Strategies for Improving the Onsite Management of Scientific Sample Assets

Introduction

Effectively managing biospecimens along with their associated data are key components of efficient clinical development. However, as clinical trials continue to grow in size and complexity, clinical trial management has become an increasingly intricate and demanding task. Even for relatively small trials, with a few hundred patients, biospecimen management necessitates sophisticated coordination between various clinical sites, multiple vendors and country-specific processes. As such, a long-term strategy for the physical storage and handling of biospecimens, along with scalable information systems to manage their related clinical data, is becoming a critical and strategic component of the drug development process.

These labor-intensive functions are frequently outsourced to specialized cold-chain-logistics and storage experts. Interestingly, more pharmaceutical and biotech companies are beginning an “onsite” approach to biospecimen mangement. Through onsite management of these activities, using external staff and technology from another company with expertise in sample management, clinical operations can remain agile and flexible, while mitigating risk and having the ability to scale as needed. For companies hesitant to build a biorepository, but in need of a platform to meet increasing biospecimen inventory, insourcing presents a viable solution. Accordingly, this article will outline the processes of biospecimen management and describe how these outsourced services and technologies can be integrated into internal clinical operations to improve onsite management of biospecimens.

Functions of Biospecimen Management

Pharma’s focus on genomics, personalized medicine and biomarker discovery in medical research has dramatically transformed the utility of properly preserved biospecimens. The value of these materials is rapidly increasing through the discoveries that can be made, not only from prospective studies, but also from retrospective analyses. As such, these invaluable materials represent assets that can not only bring significant long-term value to an organization from a commercial and scientific perspective, but can also provide the scientific insight necessary to get the right medicine to the right patient. Given these considerations, clinical trials are generating a growing amount of patient samples. For example, a relatively small 150 patient cancer study alone can account for more than 2,000 archival slides, more than 100 tissue blocks and 400 vials of serum and plasma. Extrapolate these figures to large, global trials with thousands of patients, that span multiple countries, and the challenges grow dramatically. As mentioned previously, the utility of these specimens is also growing. For instance, pharmaceutical and biotech companies regularly conduct a variety of testing, auditing, validation and qualification processes on collected specimens to:

• Detect new biomarkers
• Identify biological and genetic factors responsible for different drug responses across individuals or populations
• Reduce the time it takes to bring new drugs to the market, thus maintaining a competitive advantage
• Expedite R&D processes for new pharmaceuticals and therapeutics

The scientific value of current biospecimen inventories and studies is only a precursor to what the research community could accomplish across a multitude of scientific and disease-specific disciplines. However, there are numerous challenges to overcome to ensure the long-term integrity of biospecimens, including:

• Complex regulatory guidelines, including country-specific guidelines
• Logistical challenges in transporting temperature-sensitive biospecimens, including chain of custody
• Proper storage of temperature-sensitive biospecimens to ensure quality materials
• Developing a technical infrastructure for scalable and organized information systems to easily locate stored specimens and information
• Consistent training to ensure proper specimen handling
• Inefficiencies and collaboration challenges in managing internal and external specimen flow

Country-Specific Regulatory Guidelines

As clinical research becomes inherently more global, there are various country-specific regulations and guidelines that companies must adhere to. Depending on the country in which clinical research is being conducted, biological specimens and related supplies can be subject to strict requirement or formalities. For example, China restricts the exportation of whole blood and genetic materials. In India, sponsors who export human biological specimens for test purposes must apply for export permission from India’s Director General of Foreign Trade [1]. As these examples show, export of biological specimens can be restricted or even prohibited in some areas of the world. Therefore, familiarity with the requirements and process is critical and should be considered upfront in the study design.

Logistical Challenges in Specimen Management

With the globalization of clinical research, the safe, punctual and compliant transport of biospecimens for testing and analysis is becoming more complex. Due primarily to the strict temperature constraints placed on these materials, their timely distribution is of the utmost importance. Cold chain management defines how specimens, such as tissue, blood and DNA, are packaged and transported throughout the research and development process. Weakness or failure at any point in the chain of custody can compromise product integrity, breach security, delay shipments and ultimately result in financial loss or liability. Common issues that can have an impact on biospecimen integrity during transport include:

• Prolonged delivery delays caused by transportation glitches, security inspections or customs scrutiny
• Temperature fluctuations inside shipping vehicles
• Seasonal or climatatic differences between origination site and destination

To mitigate risk of material degradation and ensure regulatory standards are adhered to, personnel should have a broad understanding of the intricacies involved in transporting biospecimens on a global scale. In fact, the Department of Transportation and the International Airport Transportation Association require organizations and individuals that ship or receive biological materials to undergo formal training to meet their standards in packaging, labeling, documentation, declaration, hazard assessment and emergency response. Aside from the regulations, improper packaging and handling are common causes of temperature deviations. However, proper training and qualification of all cold chain partners minimizes such problems.

