Evaluation and Recommendations on Good Clinical Laboratory Practice Guidelines for Phase I–III Clinical Trials

Global clinical laboratory work performed under harmonized operations is a central component for the successful conduct of phase I–III clinical trials in multiple fields of science and medicine. However, global harmonization of clinical laboratories for the analysis of specimens from clinical trials operations (i.e., for safety, diagnostic, endpoint laboratory assays) faces international challenges (e.g., laboratory logistical and technical factors), and it is subject to different interpretations of regulations and guidance materials published by the federal government, accrediting, and non-accrediting organizations (e.g., Good Laboratory Practice [GLP] [1], Clinical Laboratory Improvement Amendments [CLIA] [2], College of American Pathologists [3], International Organization for Standardization [ISO] 15189 [4], and International Conference on Harmonization [ICH] Good Clinical Practice [GCP] [5]). In an effort to harmonize and gain consensus on international clinical laboratory operations, Good Clinical Laboratory Practice (GCLP) guidelines were originated by merging GLP and ICH-GCP principles, and were first published and copyrighted by the British Association of Research Quality Assurance (BARQA) (BARQA-GCLP) [6]. Subsequently, the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health expanded the existing knowledge on GCLP standards by publishing guidelines on GCLP (NIAID-GCLP) [7], with increased implementation guidance based on applicable portions of GLP, CLIA, the College of American Pathologists, and the International Organization for Standardization (ISO 15189). Both of these GCLP approaches were created to ensure that clinical laboratory results are reliable, repeatable, auditable, and comparable between multiple clinical laboratories. Nevertheless, differences in the implementation of GCLP by clinical laboratories have created critical inconsistencies for routine management of operations in support of clinical trials and have caused an urgent need to clarify and harmonize four central GCLP elements for optimal management and clinical laboratory operations. These GCLP elements—discussed in this paper—are training, auditing, assay validation, and proficiency testing. The differences regarding the implementation of universal standards of GCLP for clinical laboratory operations (i.e., clinical laboratories performing safety, diagnostic, and endpoint assays) in the conduct of clinical trials have been experienced in the HIV study field. However, it is expected that this problem will have broader implications in clinical trials, involving multiple fields. This paper addresses for the first time an attempt to harmonize these GCLP approaches into a single set of recommendations for optimal operations and management that can be followed by clinical laboratories, not only in the HIV field, but also possibly in other science and medical fields.