January 15, 2013 (Vol. 33, No. 2)
Biological materials collected from patients provide critical sources for a host of applications that include basic research, drug discovery and validation, and even companion diagnostics.
Thus, collecting, maintaining, and tracking biological specimens stored in repositories require development of rigorous standardized operating procedures (SOPs).
Key challenges facing biobanking include carefully and precisely obtaining the tissue or tumor sample, appropriate handling and processing, and documenting the history of patient samples. CHI’s recent “Leaders in Biobanking Congress” meeting discussed these and other issues affecting the industry.
Because more than 80% of drugs fail in clinical trials, there is an urgent need for improved predictive preclinical cellular models, indicated Florian Unger, Ph.D., scientist, drug testing and proteomics, Indivumed. “The problem is that most current cellular models do not comprehensively represent patients’ tumors. There are a number of reasons why.
“The first issue is that individual tumors are very heterogeneous in their composition of cell types and within the same type of cancer. A second important consideration is the absolute need for a process that consistently and rigorously regiments the collection of specimens to minimize artifacts of sample collection, e.g., ischemia time. The access to viable tissues of high quality is the key for creating better models.
“Finally, there are a number of choices regarding the types of analyses that should be performed to molecularly characterize specimens. These include decisions about thorough mutational analysis, creation of functional proteomic and genomic profiles, etc.”
According to Helge Bastian, Ph.D., managing director and chief commercial officer, there is a trend for outsourcing the collection, processing, and annotations of biobank samples.
“Our company basically operates as an oncology contract research organization with biobanking and laboratory services. We found that companies not only need a reliable source for comparable samples that reveal the molecular realities like in the human body, but also find it more cost efficient for the sponsor if we also provide comprehensive analytical results and molecular profiles from such samples.”
Indivumed has an oncology biospecimen repository and clinical databank from more than 15,000 patients. Dr. Bastian reported, “The specimens we place in our biobank have been collected and processed under rigorous conditions and SOPs including having specially trained study nurses in the surgery room itself. Biospecimens for clinical research studies are more valuable as more clinical data and patient information are annotated. We collect more than 250 data points per patient, which are stored in our centralized, searchable databank IndivuNet.”
Tumor samples also can serve as a source for viable organoid tumor cultures. These can be used to create a human tumor model system in vitro that represents the heterogeneity of patients’ tumors for subsequent preclinical drug testing.
“Often researchers take human tissue and implant it into mice. But over time, grafted cells do not provide a complete picture of what happens in a human setting. Our original patient-specific tumor cultures (IndivuPTC) provide an in vitro model that represents the natural tumor microenvironment in humans. This model provides a much improved way to assess the effect of drugs.”
Dr. Bastian said the company’s ultimate goal is to quickly translate new scientific discoveries into the practice of medicine by supporting the development of the best possible and individualized diagnostic and therapeutic solutions, especially targeted at cancer.
“The way to do this is at the very beginning by looking at the tumors of individuals to get a true and detailed molecular picture of a patient’s cancer as well as by applying the most sensitive and cutting-edge technologies when analyzing the samples.”
The safety, integrity, and accurate tracking of samples stored en masse in biobank freezers is of paramount importance, noted Martin Frey, Ph.D., head of storage technology market segment, Hamilton Bonaduz.
“One critical issue is temperature fluctuations during storage. Samples must be kept in a uniform temperature environment. This can be a big challenge for a number of reasons. Opening and closing doors or manually digging around for samples not only lets in warm air, but can also lead to frost buildup in the freezer, which may mask sample labels. Robotics that register, store, select, and deliver samples can help with such challenges, but even many of those are not optimal since they operate at -20°C, not the critical level of -80°C.”
Hamilton decided to solve this problem by developing a new robotic system. “We’ve just released our new ultra-cold automated sample storage system, BiOS, which has the distinguishing feature of providing robotic handling and retrieval systems that are constructed to ensure that samples stay close to -80°C while being picked.
