COMMENTARY
BIOPRESERVATION AND BIOBANKING Volume 12, Number 5, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/bio.2014.0043
From AAA + to BB - and on the Way Back Again Peter H.J Riegman
Biobank Background
T
he Erasmus Medical Center (MC) Tissue Bank serves the Erasmus MC scientific community and is also accessible for external requests. It covers all disease areas managed within the Department of Pathology, from which formalin-fixed, paraffin-embedded (FFPE) samples are routinely collected (about 200,000 yearly) in the pathology archive (2 to 3 million in total). In addition, samples that can be procured as residual samples from the diagnostic process of freshly delivered surgical specimens are routinely snap frozen and stored in liquid nitrogen, under described standard operating procedures (SOPs).1 The frozen collection is considered a high-quality collection of about 65,000 registered samples, which can be used for sensitive high-throughput techniques. Every year about 5,000 frozen samples enter the bank and about 2,000 are distributed for scientific projects. Most of the distributed samples are returned and can be reused. The biobank has a tissue bank committee for the governance and distribution of the tissues, which is different for every tissue type and includes the pathologist specializing in the requested tissue type and scientists known to work with the tissue type. The main disease area of the tissue bank concerns cancer but, when available, tissues from other diseases are collected. This depends on the involvement of pathologists and whether tissues are left over after the diagnostic process.
Financial Scale and Strategy The Erasmus MC Board of Directors decided in 2001 (the year the frozen tissue bank became operational) to contribute about 200,000 euro yearly. This yearly budget includes 2 full time equivalent (FTE) employees and a small bench fee of 17,000 euro contributed to the budget of the Pathology Department, which is almost adequate to keep the biobank operational. Two FTE employees seem perhaps low for operating a tissue bank on this scale. This is mainly because no informed consent is currently needed for medical research on residual human material or secondary use of human material in The Netherlands2. Instead an opt-out system where potential donors can object to providing tissues is sufficient. Of course no reimbursement of costs is charged when Erasmus MC scientists request samples, because the Board of Directors establishes the budget. For external parties the real costs of a sample are charged based on the expenses and the assumption that 2,000 frozen samples yearly are distributed. The real costs currently range from 150 to 250 euro
per frozen sample. Within this range no profits are made, and the received reimbursement is directly invested in the acquisition of more frozen samples. The Erasmus MC budget to sustain the frozen tissue bank can be considered somewhat low when the biobank implements new demands over the years such as: (1) always having staff available during working hours in the pathology cutting room for freezing new samples; (2) designing and maintaining biobank quality assurance (QA) and quality control (QC) programs3; and (3) implementing and maintaining departmental ISO 15189 accreditation. At the same time the biobank still has to: (1) receive and process new requests; (2) distribute samples according to the rules and regulations; (3) stay involved in changing patient engagement; (4) enlarge and maintain storage capacity (liquid nitrogen shippers and freezers); (5) acquire and maintain a good sample tracking system; (6) buy the necessary consumables; and (7) stay involved in international biobanking societies and projects. Although most frozen sample collections are prospective, the tissue bank also maintains materials without prior research questions in a retrospective collection. Long-term sustainability for a biobank depends on many factors4 and has become a very important issue for the modern biobank.5, 6 A sustainable situation exists when the income of the biobank completely supports the work in labor, consumables, equipment, and overhead, which are needed to collect and distribute a sufficient amount of highquality samples covering the array of institute research interests according to the rules and regulations. Biobanking project proposals were successfully submitted shortly after the start of the biobank in 2001 and the personnel became actively engaged in the international biobanking community. The tissue bank actively contributed and became part of the latest biobanking advances. The projects allowed the biobank much more flexibility in managing personnel and budgets, while remaining independent of funding due to the institutional contribution. In this way the tissue bank was able to evolve into a well-recognized biobank with resources to form a small research group. Funding also enabled the acquisition of dedicated equipment for research on tissues such as: laser capture microdissection, a fully automated tissue microarrayer, tissue microarray analysis software, and 3 virtual microscopes. Investigators can use the equipment in return for contributing to their maintenance. The latest development is the creation of a tissue research support unit (TRSU), where routine pathology techniques are made available for medical research on tissues on a notfor-profit basis. To accomplish this, one FTE extra from the
Pathology Department, Erasmus Medical Center, Rotterdam, The Netherlands.
