Marie-Claire Peakman: We often talk about our core competencies; for example, at Pfizer we might say that Medicinal Chemistry is one of our areas of core competency. What is your core expertise that differentiates you from other solution providers?

John Mills When we started this company, I think our concern was ensuring that companies maintain the integrity of their samples, and so our core expertise comes from the aspect of needing to store samples for the future, and for the examination of biomarkers, which has been in the sample management and sample integrity fields. Our core competency is the development of a system, which is real-time and Web-based that to enable clients to see where their samples are and to associate data with them, so if they need to be able to obtain these samples, they can do them rapidly and effectively using a Web-based system. The other thing is that from our point of view, our company’s whole sample management philosophy has been at the center of our investment, and I think that it’s unusual for a company to approach it in that way, rather than perhaps coming from being a manufacturer and then going down into the service of sample management. I think the other thing that we have started to build around that the competency is called cold chain logistics. It is all very well to bring samples, but if they are not in perfect condition during the logistic transfer, then the issue over keeping those samples is that you have to make sure that they have been kept at the right temperature and the temperature integrity has been maintained during that process.

Charlie Saller ABS has two primary core competencies. One, we have nearly 20 years of experience in the sample collection field. We have a large virtual Biobank of collection sites throughout the U.S. to obtain samples, and then we add value to those samples by performing extracts on the samples processing them. Two, we do not only provide the samples and the clinical data, but we have the ability to go beyond that and provide extracts such as DNA, RNA, proteins and isolate specific cell types from these samples. We have laser capture capabilities, and we also do extensive QC on the samples that we provide, such as RNA integrity, and we are developing a simple mix and read assays to evaluate sample quality. So basically, our competencies are the ability to supply the samples and to further process the samples with high quality.

John Masiello Masy Systems has over 20 years of validation and calibration services experience, which is directly applicable to and the reason why we decided to build a biorepository, and also upon request from our customers. Masy Systems is ISO 9001:2000 certified and ISO 9000/17025 accredited for calibration and testing, and we also have a primary temperature lab in-house, which supports all of our calibration and our validation efforts. We have qualified and validated over 3,500 chambers so we know which is the best equipment and best practices that ensures the safe and secure storage for our customers, and in the designing of our repository we incorporated these best practices into our entire offering of storage conditions, ranging from the liquid nitrogen through all of the standard ICH conditions.

Scott Reeves REMP's core of expertise has really been in the reliable, secure and efficient handling of our customers’ valuable samples in an automated and environmentally controlled environment. We have been developing and manufacturing storage systems, devices, software consumerables for sample logistics in many research laboratories of pharmaceutical, agrochemical and biotechnology companies since 1994. We are a Swiss company, and as such, we hold all of our products to a high quality standard, and through a customer-focused approach to issues, we have emerged as a world leader in the sample management market, especially over the past several years.

In 2005, REMP merged with Tecan, another leading Swiss supplier of products and solutions in the field of biopharmaceuticals, diagnostics and forensics, to further complement our comprehensive and innovative range of products and services in sample logistics. We know that in this industry, research and development is a race against time, where safety and reliability play an important and decisive role in ensuring sample traceability. Efficient, reliable, automated logistics for research laboratories is a key factor for sustainable success in this very competitive market. Continually growing challenges are really the driving force behind REMP, making the company a progressive and reliable partner for comprehensive sample management solutions in the Biobanking industry and in some other industries as well.

Through innovative thinking and unique know-how customers all over the world would benefit from advanced efficiency and productivity in their R&D laboratories. We are able to offer a comprehensive solution for all sample management needs through modular and scalable products which address a wide range of our customer's needs as well. Central to our product range are the automated sample stores where we can offer an ideal storage solution — whether it’s for a -80C to -20C, room temperature — for hundreds and millions of samples.

Dennis Fallen Fisher BioServices is over 23 years old and was founded around sample storage initially. We believe our core competency and expertise is in the handling and management of biological specimens and biological products, as well as environmental specimens. Our expertise, we believe, is demonstrated through our services that include biorepository and turnkey Biobanking services, cold chain logistics for specimens and biologics and the movement of that material, collection kit assembly and distribution of those kits for the collection of those biologic samples, biological sample processing and including the molecular lab testing DNA and RNA extraction and amplification and in a highly customizable proprietary inventory management system that can be tailored to any clients needs that they can access via the Web to look at their inventory and make requests of how we handle and process that material for them.

