Click to edit Master title style Click to edit Master subtitle style February Regulatory framework for blood and blood components Transfusion Medicine Residency Program May 31, 2011

Click to edit Master title style Click to edit Master subtitle style February What is a Regulatory Framework?  Legislative  Acts and Regulations  Non-legislative  Policies  Guidelines  Directives  Standards

Click to edit Master title style Click to edit Master subtitle style February Regulatory framework for blood and blood components Legislative  Food and Drugs Act Definition of drugs includes blood and blood components (Schedule D) Drugs not be to distributed unless safe Enforcement and powers of inspectors Regulation-making authority  Food and Drug Regulations, Part C (Drugs) Division 1General requirements Division1aEstablishment Licensing Division 2Good Manufacturing Practices Division 4Preparation from human sources (pooled blood plasma, pooled blood serum) and plasmapheresis

Click to edit Master title style Click to edit Master subtitle style February Regulatory framework for blood and blood components Non-Legislative (1)  Policies (Interpretations of the purpose and intent of the Food and Drugs Act and Regulations)  The Distinction Between Advertising and Other Activities (2000)  Guidelines (To assist in the interpretation of the policies governing statutes and regulations)  GMP for Schedule D Drugs, Part 2 - Human Blood and Blood Components (1999)  Management of Blood Establishment Submissions (2006)  Regulatory Requirements for Blood Establishment Information Technology Submission (Draft 2008)  Directives (Request for action)  Implementation of Prestorage Leukoreduction of Cellular Blood Components (1998)  Donor Exclusion to Address Theoretical Risk of Transmission of vCJD through the Blood Supply (1999, 2000, 2001, 2005)  Simian Foamy Virus (2006)

Click to edit Master title style Click to edit Master subtitle style February Regulatory framework for blood and blood components Non-Legislative (2)  Consensus standards  Developed by Standards Development Organizations International Organization for Standardization (ISO) Canadian Standard Association (CSA) American National Standards Institute (ANSI)  Participation is opened to all affected interests (manufacturers, vendors, users, consumer groups, governments, professional and/or research organizations, etc.)  Balanced is maintained among competing interests  Due process assures that all views will be considered and that appeals are possible  Are used within a regulatory framework  e.g., CSA Standard - Blood and Blood Components (Z902)  Non-consensus standards  Association/Industry Standards  Representation and review is limited  Are not used within a regulatory framework  e.g., AABB’s Standards for Blood Banks and Transfusion Services

Click to edit Master title style Click to edit Master subtitle style February Use of consensus standards in a regulatory framework  Reference consensus standard directly in Regulations  The standard can not be in conflict with any statute, regulations, or policies under which the regulator operates;  The standard is national or international in scope and approved by a Standards Development Organizations accredited by the Standards Council of Canada;  e.g., CAN/CSA-ISO 13485:2003  Reference specific clauses/sections of the standard in the regulations  e.g., Safety of Human Cells Tissues and Organs for Transplantation Regulation and the CSA Standards (Z902)  Write the requirements directly in the Regulations  Reference a Health Canada technical document in the Regulations  Recognize or translate, as applicable, the Standard in Guidelines

Click to edit Master title style Click to edit Master subtitle style February Regulatory Oversight Where does it start and end in relation to the management of the blood system?

Click to edit Master title style Click to edit Master subtitle style February Who Are The Regulators? The Big Picture CBS HPFBI (Health Canada) CBER (FDA) CNSC Provincial MOH MDB (Health Canada) BGTD (Health Canada) Medical Laboratory Functions Irradiators Procedures and Labels (Plasma for Fractionation) Inspections E/A&PDI ATE SDE Procedural Change Major/Seriousother TDG Specimens for confirmatory testing, Waste units Special Access

Click to edit Master title style Click to edit Master subtitle style February Scope of processes subject to licence amendments Donation types Regulated activitiesSupport processes  Allogeneic  Donor suitability assessment  Deviation Management*  Autologous  Collection  Recalls*  Designated  Testing  Adverse event reporting*  Directed  Processing  QC testing  Walking donor  Transformation – pooling, irradiation, washing, glyc/deglyc  Storage* if criteria changes  Transportation (shipping)  Importation  Collection of recovered plasma for further manufacturing

