Comprehensive Sample Management – Offsite, Onsite and Hybrid Outsourcing Models

Introduction

The new paradigm rapidly emerging in comprehensive sample management is being driven by a powerful and unprecedented combination of scientific, economic and regulatory factors. Continuing advances in biomarker research mandate the more efficient use and management of the estimated one billion samples in storage globally. As new therapies are developed today, who can envision how these samples – once considered as little more than a throwaway commodity – will be used tomorrow? From an economic perspective, generous research and development budgets have been reduced drastically.

Therefore, maintaining standardized samples with high integrity through best-in-class Good Storage Practices can offer significant savings to research-based organizations. In 2005, the US National Cancer Institute initiated a lung cancer study in which samples from biobanks around the world were collected at a cost of $12 million. After several months of sample collection, it was found that up to 99% of samples evaluated were not viable and the study was cancelled [1]. The average economic cost associated with a loss of just 200 biospecimens whose preservation has been compromised has been estimated at $120,000 [2]. Moreover, if samples generated in only 5% of the annual clinical trials in the US maintained consistent quality levels, it is estimated the industry could save $115 million per year [3]. Consolidated and standardized management of samples offers research organizations the ability to maximize opportunities, minimize risk and reduce costs.

This new paradigm, which defines samples as valuable assets to be optimized today for future research, demands a comprehensive sample management strategy. It manifests itself in an all-inclusive network that encompasses samples from collection to storage to present and future use and a data system that identifies, stores, tracks and reconciles every sample from storage to use to disposal. From a regulatory perspective, all the data associated with a stored sample must be connected with, and must stay connected, to that sample to establish a reliable audit trail, especially if duplication, repetition or re-analysis is required. As a result, technology has become an important tool to support the audit trail management, tracking and reporting of sample data in order to advance new and improved therapies to the market.

In the following report, four organizations discuss their different approaches to developing a comprehensive sample management strategy appropriate to their needs, priorities and business objectives. While such unique factors as financial goals, facilities utilization, core strengths and others were considered, a common concern – the scientists’ reactions to change and a perceived loss of sample control – did not become the major obstacle it was traditionally thought to be. In practice, a system that allows for better sample management through better processes and techniques frees scientists to do what they do best: research.

As you will learn, there is no generalized “best” strategy in developing offsite, onsite and hybrid outsourcing models for comprehensive sample management. Rather, every organization must challenge its assumptions, expectations and objectives to determine the comprehensive sample management strategy best suited to its unique needs, strengths and opportunities.

Strategies for Evaluating and Selecting a Sample Management Outsourcing Model

Kristina Robson
Scientific Director, Bioscience Division
EMD Millipore

As a premier service provider to biopharmaceutical companies from discovery through development, EMD Millipore performs large molecule analysis for pharmacokinetic, immunogenicity, potency, and biomarker testing to support drug development efforts and pipeline advancement. EMD Millipore is not yet a provider of comprehensive biobanking services, although it routinely stores samples on-site to meet customer needs for storage of clinical trial specimens used for the completion of bioanalysis services.

Increased interest in including a comprehensive biobanking service as part of EMD Millipore’s service portfolio was initiated through internal discussions with Merck Serono, a division of Merck KGaA, who also stores samples and for which it was determined an internal solution and service provision would be of mutual interest/benefit. Merck Serono, similarly to many companies in the pharmaceutical/biotechnology industry, stores clinical trial samples for a number of reasons such as future testing for patient stratification and efficacy assessments, to develop companion diagnostics, to reposition and rescue failed drugs as well as to answer follow-up questions from the regulatory agencies. The need for storing these samples is increasing significantly.

EMD Millipore began to explore the biobanking marketplace for the best way to expand its capabilities, to provide the best possible services to its customers and to meet Merck Serono’s needs. In order to build best-inclass biobanking service capabilities EMD Millipore considered a number of critical factors, including:

• Mass storage and capacity
• Flexibility and scalability
• Annotation and traceability
• Proximity to bioanalytical service provider
• Cold chain management
• Experience and expertise
• Cost and reliability

Based on those critical factors, preliminary internal discussions focused on either building the complete service offering or outsourcing it fully. The benefits of building were obvious: EMD Millipore’s current operations involved sample management and storage as well as equipment such as freezers and tracking systems. However, the company identified some gaps such as processes and tools required to support large-scale management of samples as part of a biorepository.