CS We have been collecting a wide variety of samples for nearly 20 years and I would say our expertise is really in the flexibility that we offer. My background is as a scientist, and so often one experimental set of guidelines or parameters is not applicable to the next experiment. So we can vary our collection procedures in accordance with the needs of the scientist. Very often, one scientist may want serum and the next one will want plasma collected in a certain way in a certain kind of tube, so we don’t believe in trying to impose our guidelines on the people doing the actual science. Rather, we try to be as flexible and as responsive as possible to the needs of scientists, so whether we are collecting a particular type of blood cell or trying to isolate a particular type of brain cell, we listen to our client and try to adapt our procedures for their needs. That is basically where our expertise lies.

JMAS Because at Masy, we haven’t focused on single sample type, we have taken the entire range of products that the industry needs to store; blood serum, tissues, API for up to level 2, and we have specialized in the stability samples, the ICH storage conditions from the temperature and humidity from down to -80 stability up to the 40 degree 75 percent. That is where we see our customers’ needs.

SR For REMP, as John pointed out from Masy systems, it’s not necessarily a question of the type of sample that works best for our solutions, but rather the storage requirements of the sample itself. As with most automation, limiting the amounts of variables introduced into a system allows for the most reliable and repeatable results. This holds true for automated sample handling. Standardizing on the minimal number of consumables to hold your diverse types of samples is probably one of the most important, but often one of the most difficult-to-achieve. Samples, especially biological samples coming in many different forms, shapes and sizes — and trying to standardize on a limited number of consumables to store these diverse samples is difficult. Another challenge is in choosing a controlled storage environment that fits the need of the majority of the samples you would like to store. As I mentioned previously, REMP offers a range of storage environment options — anything from ambient to -80 — and it is very possible that some samples require storage outside of this range. In this case, these samples will need to be addressed separately. So for any one type of sample, it is not the sample type itself, but the storage requirements that are needed for the sample, and how to properly address that where our solutions are mst effective so as to provide the best samples long-term for your Biobanking needs.

DF The wide variety of samples in biologics, and their intended use, really determine the requirements for sample handling and management, and we manage a variety of biologic drugs, vaccines, cellular therapies and manage them at a full range of temperature. I think flexibility in terms of what we handle and the range of temperatures that we can handle that material is really what we are about. We are totally committed to providing a full range of services to our clients, and as a company within the Thermo Fisher Scientific family, we are able to leverage the resources of the Thermal Fisher Scientific companies to meet specific or unusual client requirements if necessary.

JM At BioStorage Technologies, when we started the company nearly seven years ago, we built our IT system so it actually wasn’t specifically designed for any particular sample, but could handle a wide variety of samples, shapes and sizes, temperatures, and so on. But the important thing about the system is the association of data. In the future what I think will become more important is the ability to be able look at the data associated with the sample, so you have highly characterized data-rich samples that will be available to researchers across their pharmaceutical company. By the way pharmaceutical companies have sometimes been structured, it may be difficult to recognize the value and samples that are elsewhere in the company. So I think the importance here is the data associated with the sample and how we can examine and store the data as well as the sample.

MP I think all of you have mentioned at some point, one of the top priorities in biosample collection, handling and storage is the aspect of quality control. How is this reflected in your processes? What standard or guidelines do you adhere to, and what, if anything, do you believe should be standardized in the future?

JMas: For Masy, and I am sure for all others, quality is number one. As I stated earlier, this is reflected in our ISO certification though TUV and accreditation by A2LA, which is a third party globally recognized quality body. Standardization through participation and storage related organization ISBER, PDA, ISPE, OBBR and participation in developing entire repository technician certification program with ISBER. We support the efforts of ISBER’s best practices, which we like to enhance with GMP and some GLP standards.