Click to edit Master title style Click to edit Master subtitle style February Type of changes subject to licence notification  Addition of a new licensed test (Chagas)  Addition of QC testing (hemolysis)  Change in product expiry (5-day Plasma)  New transportation system for raw material  Change to Donor Selection Criteria (Age)

Click to edit Master title style Click to edit Master subtitle style February Impact of workload and BGTD’s review times (2009) Category II Target Review Time - 20 Days Total: (87%) On Time 4 (13%) Late Category III Target Review Time - 45 Days Total: 7 0 (0%) On Time 7 (100%) Late Category IV Target Review Time Days Total: 9 6 (67%) On Time 3 (33%) Late

Click to edit Master title style Click to edit Master subtitle style February Incident Reporting Requirements Type of OccurrenceReporting Timeframe (from discovery by CBS)  Errors/Accidents24 hours if Major/Serious/Critical/ may impact safety of blood system Semi-annually for all non-critical  Post-Donation InformationSemi-annual Report  Adverse Transfusion Reaction24 hours if life-threatening or fatal 15 days for others  Adverse Donor Event24 hours if life-threatening or fatal 15 days if Donor hospitalized Quarterly for others

Click to edit Master title style Click to edit Master subtitle style February  Mandatory Reporting  Voluntary Reporting  Feedback Link  BGTDBiologics & Genetic Therapies Directorate  CBSCanadian Blood Services  HPFBIHealth Products & Foods Branch Inspectorate  MDBMedical Devices Bureau  MHPDMarketed Health Products Directorate  PHACPublic Health Agency of Canada  PDIPost-Donation Information  SDESerious Donor Event  TTISSTransfusion Transmitted Injuries Surveillance System Reporting of Adverse Events Legend

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Click to edit Master title style Click to edit Master subtitle style February Errors, Accidents, Post-Donation Information & Serious Donor Events CBS Centre Donor CBS Head Office BGTD PDI or SDE Hospital CBS Staff Product Problem Error Or Accident HPFBI E/A Reportable in 24 hr or less

Click to edit Master title style Click to edit Master subtitle style February Product Problems Hospital CBS BGTD Fractionator Plasma Protein ProductsBlood & Blood Components If Problem results from Error or Accident

Click to edit Master title style Click to edit Master subtitle style February Supplier Notifications Hospital CBS Head Office BGTD Supplier MDB CBS Centres If CBS products affected HPFBI

Click to edit Master title style Click to edit Master subtitle style February Adverse Reactions to Transfusion Blood & Blood Components Hospital Provincial Blood Office TTISS CBS BGTD Fractionator MHPD Plasma Protein Products PHAC

Click to edit Master title style Click to edit Master subtitle style February Adverse Events reported to CBS Between 1 April 2009 and 31 March 2010, 113 adverse events were reported to Canadian Blood Services. TRALI or suspected TRALI33 Febrile reaction 24 TACO16 Anaphylactic 6 Suspected bacterial 4 Delayed hemolytic 6 Allergic 3 PTP 1 Miscellaneous 20

Click to edit Master title style Click to edit Master subtitle style February Regulatory Compliance  Monitor release of new / revised Regulations & Standards  Change Control Process  Work Instructions for staff

Click to edit Master title style Click to edit Master subtitle style February Regulatory Compliance  Corporate Audits  Supplier Audits  Inspection by Regulator

Click to edit Master title style Click to edit Master subtitle style February In summary  Scope of processes subject to licence notification:  For product related processes, regulatory oversight exercised through the licence notification process  For most of the support processes, regulatory oversight exercised through the audit/inspection process  Type of changes subject to licence notification:  Risk based  Reporting requirements:  Major, serious or critical

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Click to edit Master title style Click to edit Master subtitle style February