BIOPRESERVATION AND BIOBANKING Volume 8, Number 3, 2010 ª Mary Ann Liebert, Inc. DOI: 10.1089/bio.2010.8310
Information Systems for Biobanks/Biorepositories: Handling Information Associated with Compliant Sample Management F. John Mills and Andrew Brooks
Introduction
T
he first article in this series emphasized the need for good storage practice (GSP)1 and reiterated that valuable samples are often stored in an ad hoc manner without standardized processes. Storage facilities often lack the robust and scalable information systems necessary to delineate collections and maximize their use in current and future research. It was also recognized that in order for GSP to meet the FDA standards of good tissue practice (GTP), there is a need for clear documentation showing the significant steps in the handling of specimens, including their accessioning (i.e. registration and logging in of samples), storage and retrieval. Informatics systems are also required to manage sample processing, quality control (QC) data and temperature data ranging from ambient to vapor phase liquid nitrogen.
Sample Pre-Registration and Accessioning The first step in assuring high quality sample collection and data management begins with sample pre-registration and accessioning. Irrespective of sample source or service being performed by the repository, it is essential that the unique information associated with each and every sample is defined at the time of receipt in the repository. Every sample source leads to a distinctive challenge with respect to registration, selection of service and sample storage. Once a sample arrives at a given biorepository, the responsibility for that sample shifts from the study coordinator at the collection site, to the repository where the sample will be processed and stored. Often, critical information about a sample is ‘‘missing’’ or ‘‘inaccurate,’’ which can lead to very costly study-specific errors in the future. To this end, a solid informatics approach includes integration of sample preregistration, cataloging of qualitative and quantitative information at the time of accessioning, as well as defined standard operating procedures regarding sample discrepancies. One key component to sample pre-registration is capturing information, which will allow for appropriate sample and quality control reconciliation. This information can be captured electronically at the time of sample submission, or uploaded at the time of sample accessioning;
although the former leads to a more efficient workflow, it often requires a level of laboratory informatics not generally available in most repositories. Sample accessioning is the single most important step of initiating any sample-specific biorepository service. At this stage in the process, the most interaction between the sample and its path forward for processing and storage takes place, and a variety of information is collected, which can help any informatics system reconcile potential sample collection and processing errors downstream. For example, the digital documentation of a primary sample (i.e. blood tube) affords a clinic the ability to reconcile its assignment of a sample during the pre-registration process. This helps alleviate any sample discrepancies that may take place in the future. This process also allows for the documentation of a physical problem associated with a sample (e.g. a defective collection tube) that may affect sample quality during processing. Whether the problem lies with the sample at the time of collection or at the time of processing, it is the repository’s responsibility to help reconcile the issue so the sample can be a viable part of the ongoing study. Sample pre-registration and accessioning, when properly integrated into a repository’s informatics infrastructure, serves as the primary errorchecking utility, which preserves the integrity for all studies managed in the program.
Management of Laboratory Processes Biorepository informatics is essential to the tracking and proper management of sample processing services. Once a sample is received, a number of avenues can be taken to ensure samples are handled and stored properly prior to archival and distribution. The integration of a solid informatics platform is critical to the appropriate management of all repository lab processes. This process begins with service selection at the time of sample accessioning. When a sample is received, its future has already been decided. Whether the sample is destined for storage or other processing (e.g., for nucleic acid extraction), the proper protocol assignment ensures that each and every sample is handled according to approved standards. In the event that services are not assigned at the time of sample preregistration, a biorepository’s informatics infrastructure must
BioStorage Technologies Inc. and Rutgers University Cell and DNA Repository (RUCDR).