SR: I have to agree with John again, the quality of samples that are stored in many of our automated storage systems and associated data is paramount to the quality of tests and associated research data that is produced downstream in these organizations where our solutions are deployed. Sample integrity and security is the cornerstone of many of our product offerings. For example, when two technology consumers offer researchers a really unique and efficient way of managing their samples, with the technologies we employ, we hope to create high quality samples and further control and further enhance the integrity or keep the integrity of these samples long-term. Our storage systems are also controlled through a mature and sophisticated sample management software application, where all aspects of the samples’ history is maintained from a free stop cycle to users who have had access to these samples themselves. The complete audit trail of the history of the sample, gives further credibility to the quality of the sample contained within an automated storage system. As far as adheres to standards or guidelines, there is no published standard for sample storage in any automated environment that we are aware of; however, REMP is actively involved in the International Society for Biological Environmental Repositories, also known as ISBER, and within the working group of these organizations called automated repositories, and will hopefully contribute to the best practices guidelines that are being developed within this organization, especially those guidelines pertaining to automated sample management, and we are hoping to continue our contribution to improving the management of sample collections within this organization, and hopefully elsewhere as we continue providing storage solutions for high quality samples and new data.

DF Quality is certainly essential to all of our businesses, and for Fisher BioServices, again we provide services to a variety of clients that are conducting clinical research and drugs and biologics tissue products as well as in vitro diagnostics, and as a result of those relationships and the efforts of those clients that we have means we are required to comply with applicable regulations such as CGMP, good tissue practices, good laboratory practices, GLP, all based around the CFR, the 02/11, 8/20, 12/71. In addition, we also follow the industry standards such as the PDA technical report #39 for Cold Chain Guidance for medicinal products. We adhere to the U.S. Pharmacopeia 1079 for Good Storage and Shipping Practices, and we are very involved in keeping up with maintaining the expectations of the National Cancer Institute’s best practices for biospecimen resources. We have implemented a company-wide quality system based around all of these regulations and standards for biospecimen storage, and quality control on top of that is just critical. We have a QC program at multiple stages, such as in the receiving process, in place storage and shipping. In addition to operational verification, we perform an independent QC check based on statistical techniques using the ASQ standard processes. We have also incorporated a QC program as part of our processed workflow based on our validated proprietary biospecimen inventory management software system that we call INTRACK. This additional control does not allow us to ship biospecimen without proper QC authorization. So our IT system is critical towards ensuring that we meet QC standards.

JM When we started BioStorage Technologies, it was clear that there was a need for standardization across the many sites that we saw that were storing samples — be it the universities, pharmaceutical companies, and so forth — and we started early on to talk about good storage practice, and our belief is that good storage practice will drive good science. We have a precedent here, because besides storing samples for the research environment, we also store tissues that are going to be used as allografts, and you may know that in 2005, the FDA brought out good tissue practice, and in fact, we have been audited against that. There are many similarities ,I think, between good tissue practice and good storage practice, so what I believe will happen is that the FDA will start to bring in regulations that will extend good tissue practice towards good storage practice, because there are many therapeutic decisions, there are many decisions about targets for drugs, about surrogate markers and so forth, so that we could depend upon samples having been stored to the highest possible standards. So we really pioneered good storage practice, standardizing everything up to 135 standard operating procedures, and we follow others — GLP, GMP and so forth — but it is a critical question to the future development of drugs.

CS We, like the other speakers, certainly support the need for best practices and try to adhere to them. Let me mention a couple of other things that I believe need standardization. Not only do you have to standardize how the samples are handled and all the logistics of that, but also what comes with the samples, the clinical data, the research data that is associated with the samples. There is, I think, a major need for standardization there and compatibility between data sources. Very often we get samples from one site and the information that comes with them is not particularly compatible with what comes from another site. On the other end of this, it depends on what the samples are used for and what QC is necessary. First of all, the samples had to be QC’d histologically by a pathologist. Secondly, they are very often used for biochemical investigations, and QC in that respect is necessary, whether it is RNA or protein integrity. Thirdly, a lot of these samples are used for immunohistochemistry, and we put in the necessary QC to make sure that there is proper antigen presentation that these samples are actually reactive in the way that they should be. So there are a lot of things both at the front end and back end besides the storage that are necessary to be standardized and properly QC’d for the whole system to work properly.