The other option was to outsource sample storage completely. The benefits of fully outsourcing were that EMD Millipore could do this with limited resources (as it would not have to build up a new infrastructure in a short period of time), and gain the necessary expertise, processes and systems required for sample management. The negatives of this option, however, were many. EMD Millipore wanted to be able to provide a biobanking solution to Merck Serono and to its clients. EMD Millipore’s value proposition was to leverage the proximity of sample storage with the analytical testing facility thereby providing convenience and logistical simplicity. Outsourcing would not enable EMD Millipore to deliver such value to customers.

When EMD Millipore made its first fortuitous visit to BioStorage, the two parties started exploring a third option that would ultimately become a win-win solution. BioStorage had recently begun to develop solutions to bring its expertise and systems related to a biorepository to customers’ existing facilities. This created a situation where EMD Millipore could offer best-in-class biobanking service to its clients and Merck-Serono, as well as keep this important new service offering in its own facilities. Combining Biostorage’s expertise with EMD Millipore’s core business would create a mixed-use facility where EMD Millipore would hold long-term biobanked samples as well as bioanalytical samples with greatly enhanced sample management capabilities brought by Biostorage.

EMD Millipore’s decision was based on a rigorous analysis of its needs and priorities and the marketplace, with a concomitant commitment to an educational process within EMD Millipore. It was important for the organization to understand that operating a biostorage repository meant much more than putting samples into a freezer. It’s an extraordinarily complex task, and EMD Millipore realized quickly that this was not something it could do easily on its own. Regarding needs and priorities, maintaining sample quality was at the top of the list. Deciding who would hold and manage the samples, especially as the volume of samples would increase in orders of magnitude, was therefore critical. Another important priority was to keep the data connected to the samples. In order to meet those needs in a cost-effective manner it was decided that BioStorage would be responsible for managing on-site samples. BioStorage brings its expertise and experience, access to its cold chain infrastructure and its sample management system to EMD Millipore’s own facility, thereby ensuring the delivery of best-in-class services to EMD Millipore and its customers.

The on-site model combines the best of the two worlds: EMD Millipore’s analytical testing services, and BioStorage’s management of samples. EMD Millipore will be incorporating BioStorage’s systems and expertise, including ISISS® (Intelligent Specimen Inventory Storage System), and the flexible overflow capacity offered by BioStorage to deliver superior convenience and logistical simplicity cost effectively to its customers.

My Company Chose to Manage Samples Off-site Because...

Mary Rose Keller
Vice President, Clinical Operations
Sangart

The decision on whether to manage research samples off-site versus on-site involves a strategic evaluation of a company’s core business competencies, resources and infrastructure, information technology and existing quality control processes. In order to reach the best decision for your business, it is essential to understand what elements need to be addressed to identify the best sample management path in an organization.

The first step is to analyze your business strategy. My experience has been in conducting a strategic sample management analysis while working with a diagnostic development company. A key consideration our team considered was whether our organization was interested in just producing and distributing testing assays or whether we wanted to manage all testing and result reporting of the assay. Based on these considerations our company decided that we needed to maintain samples long-term to support re-analysis of testing results in the future and the development of new diagnostic developments.

An important component of the strategic analysis is evaluating your company’s core business and core competencies. For example, are you focused on a single research platform with single or multiple goals or do you have multiple research goals with a focus on different types of assays? The more samples you need to store the more expertise, infrastructure and processes you will need to manage these samples.

 If the storage of large quantities of samples is required, you will need a biobank manager, experienced sample management staff and people proficient at shipping and logistics who know how to develop packaging and labeling, how to get samples from remote locations and even how to manage import/export complexities. Key questions to ask include:

• Do you have the “right” people in the company who are qualified to perform all the functions necessary to support a sample management program? Or do you have a few key people, with much of your work supported by outsourcing?
• Do you have the resources within the organization to manage a sample bank – such as facilities staff, controlled access, quality control personnel and engineers to maintain the freezers?
• Can you expect the organization’s scientists to wait a few hours to get a sample, or have they grown accustomed to getting samples whenever they want? While this issue is frequently the biggest challenge confronting companies in their decision-making process, how can you control access to and control of samples while not impacting research timelines?
• Who will handle the samples once they arrive at your door? Samples split into multiple aliquots must be labeled correctly, entered into your clinical database and attached to the associated data.
• Do you have the Quality Assurance and regulatory experts to deal with this critical component of sample management?
• How committed are the people within the company to looking at your samples for what they are: Critical assets. Are they willing to do what is necessary to support them?