Proper Storage of Biospecimens

In clinical research, specimens must often be maintained in highly specialized and consistent conditions - sometimes for decades - before they need to be retrieved for research, testing, validation or audits. Consequently, specimens that maintain the appropriate storage temperature will yield better results than a specimen that has undergone temperature fluctuations from freeze/thaw cycles or poor handling practices. To maintain integrity for such long periods of time, standardized, secure and compliant storage is critical. For onsite management, this typically requires steep financial investments to develop, staff and sustain a fully compliant storage facility. Hard costs and time are also incurred in:

• Building specialized, secure facilities with dedicated, scalable storage space
• Purchasing state-of-the-art storage equipment
• Developing or purchasing software for inventory and logistics management
• Establishing a sophisticated cold chain logistics infrastructure
• Validating equipment, technology and processes
• Developing standard operating procedures and business continuity plans
• Ensuring adherence to an expanding array of complex industry guidelines and regulations

Information Systems for Specimen Management

While proper storage and transportation are critical, specimens 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.

Often, critical information about a sample is “missing” or “inaccurate,” which can lead to very costly study-specific errors in the future. To this end, a solid informatics approach includes integration of sample pre-registration, cataloging of qualitative and quantitative information at the time of accessioning, as well as defined standard operating procedures regarding sample discrepancies.

Because pharmaceutical and biotech labs typically implement a wide range of information systems, specimen management systems should seamlessly interface with other systems and be highly configurable to easily integrate with a variety of laboratory workflow models. To this point, recent innovations have even expanded information management systems to include mobile and Web-based solutions [2]. The integration of sample storage 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 and shorten personalized medicine research timelines.

Whether specimens are managed onsite, offsite or by an insourced biorepository service provider, it must include a robust infrastructure for biospecimen tracking and distribution. This streamlines the process of sample management, making information readily available to certified users of the system. Furthermore, it affords researchers the ability to view how much of a particular biospecimen is left in inventory. This information can be critical when determining what assays to conduct based on biospecimen inventory.

Insourcing: A Blended Approach

Companies are faced with a myriad of onsite and offsite management options. Depending on the strategy that is most suitable for a particular study, organizations may elect to have total control of their own biospecimen inventories onsite, or allocate their inventories to specialized providers based elsewhere. However, as cost concerns and risk management continue to be critical factors, companies are increasingly establishing hybrid approaches to onsite biospecimen management where inventories are stored onsite, but are dictated by standard operating procedures and data management 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.

This trend is especially advantageous for smaller biotech and pharma companies that have growing inventories, but do not have the scalable operations or infrastructure to support and maintain control over valuable biospecimens. In this scenario, the ability to integrate biospecimen data is essential to successful clinical operations.

Beyond the operational advantages, there are also business drivers that make insourcing an attractive option to companies looking to expand their specimen management. These include:

• Speed – It could take up to a year to establish a biorepository that can adequately store physical specimens needed to maximize today’s clinical endeavors. Insourcing alleviates this difficulty as appropriate infrastructure for data management and storage can be developed in a matter of months.
• Decreased Cost – Insourcing reduces infrastructure cost, thereby decreasing the need for large operations teams to manage/map data, provide governance and build custom query application.
• Scalability –Because large quantities of biological materials are generated during drug research and development, thousands of samples need to be properly stored and tracked throughout clinical trials and beyond. Through innovative partnership CONTROLmodels, insourcing can give companies the ability to move samples offsite seamlessly to add capacity.
• Quality Assurance – By leveraging standard operating procedures already developed and validated by an insourced partner, risk of specimen degradation through handling and storage techniques can be mitigated.

Companies that have some level of internal capacity may have options to use insourcing to their strategic advantage. By judiciously selecting which functions are core competencies and should be handled by internal staff, and which to outsource/insource, the use of available capacity and capabilities can be optimized.

Conclusion

Biospecimen management is a complex, strategic proposition that requires meticulous application of best practices to ensure the integrity of materials for current and future use. For companies banking on the promise of personalized medicine, a lack of strategy can be detrimental, as properly preserved samples play a vital role in leveraging today’s high-throughput technology. However, developing a strategy that incorporates all components of proper biospecimen management has become a demanding and time-consuming task. As a result, companies are often relying on outsourced partners for the onsite management of their biospecimen and data inventories. This business model provides cost and time efficiencies, as well as advantages in reduction of infrastructure needs. Most importantly, onsite management of these materials allows researchers to focus on their primary mission of developing novel pharmaceuticals and therapeutics to promote health and well-being. The more time they spend looking for samples is less time they have doing science.

References

1. Eudaric, A. Managing Clinical Logistics for Clinical Trials in Emerging Markets. Originally published in Journal for Clinical Studies. [www.parexel.com/index.php/download_file/view/69/]
2. Mills, J. Brooks, A. Information Systems for Biobanks/Biorepositories: Handling Information Associated with Compliant Sample Management. Biopreservation & Biobanking. September 2010, 8(3): 163-165.