163
164 allow for the proper sample assignment at the time of accessioning. This creates a blueprint for the life cycle of every sample within the repository. In addition, it is important to ‘‘qualify’’ samples at the time of service initiation. Depending on the services being performed, there are often a series of deviation codes, which can be applied to any given sample to help qualify its state as a function of downstream quality control. For example, if the time between the collection of a sample and its receipt in the repository falls outside of standard operating procedures for cellular or nucleic acid processing, then a specific code should be linked to that sample post processing as an indication of potential issues with the use of that sample in future analyses. Deviation code assignments include but are not limited to: volume of primary sample received, time to accessioning from collection, compromised collection tube, poor sample quality at the time of receipt, etc. Although some deviation codes terminate any further services or storage of a sample, most simply document potential quality issues that can be correlated with standard quality control metrics at the completion of a given service. The next major component of an integrated informatics program—as a function of biorepository management—is seamless integration into laboratory instrumentation. Given the daily changes in sample receipts and the careful coordination of laboratory services, it is imperative that the proper hand-off of information that drives both processing and analytical instrumentation is created. This allows for the appropriate tracking, assigning and processing of individual samples across multiple studies on a routine basis. Additionally, it leads to more efficient lab processes, given most services that require automation are maximally assigned to samples across studies. This form of informatics integration can be as simple as the import/export of standard file types (i.e. .csv or .txt) that can be used to drive liquid handling instruments, to complete and seamless integration of proprietary file type creation (with the proper drivers). This not only supplies template information for sample processing but also the physical operation of the lab instrumentation performing specific protocols. The most important component of a solid informatics infrastructure, as it pertains to sample processes and biorepository services, is the ability to fully integrate quality control measurements and metrics to specific primary (or stock) samples and all daughter (or aliquot) samples created during its life cycle. Both analytical and functional quality control measurements need to be tied to every sample in a format that allows for efficient selection of samples for downstream analyses. For example, gDNA samples require both analytical (i.e. concentration, purity, yield) and functional (i.e. SNP genotyping) information to ensure the integrity of the sample regardless of when and what it will be used for in the future. Quality control measurements are the final common pathway of all biorepository services and need to be integrated into any informatics system that manages samples and services. It is the coordination of service selection, sample qualification, management of instruments utilized for services and the direct link of quality control data that defines a state of the art informatics infrastructure. The steps can help support and grow small and large biorepositories alike. Although these features can be integrated independently at different levels, it is the synergy and efficiency of an over-arching
MILLS AND BROOKS management informatics solution that provides the level of security and operational effectiveness equal to the importance of samples’ residency in any biorepository.
Sample Storage and Retrieval Many current systems are not capable of recording the process of handling samples. Consequently, they are unable to create an auditable historical record of who handled the sample at what time/date and where the samples have been and are currently. The days of paper systems and excel spreadsheets are over since audit trails may now be created automatically by using validated computer software designed specifically for inventory management, which complies with 21CFR Part11.2 The audit trail, from the entry of a sample into the biorepository through its retrieval, coupled with temperature data on storage conditions, will form the basis of proof of the sample’s integrity. The system needs to be capable of handling samples of varying sizes and allocating space within the designated containers at the correct temperature. As research becomes more globalized, the systems should also be able to record sample data in a global database. The impact of future data requirements should not be underestimated, as the potential quantity of data that may be associated with a sample is likely to grow exponentially over the next few years (e.g., extensive genomic information could be linked to a sample). This therefore reminds the ‘‘curator’’ of the collection that one needs to employ a system that is truly scalable. If samples are to be removed later for analysis, the system should be able to retain the space vacated for future return of the sample. Where aliquots of the parent have been created, the auditable link to the originating sample should be defined in the system, as well as the positions of the daughter samples with temperature rules enforced. The parent data elements also need to be inherited by the aliquots. If necessary, the information associated with the aliquots may need to be changed on a case-by-case basis (e.g. future retrieval dates). When a sample is selected for discard or retrieval, the system needs to memorialize the event with proof of destruction or delivery.
Temperature Recording The aim of recording temperature is to provide a complete record of the temperature at which an individual sample has been stored, emphasizing any deviation in temperature, particularly freeze-thaw cycles. A key element of GSP is the ability to integrate temperature monitoring system and software into the inventory management system, which can provide complete chain-of-custody data. The system should be capable of recognizing temperature deviations within specifications identified by the originator or custodian of the sample. Those deviations should, if necessary, create alerts to staff when freezers are out of temperature range. It is also necessary to employ a hierarchal call-out system to ensure that the situation is remedied before samples are put at risk. It is clear that the days of the temperature chart are over and that modern recording apparatuses such as Elpro (http:// www.elpro.com ) and Rees (http://www.reesscientific.com) are able to create digitized temperature records, which again meet the requirements of 21 CFR Part 11.
INFORMATION SYSTEMS FOR SAMPLE MANAGEMENT
Conclusion Advances in information systems technology have enabled a great deal of data to be captured and stored, not only in association with samples but also about the samples themselves. Without these systems, it would not be possible to build the sample inventories of today that hold so much promise for the future.
References 1. Mills F. J., The need for good storage practice. Biopreservation Biobanking. 2009; 7.
165 2. TITLE 21–FOOD AND DRUGS CHAPTER I–FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICES SUBCHAPTER A—GENERAL, (March 20, 1997) Part 11 – Electronic Records; Electronic Signatures.
