Expert Advisory Committee on Blood Regulations - Record of Meeting - 2010-11-18

Date: 2010-11-18

Contact: Director General's Office

Health Canada
Health Products and Food Branch (HPFB)
Biologic & Genetic Therapies Directorate (BGTD)
Joint Meeting of Expert Advisory Committee on Blood Regulations & Expert Advisory Committee - Cells, Tissues and Organs

Record of Meeting

Thursday, November 18, 2010
8:00 a.m. - 3:00 p.m. EST
The Hilton Lac-Leamy Hotel, 3 boulevard du Casino
Gatineau, Québec

Participants

Members:
Dr. Lindsay Nicolle, Chair EAC-BR (Winnipeg, MB); Dr. Joanne Embree (Winnipeg, MB); Dr. Marina Klein (Montreal, QC) (via teleconference); Dr. Bryce Larke (Edmonton, AB); Dr. Gail Rock(Ottawa, ON); Dr. Jacob Pendergrast (Toronto, ON); Dr. Mel Krajden (Vancouver, BC); Dr. Mohammad Qadura (Hamilton, ON); Dr. Sue Robinson (Halifax, NS); Dr. Alan Tinmouth (Ottawa, ON); Ms. Corinne Weernink, Chair, EAC-CTO, (London, ON); Dr. Martin Champagne (Verdun, QC); Dr. Bruce Light (Winnipeg, MB); Dr. Jolanta Karpinski (Ottawa, ON); Ms. Linda Wright (Toronto, ON); Ms. Penny Marrett (Toronto, ON); Mr. Sean Marguerrat (Halifax, NS) (via teleconference); Mr. Tumelo Mokoena (Edmonton, AB); Pastor Ian Robb (Milford, ON); Ms. Sandra White (St. John's, NL)

Health Canada and Public Health Agency Representatives:
Dr. Elwyn Griffiths, Director General, BGTD; Ms.Angela Briginshaw, Senior Executive Director, BGTD; Dr. Peter Ganz, Director, CBTE, BGTD; Dr. Francisca Agbanyo, Chief, BGTD; Ms. Liz Anne Gillham-Eisen, Manager, OPIC, BGTD; Ms. Karen Farrell, OPIC, BGTD; Ms. Lindsay Blaney, Director, OBIRM, BGTD; Ms. Alicia Li, BGTD; Ms. Geeta Daté, BGTD; Mr. Kyle Norrie, A/Manager, BGTD; Ms. Dorothy Corbett, BGTD; Dr Carole Légaré, Manager, MHPD; Dr. Marie Goulet, MHPD; Ms. Gita Nayeri, Manager, HPFBI; Ms. Jessica Halverson, Manager, PHAC

Presenters:
Dr. Margaret Fearon, Canadian Blood Services (CBS); Ms. Jennifer Biemans, CBS; Dr. Marc Germain, Héma-Québec; Mme Suzanne Rémy, Héma-Québec

Regrets:
Dr. Jun Wu, Associate Director, PHAC, Ms. Georgette Roy, BGTD.

Joint Morning Session

Agenda Item # 1: Opening Remarks

Presenter: Dr. Elwyn Griffiths, Director General, BGTD
Context: Information Update
Major Points: Dr. Elwyn Griffiths welcomed everyone to the first joint face to face meeting of the Expert Advisory Committee on Blood Regulations (EAC-BR) and Expert Advisory Committee on Cells, Tissues & Organs (EAC-CTO).

• The BGTD underwent some re-organization earlier this year. There is now a separate centre dedicated to the evaluation of blood, cells, tissues, and organs, to better focus on the issues related to these areas. This new centre is called the Centre for Blood and Tissue Evaluation (CBTE), and Dr. Peter Ganz is the Director.
• Health Canada, along with other international regulatory authorities, is increasing its efforts to better monitor emerging infectious diseases. Some of these emerging infectious agents, including Xenotropic Murine Leukemia Virus-Related Virus (XMRV), may be potential threats to both blood and CTOs safety.
• The Food & Drug Administration (FDA) held a workshop on "Emerging Infectious Diseases" in May 2010. Dr. Peter Ganz and Ms. Liz Anne Gillham-Eisen presented on Health Canada's precautionary approach in identifying, evaluating, and developing strategies for managing threats from emerging infectious diseases on blood and CTOs.
• The Public Health Agency of Canada (PHAC) held a workshop on 'Risk Management of XMRV' in October. Dr. Ganz will discuss some of the findings from this workshop in his presentation on XMRV.
• As Health Canada continues to explore strategies to detect and respond to emerging threats to blood and CTOs, we will continue to consult the EAC-BR and EAC-CTO jointly on issues that are relevant to the mandates of both committees, which in turn may lead to future joint meetings.