SR As you have probably realized, it is often difficult to predict the future of any new storage technologies or trends in any industry, let alone the Biobanking field, which is still in its infancy with regards to automated technologies and solutions. However, we have seen some interesting technologies recently that could emerge in the next few years and potentially change some of the existing storage technologies today. For example, the Tribal Laboratory has recently presented an application in which they are using a robot to take aliquots from frozen samples without thawing samples themselves. We also see the emergence of ""Personalized Biobanking,"" as a new business model in the next few years. Our opinion is that there appears to be a number of organizations acquiring samples and setting up biobanks in which their samples and/or participants are of a focused subset of the population or their samples represent specific disease characteristics and/or phenotypes. These selective biobanks are moving away from samples from the general population towards samples that represent a specific disease or sample type so that their research is focused. Again, predicting the emergence of new trends and technologies in the Biobanking industry is not clear, but there is some interesting technology and new business trends that are being investigated right now that we need to keep our eyes on over the next few years.

DF I think the use and need for biospecimens going forward is what is going to really drive new technology. The sample strategies will emerge in support of a move towards personalized medicine. I think personalized medicine will be critical in determining what technologies are used going forward. The focus of that technology will be on high-quality, well-annotated biospecimens with the appropriate cases and controls. Science will begin to elucidate on the best specimen type for an intended scientific goal, as well as scientific testing platforms. I think the focus would be on supporting genomics, metabolomics, proteomics and sensitivity of biochemical platforms will be critical to determining the problem and association of disease with those specimens. I think additionally what is going to drive new technology will be economics and getting the biggest bang for your buck that is spent on specimen management and the drive towards best practices in the support of lean and green initiatives. Limiting the number of aliquots per specimen and encouraging storage of archival material for each specimen will be part of the effort to decrease the number of samples stored and high-cost and energy-efficient storage. The initiatives that will lead to Biobanking practices in the future that direct the type, size and biolabelling the data specimens will be accepted. This will enable large-scale use of automation to drive quality and efficiency, and I think automated biobanks will provide easily accessible and denser and less expensive storage mechanisms. Lastly, the green initiatives and rising energy costs would move away from low temperature storage powered by electricity and moving towards other cooling technologies such as the use of nitrogen.

JM The first thing to say is that certainly in my experience when it comes to the use of samples, things have changed dramatically. I grew up in endocrinology and saw that advance very rapidly and was seeing, same rapid growth and signs around companion diagnostics, and so forth, that one can use these type of samples retrospectively and analyze them to see if there are appropriate diagnostics together with therapists. We have already seen diagnostics approved with the use of bank samples. So the proof of integrity of the sample would be critical in the future; the data standardization that was mentioned by Charlie is a critical feature of this in the future. We are already seeing a real drive from scientists for greater green awareness in terms of technologies that are used, and there are technologies by Biometrica and GenVault which are able to use ambient storage for some samples — sometimes normally stored in -80 — and certainly I think a drive to greenness, the drive to retrospect this analysis, the drive to use of data is going be things which are going to see a lot over the next 10 years.

CS We are certainly seeing technological changes, as John just mentioned; dry storage of nucleic acids is coming online. A lot of researchers, too, are asking for us to do new things with the samples that we do have archived— different types of extracts, protein arrays, and there is a big need for fresh samples or samples that can be thawed out and used to generate primary cultures for various types of pathway investigations and for xenografts, and this will always be changing. There is a need for a great deal of flexibility in the system, and that’s what we have seen since the start, and I don’t expect that to change anytime soon.

JMAS One thing that Masy has seen as becoming a need in the future is energy efficiency and better monitoring, as well as redundancies for disaster contingency storage. One thing we took into consideration when designing our state-ofthe- art facility was energy efficiency, which led to implementing the cascade refrigeration system designed by environmental specialties, and a few other companies have that, which basically has a reduction of 10 to 1 in the energy consumption where the traditional method is, for example, opening a freezer -80 into ambient conditions which is a 100 degrees delta, whereas with the cascading system you go from ambient to 5 degrees and from 5 degrees to -20 and from -20 to -80. Resulting in less of an impact to the environmental change, and therefore it also saves in energy, which ultimately is transferred onto research. We are also seeing the acceptance of offsite storage for marrow banking, data recovery, long-term storage and ICH storage, where traditionally it has been kept in-house, and as we are all aware that you end up getting to a point where they temporarily have a permanent repository in-house, and without the supporting facilities and technologies to support the growth.

