National Cancer Institute U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Quality Biobanking Operations and Practices connecting the biobank with downstream applications increasing the value of your biobank Marianne K. Henderson, M.S. Chief, Division Operations and Analysis, Division of Cancer Epidemiology and Genetics (DCEG) Consultant, Center for Global Health NCI, NIH, DHHS Ex-Officio Member, ISBER Board of Directors Chair, ISBER Organizing Advisory Committee 25 September 2014
US National Cancer Institute Division of Cancer Epidemiology and Genetics (DCEG) A national program for population-based studies to identify the environmental, occupational and genetic determinants of cancer 9 branches and a core genomics laboratory Majority of studies on molecular epidemiology 350 active studies
DCEG Specimen Repository ~ 10.6 million specimens from over 500 research studies mostly blood/blood products/biofluids/some tissue Specimens are housed in one central contract repository that supports specimen receipt, bioprocessing, storage, shipping, purchasing supplies and training study field personnel Other ancillary contracts support the collection of specimens from field sites, receipt and processing of fresh specimens from field and clinical sites and specimen testing
Biobank Evolution - 1980 FFPE Pathology reviews Clinical 1980-1990 DNA, RNA NA Analysis Research 1990-2000 Data High Throughput techniques Research 2000 - Standards & Quality Research Clinical Trends: Standardization, Automation, Networking & Collaboration, Large Consortia & Big Data
What is your definition of a biobank? What is/are your goal(s)? Who/what will you support? What services will you provide? How will you achieve Quality? Biobanking commodities and service-based model From DOI: 10.1093/ncimonographs/lgr009
What is your definition of a biobank? What is/are your goal(s)? Who/what will you support? What services will you provide? How will you achieve Quality? Biobanking commodities and service-based model From DOI: 10.1093/ncimonographs/lgr009
Why is it Important to have a Good Definition: Quality Management System? A Quality Management System is an integrated system of management activities involving planning, implementation, documentation, assessment, and improvement to ensure that a process or item is of the type and quality needed for the project. Quality Management systems support the delivery of high quality services to end user communities and in doing so sustain the business, utility and research viability of collections. QA Quality Assurance QMS QC Quality Control balance cost vs. quality
Why implement a robust QMS at your Biobank? QMS Implemented -- benefits: Promote long term sustainable development Assure the quality of samples and data Support the delivery of high quality services Efficiency in operations and cuts down cost Symbol of capability, Gives advantage to project applications, mutual recognition of international quality measures, promotes the sharing of samples and data
Key Points High Quality Samples High Quality Data High Quality Service Stakeholder Satisfaction More Opportunities Higher perceived value Greater Sustainability
Current good Practices (cgp) Good Laboratory Practices (GLP) Preclinical- Good Manufacturing Practices (GMP) -Manufacturing- Good Clinical Practice (GCP) -Clinical- Quality Standards Best Practices ISBER BBRB OECD ABN IARC/WHO International Organization for Standardization (ISO) ISO9001:2008 Quality Management Standard ISO/IEC 17025:2010 Quality Systems for Testing and Calibrating Laboratories ISO/IEC 15189:2012 Medical Laboratories include requirements for quality and competence ISO Guide 34: 2009 General Requirements for the Competence of Reference Material Providers Clinical and Laboratory Standards Institute (CLSI) CLSI H3-A6 Procedures for the collection of diagnostic blood specimens by venipuncture CLSI H18-A4 Procedures for the handling and processing blood specimens for common laboratory tests CLSI MM13A Collection, transport, preparation, and storage of specimens for molecular methods Managing and validating laboratory information systems; approved guidelines Clinical Laboratory Improvement Amendments (CLIA)
ISO/TC 276 Biotechnology New ISO Standard to standardize on?? Standardization in the field of biotechnology processes that includes the following topics: Terms and definitions; biobanks and bioresources; analytical methods; bioprocessing; data processing including annotation, analysis, validation, comparability and integration; metrology. 20 Countries Participating 14 Countries Observing
Quality Management System (QMS) The establishment of a QMS crosses the organizational structure, responsibilities, procedures, processes and resource systems. Formation of plan and awareness Promotion, training, staff preparation Determine the quality policy and quality objectives Identify Process and element Allocation of responsibilities, resources Establish Document System Trial Operations Review and Audit
The Overall Quality Goal: Implementing QMS across the full spectrum of Biospecimen Processes Application / Review / Informed consent Biospecimen Collection (Blood, Tissues, Urine, etc.) Processing Annotation IT systems Storage Facilities Distribution Use/ Analysis Downstream Labs (*reach) Destruction Data Deposition / Use & Distribution / Destruction Adapted from Peggy Devine
The Overall Quality Goal: Implementing QMS across the full spectrum of Biospecimen Processes Application / Review / Informed consent Biospecimen Collection (Blood, Tissues, Urine, etc.) Processing Annotation Storage Distribution Use/ Analysis Downstream Labs (*reach) Destruction Data Deposition / Use & Distribution / Destruction Adapted from Peggy Devine
Creating your Documents Draft Retire Review Update Document Control Distribu tion 1 st Quality manual 2 nd Programmatic Retain Procedure Documentation Record Control 3 rd SOPs 4 th Record Form Evidence QMS Document System has four levels and should cover all processes in the biobank. The document system must also cover outsourced process, if applicable.
