GLP (Good Laboratory Practices) is generally defined in regulating laws from various jurisdictions as: “a set of rules and criteria for a quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, reported and archived.” [3] The majority of regulatory authorities require all non-clinical studies, which are conducted to assess the safety of test articles intended for pharmaceutical, cosmetic, and industrial chemical use and as food additives, with respect to human health and/or the environment, to follow GLP [4]. The test articles involved can be synthetic or of natural and biological origin.
What are the GLP (Good Laboratory Practices) in the Pharmaceutical industry?
The current quality and safety standards for pharmaceutical products (active ingredients or finished products) requires the generation of many lab-based measurement values to allow further human trials or final release. However, regulatory authorities have dealt with numerous situations of tampered non-clinical (toxicological and pharmacological) laboratory studies required for authorization of new drugs.
Thus, it was important to have rules and guidelines in place that would constitute minimum standards for Good Laboratory Practice (GLP). This was deemed essential not only to ensure the integrity and trustworthiness of scientific data provided to regulatory authorities but also to facilitate cooperation between laboratories from different jurisdictions, as data generated from GLP -compliant labs would be considered equally reliable.
In this article, we will explain an overview of GLP in general, with an emphasis on its application in the pharmaceutical industry.
A Brief History of Good Laboratory Practice (GLP)
The seventies of last century witnessed the emergence of multiple scandals that impacted a wide range of toxicological and pharmacological, non-clinical studies [1]. These studies were marred with numerous instances of faking data, as well as extremely poor practice during recording and reporting study-related incidents (deviations) and results. It was noted that laboratory practices followed during these studies did not guarantee the integrity and reliability of results.
In response to these grave incidents, the FDA adopted regulations in the late seventies describing a set of guidelines for good laboratory practice to ensure the integrity of laboratory-generated data. These regulations were further updated to introduce changes to other aspects of laboratory work, such as pre-approved study protocols, handling of samples and specimens, and clarifications regarding the role of quality assurance units [2]. Later on, similar regulations were adopted by the EU and the OECDto unify the practice in laboratories located in various jurisdictions, facilitate the cooperation between laboratories and boost the reliability of results produced by third-party laboratories or contract research organizations.
What is GLP? And What Are The Core Areas of Its Scope?
The scope of GLP, as identified by laws from the FDA, EU, and OCED, covers four major areas of laboratory work. These core areas are facilities, equipment, personnel, and documentation, which are in alignment with those adopted by GMP guidelines for the pharmaceutical industry. GLP regulating laws provide detailed guidelines related to each of these core areas, initially covering the facilities that will receive the test item and reference materials, as well as testing and archive facilities. Then, these laws describe the good laboratory practice guidelines concerning equipment used to conduct testing. And provide best practices for organizing personnel responsibilities; while stressing the importance of having independent quality assurance personnel within the testing facilities to guarantee the utmost integrity of the study and any results. Finally, these laws provide guidelines for best practices relevant to documentation and record keeping.
Guidelines: FDA – OECD – EU (Good Laboratory Practices/GLP in Pharmaceutical Industry)
As mentioned above, GLP regulations were established in response to scandals that impacted animal safety studies and included test articles intended for various purposes, not necessarily pharmaceutical ones. However, the application of key GLP principles in the pharmaceutical industry was found to be crucial to ensure the safety, efficacy, and quality of pharmaceutical products in general. From the early stages of preclinical studies, through to the characterization and quality control of raw materials and the assessment of finished products’ quality, laboratory testing is employed on a significant scale. This makes laboratory-generated data and results from key components of the pharmaceutical industry.
Additionally, regulatory oversight of pharmaceutical manufacturers is becoming thorough and demands conclusive evidence, many of which are laboratory-generated, for approving new products and qualifying manufacturing sites. As a result, the application of key GLP guidelines from FDA /OECD/ EU regulations gained the same importance as applying GMP to the manufacturing of pharmaceutical substances and products, making both complementary to each other.
Core Principles of GLP (Good Laboratory Practices) Applied in The Pharmaceutical Industry
As mentioned above, the scope of GLP guidelines covers four main areas of laboratory work: facilities, personnel, equipment, and documentation. The following are the core principles of GLP for each one of these areas:
The Facilities
- They should be of suitable size, construction, and design.
- The design must allow the separation of various activities required to conduct the study.
- Facilities, where testing is conducted, should be adequately separated and distinguished from receipt, storage, and archive facilities.
The Personnel
- Each organization should ensure that a sufficient number of qualified and trained personnel is available for conducting and supervising laboratory studies and work.