DF I think what is critical is upfront collaboration. The key is to establish clearly defined working relationships in a more efficient way and the setup of projects with our clients, understanding the endpoints of projects and the total scope of research initiative can assist in how a Biobank supports the overall project. That would include how data is handled and shared. That will really change the advent of personalized medicine and the desire to treat the patients as individuals rather than populations, and requires access to more personally specific data linked to patient specimen. I think the technologies and use of LIMS system such as the Nautilus Biobank System and the development of technology that would be used more efficiently to track specimens and link them back to that associated data, and the collaboration in getting to those endpoints so that you can set those projects appropriately from the beginning would be really useful.

JM I think one of the comments I would make is to when we deal with industry, we quite often deal with different divisions within. Say in a research organization, there are different collections, and so I do feel that the centralization of collections into what we would call a neutral party bank, so that the multiple divisions can look at those samples, will be an enabler to driving faster research. The other thing I think — we are going to see a lot more discussion on this — is the question of informed consent on how samples are used, and to make sure those processes are a standard that needs collaboration between those that are storing the samples and those who are obtaining them; that is, the investigators and maybe the pharmaceutical industry. I think that obviously enters into the field of medical ethics, where I think there a lot of issues — for example, the Icelandic Biobank and its association with pharmaceutical company. Having made the Biobank held by third parties that are somewhat more neutral overcome some of the issues, but I think will become more prevalent in the next few years to deal with the medical ethics of pharmaceutical companies keeping samples and what they do with them, and that might well be one of the solutions.

JMAS Quite simply, in short, through cooperation between the biotech companies and outsourcing Biobanking, this will allow the pharmaceutical and biotech companies to retain more samples for less cost, freeing up more resources for other areas, and also allows the smaller labs to compete with larger drug companies.

SR An interesting point is really that Biobanking is for the sake of the patients, and we see many institutions, whether they be pharmaceutical, biotech, academic or solution providers, eager to enter into Biobanking. However, many of the individual organizations seem to lack all the necessary resources to establish a successful Biobanking operation. We do believe that collaborative partnerships between all of these institutions will advance the field of Biobanking, because it will now allow these individual organizations, each with their own contributing specialty or expertise, an opportunity to participate in biological research using biosamples that they may not have had access to previously, as well as the complementary resources and expertise that the other collaborators bring that they most likely would not have access to either. In fact, REMP has been approached by a few organizations who have been interested venturing into the Biobanking field but have not had all the resources available to enter it successfully. We have introduced these organizations to some of our customers and have seen collaborative Biobanking partnerships start to emerge. We believe that these partnerships can only further advance the field of Biobanking and again as this is for the sake of the patient, will hopefully create some new opportunities and some new discoveries within this field to further advance health care itself.

DF I think the Biobanking industry really is maturing significantly, and the importance of what we all do in research related to disease discovery and analysis and drug development for treatments is becoming more and more critical, and I think it is very exciting the changes that are coming and the involvement that our companies have to be able to participate in going forward in disease management and drug development. I see the field of Biobanking and Biospecimen management, and so on, only growing and becoming more important, and I’m very excited about the opportunity that we all have to play a more important role of going forward.

JM It is clear that we are seeing more and more pharmaceuticals come to the market where there are definitely genetic differences in the handling of the pharmaceutical, and those can be really very significant, and certainly personalize medicine, which we talked about for as long as I can remember. I do believe it is actually just around the corner, and it is going to be dependent upon the high quality-storage of samples and, we are going to be able to look at prospectively and retrospectively to be able to examine those genetic differences for the benefit. We have to remember this is for the benefit of the patients that receive these compounds, because so often patients do not actually respond to the drugs that are given, and where we can really get into personalized medicine and hone in on response and the risk benefit ratio is greatly improved and mankind are all the better for it. So I think this is a fundamental service to the development of pharmaceuticals in the future.