Address correspondence to: Dr F. John Mills BioStorage Technologies, Inc. 2655 Fortune Circle W. Suites A-B Indianapolis, IN 46241 E-mail: [email protected]
Information Systems for Biobanks/Biorepositories: Handling Information Associated with Compliant Sample Management F. John Mills and Andrew Brooks
Introduction
T
he first article in this series emphasized the need for good storage practice (GSP)1 and reiterated that valuable samples are often stored in an ad hoc manner without standardized processes. Storage facilities often lack the robust and scalable information systems necessary to delineate collections and maximize their use in current and future research. It was also recognized that in order for GSP to meet the FDA standards of good tissue practice (GTP), there is a need for clear documentation showing the significant steps in the handling of specimens, including their accessioning (i.e. registration and logging in of samples), storage and retrieval. Informatics systems are also required to manage sample processing, quality control (QC) data and temperature data ranging from ambient to vapor phase liquid nitrogen.
Sample Pre-Registration and Accessioning The first step in assuring high quality sample collection and data management begins with sample pre-registration and accessioning. Irrespective of sample source or service being performed by the repository, it is essential that the unique information associated with each and every sample is defined at the time of receipt in the repository. Every sample source leads to a distinctive challenge with respect to registration, selection of service and sample storage. Once a sample arrives at a given biorepository, the responsibility for that sample shifts from the study coordinator at the collection site, to the repository where the sample will be processed and stored. Often, critical information about a sample is ‘‘missing’’ or ‘‘inaccurate,’’ which can lead to very costly study-specific errors in the future. To this end, a solid informatics approach includes integration of sample preregistration, cataloging of qualitative and quantitative information at the time of accessioning, as well as defined standard operating procedures regarding sample discrepancies. One key component to sample pre-registration is capturing information, which will allow for appropriate sample and quality control reconciliation. This information can be captured electronically at the time of sample submission, or uploaded at the time of sample accessioning;
although the former leads to a more efficient workflow, it often requires a level of laboratory informatics not generally available in most repositories. Sample accessioning is the single most important step of initiating any sample-specific biorepository service. At this stage in the process, the most interaction between the sample and its path forward for processing and storage takes place, and a variety of information is collected, which can help any informatics system reconcile potential sample collection and processing errors downstream. For example, the digital documentation of a primary sample (i.e. blood tube) affords a clinic the ability to reconcile its assignment of a sample during the pre-registration process. This helps alleviate any sample discrepancies that may take place in the future. This process also allows for the documentation of a physical problem associated with a sample (e.g. a defective collection tube) that may affect sample quality during processing. Whether the problem lies with the sample at the time of collection or at the time of processing, it is the repository’s responsibility to help reconcile the issue so the sample can be a viable part of the ongoing study. Sample pre-registration and accessioning, when properly integrated into a repository’s informatics infrastructure, serves as the primary errorchecking utility, which preserves the integrity for all studies managed in the program.
Management of Laboratory Processes Biorepository informatics is essential to the tracking and proper management of sample processing services. Once a sample is received, a number of avenues can be taken to ensure samples are handled and stored properly prior to archival and distribution. The integration of a solid informatics platform is critical to the appropriate management of all repository lab processes. This process begins with service selection at the time of sample accessioning. When a sample is received, its future has already been decided. Whether the sample is destined for storage or other processing (e.g., for nucleic acid extraction), the proper protocol assignment ensures that each and every sample is handled according to approved standards. In the event that services are not assigned at the time of sample preregistration, a biorepository’s informatics infrastructure must
BioStorage Technologies Inc. and Rutgers University Cell and DNA Repository (RUCDR).
