How to Plan Next-Generation Biological Repositories

Transcription

1 How to Plan Next-Generation Biological Repositories Five Critical Elements You Must Consider By Ian Pope, Ph.D., MBA, B.Sc.

2 Table of Contents Page Introduction 3 Five Key Elements in Planning Cryogenic Storage. 3 Storage Objective. 4 Biological Viability 4 Thermal Performance. 5 Environmental Impact 6 Cost Conclusion 7 About the Author. 7 2

3 How to Plan Next-Generation Biological Repositories: Five Critical Elements You Must Consider Introduction By Ian Pope, Ph.D., MBA, B.Sc. Today, there are more than 300 million biological samples in the world stored at temperatures below -80 C. Few of these samples have a storage strategy associated with them. A recent U.S. National Institutes of Health (NIH) discussion group estimated that up to 70% of all of the sample material stored at -80 C and below is unusable because of its lack of provenance. In other words, these samples do not have histories, they can t be traced, their origins are unknown, and environmental storage records don t exist. However, because this material is unknown, its custodians will not throw it away. Perhaps another reason why few organizations have global storage strategies has origins in the developmental cycles of their products. Cryo-preservation strategies are nearly always designed at the laboratory bench level. If you ask people, Why do you store your samples that way? They typically will answer, Because that s the way we always do it, or Because that s the way the last guy did it. Many times the storage type is determined by whatever system is available. If a department has an aluminum LN 2 freezer under the bench, they use it. If a -80 C system is in the corridor, they use that. Availability drives the decision making process. Rarely does a user actually look at the storage system and ask, What is the preservation strategy for this sample? And remember, in most cases, the samples will be archived for 10, 15, or 20 years. Effective planning will produce two important benefits for your sample library. The first is sample value and viability. If an organization doesn t develop a long-term storage plan, then 90% of the time the potential use of the material will be compromised. Our experience demonstrates that within 2 years of implementing a storage scheme, most organizations will discover that if they had stored their samples in the most appropriate way, their material could have been much more valuable. The second benefit is cost reduction. Unless there is thought about the reasons behind sample storage, a lot of money will go to waste. Strategic planning results in creating a cold space that fits a purpose, and then controls its use in a way that provides maximum efficiency and minimal operating expense. This paper will explore the five critical elements in planning next-generation biologic repositories, their implications on storage conditions in the preservation protocol, and their benefits for the organization. Five Key Elements in Planning Cryogenic Storage There are two types of cryogenic storage. The first is transactional storage. This covers material that typically will be used for 3 to 12 months. It might include a collection that a researcher may want to repurpose such as genetic information. If an individual is managing a drug discovery project, he or she may have cryo-preservation systems to store material that is used again and again. That s transactional storage; there is a transactional reason to manage samples for a given period of time. 3

4 How to Plan Next-Generation Biological Repositories For long-term storage, which we call archival storage, the decisions are completely different. There are five key elements that must be addressed when planning archival cold space (see figure 1). Figure 1. The five key steps in planning archival sample storage. Cost Storage Objective Why are the samples being stored? At first glance, that might appear to be a stupid question. The reason behind sample storage is important however, because one never really knows the true potential value of the material. The effort required to store the samples in a way that is regulated, tracked (with the correct information), and creates provenance represents very little additional effort compared to the generation of the samples in the first place. That little bit of effort is what instills all of the value in an organization s research material. Biological Viability Storage Objective Environmental Impact In addition, the organization needs to know how many samples it wants to store. One caveat: no one ever throws anything away. Take the number of samples planned for storage and then triple it. Thermal Performance The following example illustrates the need for identifying storage objectives: Thirty five years ago at a major healthcare facility in Boston, the healthcare professionals association was lobbying the government to vaccinate workers against several diseases. The association recruited 15,000 healthcare professionals to give blood every few months, and provided the medical screening and administration necessary to run the study. The research took several years, and the association eventually proved its case and got the vaccinations. Then it decided to continue the study. Because these people were medical professionals, they had an almost zero fallout rate. Twenty five years later, the group had assembled a massive collection of human material with associated medical records and the samples had been stored properly at -150 C. Eventually, the association was offered a large sum for the collection. With live, viable cells and complete medical records, virtually any disease that you wanted to study in the U.S. was present in that collection. In the end, they didn t sell the collection. But had they not gone through that protocol correctly at the beginning, the collection would have become a reference library at best. Biological Viability The reasons for storing biological material can vary widely and will play a major role in developing a sound sample management strategy. There are serious implications for the usability of the material associated with the temperature at which it is stored. For example, a researcher might preserve DNA and RNA for genetic testing and sequencing. For that work, -20 C storage is fine. If researchers are looking for the presence or absence of biomarkers in population studies, then storing the samples at -80 C will be sufficient. However, if concentrations of biomarkers are being studied, and the material must be stable for more 4

