Recommendations for Clinical Biomarker Specimen Preservation and Stability Assessments

Abstract

With the wide use of biomarkers to enable critical drug-development decisions, there is a growing concern from scientific community on the need for a 'standardized process' for ensuring biomarker specimen stability and hence, a strong desire to share best practices on preserving the integrity of biomarker specimens in clinical trials and the design of studies to evaluate analyte stability. By leveraging representative industry experience, we have attempted to provide an overview of critical aspects of biomarker specimen stability commonly encountered during clinical development, including: planning of clinical sample collection procedures, clinical site training, selection of sample preservation buffers, shipping logistics, fit-for-purpose stability assessments in the analytical laboratory and presentation of case studies covering widely utilized biomarker specimen types.

Integrating exosomal microRNAs and electronic health data improved tuberculosis diagnosis

“…Reasoning that an ideal miRNA biomarker should remain stable in plasma, we evaluated the freeze-thaw stability and short-term (bench-top) stability of samples, which were commonly encountered in clinical practice [38]. We randomly selected plasma samples from 6 healthy individuals, and their plasma samples were subjected to different conditions such as prolonged incubation at 4 °C (0 h, 1 h, 2 h, 6 h, 12 h, and 24 h, respectively) and repeated freeze-thaw cycles (0, 1, 2, and 4 times, respectively), as described in Supplemental Material (Section 6).…”

2017 White Paper on Recent Issues in Bioanalysis: A Global Perspective on Immunogenicity Guidelines & Biomarker Assay Performance (Part 3 – Lba: Immunogenicity, Biomarkers and PK Assays)

“…While the discovery and development of biomarkers holds huge promise, it is clear that in order to draw meaningful conclusions, the analysis needs to be as close as possible to the time of collection of samples. This seemingly simple task is ridden with multiple challenges including preanalytic factors (e.g., collection, storage, shipping and handling), which can have a huge impact on the biomarker's stability, thereby affecting data reliability [48,49]. Since the impact on sample analysis can be quite substantial, it is important to evaluate sample collection and handling procedures in the assay development phase and subsequently provide the clinical sites with detailed instructions on controlling preanalytical variables [50] in a procedure manual (or lab manual), including specifics such as collection kits, collection tubes, exact pro-cessing methods with detailed steps, timing and temperature of each step, rate of freezing, aliquot size, etc.…”

“…-Existing literature outlining the FFP validation requirements [49,56] should be used, and layers of validation from CLSI documents added as appropriate to the COU.…”

A Critical Evaluation of Wet Biomarkers for Huntington’s Disease: Current Status and Ways Forward

“…It is, therefore, important that the storage temperature of samples is appropriate for the analyte tested [ 193 ]. Thus, biomarker studies should standardise and document the temperature and the duration of sample storage [ 194 ].…”

“…As highlighted above, differences in sample preparation can influence absolute analyte levels. Therefore, to ensure that preanalytical variability is kept to a minimum in multi-centre studies, SOPs for collection, processing, storage and transport of samples should be created, formalised, and strictly adhered to [ 194, 197, 198 ]. The importance of standardising pre-analytical variables was clearly demonstrated in a study of BDNF in serum and plasma [ 189 ] where the authors found many issues concerning BDNF detection that make reliable measurement difficult.…”