163
164 allow for the proper sample assignment at the time of accessioning. This creates a blueprint for the life cycle of every sample within the repository. In addition, it is important to ‘‘qualify’’ samples at the time of service initiation. Depending on the services being performed, there are often a series of deviation codes, which can be applied to any given sample to help qualify its state as a function of downstream quality control. For example, if the time between the collection of a sample and its receipt in the repository falls outside of standard operating procedures for cellular or nucleic acid processing, then a specific code should be linked to that sample post processing as an indication of potential issues with the use of that sample in future analyses. Deviation code assignments include but are not limited to: volume of primary sample received, time to accessioning from collection, compromised collection tube, poor sample quality at the time of receipt, etc. Although some deviation codes terminate any further services or storage of a sample, most simply document potential quality issues that can be correlated with standard quality control metrics at the completion of a given service. The next major component of an integrated informatics program—as a function of biorepository management—is seamless integration into laboratory instrumentation. Given the daily changes in sample receipts and the careful coordination of laboratory services, it is imperative that the proper hand-off of information that drives both processing and analytical instrumentation is created. This allows for the appropriate tracking, assigning and processing of individual samples across multiple studies on a routine basis. Additionally, it leads to more efficient lab processes, given most services that require automation are maximally assigned to samples across studies. This form of informatics integration can be as simple as the import/export of standard file types (i.e. .csv or .txt) that can be used to drive liquid handling instruments, to complete and seamless integration of proprietary file type creation (with the proper drivers). This not only supplies template information for sample processing but also the physical operation of the lab instrumentation performing specific protocols. The most important component of a solid informatics infrastructure, as it pertains to sample processes and biorepository services, is the ability to fully integrate quality control measurements and metrics to specific primary (or stock) samples and all daughter (or aliquot) samples created during its life cycle. Both analytical and functional quality control measurements need to be tied to every sample in a format that allows for efficient selection of samples for downstream analyses. For example, gDNA samples require both analytical (i.e. concentration, purity, yield) and functional (i.e. SNP genotyping) information to ensure the integrity of the sample regardless of when and what it will be used for in the future. Quality control measurements are the final common pathway of all biorepository services and need to be integrated into any informatics system that manages samples and services. It is the coordination of service selection, sample qualification, management of instruments utilized for services and the direct link of quality control data that defines a state of the art informatics infrastructure. The steps can help support and grow small and large biorepositories alike. Although these features can be integrated independently at different levels, it is the synergy and efficiency of an over-arching
MILLS AND BROOKS management informatics solution that provides the level of security and operational effectiveness equal to the importance of samples’ residency in any biorepository.
Sample Storage and Retrieval Many current systems are not capable of recording the process of handling samples. Consequently, they are unable to create an auditable historical record of who handled the sample at what time/date and where the samples have been and are currently. The days of paper systems and excel spreadsheets are over since audit trails may now be created automatically by using validated computer software designed specifically for inventory management, which complies with 21CFR Part11.2 The audit trail, from the entry of a sample into the biorepository through its retrieval, coupled with temperature data on storage conditions, will form the basis of proof of the sample’s integrity. The system needs to be capable of handling samples of varying sizes and allocating space within the designated containers at the correct temperature. As research becomes more globalized, the systems should also be able to record sample data in a global database. The impact of future data requirements should not be underestimated, as the potential quantity of data that may be associated with a sample is likely to grow exponentially over the next few years (e.g., extensive genomic information could be linked to a sample). This therefore reminds the ‘‘curator’’ of the collection that one needs to employ a system that is truly scalable. If samples are to be removed later for analysis, the system should be able to retain the space vacated for future return of the sample. Where aliquots of the parent have been created, the auditable link to the originating sample should be defined in the system, as well as the positions of the daughter samples with temperature rules enforced. The parent data elements also need to be inherited by the aliquots. If necessary, the information associated with the aliquots may need to be changed on a case-by-case basis (e.g. future retrieval dates). When a sample is selected for discard or retrieval, the system needs to memorialize the event with proof of destruction or delivery.
Temperature Recording The aim of recording temperature is to provide a complete record of the temperature at which an individual sample has been stored, emphasizing any deviation in temperature, particularly freeze-thaw cycles. A key element of GSP is the ability to integrate temperature monitoring system and software into the inventory management system, which can provide complete chain-of-custody data. The system should be capable of recognizing temperature deviations within specifications identified by the originator or custodian of the sample. Those deviations should, if necessary, create alerts to staff when freezers are out of temperature range. It is also necessary to employ a hierarchal call-out system to ensure that the situation is remedied before samples are put at risk. It is clear that the days of the temperature chart are over and that modern recording apparatuses such as Elpro (http:// www.elpro.com ) and Rees (http://www.reesscientific.com) are able to create digitized temperature records, which again meet the requirements of 21 CFR Part 11.
INFORMATION SYSTEMS FOR SAMPLE MANAGEMENT
Conclusion Advances in information systems technology have enabled a great deal of data to be captured and stored, not only in association with samples but also about the samples themselves. Without these systems, it would not be possible to build the sample inventories of today that hold so much promise for the future.
References 1. Mills F. J., The need for good storage practice. Biopreservation Biobanking. 2009; 7.
165 2. TITLE 21–FOOD AND DRUGS CHAPTER I–FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICES SUBCHAPTER A—GENERAL, (March 20, 1997) Part 11 – Electronic Records; Electronic Signatures.
Address correspondence to: Dr F. John Mills BioStorage Technologies, Inc. 2655 Fortune Circle W. Suites A-B Indianapolis, IN 46241 E-mail: [email protected]
