The biorepository: The cornerstone of drug development

Properly managing biospecimens and their associated data hasbecome an increasingly important component of today's drug development anddiscovery process. Today, biomaterials such as whole blood, human tissue, DNAand RNA serve as the foundation for translational research that holds thepromise of bringing personalized therapeutics from bench to bedside. Thesematerials are being leveraged by organizations around the world as the basisfor biomarker programs, which can give researchers insight into predictingfuture patterns of disease.

By incorporating biospecimen and biomarker components intodiscovery initiatives, researchers can incorporate information about cellbiology and its impact on treatment options and patient prognosis. Through thisnew understanding, novel treatment options may be developed to target specificpathways for all manners of diseases such as cancer and Alzheimer's. Biomarkerassays may also help identify patients with specific mutations or abnormalprotein expression in certain cell pathways, allowing for individualization oftherapies addressing specific abnormalities.

Given the intrinsic value of these materials, preservingspecimens to the highest of standards is critical, not only from an operationaland scientific perspective, but also from a regulatory and financialstandpoint. As a result, it has become critical for biotechnology andpharmaceutical companies of all sizes to have a profound understanding ofsample management strategies, and biorepository operations that help ensure thelong-term preservation of biospecimen samples. Here, we outline preparationtechniques, best practices for sample storage and transportation, and explainhow information systems can enhance global biorepository operations and helpoptimize biospecimen integrity.

Techniques forpreparation of biological samples

Pre-analytical variables introduced during clinical samplecollection and processing significantly impact the molecular integrity ofspecimens and bias the results of assays and/or biomarker studies. Therefore,an essential component of any sample management strategy is a set ofstandardized protocols for sample preparation techniques.

Inexact sample preparation can lead to sample loss,reprocessing or complicated data interpretation. For example, to preventdegradation of RNA and DNA, stabilize the matrix (e.g., with alcohol)immediately upon collection. After the matrix has been stabilized, store it atthe proper temperature without temperature excursions.

Compartmentalizedstorage equipment, continuous temperature monitoring and redundant powersources are essential. Furthermore, because modern assay technology requiresvery small volumes for most tests, it could be useful to divide biospecimensamples into multiple controlled-volume vessels.

Good storagepractices for long-term specimen management

To ensure biospecimens are properly handled, transported andstored, many drug developers and research organizations are aware of and adhereto Good Storage Practices (GSP) guidelines. While GSP is not a regulatorymandated requirement, the International Society of Biological and EnvironmentalRepositories (ISBER) as well as governmental organizations like the U.S.National Cancer Institute (NCI) have established specific good storagepractices guidelines.

In 2008, ISBER drafted guidance of best practices for thecollection, storage, retrieval and distribution of biological materials for research.Even more recently, the College of American Pathologists has launched itsaccreditation for biorepositories program, which will begin in 2012. Theprogram aims to help biorepositories identify stages in the biospecimenmanagement sequence, from patient to analysis, where documentation variancescan render specimen quality unknown and introduce variables that may alterspecimens' molecular structure. Industry experts expect these guidelines toevolve into regulations such as those that exist in other GXP environments (forexample, GTP, GCP, GLP and GMP). The guiding principles of GSP mandatesstandardization of sample handling and management processes to ensure materialsare prepared and stored in consistent conditions.

Factors that should be considered in defining sound storagepractices include:

Secure, modern and scalable facilities strategically located to reduce environmental risks and other external threats
Advanced and scalable storage and inventory management technologies and systems
A wide range of storage temperature capabilities, from controlled-room temperature to vapor phase liquid nitrogen (-190°C)
Reliable, state-of-the-art storage and temperature-monitoring equipment
A robust scalable operational infrastructure
Expert, highly trained staff
Thorough, consistently applied standard operating procedures (SOPs)
Regulatory compliant processes, systems and technologies

Cold chain logisticsand management

Cold chain management defines how temperature-sensitivematerials such as biospecimens, study drugs and active pharmaceuticalingredients are packaged, transported and stored throughout the research anddevelopment process. Weakness or failure at any point in the chain cancompromise product integrity, breach security, delay shipments and ultimatelyresult in financial loss or liability.