Agenda Item # 2: Review of Today's Agenda

Presenter: Dr. Lindsay Nicolle, Chair
Context: Administrative
Major Points: Dr. Nicolle welcomed all participants to the first joint meeting of the EAC-BR and EAC-CTO. The agenda was approved.

Agenda Item # 3: Declaration of Affiliations and Interest for this Meeting

Presenter: Dr. Lindsay Nicolle, Chair
Context: Administrative
Major Points: Dr. Larke, Dr. Krajden, and Dr. Champagne declared their affiliations with the Canadian Blood Services (CBS) and Héma-Québec (HQ). Dr. Rock declared her affiliation with the Canadian Apheresis Group. Dr. Pendergrast declared his affiliation with the Thalassemia Foundation of Canada. Ms. Weennink and Mr. Mokoena declared their possible conflict for the agenda item on composite tissue transplant. Dr. Larke declared his position as the chair of the Safety Advisory Committee for Héma-Québec as a conflict of interest for the agenda item on HIV-1 Group O. All members submitted their affiliations and interests in writing.

Agenda Item # 4: HIV and AIDS in Canada, PHAC Surveillance Report to December 31^st 2009

Presenter: Ms. Jessica Halverson, PHAC
Context: Information & Discussion
Major Points: Ms. Halverson presented key findings from the "HIV and AIDS in Canada: Surveillance Report to December 31^st 2009".

In 2009, 2,417 HIV cases were reported in Canada, a decrease of 8.3% since 2008. When looking at the different risk exposures for HIV, men who have sex with men (MSM) was the leading risk exposure in Canada. This group accounted for 41.8% of all positive HIV cases reported in 2009 with known exposure category. The second most reported exposure category was heterosexual contact (30.7%). Injection drug use (IDU) was the third most frequently reported exposure category, representing 21.6% of HIV reports among adults in 2009.

From 1998-2009, HIV cases reported to PHAC revealed differences in HIV exposure categories among different ethnic groups. Aboriginal people had the highest proportion of HIV reports attributed to injection drug use (60.3%). There were some questions on the geographical distribution of HIV infections in Aboriginal people. PHAC responded that it is very difficult to draw conclusions from the surveillance data because Ontario and Québec do not submit ethnic status information with HIV test reports. From the ethnic information available from other provinces, the Eastern provinces have relatively low levels of HIV in Aboriginal people. In the Western provinces, the highest levels of HIV incidence occurred in Aboriginal people in Saskatchewan.

Some questions were raised on the immigration trends from countries that are highly endemic for HIV infections. PHAC responded that there is publicly available data on different patterns of immigration trends; however, PHAC does not have access to information on the HIV status of immigrants. The surveillance data does not provide any information on whether an individual with HIV acquired the disease in the country of origin or after arrival in Canada. PHAC has implemented several enhanced surveillance systems to help monitor HIV prevalence and risk behaviors among some key populations; it hopes to expand these systems to additional populations, including people from HIV-endemic countries.

In response to a question on the undiagnosed HIV cases, PHAC commented that the surveillance data indicated that the highest proportion of undiagnosed cases occurred in the heterosexual contact category. The lowest proportion of undiagnosed cases occurred in the injection drug use and MSM categories.

Agenda Item # 5: Review of Current Policies on MSM in Blood and CTO Donations in Canada

Presenter: Dr. Peter Ganz, BGTD, Health Canada
Context: Information
Major Points: Dr. Ganz provided a comprehensive presentation on Health Canada's regulatory role and current policies for managing infectious agent transmission via blood transfusion and CTO transplantation.

