Regulatory Processes and the Blood Service

1. Regulatory Processesand theBlood Service Tutorial for Transfusion Medicine Residents

2. What are Regulations and Standards? • 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

3. What are Regulations and Standards? • 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)

4. What are Regulations and Standards? • 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

5. What are Regulations and Standards? • 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)

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

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

8. Who are the Regulators? – HEALTH CANADA

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

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. 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. 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. 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. Where do I find the Regulations? • 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?)

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. 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. 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. What are the rules?Submissions to BGTD

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

20. Errors, Accidents, Post-Donation Information & Serious Donor Events Donor PDI or SDE Error Or Accident Product Problem CBS Centre CBS Staff Hospital E/A Reportable in 24 hr or less CBS Head Office HPFBI BGTD

21. What are the rules?Reporting to BGTD

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