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

Date Published: May 5, 2009

Publisher: Public Library of Science

Author(s): Marcella Sarzotti-Kelsoe, Josephine Cox, Naana Cleland, Thomas Denny, John Hural, Leila Needham, Daniel Ozaki, Isaac R. Rodriguez-Chavez, Gwynneth Stevens, Timothy Stiles, Tony Tarragona-Fiol, Anita Simkins

Abstract: Marcella Sarzotti-Kelsoe and colleagues harmonize various approaches to Good Clinical Laboratory Practice for clinical trials into a single set of recommendations.

Partial Text: 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]).

The Global HIV Vaccine Enterprise (GHAVE) [8] created an alliance of independent organizations around the world dedicated to the development of a preventive HIV vaccine, spanning vaccine discovery, product development, manufacturing, and clinical trials. Both the International AIDS Vaccine Initiative (IAVI) and DAIDS are globally recognized organizations and work collaboratively in clinical trials under GHAVE. In the HIV field, clinical laboratory standardization based on GCLP compliance is one of GHAVE’s primary goals. Currently, within GHAVE there are two approaches on how to achieve GCLP compliance in a clinical laboratory environment. The first approach is followed by IAVI, and it is based on BARQA-GCLP [6],[9],[10]. The second approach is followed by DAIDS, and it is based on NIAID-GCLP [7]. The two approaches cover the same general core elements [6],[7], as listed in Table 1: BARQA-GCLP and NIAID-GCLP Core Elements.

The purpose of this paper is to propose a harmonized interpretation of the four GCLP critical elements listed above, for optimal management of clinical laboratory operations, which are critical for successful conduction of clinical trials. These GCLP elements were selected upon reviewing inconsistencies in the BARQA-GCLP and the NIAID-GCLP guidelines, which have affected the harmonization of clinical laboratory operations. The ultimate goal of this paper is to raise public awareness on the need to harmonize GCLP for clinical laboratory operations to optimally support clinical trials, and to call on the attention of the United States Food and Drug Administration, the Organization for Economic Co-operation and Development, the European Medicines Agency, and all other regulatory agencies worldwide to consider the information presented here, so that universal GCLP standards are developed. This paper was originated from a group of authors with expertise in phase I–III HIV clinical trials, GCLP, and regulatory materials such as GLP [14] and GCP, who convened the “Workshop on GCLP Guidelines for International Clinical Trials: Interpretation and Implementation” (October 9–10, 2007, in Raleigh, North Carolina [15]), but its scope extends to other study fields, such as cancer, malaria, tuberculosis, stem cell, or other therapeutic interventions.

This section consists of the GCLP recommendations agreed upon by the authors during the Workshop and from follow-up sessions.

Standardized GCLP requirements would benefit clinical laboratories conducting safety, diagnostic, and endpoint assays in support of clinical trials and would potentially benefit other laboratories globally, both by providing a consistent direction in GCLP compliance, and by allowing laboratories to put into practice a unified set of GCLP-defined procedures that will enhance reproducibility and reliability of results. The latter is especially critical when conducting trials that use multiple international laboratory sites.

Harmonization exists among global organizations as to the need for a quality system in clinical laboratories that analyze specimens from clinical trials. The authors reached a consensus that GCLP compliance is the minimal requirement that clinical laboratories should meet to increase adherence to standardized practices and procedures, optimize management operations of clinical laboratories, and enhance obtaining reproducible and reliable results, while ensuring the safety of human research participants.



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