Transmissible Spongiform Encephalopathies Advisory Committee 23 rd Meeting Gaithersburg, MD –...

Transmissible Spongiform Encephalopathies Advisory Committee

23rd Meeting Gaithersburg, MD – August 1, 2011

CJD and vCJD Donor Policies:

Blood and Blood Components

Luisa GregoriDivision of Emerging and Transfusion-Transmitted Diseases

OBRR/CBER/FDA

1|Gregori|TSEAC, August 1, 2011

Overview of FDA Policies Regarding Deferral of Blood Donors at Increased Risk

for CJD and vCJD

Rationale for blood donor deferrals

History of FDA policies

Current Guidance


Rationale for Blood Deferrals

Fatal No cure or therapy No test to identify asymptomatic CJD or vCJD

blood donors No infectivity removal technology for all cellular

components RBC filters are under development

Limited clearance studies with TSE agents for plasma products (FDA allowed claims)


Endogenous Infectivity in Blood

TSE infectivity was transmitted by blood transfusion in animal studies Sheep with scrapie or BSE Deer with CWD

Four cases of transfusion-transmitted vCJD One case of transmission by UK plasma-derived Factor

VIII No cases of transmission with CJD

Is CJD infectivity transmissible by blood transfusion?


Transmissibility by Blood Transfusion of vCJD versus CJD


Disease (or infection)

NoDisease

vCJD 4 29

CJD* 0 144

* Dorsey et al, Transfusion 2009

Recipients surviving > 5 yr post transfusion

Look-back studies suggest no evidence of transmission of CJD by blood transfusion Relatively small number of patients High rate of lost-to-follow up Limited medical records No autopsies to rule out preclinical CJD infection


CJD Infected Blood Poses a Theoretical Risk (1)

Hewitt et al, Vox Sang 2006; Dorsey et al, Transfusion 2009

One recent case-study suggests a possible association with history of blood transfusion but only in cases with 10-year lag (Puopolo et al, Transfusion 2011)

Prone to biases Difficult to select control cases A UK study shows no evidence of association (in press)

Theoretical risk of transfusion transmission for CJD versus demonstrated risk for vCJD


CJD Infected Blood Poses a Theoretical Risk (2)

History of FDA Policies to Reduce CJD and vCJD Risks (1)

1978 & 1983. Evidence of infectivity in buffy coat of rodents experimentally infected with CJD and GSS agents

1983. FDA recommended withdrawal of CJD-implicated blood components (post-donation diagnosis of CJD in a donor)

1987. FDA recommended deferring donors treated with human cadaveric pituitary growth hormone, later other donors at increased TSE risk

1991 & 1996. FDA recommended withdrawal of in-date plasma derivatives manufactured from pooled plasma containing donation from an individual with CJD or at increased risk of CJD. This recommendation was rescinded in 1998


History of FDA Policies to Reduce CJD and vCJD Risks (2)

1996. First cases of vCJD reported from UK and France 1999. FDA recommended deferral for 6 mo total residence

in UK 1980-1996 2000. First report of transfusion-transmitted BSE in sheep 2002. FDA recommended enhanced geographic vCJD

deferrals—retained in the current guidance (including donors transfused in UK since 1980)

2003-2007. UK reported 4 cases of presumptive transfusion-transmitted (TT) vCJD


History of FDA Policies toReduce CJD and vCJD Risks (3)

2006. FDA published draft guidance for comment to defer blood/plasma donors transfused in France after 1980

2009. UK reported evidence (PrPTSE in spleen) of elderly man with haemophilia treated with UK plasma-derived FVIII

2010. CBER issued revised guidance to defer blood donors with history of transfusion after 1980 in France


Guidance for Industry: Revised Preventive Measures to Reduce the

Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) & Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood

ProductsMay 10, 2010

www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/UCM213415.pdf


http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/UCM213415.pdf

http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/UCM213415.pdf

Recommendations for donor deferral, product retrieval, quarantine and disposition

Based on risk in the donor and product Effect that donor deferral and product withdrawal

might have on the supply Indefinite deferral for individuals at increased risk

for CJD or vCJD CJD includes all familial CJD-like diseases such as

GSS and FFI


Recommendations in the 2010 Guidance

Balance between “benefit of risk reduction compared with potential adverse effects of a decreased availability of the blood supply”


To Be Considered


FDA Policy for Indefinite Blood Donor Deferral for vCJD Risks

Residence Time of ResidenceUK ≥ 3 mo from 1980-1996

History of blood transfusionFrance ≥ 5 y from 1980-

present

Europe* (UK and France not included)

≥ 5 y from 1980-present

US military bases North of the Alps

≥ 6 mo from 1980-1990

US military bases South of the Alps

≥ 6 mo from 1980-1996

Albania, Austria, Belgium, Bosnia-Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Finland, Germany, Greece, Hungary, of Ireland, Italy, Liechtenstein, Luxembourg, Macedonia, Netherlands, Norway, Poland, Portugal, Romania, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, and [former] Federal Republic of Yugoslavia.

* Donors eligible to donate Source Plasma


FDA Policy for Indefinite Blood Donor Deferral for CJD and vCJD Risks

Increased risk for all CJDDiagnosis of any form of CJD including vCJD and all familial TSE such as GSS and FFI

≥ 1 blood relatives diagnosed with CJD*

Recipients of dura mater or human-derived pituitary growth hormone

Users of UK bovine-derived insulin since 1980 (vCJD risk)

* A donor is eligible for reentry if either it can be concluded that CJD was iatrogenic (or non-familial) or testing of the donor excludes a mutation associated with familial CJD.

Donor deferral is the only current action available to protect the US blood supply from transfusion-transmitted CJD and related diseases including vCJD

Current US policies would not have deferred the US or Canadian Saudi cases


Conclusions

Acknowledgements

• Steven Anderson OBE• David Asher OBRR• Jay Epstein OBRR• Melissa Greenwald OCTGT• Ginette Michaud OBRR• Pedro Piccardo OBRR• Martin Ruta OBRR• Jennifer Scharpf OBRR• Alan Williams OBRR• Hong Yang OBE


Transmissible Spongiform Encephalopathies Advisory Committee 23 rd Meeting Gaithersburg, MD –...

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