Presentation on theme: "Best Practices of Biobanking and Specimen Collection: Quality Control Systems in Biobanking and Impact on Validity of Research Results Lunch and Learn."— Presentation transcript:
1Best Practices of Biobanking and Specimen Collection: Quality Control Systems in Biobanking and Impact on Validity of Research ResultsLunch and LearnASIP Annual Meeting at Experimental Biology 2012April 23, 2012Mark E. Sobel, MD, PhDASIP Executive Officer
2Outline ISBER Best Practices Biospecimen Science Quality Control and Proficiency TestingNCI Best PracticesHuman Biological MaterialsSpecial Ethical Considerations
3Acknowledgments Fay Betsou, PhD Integrated Biobank of Luxembourg Presentation at ASIP Annual Meeting at Experimental Biology 2011Carolyn Compton, MDOffice of Biorepositories and Biospecimen ResearchNational Cancer InstituteNational Institutes of HealthOBBR slides in this presentation have been revised
4International Society for Biological and Environmental Repositories Best Practices for Repositories:Collection, Storage, Retrieval and Distribution of Biological Materials for ResearchSecond Edition: Cell Preservation Technology, Volume 6, Number 1, 2008Third Edition: Biopreservation and BiobankingVolume 10, Number 2, 2012
5Biospecimen Science What is biospecimen science? Biospecimen Science is the multidisciplinary field of study responsible for establishing tested and proven biospecimen resource-related procedures based on experimentation in the areas of specimen collection, processing, shipping, and storageWhy is it needed?Biospecimens are composed of active and reactive living cells or cell products, making them highly complex.The collection, handling, and storage process can profoundly alter the molecular profile and quality of biospecimens.Such alterations, though artificial, can be misinterpreted as disease related or disease specific.High degrees of sensitivity and specificity in new molecular techniques raise the bar for analyte (specimen) data and quality.
6Biospecimen ScienceQuality of human biospecimens is multifactorial and is determined by:Type of specimen: Normal tissue, tumor tissue, serum, plasmaPhysical state of the specimenAmount and type of specimen characterization dataAmount and type of quality control exercisedAmount and type of clinical dataPermitted use of the specimenThe analysis to be performed and the biomolecules targeted by the analysisThe goal of the research (application of the data)
7Quality Control - definition « the operational techniques and activities that are used to satisfy quality requirements », ISO9000:2000Nestler W. Effect of Quality Control programs on the organizational structureof the hospitals. Bull. NY Acad. Med. 1976;52:Glenn GC, Hathaway TK. Effects of specimen evaporation on quality control.Am. J. Clin. Pathol. 1976;66:Calam RR. Reviewing the importance of specimen collection.J. Am. Med. Tech. 1977;39:« confirmation through provision of objective evidencethat requirements for a specific intended use or application are fulfilled », ISO9000:2000
8Integrated Quality Control Systems QC / ValidationBiobankBiobank or Research LabSample Processing MethodQuality Control AssayMethod Validation / Proficiency Testing
9ISBER Proficiency Testing Program: Interlaboratory comparisons to identify problems in laboratories and interlaboratory differencesLaunched in 2011DNA QuantificationRNA Integrity and QuantificationPlans for 2012 (to be confirmed May 2012)Cell ViabilityTissue HistologyTissue Antigenicity
11in vitro Preanalytical Variables Collection tubesshedding of components from the tubesilicones, polymeric surfactants, clot inhibitors or activators, rubber stoppers and plasticsadsorption of serum proteins, RNA, DNA to the tubeAnticoagulantscitrate (dilution)heparin (binding)EDTA (platelet clumping)Clotting time and time of incubation before centrifugationStorage conditionsRT, changes after 8h (m/z<3000)4°C, changes after 48hfreeze-thaw cycles, controversy (peptide aggregation, precipitation and adsorption)
12SPREC-01 Biospecimen preanalytical code Standard Preanalytical Coding for BiospecimensCancer Epidemiology Biomarkers and Prevention 2010;19:
13Ideal QC Biomarkers Measurable by widely accessible methods UbiquitousMeasurable by widely accessible methodsOn/Off responseStability :capability of a sample material to retain the initial value of a measured quantity for a defined period of time within specific limits when stored under defined conditionsISBER BS WG, Cancer Epidemiol Biomarkers Prevention 2009;18:
14Why validate QC methods ? give full confidence in sample qualityuse samples after a long timeprovide « reference materials »ensure validity of research results
15NCI Best Practices for Biospecimen Resources Office of Biorepositories and Biospecimen ResearchNational Cancer InstituteNational Institutes of HealthU.S. Department of Health and Human Services