Logistics and space present another fertile field for inquiry when evaluating a sample management solution. Space, always an important financial and operational consideration, is a special challenge with regard to sample management. Do you rent or own the space, and how much do you want to invest in a rented facility, for example, to render it workable for biobanking? Is there enough space to house a centralized biobank, or will you be operating random freezer plots scattered about? What about contingency planning in regard to power? What is the risk you will be without power at some point and for how long? You’ll need a consistent power supply, along with a backup generator system to ensure the longterm protection and viability of samples for future research.

With regard to sample management processes within an organization, it is important for your company to have a robust sample definition and lifecycle management process. It is common when developing a diagnostic that scientists have definite ideas about what materials they want to work with and how much they will need. It’s also common that this information does not get communicated to the clinical organization. What samples will need to be collected in the field? How will the samples need to be transported to your facility? And, ultimately, how will the samples be stored in your freezer? Deciding how to manage samples requires that you first know what you’re going to be managing.

Robust information technology systems are needed to support effective audit trail tracking, inventory management and reporting of samples in storage. While our company’s homegrown sample tracking system accepted many different sample storage sizes, we were experiencing inefficient use of our limited storage space, even though a spreadsheet was being used to track samples. Labels fall off or samples get over-labeled, and without a system to monitor individual sample locations – when conserving space is a priority -- things end up where you don’t intend them to be. The use of a technology system that can enable a company to maximize the use of its research space offers significant cost-savings opportunities to a business.

In addition, a professional approach to sample management mandates that your sample and its data remain together. Do you have data management personnel who can understand what the database should look like and can they access this data when needed? Can your information technology system connect the sample with its associated data? Establishing sample management technology systems that provide the virtual view into sample inventories and support the research process is vital to the effective management of these valuable research assets.

Quality and compliance is one of the most challenging aspects of sample management. How do you maintain and access patient consent on your samples? Do you have a technology system that can enable you access to samples while restricting access to confidential patient information and clinical data? Are you able to quickly access what permissions are associated with a sample so you can select the right samples for the tests you want to perform? The tracking of the chain of sample control from the time the sample is taken until its destruction is critical to support regulatory audits. In summary, compliance comes down to the GIGO – garbage in, garbage out – and if you don’t have a pristine controlled environment, what you get at the end isn’t going to be what you expect or need to support regulatory reviews and inquiries.

A major challenge to our decision was the concern our research scientists expressed about who was best qualified to protect our samples. They preferred to have “their” samples close to them – a sentiment commonly shared by research scientists. We took time to convince our scientists that they could meet their timelines and achieve their milestones even though “their” samples were not physically nearby. Initially, they were concerned about securing samples in a timely manner; however, we did not encounter any problems in that regard. We recognized early in the process that offsite storage required adding a step to their plans, but it generated two ancillary benefits. It helped the scientists organize their work more efficiently and it provided a measure of their productivity that had not been available.

After an exhaustive strategic sample management analysis, our decision was to outsource sample management to BioStorage Technologies. By outsourcing sample management, it has been possible for us to establish an orderly, organized system that served our needs much more efficiently and cost-effectively. Once our scientists saw the system in operation, with its barcoded and scanned samples delivered to them as requested, they were more comfortable with the change and much less concerned about sample proximity.

The true value of a sample is not based solely on the cost of the freezers and length of storage time. The value has more to do with the future research potential of a sample. The high, frequently unrecognized – and many times unappreciated -- value of what a research sample freezer contains can be revealing and surprising. Maintaining the integrity of research samples so they can be used for future research should be the key objective of a long-term sample strategy. Proper management of research samples enables companies to bring new products to the market in a more timely and cost-effective manner.

Onsite Management of Research Samples: Leveraging Technology to Advance Research for Management of Clinical Trials

Steve Sweeney
Head of Clinical Information Systems
Infinity Pharmaceuticals, Inc.

Infinity Pharmaceuticals implemented a onsite sample management model with BioStorage Technologies a little less than a year ago and we want to share with you our experience in optimizing that model.

At the time when we decided to implement an onsite model, we had 200 specimens; today, we have 8,500 samples, indicative of our growth over the course of a year. We are conducting a number of large global studies, with a high biospecimen capture burden. About the same time, we invested heavily in our molecular pathology group and the question was asked: what are we going to do with these specimens?

Typically, a company such as ours would make a large investment in the internal infrastructure by investing in the appropriate software system, hardware, perhaps, install it and add the personnel to manage it. We didn’t have the time to do all this and master the complexity of managing all our specimens. Establishing a relationship with an expert biospecimen management company would allow us to get things up and running much quicker by bringing all its expertise and systems in-house.

