In recent years, both basic and clinical research have joined their efforts to translate scientific discoveries into practice, from bench to bedside applications. Therefore a rapidly increasing number of laboratories are now establishing the molecular technologies to be used both in a clinical and a translational research setting. This results in an obvious need for standardization and harmonization of the developed test systems and of the laboratory procedures among different institutions.

Good Laboratory Practice (GLP) generally refers to a quality system concerned with the organizational process and the conditions under which studies are planned, performed, monitored, recorded, archived, and reported. The main goal of this system is to ensure the consistency and reliability of the results and therefore their mutual acceptance among all countries [1]. To this regard, many regulatory and guidance materials have been developed over time by governmental authorities and by accrediting or nonaccrediting organizations.

A first set of regulatory standards was developed in the late 1970s by the Organization for Economic Cooperation and Development (OECD) and by the Food and Drug Administration (FDA) [2] for assessing chemicals and testing safety of chemical products, including pharmaceuticals. The OECD standards, reviewed in 1997, dealt with a set of core elements including organization, quality assurance, facilities, test systems, controls, study design, and reporting of results relevant to nonclinical health and environmental safety studies (Table 50.1) [1]. Almost in the same time frame, the International Organization for Standardization (ISO) extended the applicability of GLP to laboratories performing clinical analysis (ISO/DIS 15189:1998, Quality Management in the Medical Laboratory). This standard introduced guidelines on specimen management, personnel safety, and verification of performance (mainly based on the ISO 17025:1999, the generic standard for testing and calibration laboratories), as core elements of the GLP. Currently, the ISO 15189 and 17025 guidelines are still relevant to all general clinical chemistry laboratories, and compliance to their standards is required for laboratory accreditation [3–5]. However, the ever-growing demand for molecular genetic testing still awaits coverage from ISO standards [6]. A draft of the best practice guidelines addressing testing for inherited disorders was developed by the European Molecular Genetics Quality Network (EMQN) in 2001 [7] and the draft for quality assurance in genetic testing was finally issued by OECD in 2006 [6]. Importantly, this latter draft recognized that research laboratories play a pivotal role in providing tests for genetic disorders, and supplied guidance standards for the validation and translation into clinical practice of new tests.

Table 50.1 GLP and GCLP core elements
Full size table

Particular surveillance and standardization are needed by activities of laboratories that perform the analysis or evaluation of samples collected as part of a clinical trial. In 1997, the European Medicine Agency (EMEA) introduced a set of regulatory elements ­concerning ethical and scientific quality standards for designing, conducting, recording, and reporting trials that involve the participation of human subjects (Good Clinical Practice, GCP) [8]. More recently, GCP was recognized as too vague with respect to sample analysis to ensure practical implementation in clinical trials [9]. Consequently, GCP was implemented with applicable portions of GLP and ISO 15189 standards [4, 10] by the joined effort of the British Association of Research Quality Assurance (BARQA) and USA ­governmental authorities [11, 12]. This resulted in the creation of the hybrid Good Clinical Laboratory Practice (GCLP) guidelines, which allowed connecting activities of basic research and clinical research laboratories (Table 50.1) [13–15].

To date, many relevant fields are still waiting for dedicated protocols from GLP standards. For example, only peculiar branches of basic and translational molecular research on human archive tissues have been addressed so far. Among these, requirements for biospecimen resource centers were formalized by OECD and NCI in 2007 [16, 17]. Although these guidelines recognize that the reliability of data from molecular assays is heavily dependent on the quality and consistency of the analyzed biospecimens, they do not specify in detail the technical requirements for preanalytical managing of tissues [18]. Many other relevant issues of translational research, such as RNA testing and proteomics, do not benefit from dedicated items in current international standards. This is even more important because, in our experience, standardization of the methods by commercial kits is not sufficient to guarantee reproducibility; good laboratory practice is absolutely necessary to obtain reliable results [20].