16The Premise of Biospecimen Science Quality of human biospecimens is multifactorial and is determined by the:Type of specimen: Normal tissue, tumor tissue, serum, plasmaPhysical state of the specimenAmount and type of specimen characterization dataAmount and type of quality control exercisedAmount and type of clinical dataPermitted use of the specimenThe analysis to be performed and the biomolecules targeted by the analysisThe goal of the research (application of the data)
17The Role of Biospecimen Resources in 21st Century Medicine Biospecimen resources encompassing large quantities of high-quality, clinically annotated biospecimens are needed to:Identify and validate targets for detection, diagnosis, treatment, and preventionIdentify disease mechanismsDevelop a molecular-based taxonomy of cancerDevelop screening tests for biomarkers associated with certain disease subtypesGroup patients for testing of new drugs based on their genetic characteristics and likelihood of positive responseGroup patients based on the biomarkers of their disease to determine which treatment is appropriateBiospecimen resources are critical to accelerate the development of molecular-based diagnostics and therapeutics for personalized medicine
18Key Requirements for Biospecimen Resources in the Post-Genomic Age Diversity of cancer types and populations based on continual review of researcher needsAccess through a timely, centralized, peer-review processEthical and privacy compliance through a chain of trustResources provided without intellectual property restrictionsPathology and clinical annotation (including longitudinal)State-of-the-art informatics system to streamline the research production process and create in silico research capabilitiesCommunication and outreach effortsBest practice-based and data-driven SOPs to enable reproducible and comparable (additive) results
19Specimen Collection, Processing, Storage, Retrieval, and Dissemination Handle specimens as appropriate for specimen type and study design.Minimize collection/processing time as appropriate.Develop a comprehensive quality management system to include SOPs to document all protocols and a training program for all appropriate personnel.Annotate specimens with key collection, processing, and storage data.Monitor specimen inventory with a tracking system.Store specimens in a stabilized state without unnecessary thawing/refreezing. Dispose of specimens according to clear rules.Review and document storage equipment performance on a regular basis.Follow specimen-appropriate biosafety, packaging, and shipping procedures.Train personnel to adhere to specimen shipping regulations. Control and monitor required shipping temperature.
20Collecting/Managing Clinical Data/QA/QC Collecting and Managing Clinical DataCollect and store relevant clinical and epidemiologic data associated with a specimen, including longitudinal data, if applicable.Use an informatics system that tracks all aspects of collection, processing, and distribution.Comply with applicable privacy rules and human subjects regulations.Quality Assurance/ Quality ControlAdhere to a written quality management system that describes QA and QC procedures.Maintain QA/QC training records for personnel.Adhere to and periodically review SOPs.Have security systems in place, including alarms and backup power.Include a computerized inventory tracking system in the data management plan.Develop a facility disaster plan.Maintain all equipment properly according to SOPs.
21BiosafetyAssume that all specimens are potentially infectious – provide appropriate vaccines, e.g., hepatitis.Adhere to governmental and accrediting agency requirements.Identify and address biosafety risks.Record exposure incidents and provide personnel with appropriate treatment.Establish indemnification agreements with users of biospecimens (except where prohibited by law).Develop additional policies and procedures as appropriate for chemical, electrical, fire, occupational, and radiological safety.Biosafety
22Biospecimen Resource Informatics Assign a unique identifier (number and/or barcode) to each specimen.Update the biospecimen resource database each time the specimen is moved or modified.Use informatics systems that support the linking of specimens with associated data and protect the health information of patients.Adhere to or initiate review of NCI Center for Bioinformatics guidelines and tools; caBIG™ “silver-level” compatibility is recommended.Biospecimen Resource Informatics: Data Management, Inventory Control, and Tracking
23Access to Biospecimens and Data Develop clear policies for specimen and data access.Develop clear guidelines for sample distribution and clinical data sharing (note: NCI Best Practices state that protocol-specific requirements should be met before other access is considered).Ensure that investigators have timely, equitable, and appropriate access, without undue administrative burden.Charge for samples only to recover costs.If a biospecimen resource needs to close, announce the availability of specimens for transfer.Restrict access to subjects’ identities and medical, genetic, social, and personal histories via data access system with defined privilege levels.