At the time of our decision to hire BioStorage Technologies, we knew very little about the storage of samples but we did know we were going to invest heavily in and develop targeted therapies. We were going to manage the science in-house so we had no choice but to be able to locate, inventory and control all our clinical research samples quickly and accurately.

Because each sample is tremendously valuable to our company, we wanted a detailed chain of custody between sites and our internal facility. In order to feel confident that the research was being optimized, we had to trust that the specimens were being managed correctly. We also saw significant value in establishing linkages between patient samples, patient consent and clinical results from the samples, so we could make better decisions about which samples we sent to the research bench for specific testing. If we were audited, we wanted to have a system in place that could answer every question and provide proof of the accuracy and validity of our work. Today, we’re getting specimens from all over the world and we can address these questions globally.

Because we need better managed and coordinated samples, a BioStorage Technologies technical representative is allowed in our freezers, an issue which concerned many of our scientists. With our small, Cambridge-style entrepreneurial spirit within the company, prohibiting our scientists from our accessing the freezers was initially met with varying amounts of consternation and dismay.

To overcome that reaction, we took a series of steps: First, we got organized. All our samples are fully accounted for in our freezers with respect to every trial. Second, we had to build the processes and technologies to govern those specimens. Samples are a non-renewable resource, and it was imperative that we make certain every specimen we pulled from storage had some governance attached to it. BioStorage does a very good job in organizing the samples, but we owned this space. How do we get them out of storage and how do we know when the last critical sample is going to be used?

All specimens in the freezer that are removed are tied to an experiment and approved through a workflow process. We’re using ISISS® in house, and we put a process around that. A new tissue governance board was formed to oversee the management of clinical samples and to ensure:

• Cost-effective, high-quality and compliant management of biospecimens derived from clinical trials
• Facilities, process and technology are effective and scaled with the number of samples under management
• Documented review and approval of all non-requisite testing

The Board also reviews and approves the use of all samples requested and approved through our workflow tool. The process ensures that all sample requests are tied to categorized experiments. The software workflow tool we utilize is SAMURAI, which allows a scientist to search on very precise parameters for samples within our biospecimen database. This provides for fast access and approvals.

The goal now is to make this system even more efficient. One avenue is to move the data associated with a slide by using barcodes, but we’re limited by the amount of information we can store there. Without the ability to move the data around with the slide via a barcode, we force our scientists to type information into downstream systems. Using web services, we merge the data in SAMURAI with the sample information in ISISS®. That enables us to print labels which incorporate data that can be moved with the slide.

It’s obvious that we moved very quickly in developing this new model. We organized our samples, we built a system and we established a governance process with a low capital investment. The on-site model has worked very well for us. It would have taken a long time for us to develop the custom software that BioStorage Technologies made available to us. It’s also important to emphasize that our scientists thought they would lose control but have realized they actually gained control with this onsite sample management model by improving their knowledge of what sample assets exist and becoming better able to select the best samples for specific research tests.

Utilizing A Hybrid Sample Management Model: Improving Asset Utilization

 Jay Schiestle
Senior Director of Operations
Exact Sciences Corporation

A little more than a year ago, we were managing our roughly 50,000 samples from multiple studies and collaborators on-site. Our R&D scientists needed fast access to those samples, which we were able to provide from our 40-unit, -80C° freezer farm spread throughout the building and managed with a homegrown sample tracking system. Roughly 30% of this space was unusable, primarily due to tracking system issues.

We had staff managing our samples on-site, but we were having difficulty locating the right samples efficiently due to limitations imposed on us by our software and storage issues.

On our immediate horizon was a pivotal trial costing more than $25 million, utilizing more than 70,000 samples and involving approximately 10,000 patients across more than 60 sites. The trial compelled us to establish a list of high-priority needs and to make some important decisions expeditiously. The success of the clinical trial hinged on the proper management of the samples coming to us.

Almost immediately, we realized we would need a partner that could help us with:

• Fast, efficient, compliant tracking of pivotal trial samples. We had to be certain our samples were well managed.
• Adequate storage capacity. We were at capacity and we knew we would more than double the number of samples we had to manage.
• The ability to provide multiple stakeholders sample data. We are engaged with multiple CROs and need to provide easy access to the sample data.
• The ability to support multiple parallel studies. While this pivotal trial was going on, we needed to support additional studies and collaborators.
• The ability to provide R&D fast access to samples from parallel studies.