The donor screening questions, including the MSM question, seek to identify prospective donors who have taken part in activities that have been identified as placing participants at higher risk of infections that are transmissible via blood, cells, tissues, and organs. In blood donations, a man who has had sex with another man even once since 1977 is indefinitely deferred. In the case of CTO donations, the MSM exclusionary criterion in Annex E of the CTO Regulations includes men who have had sex with another man in the preceding five years. Section 40 of the Regulations, Exceptional Distribution, allows for the use of CTOs (in the absence of any suitable CTO available) from donors with risk factors based on the judgment of the transplanting physician and with the informed consent of the recipient.

The major issues with changing the deferral period for the MSM indefinite deferral were discussed. Peer reviewed modelling studies published in the scientific literature indicated that if the deferral for MSM were relaxed from indefinite to 1, 5, or 10 years, the risk of transmission of HIV through blood transfusion would increase above the very low levels observed today. Epidemiological studies have shown that the MSM group has a higher prevalence than the general population for other infectious diseases that can be transmitted through blood for which screening tests are currently not available. In addition, although current nucleic acid based testing is highly sensitive and specific, it is not completely error free and there remains the possibility of false negative results.

The current policies on MSM deferral in other countries, including the United States and European Union, were presented. A comparison of Health Canada's current and future strategies for addressing infectious agent risks to blood safety was also provided.

A presentation on the "Freeman Case" was provided. The Freeman litigation, the Ontario Superior Court Decision by Justice Aitken, and some observations from the court case were discussed.

There were questions on the peer reviewed modelling studies that indicated an increased risk of transmission of HIV through blood transfusion if the MSM deferral were relaxed from indefinite to 1, 5, or 10 years. Health Canada stated that although the increase in risk demonstrated in these modelling studies is very small, blood recipients expect the regulatory authority to increase blood safety, not decrease it. In response to a question on any data to demonstrate that there is no threat to Canada's blood supply, Health Canada responded that CBS and HQ have not reported any shortages of labile blood components in Canada.

Agenda Item # 6: Review of HHS ACBSA June 10th 2010 Meeting & Recommendations

Presenter: Dr. Peter Ganz, CBTE, BGTD, Health Canada
Context: Information
Major Points: On June 10 -11, 2010, the Human and Health Services Advisory Committee on Blood Safety and Availability (HHS ACBSA) met to discuss the current Food and Drug Administration (FDA) policy on men who have sex with other men. Dr. Ganz presented on Health Canada's policy on MSM at this meeting.

An overview of the ACBSA's recommendations on the current donor deferral policies was presented. In summary, the ACBSA committee recommended that the current MSM deferral policy not be changed at this time.

Agenda Item # 7: Joint EAC-BR & EAC-CTO Discussion regarding the deferral of MSM

Moderator: Dr. Lindsay Nicolle, Chair, EAC-BR
Context: Discussion and Recommendation
Major points: The EAC-BR and EAC-CTO engaged in deliberations and discussed the following: does the recently published Canadian epidemiological data warrant a change to the donor screening criteria, particularly the current deferrals for MSM in blood and CTO donations?

The committees concluded that the latest available surveillance data are inadequate to support a change to the current MSM deferrals in blood and CTO donations. Therefore, both the EAC-BR and EAC-CTO recommended that the current MSM donor screening criteria in blood and CTO donations not be changed at the present time. The committees, however, acknowledged that there are limitations to the current screening questions in accurately and effectively identifying all potential high risk donations and limitations in available data with which to make an informed decision.

The EAC-BR and EAC-CTO made the following recommendations in order to better address this issue in the future and inform future discussions about potential changes:

1. Explore modifications to the donor screening questions to develop the most effective questions for accurately identifying high risk behaviors.
2. Evaluation of data from published modeling studies for relaxation of deferral for MSM blood donors from indefinite to 1, 5, 10 years, or longer.
3. Evaluation of epidemiology data of other infectious viruses that are transmissible through blood, cells, tissues, and organs.
4. Create a job aid with information on the potential risk of infectious disease transmission associated with higher risk behaviors for CTOs that would be helpful in the informed consent discussion between the transplanting physician and recipient.
5. Evaluation of global data on individual cases of HIV transmission through blood, cells, tissues, and organs and the origin of each case.
6. Re-assessment of the blood donor deferral period of men who have sex with other men even once since 1977. With the current deferral period set at 1977, it is increased by one year annually. This yearly increase is not justified by scientific evidence.

