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From: TSS (216-119-132-23.ipset12.wt.net)
Subject: Transmissible Spongiform Encephalopathies Advisory Committee Issue Summary 16th Meeting
Date: October 14, 2004 at 3:18 pm PST

-------- Original Message --------
Subject: Transmissible Spongiform Encephalopathies Advisory Committee Issue Summary 16th Meeting
Date: Thu, 14 Oct 2004 17:25:27 -0500
From: "Terry S. Singeltary Sr."
To: Bovine Spongiform Encephalopathy
CC: cjdvoice@yahoogroups.com

Issue Summary

Transmissible Spongiform Encephalopathies Advisory Committee

16th Meeting

Oct 14, 2004

Silver Spring, Maryland

Topic #6. Consideration of Current FDA-Recommended Safeguards to Reduce
the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and
Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products

Issue

FDA seeks advice from the FDA Transmissible Spongiform Encephalopathies
(TSE) Advisory Committee (TSEAC) on whether recent data regarding vCJD
warrant consideration of the need for additional safeguards for blood
and blood products.

Background

Most attempts to detect infectivity in blood or serum of animals with
TSEs failed until 1978, when Elias Manuelidis and colleagues
demonstrated the transmissible agent in crude buffy coat preparations of
13 guinea pigs injected with brain material of other guinea pigs with
experimental Creutzfeldt-Jakob disease [1], detected throughout most of
the incubation period. Assay guinea pigs had long incubation periods
(some over a year), suggesting that amounts of infectivity in donor
guinea pig blood were probably very small. In 1983, NIH investigators
demonstrated that the blood buffy coats of mice infected with a TSE
agent derived from a patient with the Gerstmann-Sträussler-Scheinker
disease (GSS)—similar to familial CJD—also contained infectivity,
detectable from the middle of the incubation period through terminal
illness [2]. The finding of small amounts of TSE infectivity in blood
was later confirmed in a variety of other animals with TSEs [3-5],
including sheep with naturally-acquired scrapie [6] and experimental
bovine spongiform encephalopathy (BSE) [7] and chimpanzees injected with
brain material from a GSS patient [8]. Although much infectivity was
associated with nucleated cells [5, 8-12], plasma contained substantial
amounts as well [13].

During the past 20 years the FDA has made recommendations to the blood
industry intended to reduce the theoretical risk of transmitting the
infectious agents of Creutzfeldt-Jakob disease (CJD) and variant CJD
(vCJD) by blood and blood products. The history of FDA’s policies in
this area is summarized in Appendix I. Because no validated screening
tests are available to identify infected units, safety must rely on
precautionary deferrals of donors thought to be at increased risk for
CJD and vCJD and withdrawal of products when post-donation information
reveals that a donor should have been deferred. The Agency, aware of the
uncertainties surrounding the magnitude of the risk, the effectiveness
of available risk-reducing measures, and the potential for contributing
to shortages of life-sustaining blood products, is committed to review
at frequent intervals its policies regarding CJD and vCJD. FDA has taken
a proactive approach in addressing potential risks from CJD and vCJD
consistent with the findings of the Institute of Medicine regarding
decision making that took place for HIV and the blood supply [14]. In
particular, FDA blood safety policies regarding CJD and vCJD have
generally been reviewed publicly with the TSE Advisory Committee,
especially when new information suggests that risks should be
reevaluated. Since the last meeting of the TSEAC in Feb 2004, the
following new information on vCJD has come forward.

Presumptive transmission of vCJD from blood of a second clinically
healthy donor. The UK Transfusion Medicine Epidemiology Review (TMER)
[15] has identified and enrolled 50 recipients of labile blood
components from 16 donors later found to have vCJD in an on-going
look-back” study. (In addition, TMER identified nine vCJD donors who
contributed plasma to 23 pools used for fractionation into derivatives
before 1999.) As of Aug 12, 2004, 13 of 18 surviving recipients of
labile blood components had been enrolled in TMER for at least five
years; thirty-two recipients had died, two with evidence of vCJD.

On 17 Dec 2003 the UK Department of health announced that one recipient
of non-leukoreduced red blood cells had died with vCJD. (The case has
been described in detail [16] and was presented at the 15th meeting of
TSEAC [17].) In Mar 1996, a clinically healthy young blood donor donated
Whole Blood to the UK National Blood Service. Red blood cell
concentrate—not leukoreduced—was transfused into an older surgical
patient. Three years four months later the donor developed signs of
vCJD, confirmed at autopsy. Six and a half years after the transfusion
the recipient became progressively demented with other neurological
signs and died after 13 months; autopsy revealed vCJD. The recipient was
found to be homozygous for methionine at codon 129 of the
prion-protein-encoding (PRNP) gene, as had been all other persons with
vCJD tested. UK authorities estimated the recipient's age-adjusted
food-borne risk of vCJD to have been from 1:15,000 to 1:30,000.