Our over-riding goal was to find a partner we could trust with our clinical samples. It was critical that we gain a validated process to track our samples and that when needed we could provide the full life history for each sample. That meant the samples had to be stored properly and managed accurately. We wanted to minimize or eliminate, if possible, the risk that our samples would be lost, or they would be excluded because they weren’t properly managed.

We considered a number of options and selected BioStorage as our partner of choice. The firm offered us an innovative program that initially provided on-site sample management with their personnel on-site, with access to its ISISS® system. We have since migrated to a hybrid model, with storage of some of our samples off-site. The development of this model followed from discussions about what to keep in-house and what to store remotely. We had to establish the criteria – including cost-effective methods for sending samples back and forth.

This hybrid model continues to serve us well. In our nomenclature, BioStorage “dropped in” its expertise and systems. We have its expertise as represented by its personnel in our facility; we have access to ISISS®, (Intelligent Specimen Storage Inventory System) to manage our samples; and access to the full set of their SOPs (Standard Operating Procedures). ISISS®, which gives us global, web-based access and control to track sample information, enables our scientists to request and access samples within a day from common freezers. Our scientists applaud this feature. We decided that certain freezers with pivotal trial samples would be managed only by BioStorage; the common freezers were accessible with an interface that defi ned the information to be provided to them when Exact Sciences personnel placed samples in them or requested samples from them.

During the course of the pivotal trial, and other studies, their personnel on-site frequently identifi ed options available but unknown to us, simply because we didn’t have their expertise in-house.

Later this year, for example, we’re going do something we’ve not done. Rather than collecting samples, we’re going to be distributing them to the laboratories where they will be tested. Because we already had the BioStorage system in place, what could have been an extremely complex and time-consuming task was very simple to implement.

Retrospectively, can we say the needs we identifi ed before we established this innovative hybrid partnership with BioStorage have been met? Yes. With ISISS®, we have fast, effi cient and compliant tracking of pivotal trial samples and we can provide multiple stakeholders with sample data. Our model provides necessary storage capacity. On site, we are storing samples from the smaller collaborative studies and those our scientists need to access immediately. Samples from our pivotal trial come into our offi ce and are shipped to BioStorage on a regular basis for storage. We are now supporting seven parallel studies, and we can provide sameday access to samples from those studies.

The model enables us to capitalize on our own assets and to use their capabilities to meet emerging needs. We have realized immeasurable value in the consultative expertise available from BioStorage – and our people have been freed to focus on our business opportunities and advancing our novel technology.

Summary

Establishing a comprehensive sample asset management strategy provides an organization with three signifi cant benefi ts:

• It helps minimize risk and reduce research costs.
• It facilitates the work of the organization’s scientists.
• It optimizes the value of the sample assets today for future research purposes.

To develop a comprehensive sample asset management strategy, an organization must identify and evaluate its unique research objectives, opportunities and constraints. While a rigorous quantitative analysis of quantity, quality and location of sample assets is essential, an equally thorough qualitative inquiry will address such corporate-wide issues as staff expertise, internal capabilities, current sample management processes and cultural habits. Moreover, the organization should be fl exible and creative in its analysis to consider all possible options – from exclusively in-house operations to fully outsourced sample storage and management to an innovative hybrid that best meets its identifi ed needs.

Regardless of the organization’s decision, understanding and appreciating the real value of samples as highly strategic assets throughout the research organization is requisite to the successful implementation of a new sample management model. The vision and directive by senior management for the organization to change is essential to the process. Focused communication and education with the research scientists and operational staff that will need to utilize and support the chosen sample management model is an important step in how quickly the new process is adopted. The integration of advance virtual sample management technology solutions which create global transparency to sample assets linked to clinical results provides opportunities for improved optimization of sample assets during the research process, faster drug development timelines and, ultimately, more effective new therapies with less side effects.

Finally, the organization must view its decided-upon comprehensive sample management strategy as a dynamic platform for continued business improvement as the industry’s scientifi c, economic and regulatory factors continue to change and to evolve.

References

1. Steve Silberman. The Flesh Files. WIRED, June 20, 2010, p. 160

2. Joyce Rogers, Todd Carolin, Jimmie Vaught, Carolyn Compton. Biobankonomics: A Taxonomy for Evaluating the Economic Benefi ts of Standardized Centralized Human Biobanking for Translational Research. Journal of the National Cancer Institute Monographs, No. 42, 2011, p. 34.

3. Ibid, p. 36