Agenda Item # 8: XMRV Risk Management Strategies

Presenter: Dr. Peter Ganz, CBTE, BGTD, Health Canada
Context: Information, Discussion and Recommendation
Major Points: Dr. Ganz provided a detailed presentation on the risk management of the potential emerging infectious agent, Xenotrophic Murine Leukemia Virus Related Virus (XMRV).

In 2009, Lombardi et al, reported in Science the detection of XMRV DNA in 67% of persons suffering from chronic fatigue syndrome (CFS) compared with a 3.7% infection rate in healthy controls. However, subsequent reports from four independent groups of investigators have failed to find evidence of any association between XMRV and CFS. More recently, a study published in the journal Proceedings of the National Academy of Sciences, confirmed a linkage of Murine Leukemia Virus (MLV)-related virus gene sequences in patients with CFS showing positivity of 86.5% of CFS patients compared with 6.8% of healthy blood donors.

Currently, there is no direct evidence to support XMRV transmission through blood or CTOs. The potential risks of XMRV to blood recipients were extensively discussed. The various regulatory and operational measures that have been evaluated internally by Health Canada for managing potential XMRV risks were presented.

The results of preliminary studies on XMRV conducted by the Public Health Agency of Canada to determine evidence of infectivity of the virus in certain study cohorts were presented. The evidence to date does not prove a link between XMRV infection and CFS. But as a precautionary measure, CBS has chosen a passive deferral for individuals with CFS.

In conclusion, Health Canada raised the following questions to the EAC-BR and EAC-CTO for discussion:

• Are the current risk mitigation efforts appropriate?
• If there are gaps in strategy, what other measures should be evaluated?

On the CTO side, the EAC-CTO recommended the status quo at this time on this issue; no additional screening question needs to be added to the donor assessment questionnaire in relation to chronic fatigue syndrome.

A member expressed the concern that if future studies show that there is no link between XMRV and CFS, how much evidence is necessary to discontinue the passive deferral and allow these individuals to donate blood. Due to the controversial evidence surrounding the potential link between XMRV and CFS, a member mentioned the possibility of virus detection from laboratory contamination that resulted in false positives.

A member commented that international regulatory authorities should establish a consistent framework for the risk mitigation of emerging threats to the blood system.

In conclusion, the EAC-BR did not recommend any additional measures to be evaluated in Health Canada's current risk mitigation efforts in managing XMRV. However, the committee expressed interest in getting updates on this issue from Health Canada in the next meeting / teleconference.

Agenda Item #9: Review of the joint portion of the Meeting

Presenter: Dr. Lindsay Nicole, Chair EAC-BR
Context: Information
Major Points:

• Dr. Griffiths welcomed everyone to the first joint meeting of the EAC-BR and EAC-CTO. He informed the committee of developments in the BGTD in his opening remarks.
• The agenda was reviewed and approved.
• Declarations of affiliations and interests were submitted in writing.
• PHAC presented the latest surveillance data on HIV/AIDS. The MSM group still represents the highest proportion of new HIV infections in Canada.
• Dr. Peter Ganz provided an overview of the MSM policies in Canada and other international jurisdictions. He also provided a review of the Freeman litigation.
• The EAC-BR and EAC-CTO recommended that the current MSM donor screening criteria in blood and CTO donations not be changed at the present time. The committees made recommendations for additional data in order to better address this issue in the future.
• Dr. Ganz provided a detailed presentation on XMRV and Health Canada's risk mitigation approaches on this issue. The committees expressed interest in getting more updates on this issue in the future.

Agenda Item #10: Adjournment of joint session

The joint morning session was adjourned at 12:15 pm.