292
SUSTAINABILITY IN BIOBANKING
pathology lab is integrated in the biobank team to coordinate the work in the pathology lab. The reimbursement of costs is of course in this case to the pathology lab and not to the tissue bank, because the pathology lab personnel perform the coordinated work. The support of one technician is a small investment for the biobank in return for the complete integration of the tissue bank into the pathology department. In addition, the activity itself results in improved outcomes of research based on tissue samples, making the biobank more attractive for research. Indeed, funding is not a steady form of income for a biobank. It can vary a lot depending largely on issues faced by the funding sources. The tissue bank was very well sustained for over a decade in this way. The real danger for sustainability however, was hidden in the enormous cut backs and reorganizations in the regular health care system in the years following the recent economic financial crisis. These factors, in combination with a badly introduced new health care cost recovery system, resulted in rigorous financial measures for health care during the start of 2013. In addition, departments were forced to reorganize and become more budget efficient, with a special focus on eliminating duplication of activities within and between departments. Although the biobank was actually very well positioned on the revenue side, mainly due to the reimbursement of biobank personnel actively involved in biobank project activities, all savings to buy large equipment were declared frozen (now no longer available) and the bench fee was halved. The department declared the 2001 agreement no longer valid, and new ways of financing the biobank needed to be considered. An inventory of all the biobank costs needed to be made. Especially, the hidden routine costs involving the pathology lab needed to identified. These costs were subsequently put into a plan where the biobank would be financed through the departmental cost recovery. Charging a small surplus on every routine FFPE block produced (200,000 are produced yearly), would be sufficient. In fact, a small surplus percentage per block would generate 200,000 euro, enough to support the biobank. This enables the tissue bank to operate without requesting that Erasmus MC scientists reimburse the costs for samples. All client departments that are contributing components of the price of the block still have to agree on that matter. In turn, the tissue bank will stay accessible without any additional cost to scientists of the client departments. In addition, the TRSU will become fully integrated within the pathology lab, enlarging the workforce capacity and efficiently utilizing the pathology lab peak capacity of personnel and equipment during slower times. In the new plan, the tissue bank will become more efficient and more integrated within the pathology lab, where routine personnel take over the snap freezing process, but the process remains under the quality control of biobank personnel. This way, the tissue bank personnel can be much more devoted to sustaining the growth of the biobank and handle a larger bulk of coordinating requests for tissue samples and research support. In addition, the tissue bank will be able to offer more complete services such as generating tissue microarrays, RNA/ DNA isolation from tissues, or bulk laser microdissections. The tissue bank will continue to collect samples without having a direct research question attached and maintain a backlog of follow up materials kept over long periods of time.
293
In case the other departments do not agree, the alternative would be to ask for reimbursement of costs from Erasmus MC scientists requesting samples. However, caution should be exercised in this regard, because asking for reimbursement will result in the emergence of many private collections again. It is not hard to imagine that as a consequence the sample quality issues (SOPs, QA and QC), sample tracking, adherence to local and international rules, access, and patient engagement could become compromised. The final alternative would be to collect only prospective material without the opportunity to continue follow-up collections for materials to be stored for the long term.
Lessons Learned If your biobank seems to be in a financially stable situation, remember that the situation can change very rapidly. Have your biobanking cost structure and inventory always ready to present at any time, in order to respond to institutional inquiries in a timely fashion. The latter is not always easy when you are actively engaged in many international projects and societies. Not all changes are bad, and the tissue bank has a fair chance to emerge in a better and stronger state.
Author Disclosure Statement The author has no conflicts of interest or financial ties to disclose.
References 1. Mager SR, Oomen MH, Morente MM et al. Standard operating procedure for the collection of fresh frozen tissue samples. Eur J Cancer. 2007; 43:828–834. 2. Riegman PH, van Veen EB. Biobanking residual tissues. Hum Genet. 2011;130:357–368. 3. Kap M, Oomen M, Arshad S, de Jong B et al. Fit for purpose frozen tissue collections by RNA integrity number-based quality control assurance at the Erasmus MC tissue bank. Biopreserv Biobank. 2014; 12:81–90. 4. Vaught J, Rogers J, Carolin T et al. Biobankonomics: Developing a sustainable business model approach for the formation of a human tissue biobank. J Natl Cancer Inst 2011; 42:24–31. 5. Simeon-Dubach D, Watson P. Biobanking 3.0: Evidence based and customer focused biobanking. Clin Biochem. 2014; 47:300–308. 6. Watson PH, Nussbeck SY, Carter C et al. A framework for biobank sustainability. Biopreserv Biobank. 2014 12:60–68.