“The BiOS units also feature a security system by including a fully redundant refrigeration system with additional back-up refrigeration. Compared to traditional storage for samples, these new systems provide a much higher level of quality.”
Aside from temperature, Dr. Frey explained that other critical issues include sample tracking and auditing. “More and more journals are now requesting documentation, validating sample quality. Therefore, we also offer easy-to-learn sample-management software providing audit trails and temperature logs.
“The BiOS Inventory software supports 21 CFR Part 11 compliance and access control in order to meet the rigorous demands for sample security. This is very important as some studies have demonstrated up to half of samples in freezers were in the wrong place or had incorrect sample descriptions. Security also can be an issue, especially when dealing with forensics or infectious samples. Thus a higher degree of automation can provide a continuous tracking of individual sample histories noting all these important parameters.”
Integrated Technology Infrastructure
A newly formed collaboration—The Bioprocessing Solutions Alliance—pairs the commercial arm of Rutgers University Cell and DNA Repository (RUCDR Infinite Biologics) with Biostorage Technologies. “This partnership provides the bioscience industry with a state-of-the-art scientific approach coupled with the technology infrastructure for delivering integrated biobanking and analytical solutions and advanced sample bioprocessing,” said Andrew Brooks, Ph.D., COO of RUCDR Infinite Biologics and associate professor of genetics.
“The idea is to improve sample optimization, create renewable biological resources, and maintain sample integrity while reducing costs by fully integrating bioprocessing services and comprehensive biobanking solutions.”
Dr. Brooks noted that the strategic alliance encompasses all of their biorepository functions including a host of services such as tissue collection, clinical sample bioprocessing, nucleic acid extraction, cell-line establishment, sample-management consulting, and, of course, sample storage. “We also provide a host of analytical services including gene expression analysis, next-gen sequencing, genotyping, and bioinformatics.
“With a current inventory of more than eight million biosamples and growing, the undertaking is an enormous effort requiring the utmost safety, tracking, and coordination.”
Kristina Robson, Ph.D., senior director of comprehensive solutions at BioStorage Technologies noted that the alliance comes at an opportune time. “There are significant changes in the industry. More and more emphasis is being placed on evaluating tissue samples to identify biomarkers for diagnostics as well as for assessing treatments. Yet at the same time, we are also seeing a move to downsize and streamline operations to provide more cost-effective solutions.
“Ten years ago, many labs were buying equipment and doing things more in-house. Now, we are seeing a shift to strategic partnerships and professional relationships. We felt that forming this alliance was a great way to enhance quality, efficiency, and cost-effectiveness. It’s the best of all worlds.”
Dr. Robson said the alliance also leverages the company’s sample management system, the Intelligent Specimen Inventory Storage System (ISISS®).
“This provides a number of critical features. It maintains a historical electronic audit trail of samples that can link aliquots to parental samples, allowing complete data tracking and regulatory compliance for future audits. Clients can also use their preferred barcode nomenclature or even choose study-specific, custom barcode labels. Finally, we provide a single global database that gives users complete access to samples with the ability to quickly and safely ship anywhere in the world within 24 hours. We have been doing that for a number of years.”
According Dr. Brooks, an alliance of this magnitude required overcoming a number of challenges. “We wanted to have a smooth, streamlined integration of operations between our two businesses. To accomplish this complementary effort, we have incorporated the ISISS system with our existing technology and workflow in order to deliver a streamlined view of sample inventory from the research bench to storage.
“Another challenge was the need to tailor services to meet the requirements of industry and pharma, not just academia. But through our alliance with BioStorage, we are making great strides to move into this area as well. The recent CAP accreditation of our biorepository is an example of our industry leadership and ability to deliver the service-level quality required by commercial clients. We are very excited about this alliance and feel we are breaking ground on a new level of expertise in biospecimen processing and storage that has significant benefits for the industry.”