EAC-BR Break-out Session

Agenda Item #11: Approval of 2010-03-22 EAC-BR Meeting Minutes

Presenter: Dr. Lindsay Nicolle, Chair EAC-BR
Context: Information
Major Points: The minutes of the EAC-BR teleconference held on March 22, 2010 were approved.

Agenda Item #12:

Presenter:
Context:
Major Points: "These Minutes have been edited for confidential information in accordance with the Treasury Board Manual - Policy & Guidelines on Security. Confidential & proprietary information has been removed."

Agenda Item #13:

Presenter:
Context:
Major Points: "These Minutes have been edited for confidential information in accordance with the Treasury Board Manual - Policy & Guidelines on Security. Confidential & proprietary information has been removed."

Agenda Item #14:

Presenter:
Context:
Major Points: "These Minutes have been edited for confidential information in accordance with the Treasury Board Manual - Policy & Guidelines on Security. Confidential & proprietary information has been removed."

Agenda Item #15:

Presenter:
Context:
Major Points: "These Minutes have been edited for confidential information in accordance with the Treasury Board Manual - Policy & Guidelines on Security. Confidential & proprietary information has been removed."

Agenda Item #16:

Presenter:
Context:
Major Points: "These Minutes have been edited for confidential information in accordance with the Treasury Board Manual - Policy & Guidelines on Security. Confidential & proprietary information has been removed."

Agenda Item #17: 2008/2009 TESS Update

Presenter: Ms. Cindy Hyson, PHAC
Context: Information
Major Points: PHAC provided a 2008/2009 update on the Transfusion Error Surveillance System (TESS). TESS is a national blood transfusion 'error' pilot projected funded by PHAC since 2005. The national goal is to document transfusion errors along the transfusion chain to allow for corrective action and process improvement, which will result in increased patient safety and national expansion of TESS. A summary of the key data and trends collected in 2008/2009 was provided. The most concerning issue during the pilot period (2005 to 2009) was the failure to accurately label a blood bank sample with the correct patient information. The strengths of TESS as identified by the participating sites were discussed. The conclusions that PHAC drew from the analysis of the data were provided. A rigorous approach to transfusion errors is warranted to further optimize patient transfusion safety and reduce product wastage.

A member commented that it might be worthwhile for the stakeholders involved in the TESS pilot project to develop a checklist for transfusion procedures to augment compliance and minimize errors.

In response to a question on the variations in blood ordering/tracking systems in different hospitals, PHAC responded that different hospitals use a variety of tracking systems, including computerized and electronic systems and there is at least one hospital that uses a bar coding system.

The EAC-BR commended PHAC's work on the TESS pilot project.

Agenda Item #18: Review of Afternoon EAC-BR session

Presenter: Dr. Lindsay Nicolle, Chair, EAC-BR
Context: Information
Major Points:

• Confidential & proprietary information has been removed.
• Confidential & proprietary information has been removed.
• Confidential & proprietary information has been removed.
• PHAC provided a comprehensive update on TESS.
• The chair thanked Health Canada and the committee members for attending this meeting.

Agenda Item #19: Adjournment of Afternoon EAC-BR session

The meeting was adjourned at 3:00 pm.

Acronyms

AIDS

Acquired immunodeficiency syndrome

BGTD

Biologics and Genetic Therapies Directorate

CBS

Canadian Blood Services

CBTE

Center for Blood and Tissue Evaluation

CFS

Chronic Fatigue Syndrome

EAC

Expert Advisory Committee

EAC-BR

Expert Advisory Committee - Blood Regulation

EAC-CTO

Expert Advisory Committee - Cells, Tissues and Organs

FDA

Food and Drug Administration

HHS ACBSA

Human and Health Services Advisory Committee on Blood Safety and Availability

HIV

Human immunodeficiency virus

HPFB

Health Products and Food Branch

HPFBI

Health Products and Food Branch Inspectorate

HQ

Héma-Québec

MHPD

Marketed Health Products Directorate

MSM

Men-who-have-sex-with-men

PHAC

Public Health Agency of Canada
Confidential & proprietary information has been removed.

TESS

Transfusion Error Surveillance System

XMRV

Xenotrophic murine leukemia virus-related virus