1. Tutorial for Transfusion Medicine Residents Regulatory Processes and the Blood Service

2. 2 Standards –Usually published by non-governmental organisations (e.g. CSA, CSTM, AABB, ISO), but foreign Regulations also included –Compiled by panels of experts –Represent what is considered “competent” and “reasonable” –Compliance is voluntary –May be used as evidence in a civil suit for negligence What are Regulations and Standards?

3. 3 Some of the Standards that are applicable to CBS: –CSA Standard Z902-04, Blood and Blood Components –CSA Standard Z900.1-03, Cells, Tissues and Organs for Transplantation and Assisted Reproduction: General Requirements –CSA Standard Z900.2.5-03, Lymphohematopoietic Cells for Transplantation –US Code of Federal Regulations (CFR) What are Regulations and Standards?

4. 4 Regulations –Published by government agencies –Compiled by agency staff in consultation with the industry and the public –Represent minimum requirement –Compliance is mandated –Failure to comply can be prosecuted, usually under Criminal Code What are Regulations and Standards?

5. 5 Some of the Regulations CBS must comply with: –Food and Drug Regulations Division 2 - Good Manufacturing Practices Division 4 - Biologics –Health Canada Directive, Technical Requirements to address the Safety of Cells, Tissues and Organs for Transplantation (July, 2005) –Nuclear Safety and Control Act –Laboratory & Specimen Collection Centre Licensing Act (Ontario) & Laboratories Regulations –Medical Laboratory Licensing Act & Regulations (Saskatchewan) What are Regulations and Standards?

6. 6 Who are the Regulators? The Big Picture CBS HPFBI CBER CNSC Provincial MOH MDB BGTD Medical Laboratory Functions Irradiators Procedures and Labels (Plasma for Fractionation) Inspections E/A&PDI ATE SDE Blood Collection Systems Test Systems Procedural Change Major/Seriousother TDG Specimens for confirmatory testing, Waste units Special Access

7. 7 Who are the Regulators?HEALTH CANADA Agencies Chief Public Health Officer Public Health Agency of Canada Canadian Institutes of Health Research Hazardous Materials Information Review Board Patented Medicine Prices Review Board Ministry of Health Deputy Minister Associate Deputy Minister Audit & Accountability Bureau Chief Financial Officer Branch Corporate Services Branch First nations and Inuit Health Branch The Office of the Chief Dental Officer Health Environments and Consumer Safety Branch Health Policy Branch Health Products and Food Branch Communications, Marketing and Consultation Directorate Departmental SecretariatLegal Services Office of the Chief ScientistOffice of the Cameron Visiting Chair Pest Management Regulatory Agency British Columbia & Yukon Region Alberta and NWT Region Manitoba & Saskatchewan Region Ontario & Nunavut Region Quebec Region Atlantic Region Regional Presence Branches of Health Canada From A. Arias, “Role of BGTD”, PAHO Workshop, Managua, 2006-10-03/05

8. 8 Who are the Regulators? – HEALTH CANADA

9. 9 Biologics & Genetic Therapies Directorate Centre for Policy and Regulatory Affairs Centre for Biologics Evaluation Centre for Evaluation of Radiopharmaceuticals & Biotherapeutics Centre for Biologics Research Blood, Tissues, Organs, & Xenografts Clinical Evaluation Hemostatic Agents & Blood Substitutes Plasma Derivatives Vaccines Who are the Regulators? – HEALTH CANADA From A. Arias, “Role of BGTD”, PAHO Workshop, Managua, 2006-10-03/05

10. 10 Where Do I Find The Regulations? Food and Drugs Act –Requires that drugs must be safe and efficacious. –Applies only to “Sale” or distribution of drugs (whether money or other consideration is returned or not). –Regulations, Guidelines and Directives establish technical and labelling requirements for specific products

11. 11 Where do I find the Regulations? Food and Drug Regulations Division 2 - Good Manufacturing Practices –Health Canada also publishes a Guideline on interpretation and application of these Regulations –Guideline includes Annexes for Biologics and for Blood and Blood Components –Principal thrust – there must be a Quality System and a Quality Department

12. 12 Where do I find the Regulations? Food and Drug Regulations Division 4 - Biologics –Only a small portion of this Division deals with Blood or Blood Components. –Most of this (C.04.400 to C.04.423) addresses Source Plasma (plasma collected by apheresis for the production of plasma fractions).

13. 13 Where do I find the Regulations? CSA Standard Z902-04, Blood and Blood Components –Will be referenced in new Regulations to be issued for comment in the first half of (calendar) 2008. –New Regulations will include requirements applicable to hospital transfusion services. –New version of the standard currently in approval process. CSA Standard Z900.1-03, Cells, Tissues and Organs for Transplantation and Assisted Reproduction: General Requirements; January 2003 CSA Standard Z900.2.5-03, Lymphohematopoietic Cells for Transplantation; February 2003 –Regulations referencing these standards have been published to take effect on 2007-12-07. Will become part of Division 4. –Guidance Document has been published for comment. –New versions of the standards are currently at press.

14. 14 The Act and the Regulations are enforced to the letter. Alternative approaches having equivalent outcomes are not permitted unless the regulatory text includes terms such as “adequate” or “effective” or “sufficient”. Guidelines and Standards can be interpreted (Is the intent achieved?) Where do I find the Regulations?

15. 15 Where Do I Find The Regulations? Nuclear Safety and Control Act Protection of staff and public Most recent concern – preventing theft of isotopes Laboratory & Specimen Collection Centre Licensing Act (Ontario) & Laboratories Regulations Medical Laboratory Licensing Act & Regulations (Saskatchewan) Define requirements for operators. US Code of Federal Regulations Applies to plasma entering USA for fractionation Most requirements waived via Import for Export Exemption

16. 16 What are the Rules? Change Process – Food & Drug Regulations Biologics manufacturers must obtain an Establishment Licence for their facilities and must have each drug they make listed in an Annex to the Licence. Licence applications must describe the facilities, equipment (including computer systems) and manufacturing processes used and must identify the personnel in charge. Must also submit Monograph describing drug and its use and labels applied to product.

17. 17 What are the Rules? Change Process (continued) The Regulator must be notified in advance of significant changes to information contained in the Licence Application. Changes to labels must be submitted. Labelling (other materials describing the product) must be consistent with the Monograph.) Hospital-based establishments are exempted from these rules.

18. 18 What are the rules? Submissions to BGTD CategoryIIIIIIIV Potential for adverse effect on safety or efficacy None Administrative Change MinimalModerateSubstantial BGTD Performance Target (90-day administrative default for all Categories) None CBS must notify within 15 days 20 calendar days + 5 days screening 30 calendar days + 15 days screening 90 calendar days + 15 days screening

19. 19 Adverse Reactions to Transfusion Hospital Provincial Blood Office TTISS CBS BGTD Fractionator MHPD Plasma Protein Products Blood & Blood Components CTOs monthly

20. 20 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

21. 21 What are the rules? Reporting to BGTD Type of OccurrenceReporting timeframe (from discovery by CBS) Errors Accidents Post-Donation Information Incidents (IT only) 4 hours if “Catastrophic” 24 hours if Major/Serious/”Critical” 15 days if Significant 45 days for most Adverse 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

22. 22 Q uestions ?... and on behalf of Q&RA, Thank You.