- The responsibilities of each individual should be clearly defined, ideally in a position description. And, a record of the qualifications and training of all individuals involved in the study or lab work should be maintained.
- Finally, personnel in the quality assurance department must be independent of lab work or study conducted, as they are responsible for assuring compliance and adherence to GLP principles.
The Equipment
- All equipment used in the generation, measurement, and assessment of data should be placed in a suitable location and of the appropriate design and adequate capacity.
- They should be operated, cleaned, inspected, and calibrated according to pre-approved standard operating procedures.
- Chemicals and reagents used in lab work should be clearly labeled to indicate the identity, storage conditions, purity, necessary warnings and expiry date.
The Documentation
- GLP regulations require the establishment of Standard Operating Procedures that are technically valid and approved by themanagement for the test facility and each separate unit.
- Any subsequent revisions or amendments should be approved by the management prior to application. Deviations from SOPs should be documented and acknowledged by management.
- SOPs should be available for various activities conducted within the testing facilities; this may include the following:
- Receipt, identification, handling, sampling, and storage of test or reference items.
- Use, maintenance, and calibration of equipment, as well as validation, operation, and backup of computerized systems.
- Record keeping, reporting, archiving, and retrieval of records.
- In addition to SOPs, documents related to specific studies or analytical work, such as testing monographs, study plans (or protocols), study conduct (testing records), and study final reports should be available prior to, during, and after the execution of the study or lab work.
When is GLP (Good Laboratory Practices) compliance required by my business?
Compliance with GLP guidelines is required by all laboratories conducting non-clinical (toxicity and environmental safety) studies related to pharmaceutical, cosmetic, veterinary, food products, and other industrial chemicals. In the pharmaceutical industry, quality control and in some cases, research and development laboratories are increasingly required to comply with GLP guidelines when conducting chemical and physical testing. This enhances the reliability of any data related to products’ quality and stability when submitted to various regulatory authorities for marketing authorization. In addition, contract research organizations (CROs) are required to submit proof of their stance with regard to GLP prior to the approval of any testing data produced in these labs.
How Do You Get a GLP (Good Laboratory Practices) Certification?
There is no straightforward certification pathway that would state the GLP compliance of any testing facility. Yet, GLP compliance is established by successfully passing through inspections performed by a competent national authority responsible for ensuring GLP guidelines are properly followed. Any laboratory facility wishing to be acknowledged as adhering to GLP should join a GLP compliance monitoring program. In this program, the laboratory is periodically inspected to confirm its situation of adherence to current guidelines. A record of all GLP inspections performed and their results are accepted as proof of compliance and, usually, accompanies any studies conducted within the facilities.
The following are some essential good laboratory practices:
– The receipt of the test or reference items should be done in dedicated facilities separate from the testing facilities.
– The responsibilities of involved individuals should be clearly determined prior to the study.
– All activities conducted within the testing facility should follow pre-approved Standard Operating Procedures (SOP).
– Any deviations or incidents occurring during testing should be captured and reported to the management and quality assurance.
– Computerized systems should be adequately validated to perform their purpose. It is important to have audit trails that record details of new entries or modifications to existing ones.
The following are some examples of GLP:
– Any study conducted should follow a protocol that is pre-approved by management, and clearly specify the individual responsibilities of involved personnel.
– Deviations or incidents occurring during the study should be captured, recorded, and reported to the management and quality assurance.
– Equipment used for testing or evaluating results should be qualified and calibrated periodically.
GLP is a set of organizational rules aimed at ensuring the presence of a standard quality system under which laboratory work and non-clinical studies are conducted, documented, and archived. An important example of GLP is the presence of an independent quality assurance (QA) unit separate from the study of work conducted and reports directly to study or laboratory management. The QA unit is responsible for ensuring GLP is followed prior to, during, and after the execution of the study or laboratory testing.
GLP is set of organisational rules aimed at ensuring the presence of a standard quality system under which laboratory work and non-clinical studies are conducted, recorded and archived. An important example of GLP is the presence of independent quality assurance (QA) unit separate to the study of work conducted and reports directly to study or laboratory management. The QA unit is responsible for ensuring GLP is followed prior, during and after the execution of the study or laboratory testing.
The adherence to GLP guidelines from FDA, EU, and OCED laws depends on the presence of the following major requirements:
– Properly designed and qualified facilities that allow separation of activities.
– Qualified and trained personnel with clearly defined responsibilities.
– The presence of suitable and properly qualified equipment to conduct the testing or the study of interest.
– Pre-approved documentation that describes the role of each technical unit in conducting the study or laboratory work in general.