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The biorepository: The cornerstone of drug development
Properly managing biospecimens and their associated data has become an increasingly important component of today's drug development and discovery process. Today, biomaterials such as whole blood, human tissue, DNA and RNA serve as the foundation for translational research that holds the promise of bringing personalized therapeutics from bench to bedside. These materials are being leveraged by organizations around the world as the basis for biomarker programs, which can give researchers insight into predicting future patterns of disease.
By incorporating biospecimen and biomarker components into discovery initiatives, researchers can incorporate information about cell biology and its impact on treatment options and patient prognosis. Through this new understanding, novel treatment options may be developed to target specific pathways for all manners of diseases such as cancer and Alzheimer's. Biomarker assays may also help identify patients with specific mutations or abnormal protein expression in certain cell pathways, allowing for individualization of therapies addressing specific abnormalities.
Given the intrinsic value of these materials, preserving specimens to the highest of standards is critical, not only from an operational and scientific perspective, but also from a regulatory and financial standpoint. As a result, it has become critical for biotechnology and pharmaceutical companies of all sizes to have a profound understanding of sample management strategies, and biorepository operations that help ensure the long-term preservation of biospecimen samples. Here, we outline preparation techniques, best practices for sample storage and transportation, and explain how information systems can enhance global biorepository operations and help optimize biospecimen integrity.
Techniques for preparation of biological samples
Pre-analytical variables introduced during clinical sample collection and processing significantly impact the molecular integrity of specimens and bias the results of assays and/or biomarker studies. Therefore, an essential component of any sample management strategy is a set of standardized protocols for sample preparation techniques.
Inexact sample preparation can lead to sample loss, reprocessing or complicated data interpretation. For example, to prevent degradation of RNA and DNA, stabilize the matrix (e.g., with alcohol) immediately upon collection. After the matrix has been stabilized, store it at the proper temperature without temperature excursions.
Compartmentalized storage equipment, continuous temperature monitoring and redundant power sources are essential. Furthermore, because modern assay technology requires very small volumes for most tests, it could be useful to divide biospecimen samples into multiple controlled-volume vessels.
Good storage practices for long-term specimen management
To ensure biospecimens are properly handled, transported and stored, many drug developers and research organizations are aware of and adhere to Good Storage Practices (GSP) guidelines. While GSP is not a regulatory mandated requirement, the International Society of Biological and Environmental Repositories (ISBER) as well as governmental organizations like the U.S. National Cancer Institute (NCI) have established specific good storage practices guidelines.
In 2008, ISBER drafted guidance of best practices for the collection, storage, retrieval and distribution of biological materials for research. Even more recently, the College of American Pathologists has launched its accreditation for biorepositories program, which will begin in 2012. The program aims to help biorepositories identify stages in the biospecimen management sequence, from patient to analysis, where documentation variances can render specimen quality unknown and introduce variables that may alter specimens' molecular structure. Industry experts expect these guidelines to evolve into regulations such as those that exist in other GXP environments (for example, GTP, GCP, GLP and GMP). The guiding principles of GSP mandates standardization of sample handling and management processes to ensure materials are prepared and stored in consistent conditions.
Factors that should be considered in defining sound storage practices include:
Cold chain logistics and management
Cold chain management defines how temperature-sensitive materials such as biospecimens, study drugs and active pharmaceutical ingredients are packaged, transported and stored throughout the research and development process. Weakness or failure at any point in the chain can compromise product integrity, breach security, delay shipments and ultimately result in financial loss or liability.
As such, the importance of training site personnel in correct shipping and receiving processes for temperature-sensitive materials cannot be overstated. Set-up and handling are common causes of temperature deviations; it is crucial that all cold chain partners are properly qualified and have been adequately instructed in handling these materials. In fact, the International Air Transport Association (IATA) requires organizations and individuals that ship or receive biological materials to be trained properly in packaging, labeling, documentation, declaration, hazard assessment and emergency response. This is of the utmost importance, as lack of compliance can delay shipments at inspection points. This bottleneck can delay studies, thereby reducing a potential drug candidate's time on the market.