24Privacy Protection/Custodianship Protect the privacy of information and follow applicable regulations.Follow documented policies on employee access to data or specimens.Provide levels of security that are appropriate to the type of biospecimen resource.CustodianshipInclude plans for custodianship of collected specimens and associated data in biospecimen resource protocols.Develop plans to handle/dispose of specimens and associated data:At end of the budget period of the grantAt completion of the specific research objectives of the studyIdentify and disclose financial conflicts of interest.In informed consent language, disclose that specimens may help to develop products, tests, or discoveries that may have commercial value.
25Types of Human Biological Materials Germline vs. Somatic cellGermlineInheritabilityImplications for immediate and extended familyImplications for ethnic groupUse of “normal” tissuesSomatic cellAcquired mutationsUse of diseased tissuesNo implications for familyClick and type your text here32
26Types of Human Biological Materials Unidentifiable vs IdentifiableUnidentifiableAnonymousAnonymizedIdentifiableCoded (Linked)IdentifiedClick and type your text here32
27Ethical Principles The Belmont Report Respect for persons (personal autonomy)BeneficenceJustice
28Federal RegulationsDepartment of Health and Human Services Common Rule, 45 CFR 46Food and Drug Administration: 50 CFR 56Institutional Review BoardsInformed consentOHRP: Office of Human Research ProtectionsHIPAA- April, 2003Inconsistencies between HIPAA and the Common RuleClick and type your text here23
29Human Subjects Protection: Use of Human Biological Materials HBMs include:Tissue samplesBlood, sputum, urine, bone marrow, etc.Freshly obtained and archived materialsHBMs are subject to the same regulations as human subjects directly enrolled in studiesTherefore, informed consent and approval by an IRB may be required before using HBMsClick and type your text here32
30Identifiable HBMs- The Common Rule Any HBM that can be identified by any one person, anywhere, is an identifiable sampleIf a sample is coded, and any investigator keeps a key to the code, the sample is identifiableException: If the recipient of the HBMs signs an agreement that there is no intent to identify the samples, the sample may be considered unidentifiable.Click and type your text here32
31Definition of a Human Subject-The Common Rule Does NOT include:Deceased persons (autopsy specimens)Publicly available informationUnidentifiable (Anonymous, Anonymized) SamplesClick and type your text here32
32Waivers of Informed Consent-Common Rule An IRB may grant a waiver of informed consentunder the Common Rule (not the FDA) if fourcriteria are met:Minimal riskRespect for autonomy and the rights of the individualImpracticableNotificationClick and type your text here32
33Waivers of Informed Consent-Common Rule Waivers are rarely granted for identified samplesWaivers are usually (but not always) granted for collecting anonymous samplesWaivers are usually (but not always) granted for using anonymous or anonymized samplesWaivers are occasionally granted for coded (linked) samples:GermlineSomatic cellClick and type your text here32
34OHRP Guidance: Components of Repositories Repository activities involve three components, each of which must satisfy certain requirements:collectors of tissue samplesrepository storage and data management centerrecipient investigators
35OHRP Repository Guidance Tissue collectorRecipient InvestigatorRepository StorageandData ManagementCenterTissue collectorRecipient InvestigatorTissue collectorRecipient InvestigatorIRB ReviewInformed ConsentSubmittal AgreementAssurance of ComplianceIRB ReviewSample Informed ConsentCertificate of ConfidentialityAssurance of ComplianceRecipient AgreementLocal Policies
36Ethical Principles for the 21st Century Respect for persons (personal autonomy):Informed consentRespect for privacy and confidentialityBeneficenceJustice