Regulatory Processes
and the
Blood Service
Tutorial for Transfusion Medicine Residents
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
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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)
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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
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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)
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Who are the Regulators?
The Big Picture
BGTD
HPFBI
Major/Serious
Inspections
CBER
E/A&PDI
Procedures and Labels
(Plasma for Fractionation)
Irradiators
CNSC
other
CBS
Procedural
Change
Special Access
Specimens for
Medical Laboratory
confirmatory testing,
Functions
Waste units
TDG
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Blood Collection
Systems
Test Systems
ATE
SDE
Provincial
MOH
MDB
Who are the Regulators?
HEALTH CANADA
Ministry of Health
Branches of
Health Canada
Regional Presence
Deputy Minister
Associate Deputy Minister
Agencies
Chief Public
Health
Officer
Audit & Accountability Bureau
British Columbia & Yukon Region
Chief Financial Officer Branch
Alberta and NWT Region
Corporate Services Branch
Public Health
Agency of Canada
Manitoba & Saskatchewan Region
First nations and Inuit Health Branch
Quebec Region
The Office of the Chief Dental Officer
Canadian Institutes of
Health Research
Health Environments and Consumer Safety Branch
Ontario & Nunavut Region
Health Policy Branch
Hazardous Materials
Information Review
Board
Atlantic Region
Health Products and Food Branch
Patented Medicine
Prices Review Board
Legal Services
Office of the Chief Scientist
Communications, Marketing and Consultation Directorate
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From A. Arias, “Role of BGTD”, PAHO Workshop, Managua, 2006-10-03/05
Departmental Secretariat
Office of the Cameron Visiting Chair
Pest Management Regulatory Agency
Who are the Regulators? – HEALTH CANADA
Health Products
And
Foods
Branch
Policy, Planning &
International Affairs
Directorate
Therapeutic
Products
Directorate
Health Products
& Foods
Branch
Inspectorate
Natural
Health
Products
Directorate
Drugs
Medical
Devices
Biologics
&
Genetic Therapies
Directorate
Special Access
Program
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Marketed
Health Products
Directorate
Veterinary Drugs
Directorate
Food
Directorate
Who are the Regulators?
– HEALTH CANADA
Biologics & Genetic Therapies Directorate
Centre for Policy
and Regulatory
Affairs
Centre for
Biologics
Evaluation
Blood, Tissues, Organs,
& Xenografts
Clinical Evaluation
Plasma Derivatives
Hemostatic Agents & Blood Substitutes
Vaccines
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Centre for Evaluation of
Radiopharmaceuticals &
Biotherapeutics
From A. Arias, “Role of BGTD”, PAHO Workshop, Managua, 2006-10-03/05
Centre for
Biologics
Research
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
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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
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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).
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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.
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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?)
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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
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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.
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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.
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What are the rules?
Submissions to BGTD
Category
Potential for
adverse
effect on
safety or
efficacy
BGTD
Performance
Target
I
II
III
IV
None
Minimal
Moderate
Substantial
20
calendar
days
+ 5 days
screening
30
calendar
days
+ 15 days
screening
90
calendar days
+ 15 days
screening
Administrative
Change
None
CBS must notify
within 15 days
(90-day
administrative
default for all
Categories)
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Adverse Reactions to Transfusion
Blood & Blood Components
CTOs
Plasma Protein Products
Hospital
monthly
Provincial
Blood Office
MHPD
CBS
TTISS
Fractionator
BGTD
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Errors, Accidents, Post-Donation
Information & Serious Donor Events
Donor
PDI or SDE
Product
Problem
Hospital
CBS
Error
Or
Accident
Centre
CBS
CBS Staff
E/A
Reportable
in 24 hr or less
Head Office
HPFBI
BGTD
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What are the rules?
Reporting to BGTD
Type of Occurrence
Reporting 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 Reaction
24 hours if life-threatening or fatal
15 days for others
Adverse Donor Event
24 hours if life-threatening or fatal
15 days if Donor hospitalized
Quarterly for others
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uestions ?
. . . and on behalf of Q&RA,
Thank You.
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