To ensure compliance and optimize the biomaterial cold chain, organizations should take a holistic approach to cold chain management in which processes are an integrated component of the organization's overall best practices.
Information and data management for global sample inventories
While proper storage and transportation are critical, samples are useless unless they can be located with their associated data, in a timely fashion. In the past, researchers applied ad-hoc tracking systems such as spreadsheets to track and plot information associated with biospecimens. Today, the complexity of clinical trial research has rendered these outdated and archaic systems inefficient to handle expanding biospecimen inventories. The ideal system should offer tracking and reporting processes through all stages of a sample's shipping, handling and storage lifecycle.
Because pharmaceutical and biotech labs typically implement a wide range of information systems, sample management systems should seamlessly interface with other systems, provide global data integration and access, and be highly configurable to easily integrate with a variety of laboratory workflow models. The integration of sample storage, consent authorization and clinical result data is another area of expansion occurring due to the advent of new technology systems. Connecting information on sample storage location, temperature and pre-testing evaluation with the resulting data from a clinical study can enable researchers to improve their selection of samples for biomarker testing while shortening development timelines.
The growing role of outsourcing in global sample management
Organizations initiating a sample management strategy have a number of options when deciding where and how to store their specimen inventories, including storing on-site, off-site or both. However, due to the exponential amount of biospecimen samples generated during clinical research and the complexity of handling and transporting these temperature-sensitive materials across international borders, it has become commonplace for organizations to outsource their biorepository operations to specialized providers.
These services are well-suited for outsourcing due to their required capital investments in equipment, facilities, trained personnel, technology, security and transportation infrastructure. Additionally, organizations are outsourcing their storage operations with increased frequency as a result of escalating and costly industry regulations regarding audit trails, reporting requirements and chain-of-custody procedures.
Central laboratories that test blood and tissue samples sometimes offer storage as an ancillary service. However, given the increased value gained over many years of storage, it is essential that biorepository facilities be optimized for reliable, long-term storage and information management. Specialized biorepository vendors may provide services such as automated sample tracking and reporting, fully verifiable audit trails; extraction of nucleic acid; verification of DNA purity, yield and concentration; and volumetric and normalized aliquoting. These services allow researchers to customize various quantities of samples from a given subset of subjects into the sample size and tubes required for testing.
As cost concerns and risk management continue to be critical factors, companies are increasingly establishing hybrid approaches to on-site sample management where inventories are stored on-site, but are dictated by standard operating procedures and technology provided by an outsourced provider. This allows for the appropriate tracking, assigning and processing of individual samples across multiple studies on a routine basis. Additionally, it leads to more efficient lab processes, given that most services that require automation are assigned to specimens across studies.
Like many aspects of drug development, selecting a biorepository partner is a complex, strategic proposition. Only by carefully screening and evaluating all available options can an organization identify a biorepository service provider that is truly a partner.
The industry recognizes the one-size-fits-all approach to drug development is no longer the pathway to success. Today, the industry is focused on a more targeted approach to drug development, where the right treatment is prescribed to the right person, at the right time. As personalized medicine and genomic-based therapies become the gold standard in drug discovery, specimens such as blood, serum and tissue may hold the key to better understanding some of the world's most devastating diseases. With this in mind, now is the time for pharmaceutical and biotech companies, both large and small, to assess their current sample management strategies to ensure current and future drug discovery is not jeopardized by sub-optimal management processes or samples or lack of sample data.
Gregory Swanberg is CEO of BioStorage Technologies in Indianapolis. He has provided management and consulting support, both domestically and globally, to companies including Pfizer Inc., Merck & Co. Inc., Genentech Inc., Novartis AG, Eli Lilly & Co. Inc., Morgan Stanley, AT&T, Whirlpool and Lexmark. Swanberg holds a bachelor's degree from the University of Kentucky, a master's degree in public administration from Georgia Southern University and a master's degree in business administration from Northwestern's Kellogg Graduate School of Management.