5 than 6 months, -80 C storage isn t cold enough because there is still enzymatic activity present. For cellular viability studies, the cells must be returnable to a condition where they will thrive and proliferate. If cord blood is stored at -80 C, it will be useless after 6 months. If stored at -150 C, it will last for 20,000 years. Part of the planning process must be to understand the implications of the storage strategy on long-term cell viability. How long will the samples be stored? In the vast majority of cases, the question is never asked. If the samples must thrive when removed from a cold environment, the storage temperature will have a profound effect on how long the material can be kept. Minus 135 C is considered the normal transition point for cryogenic storage media. All of the research demonstrates that if the samples have been prepared properly, and stored below -135 C, it is possible to keep the material infinitely and still have biofunction when removed. Once the storage temperature rises above -135 C, this is no longer the case. At that point, it is a question of how long the material can be archived before it degrades. So it is important to know what temperature is appropriate for the lifetimes of the samples. That modality choice must be driven by whether the samples are being stored for transactional or archival purposes. The organization also must decide what it is going to store, and know what it is going to store it in. These questions are very relevant. It doesn t matter what type of biocryogenic storage is being considered an under-bench refrigerator, a biostore that holds two million samples, or a liquid nitrogen dewar unless these questions can be answered, the chances are the organization will not create the right environment for the material. Thermal Performance When an organization begins to develop these strategies, the creation and management of the storage systems are key issues. One of the things worth remembering when creating cold space is that the real investment is in insulation. The method by which the heat energy is removed is almost irrelevant. For example, the reason a liquid nitrogen storage dewar is so much more efficient than an -80 C mechanical freezer has nothing to do with the fact that one uses liquid nitrogen and the other uses a mechanical compressor. Instead, it is because one has 100 times better insulation than the other. If samples must be stored at a specific temperature, then the biorepository must be evaluated to make sure it can create and maintain that desired temperature level. When reviewing the modalities of cold storage, there are many choices liquid nitrogen-based systems, Sterling engine-based systems, or standard cascade compressor systems. The reason one type of cold space is more efficient than another has very little to do with the method used to remove the energy. Instead, it is much more about the quality of the space s insulation. For example, if you compared a Vario liquid-nitrogen-based storage system to a mechanically-cooled storage box, the difference in thermal performance would have little to do with the systems cooling technologies. The difference between the two boxes is that one has 3 inches of expanded polyurethane foam and the other has a sub-5-micron vacuum system with super insulation. The amount of heat energy that gets into the Vario s space is a thousand times less than the energy that will penetrate the mechanical box. Any cold space, no matter how it is powered or cooled or sized, will increase its thermal performance and efficiency most effectively by improving the insulation. 5