Address correspondence to: Peter H.J. Riegman, PhD Head Erasmus MC Tissue Research Support Unit Department of Pathology, Be 201 Erasmus Medical Center PO Box 2040 3000CA Rotterdam The Netherlands E-mail: [email protected]
BIOPRESERVATION AND BIOBANKING Volume 12, Number 5, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/bio.2014.0043
From AAA + to BB - and on the Way Back Again Peter H.J Riegman
Biobank Background
T
he Erasmus Medical Center (MC) Tissue Bank serves the Erasmus MC scientific community and is also accessible for external requests. It covers all disease areas managed within the Department of Pathology, from which formalin-fixed, paraffin-embedded (FFPE) samples are routinely collected (about 200,000 yearly) in the pathology archive (2 to 3 million in total). In addition, samples that can be procured as residual samples from the diagnostic process of freshly delivered surgical specimens are routinely snap frozen and stored in liquid nitrogen, under described standard operating procedures (SOPs).1 The frozen collection is considered a high-quality collection of about 65,000 registered samples, which can be used for sensitive high-throughput techniques. Every year about 5,000 frozen samples enter the bank and about 2,000 are distributed for scientific projects. Most of the distributed samples are returned and can be reused. The biobank has a tissue bank committee for the governance and distribution of the tissues, which is different for every tissue type and includes the pathologist specializing in the requested tissue type and scientists known to work with the tissue type. The main disease area of the tissue bank concerns cancer but, when available, tissues from other diseases are collected. This depends on the involvement of pathologists and whether tissues are left over after the diagnostic process.
Financial Scale and Strategy The Erasmus MC Board of Directors decided in 2001 (the year the frozen tissue bank became operational) to contribute about 200,000 euro yearly. This yearly budget includes 2 full time equivalent (FTE) employees and a small bench fee of 17,000 euro contributed to the budget of the Pathology Department, which is almost adequate to keep the biobank operational. Two FTE employees seem perhaps low for operating a tissue bank on this scale. This is mainly because no informed consent is currently needed for medical research on residual human material or secondary use of human material in The Netherlands2. Instead an opt-out system where potential donors can object to providing tissues is sufficient. Of course no reimbursement of costs is charged when Erasmus MC scientists request samples, because the Board of Directors establishes the budget. For external parties the real costs of a sample are charged based on the expenses and the assumption that 2,000 frozen samples yearly are distributed. The real costs currently range from 150 to 250 euro
per frozen sample. Within this range no profits are made, and the received reimbursement is directly invested in the acquisition of more frozen samples. The Erasmus MC budget to sustain the frozen tissue bank can be considered somewhat low when the biobank implements new demands over the years such as: (1) always having staff available during working hours in the pathology cutting room for freezing new samples; (2) designing and maintaining biobank quality assurance (QA) and quality control (QC) programs3; and (3) implementing and maintaining departmental ISO 15189 accreditation. At the same time the biobank still has to: (1) receive and process new requests; (2) distribute samples according to the rules and regulations; (3) stay involved in changing patient engagement; (4) enlarge and maintain storage capacity (liquid nitrogen shippers and freezers); (5) acquire and maintain a good sample tracking system; (6) buy the necessary consumables; and (7) stay involved in international biobanking societies and projects. Although most frozen sample collections are prospective, the tissue bank also maintains materials without prior research questions in a retrospective collection. Long-term sustainability for a biobank depends on many factors4 and has become a very important issue for the modern biobank.5, 6 A sustainable situation exists when the income of the biobank completely supports the work in labor, consumables, equipment, and overhead, which are needed to collect and distribute a sufficient amount of highquality samples covering the array of institute research interests according to the rules and regulations. Biobanking project proposals were successfully submitted shortly after the start of the biobank in 2001 and the personnel became actively engaged in the international biobanking community. The tissue bank actively contributed and became part of the latest biobanking advances. The projects allowed the biobank much more flexibility in managing personnel and budgets, while remaining independent of funding due to the institutional contribution. In this way the tissue bank was able to evolve into a well-recognized biobank with resources to form a small research group. Funding also enabled the acquisition of dedicated equipment for research on tissues such as: laser capture microdissection, a fully automated tissue microarrayer, tissue microarray analysis software, and 3 virtual microscopes. Investigators can use the equipment in return for contributing to their maintenance. The latest development is the creation of a tissue research support unit (TRSU), where routine pathology techniques are made available for medical research on tissues on a notfor-profit basis. To accomplish this, one FTE extra from the
Pathology Department, Erasmus Medical Center, Rotterdam, The Netherlands.