As such, the importance of training site personnel incorrect shipping and receiving processes for temperature-sensitive materialscannot be overstated. Set-up and handling are common causes of temperaturedeviations; it is crucial that all cold chain partners are properly qualifiedand have been adequately instructed in handling these materials. In fact, theInternational Air Transport Association (IATA) requires organizations andindividuals that ship or receive biological materials to be trained properly inpackaging, labeling, documentation, declaration, hazard assessment andemergency response. This is of the utmost importance, as lack of compliance candelay 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 coldchain, organizations should take a holistic approach to cold chain managementin which processes are an integrated component of the organization's overallbest practices.

Information and datamanagement for global sample inventories

While proper storage and transportation are critical,samples are useless unless they can be located with their associated data, in atimely fashion. In the past, researchers applied ad-hoc tracking systems such as spreadsheets to track and plotinformation associated with biospecimens. Today, the complexity of clinicaltrial research has rendered these outdated and archaic systems inefficient tohandle expanding biospecimen inventories. The ideal system should offertracking and reporting processes through all stages of a sample's shipping,handling and storage lifecycle.

Because pharmaceutical and biotech labs typically implementa wide range of information systems, sample management systems shouldseamlessly interface with other systems, provide global data integration andaccess, and be highly configurable to easily integrate with a variety oflaboratory workflow models. The integration of sample storage, consentauthorization and clinical result data is another area of expansion occurringdue to the advent of new technology systems. Connecting information on samplestorage location, temperature and pre-testing evaluation with the resultingdata from a clinical study can enable researchers to improve their selection ofsamples for biomarker testing while shortening development timelines.

The growing role ofoutsourcing in global sample management

Organizations initiating a sample management strategy have anumber of options when deciding where and how to store their specimeninventories, including storing on-site, off-site or both. However, due to theexponential amount of biospecimen samples generated during clinical researchand the complexity of handling and transporting these temperature-sensitivematerials across international borders, it has become commonplace fororganizations to outsource their biorepository operations to specializedproviders.

These services are well-suited for outsourcing due to theirrequired capital investments in equipment, facilities, trained personnel,technology, security and transportation infrastructure. Additionally,organizations are outsourcing their storage operations with increased frequencyas 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 samplessometimes offer storage as an ancillary service. However, given the increasedvalue gained over many years of storage, it is essential that biorepositoryfacilities be optimized for reliable, long-term storage and informationmanagement. Specialized biorepository vendors may provide services such asautomated sample tracking and reporting, fully verifiable audit trails;extraction of nucleic acid; verification of DNA purity, yield andconcentration; and volumetric and normalized aliquoting. These services allowresearchers to customize various quantities of samples from a given subset ofsubjects into the sample size and tubes required for testing.

As cost concerns and risk management continue to be criticalfactors, companies are increasingly establishing hybrid approaches to on-site samplemanagement where inventories are stored on-site, but are dictated by standardoperating procedures and technology provided by an outsourced provider. Thisallows for the appropriate tracking, assigning and processing of individualsamples across multiple studies on a routine basis. Additionally, it leads tomore efficient lab processes, given that most services that require automationare assigned to specimens across studies.

Like many aspects of drug development, selecting abiorepository partner is a complex, strategic proposition. Only by carefullyscreening and evaluating all available options can an organization identify abiorepository service provider that is truly a partner.

The industry recognizes the one-size-fits-all approach todrug development is no longer the pathway to success. Today, the industry isfocused on a more targeted approach to drug development, where the righttreatment is prescribed to the right person, at the right time. As personalizedmedicine and genomic-based therapies become the gold standard in drugdiscovery, specimens such as blood, serum and tissue may hold the key to betterunderstanding 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 andfuture drug discovery is not jeopardized by sub-optimal management processes orsamples or lack of sample data.

Gregory Swanberg isCEO of BioStorage Technologies in Indianapolis. He has provided management andconsulting support, both domestically and globally, to companies includingPfizer Inc., Merck & Co. Inc., Genentech Inc., Novartis AG, Eli Lilly &Co. Inc., Morgan Stanley, AT&T, Whirlpool and Lexmark. Swanberg holds abachelor's degree from the University of Kentucky, a master's degree in publicadministration from Georgia Southern University and a master's degree inbusiness administration from Northwestern's Kellogg Graduate School ofManagement.