6 How to Plan Next-Generation Biological Repositories Environmental Impact The environmental impact of a large biological repository can be substantial due to its cooling requirements and energy consumption. For example, three -80 C freezers have the same environmental footprint as a typical family car. Five freezers have the same impact as a domestic dwelling s annual power consumption. Insulation can make a dramatic difference in environmental impact. If the cooling capacity shuts off in an ultra-high efficiency cold space, the temperature will be maintained for about 1 week. In a mechanically cooled box, the temperature will start to rise in about 1 hour after the cooling stops. Organizations that value environmental sustainability must consider energy efficiency and insulation types when planning their sample storage and management systems. Cost Cost is always an important issue. However, when evaluating cost, it is important to consider holistic cost, or the total cost of ownership. Typically, when a lab runs out of -80 C storage space, it buys another $10,000 freezer and plugs it into the wall. It doesn t consider the cost of the electricity because it gets paid from a different budget. In addition, the organization also must pay for the air conditioning that removes the excess heat generated by the freezer. There are costs associated with maintenance and repairs, too. All of these expenses must be considered when planning a sample storage strategy. The majority of storage strategies, particularly in grantfunded research, are developed on an individual basis. If one considers a university where there are 300 researchers, the storage strategy associated with that institution is the sum of all of those individuals. The university must make large expenditures each year for the collection of genetic material to be processed, aliquoted, and stored. This might involve collecting 50 million samples for 300 studies. But much of the material that is collected is the same. The institution probably could collect 20 million tubes, make them available to all of the studies, and experience significant savings in cost, labor, and time. At a large research organization, the total cost of ownership can represent a huge sum. One such facility has 7,700 mechanical refrigeration units on site. The annual operating bill for these units is about $25 million when the total cost of power, associated air conditioning, environmental monitoring, plus maintenance and repair is considered. The decentralization of the sample storage is primarily due to the funding process. When they pay for the equipment, they don t pay to plug it in. The grant funding process has led to this highly decentralized refrigeration strategy. As a result, the organization has a proliferation of mechanical freezers that each cost about $2,500 per year to operate and maintain. On the other hand, the cost of operating a centralized, ultra-high efficiency storage system might be as low as $100 per year for equivalent capacity. The strategy to migrate to a large, centralized store provides much higher economies of scale, better footprint per sample, and greater unit control and record keeping. While the downside is inconvenience (the material isn t under the researcher s bench), the institution has potentially reduced its annual operating costs from $25 million to $1 million. In addition, the material is housed in a much more effectively controlled environment. Because samples are centrally stored, and information is required to access the cold space, the institution begins to understand what material is in the store. Today, the central office only knows they are spending $25 million on boxes that are cold. It doesn t know what s in them or when the material s efficacy will expire. The cost of storing a sample vial at the individual level in a lab is about four or five times higher than the cost of storage 6

7 in a large repository. So today, the grant authority is giving the researcher five times more money than needed to store the samples. But they are doing it because the funding structure works that way. The bottom line: an organization can massively reduce storage costs by moving from a decentralized to a centralized strategy, plus achieve much more effective sample control and management. Conclusion It s clear that most diversely operating research environments engaging in cold biologic storage are in dire need of well-planned storage strategies. If research organizations are collecting and synthesizing biological material, there are five elements to consider in creating protocols that move material from ambient temperature to long-term cryogenic storage and then return it to the bench for scientific purposes. When planning a next-generation biorepository strategy, these five key elements storage objective, biological viability, thermal performance, environmental impact, and cost must be evaluated. Whether considering a highlevel strategy that covers all aspects of organizational storage, or an instrumental strategy that evaluates equipment, addressing these five basic elements will improve sample value, reduce costs, and enhance material control. About the Author Ian Pope is currently senior director/general manager, Cryo Solutions at Brooks Life Science Systems. The company is a specialist in automation and cryogenic solutions. Mr. Pope has worked in the area of cryogenic systems for over 25 years, initially as managing director of Planer PLC, the original manufacturer of controlled-rate freezers. He later ran the BioMedical Division of MVE/Chart, the world s largest provider of cryogenic storage freezers and liquid distribution systems and co-owned Core Cryolab, a unique bio-repository, cord blood bank, and international consulting group in Toronto, Canada. Mr. Pope works with and consults for many of the major repository operations in the U.S. and abroad, and sits on the ISBER CRT (Certified Repository Technician) working group. His expertise lies in the area of the practical application of cryogenics to the storage and preservation of biological materials; the design, operation, accreditation, validation, and best practices of biorepositories; and in the environmental and sustainability aspects of cold-space provision. Contact: Ian M. Pope ian.pope@brooks.com (cell) (office) 7

8 Brooks Life Science Systems U.S.A. 15 Elizabeth Drive Chelmsford MA Tel: Fax: Europe Northbank, Irlam Manchester M44 5AY United Kingdom Tel: +44 (0) Fax: +44 (0) Japan Nisso Bldg. No 16, 9F Shin-Yokohama, Kohoku-Ku Yokohama, Kanagawa T: Brooks Automation, Inc. Brooks Automation, Brooks Life Science Systems and the Brooks logos are trademarks of Brooks Automation, Inc. All other trademarks are the property of their respective owners July 2015