292
SUSTAINABILITY IN BIOBANKING
pathology lab is integrated in the biobank team to coordinate the work in the pathology lab. The reimbursement of costs is of course in this case to the pathology lab and not to the tissue bank, because the pathology lab personnel perform the coordinated work. The support of one technician is a small investment for the biobank in return for the complete integration of the tissue bank into the pathology department. In addition, the activity itself results in improved outcomes of research based on tissue samples, making the biobank more attractive for research. Indeed, funding is not a steady form of income for a biobank. It can vary a lot depending largely on issues faced by the funding sources. The tissue bank was very well sustained for over a decade in this way. The real danger for sustainability however, was hidden in the enormous cut backs and reorganizations in the regular health care system in the years following the recent economic financial crisis. These factors, in combination with a badly introduced new health care cost recovery system, resulted in rigorous financial measures for health care during the start of 2013. In addition, departments were forced to reorganize and become more budget efficient, with a special focus on eliminating duplication of activities within and between departments. Although the biobank was actually very well positioned on the revenue side, mainly due to the reimbursement of biobank personnel actively involved in biobank project activities, all savings to buy large equipment were declared frozen (now no longer available) and the bench fee was halved. The department declared the 2001 agreement no longer valid, and new ways of financing the biobank needed to be considered. An inventory of all the biobank costs needed to be made. Especially, the hidden routine costs involving the pathology lab needed to identified. These costs were subsequently put into a plan where the biobank would be financed through the departmental cost recovery. Charging a small surplus on every routine FFPE block produced (200,000 are produced yearly), would be sufficient. In fact, a small surplus percentage per block would generate 200,000 euro, enough to support the biobank. This enables the tissue bank to operate without requesting that Erasmus MC scientists reimburse the costs for samples. All client departments that are contributing components of the price of the block still have to agree on that matter. In turn, the tissue bank will stay accessible without any additional cost to scientists of the client departments. In addition, the TRSU will become fully integrated within the pathology lab, enlarging the workforce capacity and efficiently utilizing the pathology lab peak capacity of personnel and equipment during slower times. In the new plan, the tissue bank will become more efficient and more integrated within the pathology lab, where routine personnel take over the snap freezing process, but the process remains under the quality control of biobank personnel. This way, the tissue bank personnel can be much more devoted to sustaining the growth of the biobank and handle a larger bulk of coordinating requests for tissue samples and research support. In addition, the tissue bank will be able to offer more complete services such as generating tissue microarrays, RNA/ DNA isolation from tissues, or bulk laser microdissections. The tissue bank will continue to collect samples without having a direct research question attached and maintain a backlog of follow up materials kept over long periods of time.
293
In case the other departments do not agree, the alternative would be to ask for reimbursement of costs from Erasmus MC scientists requesting samples. However, caution should be exercised in this regard, because asking for reimbursement will result in the emergence of many private collections again. It is not hard to imagine that as a consequence the sample quality issues (SOPs, QA and QC), sample tracking, adherence to local and international rules, access, and patient engagement could become compromised. The final alternative would be to collect only prospective material without the opportunity to continue follow-up collections for materials to be stored for the long term.
Lessons Learned If your biobank seems to be in a financially stable situation, remember that the situation can change very rapidly. Have your biobanking cost structure and inventory always ready to present at any time, in order to respond to institutional inquiries in a timely fashion. The latter is not always easy when you are actively engaged in many international projects and societies. Not all changes are bad, and the tissue bank has a fair chance to emerge in a better and stronger state.
Author Disclosure Statement The author has no conflicts of interest or financial ties to disclose.
References 1. Mager SR, Oomen MH, Morente MM et al. Standard operating procedure for the collection of fresh frozen tissue samples. Eur J Cancer. 2007; 43:828–834. 2. Riegman PH, van Veen EB. Biobanking residual tissues. Hum Genet. 2011;130:357–368. 3. Kap M, Oomen M, Arshad S, de Jong B et al. Fit for purpose frozen tissue collections by RNA integrity number-based quality control assurance at the Erasmus MC tissue bank. Biopreserv Biobank. 2014; 12:81–90. 4. Vaught J, Rogers J, Carolin T et al. Biobankonomics: Developing a sustainable business model approach for the formation of a human tissue biobank. J Natl Cancer Inst 2011; 42:24–31. 5. Simeon-Dubach D, Watson P. Biobanking 3.0: Evidence based and customer focused biobanking. Clin Biochem. 2014; 47:300–308. 6. Watson PH, Nussbeck SY, Carter C et al. A framework for biobank sustainability. Biopreserv Biobank. 2014 12:60–68.
Address correspondence to: Peter H.J. Riegman, PhD Head Erasmus MC Tissue Research Support Unit Department of Pathology, Be 201 Erasmus Medical Center PO Box 2040 3000CA Rotterdam The Netherlands E-mail: [email protected]
