In the experimental (non-clinical) research arena, good laboratory practice or GLP is a quality system of management controls for research laboratories and organizations to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical (including pharmaceuticals) non-clinical safety tests; from physio-chemical properties through acute to chronic toxicity tests.[1]
GLP was first introduced in New Zealand and Denmark in 1972, and later in the US in 1978 in response to the Industrial BioTest Labs scandal. It was followed a few years later by the Organization for Economic Co-operation and Development (OECD) Principles of GLP in 1992; the OECD has since helped promulgate GLP to many countries.
GLP applies to non-clinical studies conducted for the assessment of the safety or efficacy of chemicals (including pharmaceuticals) to man, animals and the environment.[1] GLP, a data quality system, is not the same as standards for laboratory safety - appropriate gloves, glasses and clothing to handle lab materials safely. The principles of GLP aim to ensure and promote safety, consistency, high quality, and reliability of chemicals in the process of non-clinical and laboratory testing. GLP is not limited to chemicals and also applies to medical devices, food additives, food packaging, colour additives and other non-pharmaceutical products or ingredients.
GLP principles include
- Organization and Personnel
- Management-Responsibilities
- Sponsor-Responsibilities
- Study Director-Responsibilities
- Principal Investigator-Responsibilities
- Study Personnel-Responsibilities
- Quality assurance program
- Quality Assurance Personnel
- Facilities
- Test System Facilities
- Facilities for Test and Reference Items
- Equipment, reagents and materials
- Test systems
- Physical/Chemical
- Biological
- Test and reference items
- Standard operating procedures
- Performance of study
- Study Plan
- Conduct of Study
- Reporting of results
- Archival - Storage of Records and Reports
Klimisch score[edit]
The Klimisch score system tries to rank the reliability of toxicity studies for use by risk assessors (regulatory agencies). It was published in 1997, by BASF (a chemical company) authors.[6] Studies performed according to GLP are assigned the top rank of 1 (reliable without restriction) and are preferred by agencies. When no GLP study is available for a particular endpoint, a study with a rank of 2 is usually accepted by an agency. Lower ranks typically require a new study to be performed. Klimisch scoring is very widely used in chemical risk assessments. Critics say it is a self-interested bias on objectivity, that a quality system from the regulated party gives their own GLP-complying studies the top rank.
Good laboratory practice or GLP is a set of principles intended to assure the quality and integrity of non-clinical laboratory studies that are intended to support research or marketing permits for products regulated by government agencies. The term GLP is most commonly associated with the pharmaceutical industry and the required non-clinical animal testing that must be performed prior to approval of new drug products. However, GLP applies to many other non-pharmaceutical agents such as color additives, food additives, food contamination limits, food packaging, and medical devices.
The actual regulations in the United States can be found in 21CFR58 (link) and for the European Union via the Organization for Economic Co-operation and Development (OECD, link). This post is not intended to be a comprehensive review of GLP regulations; however, there are some key areas of interest that touch pharmacokineticists. The most important area is the scope of these regulations. Too often the GLP regulations are applied when they should not be used, creating confusion, extra work, and additional costs. Let’s take a look at the scope of GLPs from the FDA documents and the OECD (italics added for emphasis):
This part prescribes good laboratory practices for conducting
non-clinical laboratory studies … (FDA 21CFR58)These Principles of Good Laboratory Practice should be applied to the non-clinical safety testing … (OECD, No.1)
GLP only applies to non-clinical studies and testing. It does not apply to clinical studies. This is extremely important because clinical studies are governed by Good Clinical Practices (GCP), the Declaration of Helsinki, and other regulations intended to protect human participant safety. Furthermore, much of the GLP structure depends on the roles and responsibilities of the Study Director, a single individual that is responsible for the oversight and execution of all aspects of the non-clinical study. Study Directors do not exist in the clinical study arena, thus GLP principles cannot be applied effectively in the clinical setting.
Beyond the scope, there are two other items I would like to discuss. First, GLP is a quality management system, not a scientific management system. Or, in other words, GLP defines a set of quality standards for study conduct, data collection, and results reporting. GLP does not define scientific standards. If a study follows GLP, then you can be reasonably sure that the reported results were collected as outlined in the study protocol; however, you cannot be sure that the study actually addresses the scientific hypothesis. In the world of cooking, GLP would ensure that someone follows the recipe exactly as written; however, it does not assure you that the recipe was good or that the resulting item will be tasty!
Second, a key component of the GLP system of quality standards is the idea of a Quality Assurance unit (QA). This QA unit is intended to be an independent group or individual that monitors the entire study conduct, analysis, and reporting. The purpose of QA is to verify that all written procedures are followed throughout the study. As an example, perhaps there is an SOP that says that a senior pharmacokineticist must review the results prior to finalization. The QA auditor will verify that this review occurred. Verification could be done by reviewing a signed document, reviewing an electronic signature, or even speaking directly with the reviewer. The QA auditor will ensure that the senior pharmacokineticist has adequate training (as defined by SOPs in the organization) to perform his or her duties. This quality audit permits confidence that procedures were followed. But again, this audit does not ensure that the procedures are of high quality, or that no errors are made in the analysis.
Here are a few examples of how I think GLPs are misinterpreted:
- Using GLP to perform bioanalysis for human clinical trials. As noted in the scope for both GLP and OECD GLP, the principles of GLP only apply to non-clinical studies. Therefore, following GLP, particularly with respect to QA reviews is an unnecessary cost. It is more important to follow analytical validation plans.
- Performing GLP as a single person. GLP work requires at minimum 2 or 3 individuals. These are the person performing the work (analyst), a person reviewing the work (management), and a quality assurance reviewer (QA). If SOPs are written well, the analyst and the management can be the same individual; however, QA must always be an independent person.
- Results of GLP studies are “right.” A statement that a study was conducted in conformance with GLP simply means that quality systems were followed, and that the results of the study accurately report the conduct of the study. It does not indicate that the conclusions drawn are accurate, scientifically robust, or even useful!
I hope you take some time to learn more about GLP and apply it correctly in your future work.
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The main objective of microbiological laboratory safety is to maintain the pure culture for practical study. It is very important to maintain a clean environment in the microbiology laboratory.
1. The laboratory should have proper aeration and ventilation facilities.
2. The floor must be wiped with 10% detergent solution every day.
3. The working surface must be cleaned with 70% ethanol.
4. The glassware, inoculation loop, and microscopic slide must be surface sterilized with 70% ethanol.
5. The working individuals should keep their personal belongings outside the laboratory. E.g: bag, wallet, cell phones and other materials which are not required for practicals.
6. Do not dispose of hazardous chemicals, live or dead cultures through the sink.
7. The glassware should be washed with a disinfectant solution, then rinsed with distilled water. The glassware should be free of moisture and salt.
8. Inoculation loop, microscopic slide, Petri dishes, "L" rod and other materials required for microbial culture must be surface sterilized with flame and 70% ethanol.
9. The microbial live culture works (inoculation, plating, staining etc..) must be done inside the Laminar Air Flow chamber.
10. The surface sterilization of inoculation loop, "L" rod, microscopic slide and Petri dishes must be done with the blue flame (energy released by the collision of the excited state of molecular carbon dioxide - complete combustion) and not with the yellow flame (energy released by soot-forming or incomplete combustion causing incandescent carbon particles)
11. All the electrical units must be switched off before closing the laboratory except refrigerators.
12. All incinerators must be turned off once the experiment purpose is over and has to be checked once before leaving the laboratory.
13. Sterilization of glassware and other materials must be done by proper procedures.
14. Do not displace anything in the lab without prior permission of the instructor.