
- Composition
- Stability;
- Date of receipt;
- Expiry date;
- Storage instruction;
- Quantity received;
- Quantity used.
Facility and equipment
The test facilities should establish separate areas for various activities.
Different areas should be suited for:
- Receiving and storing test articles;
- Mixing them with carriers;
- Storing mixtures;
- Housing test systems.
Regular calibration and maintenance of equipment are imperative, with the data recorded accessible to operators.
Study plan or protocol
The study plan or protocol serves as the master guidance document, outlining the study’s methodology, schedule, and materials used.
It undergoes a thorough approval, review, and discussion process before the study begins.
Storage of records
Throughout the study, the study director is responsible for capturing and storing all data related to the study.
Archived records, including the protocol, final report, and SOPs, are securely stored, and only authorized personnel can access them.
Standard operating procedures (SOPs)
SOPs, especially for routine procedures, must be established for each separate area within the testing facility.
These procedures require approval from the testing facility manager, and any deviations should be authorized by the study director.
Retention of records
The duration for retaining archived records varies based on national GLP regulations.
For research laboratories in the US, the retention period depends on factors such as FDA submission, application status, and study completion, ranging from 2 to 5 years.
Final report
Prepared and approved by the study director, the final report provides a comprehensive and accurate account of the study.
It includes deviations, results interpretation, and a GLP compliance statement.
Regulatory requirements for GLP
Adherence to regulatory requirements is integral to maintaining the quality and integrity of non-clinical laboratory studies conducted under GLP. These regulations, outlined by regulatory authorities, span key aspects of the research process.
Firstly, personnel qualifications are crucial, with the appointment of a qualified study director and the establishment of an independent Quality Assurance Unit (QAU) being mandatory. The facility infrastructure must adhere to standards ensuring the separation of activities, preventing interference, and preserving the integrity of the study.It’s important to thoroughly describe and document each test and control item to stay compliant.
The regulatory process involves carefully reviewing and approving the study plan before it starts, making sure it meets all the required standards. The final report must be accurate and complete, including any unexpected changes, scientific explanations, and a statement from the study director confirming that the study followed GLP rules.
Lastly, secure storage and meticulous record retention, with access limited to authorized personnel, are mandated throughout the study’s duration, meeting specific regulatory timelines for archived records.
Adhering to these regulatory requirements is essential for research laboratories to uphold the credibility and mutual acceptance of their study data within the scientific and regulatory communities.
In the past years, GLP has proven itself to be a staple of integrity and safety in the medical community. Learning how to implement its practices and principles can be extremely beneficial.
There are a lot of aspects to it combined with considering its regulatory requirements as well. It is an undeniable fact, however, that having a better grasp on GLP can improve the way any medical research is carried out and ensure a safer environment for future growth.
Ivan is a Technical Copywriter with extensive experience in the field of medical technology and software development. He specializes in translating complex technical concepts into clear and engaging content tailored for both industry professionals and broader audiences.
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