Examples of Types of Records to be Maintained in SOPs Work-Related SOPs for every repository practice Training documents Procurement & delivery Testing results Equipment maintenance Emergency Planning Audit/review Specimen storage location Chain of custody tracking Sample distribution QA activities Specimen Donor-Related (if within the bank s purview) Informed Consent documents Study protocols Specimen requested, removal/destruction Any confidential patient information, with access to records strictly on a need-to-know basis Based on the type of Biobank, goals, customers, services the number and type of SOPs will be different (more? less?)
Biobank Records Control Establish a documented procedure to define the controls needed for the identification, storage, protection, retrieval, retention and disposition of records. Design and confirm forms & worksheets Fill in the data form records Unique Identification Record Collection Catalog of the records Archiving and Retention Retrieval and Search Records Identification, Storage, Security Destruction & Disposal
Management Responsibilities for the QMS Measurement Management Commitment Needs & Expectations Review Improvement Management Responsibilities Quality Policy QMS Planning Responsibility & Authority Communication Management Review Audit Plan Do Check Act Annual Internal Audit should cover the implementation of all SOPs, as well as all places, sites, facilities and departments. AUDITORS MUST BE INDEPENDENT of the activity being audited.
Resource Management Management must plan and provide resources needed for the development and implementation of a QMS and for continual improvements to gain efficiencies. Human Resources *Certification Facilities & Environment Equipment *Validation Reagents & Consumables Information Management System Supporting Services
Quality Control at our Biorepository Standard Operating Procedures Alarms local and remote Remote monitoring of equipment Inventory tracking system BSI-II Proper labeling, storage Back up generators weekly tests Knowledge of shipping regulations (www.saftpak.com) Freezer temperature mapping (below)
QA/QC Detailed for Each Process *From NCI BBRB
Certification and Accreditation Certification: Procedure by which a third party gives written assurance that a product, process or service conforms to specified requirements. Accreditation: Procedure by which an authoritative body gives formal recognition that a body or person is competent to carry out specific tasks. Accreditation is the proof (testimony) of the competence, the impartiality and the independence of a certification body in view of existing norms. Accreditation allows confidence in certificates delivered by third parties.
College of American Pathologists Accreditation Programs Biorepository Accreditation Program - integrates rigorous biorepository guidelines and best practices to create the first set of standards for biorepositories. Sources for the accreditation standards include: http://www.cap.org
Don t forget QA/QC Downstream to Inform Upstream at the Biobank Validation: establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specification and quality attributes - FDA QC checks Analytical method Validation Analytical instrument qualification Method QC and Validation: To evaluate many of the pre-analytical variables that may potentially impact the outcome of results, but are not related to inherent sample differences. e. g. In my Division: DNA and Staging Laboratory Hormone Analysis Laboratory Validation depends on the end-use method or parameter or machinery
Factors of Variability Is it your method or your collection process or inherent in the sample? SAMPLE ENVIRONMENT decontamination Stability of electrical power degradation Precision Accuracy logistics humidity temperature Electromagnetic parasites characteristics vibration VARIABILITY reactives concentration quantity calibrators interpreting manipulating calibrating SOP Instrument qualification reproducibility repeatability OF RESULT Courtesy of: consumables cleaning calibration MATERIALS TECHNICIAN METHOD
Why Validate Downstream? To give confidence in & to our academic and industrial partners To ensure that Inter-laboratory assays give the same results. Verifying quality methods before large-scale use Pilot studies to validate assays (precision, accuracy) To avoid wasting precious specimens and $$ To be confident of processes being carried out (QC, CoV) To be confident in sample quality e.g. DNA extraction/quality checks before genomics assays - standardized staging & automated pipeline
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Standard PREanalytical Code (SPREC) Developed by the ISBER Biospecimen Science Working Group Manage and track pre-analytical variations impacting biospecimen integrity Comprises 7 elements for both fluid and solid samples Defines the sample and primary container type, periods of cold and warm ischemia, and subsequent handling steps Cancer Epidemiology Biomarkers and Prevention 2010, 19:1004-11 28
Quality at the Biobank = Value for Investors/Researchers & to the Public Intrinsic value to each specimen Quality, types and # s of specimens Associated data QMS - Uniformity of practices in collections and in biobank SOPs Fit for Purpose with downstream processes Cost of access recognition of value Input vs. Output (Use of samples/services) Public Perceptions Social trust
Quality at the Biobank Value for Investors/Researchers & to the Public Harmonization of Practices (in bank and in your network) Best Practices Accreditation Training certifications Proficiency testing SPREC, BRISQ e.g. documenting processes in publications BRIF indexing your quality operations
THANK YOU! Marianne K Henderson (mk149c@nih.gov)