Biomarker development has been identified as one of the most important areas for improving drug development and diagnosis by the FDA’s Critical Path Initiative. The two main causes of failure for drug candidates during clinical trials include safety problems and lack of effectiveness. The inability to predict these failures before human testing or early in clinical trials dramatically escalates costs.
The goal of critical path research is to develop new, publicly available scientific and technical tools such as biomarkers that will make the development process more efficient and effective. Such tools will make it easier to identify, earlier in the process, those products that do not hold promise, thus reducing time and resource investments. In addition, these advances will facilitate the creation of effective diagnostic tools and medical treatments for patients.
Biomarkers are measurable characteristics in animals or humans that can help predict the performance of a product during development, reducing uncertainties about safety or effectiveness. Biomarker discovery and validation are active, emerging fields of research. Well-characterized and clinically annotated biospecimens that accurately reflect various disease states are critical to successful biomarker discovery and development research.
Access to diseased tissues provides an opportunity to identify disease-related target/biomarkers and to investigate any disease-related differences in the pharmacology of drug compounds. Although sourcing appropriate samples can be a challenge, the quality of samples analyzed will ultimately determine the suitability of the biomarkers produced. Factors such as the procurement process, quality assurance procedures, donor clinical annotation, and storage conditions must, therefore, be taken into consideration when choosing a supplier for procuring tissues.
Access to Human Biospecimens
Asterand is a supplier of high-quality well-characterized human tissue. The company offers access to human tissue from its network of collaborative donor institutions through its XpressBANK™ and ProCURE™ product brands. Asterand’s XpressBANK biobank contains several hundred thousand specimens from a broad range of therapeutic areas. Through its ProCURE service, human tissues and clinical data can also be custom collected to meet special requirements. This includes the collection of follow-up data related to patient outcome.
The human biospecimens obtained by Asterand are well-suited to biomarker development and validation studies. The company has stringent quality-control covering specimen collection, characterization, and the corresponding clinical data. As part of this process, pathology is independently confirmed, and the RNA integrity of each tissue is assessed.
These parameters give researchers assurances on the molecular integrity of the sample, as well as confirmation of the disease stage and progression. The results of the QC testing are provided to researchers before they make a purchase so they can choose samples that will best meet their scientific requirements.
In particular, Asterand’s Quad Set™ Plus format, which is part of its XpressBank family of products, offers a platform for accelerating biomarker discovery and validation studies. A Quad Set Plus biospecimen collection consists of tumor and normal samples from a single case that is sliced into two pieces. One section from each specimen is preserved in liquid nitrogen or isopentane and the other is fixed in formalin and is available as a FFPE sample. In addition, serum and plasma samples from each clinical case are procured.
This format has several advantages for biomarker research. A key component of the discovery process is the isolation and relation of the biomarker of interest to the specific disease state. Not only can the diseased material be used to determine the presence of the biomarker but adjacent normal tissue from the same case can be utilized as a control to rule out the presence of the biomarker of interest in nondiseased samples.
Another challenge for scientists is the suitability of specimens for various discovery and validation platforms. It has been suggested that a combination of methods should be used to detect biomarkers. For example, in addition to searching for biomarkers in blood, researchers should also focus their discovery efforts on the site of the disease or the fluid bathing the tissue of interest.
The Quad Set Plus collection includes multiple biospecimen formats from each case. This allows researchers the opportunity to use the same cohort of donor material across different research platforms— matching the most appropriate format and allowing for a cross validation of results. This is especially useful for the validation phase of biomarkers, because it allows confirmation of the presence of a biomarker at the site of the disease and the ability to verify if the biomarker of interest can also be detected within patient serum and plasma samples.
As a result, scientists can determine if it is possible to transfer the biomarker detection to a diagnostic platform that uses a noninvasive sample. This may result in a biomarker test that is useful for continued monitoring during treatment or clinical trials. Finally, all samples are available as nonpooled aliquots from individual cases. This is important as most practitioners believe that the intrinsic biological variability present in individual samples contains important information, and pooled samples may mask these differences.
There is an increased level of acceptance within the industry and academia with respect to application of biomarkers as preclinical and clinical endpoints in the evaluation of new drugs and medical devices. Detection of biomarkers may allow for earlier go/no go decisions in developing treatments and help shave years and costs off of the development process by providing a clearer indication of a treatment’s efficacy, dosage, or safety.
Biomarkers are the foundation of evidence-based medicine, making the practice of medicine more personalized, predictive, and preemptive. In order to detect them accurately, however, one needs to have access to a variety of human biomaterials. Asterand’s Quad Set Plus allows scientists to source human biospecimens from a range of therapeutic areas from one company, thus helping them to focus on their research while saving time and resources.