In Jul 2004, UK authorities announced that preclinical vCJD had been
diagnosed the previous year in a second person in the TMER cohort. (The
case has been partially described in the medical literature [18].) The
second recipient was transfused in 1999 with non-leukoreduced red blood
cells from a clinically healthy donor who developed signs of vCJD 18
months later, confirmed at death in 2001. Five years after transfusion,
the recipient died of a ruptured abdominal aortic aneurysm without signs
of neurological disease. Abnormal prion protein typical of vCJD was
detected at autopsy in several areas of the spleen and in a cervical
lymph node, suggesting that infection was present but had not yet spread
to the brain. It seems highly improbable that two cases of vCJD
resulting from coincidental food-borne transmission would occur by
chance in the small TMER cohort during a short period of time.

Variant CJD in a person heterozygous for methionine at codon 129 of the
PRNP gene. The second presumptive transfusion-transmitted case of vCJD
was in a person heterozygous for methionine at PRNP codon 129 [18]—the
first time that genotype has been found in any patient with vCJD to be
tested. (As noted above, all other vCJD patients tested have been
homozygous for methionine at PRNP codon 129.) Although the case was
preclinical, it seems probable that infection would eventually have
progressed to involve the nervous system had the patient not died of an
unrelated disease. Homozygosity for methionine or valine at PRNP codon
129 is known to be over-represented in persons with iatrogenic and
sporadic forms of CJD [19], however heterozygotes have not been
completely spared from those diseases. The finding of a
transfusion-transmitted vCJD infection in a heterozygote implies that
such individuals are unlikely to be absolutely resistant to infection
with the BSE agent and that food-borne vCJD cases may be expected in all
PRNP genotypes, possibly in smaller numbers and with longer incubation
periods than for homozygous individuals. In any case, persons
heterozygous for methionine/valine at codon 129 of the PRNP gene
(comprising about half the population in the UK) appear to be
susceptible to blood-borne infection with human-adapted BSE agent.

New cases of vCJD per annum peaked in the UK in 1999 and deaths in 2000;
only one new case has been reported recently outside the UK [17]. The
current total stands at 157 definite or probable cases in UK, three
presumably UK-acquired cases dying outside UK (Canada, Ireland, US),
seven cases thought to have been acquired in France and one in Italy.
The times of residence in and departure from the UK of two cases in
North America suggest that the incubation periods of food-borne vCJD may
be as short as nine years (Will RG, unpublished observation).

Predictions of vCJD infection rates based on finding of abnormal prion
protein in lymphoid tissues of preclinical vCJD.

Shortly after the first descriptions [20], it was noted that lymphoid
tissues of a person dying with vCJD (spleen, lymph nodes) contained
detectable amounts of abnormal protease-resistant prion protein (PrPsc)
[21, 22]. The appendix removed from an otherwise healthy person who
developed signs of vCJD eight months later also contained PrPsc [23], as
did another appendix removed two years before onset (a third removed 10
years before onset was negative) [24]; those fortuitous findings
suggested that a survey of archived tonsils and appendices might provide
some estimate of the minimum number of persons with preclinical vCJD in
the UK population. Two such surveys have been reported to date: the
first found one positive appendix among 8318 adequate specimens saved
from patients 10 to 50 years old between 1995 and 1999, yielding an
estimated rate of 120/million (95% CI, 0.5 – 900/million) in that
population [24]; the second yielded three positives among 12,674
appendices for an estimated rate of 237/million (95% CI, 49 –
692/million) [25]. All tonsils were negative. It is interesting to note
that both tonsils and appendix of the second presumptive
transfusion-transmitted case were negative for PrPsc, attributed to the
non-food-borne route of infection [18].


Charge to the TSE Advisory Committee

For many years the FDA and other regulatory authorities [26]) have taken
very seriously the theoretical possible transmission of all forms of CJD
by blood products and has advised blood and plasma establishments to
defer donors thought to be at increased risk for CJD.

There have been six general bases for CJD/vCJD-related deferrals [27]:

A. General CJD risk reduction (1) CJD in a donor, (2) history of
treatment with pit-hGH or dura mater allograft, and (3) history of CJD
in a relative unless confirmed to be other than familial CJD or the
donor PRNP genotype is found to be normal

B. vCJD risk reduction (1) history of prolonged residence in most BSE
countries (defined by USDA list of BSE-related import prohibitions)
currently including UK, France or other European countries west of the
Former Soviet Union (or residence/employment on a US military base in
Europe during periods when beef was procured from UK), (2) history of
transfusion in UK in or after 1980, and (3) injection with bovine
insulin of UK origin in or after 1980

The FDA CJD/vCJD blood safety policies have been recommended to reduce
the risk that a donor might be incubating CJD of any kind while not
deferring so many donors as to compromise the supply of blood products.
The TSEAC is now asked to consider whether the CJD/vCJD deferral
policies currently recommended by FDA to protect the safety of the blood
supply remain justified and, if so and considering recent additional
information about BSE and vCJD, they are still adequate. If TSEAC
considers any current policy inadequate, FDA solicits its advice in
suggesting enhancements to existing policies or possible additional
policies that might reduce the risk further without jeopardizing an
adequate supply of life-sustaining and health-sustaining blood products.


Questions for the Committee

1. Are the measures currently recommended by FDA to reduce the risk
of transmitting CJD and vCJD by blood and blood products still
justified?
2. Do the recent scientific data on vCJD warrant consideration by FDA
of any additional potentially risk-reducing measures for blood and
blood products?
3. If so, please comment on the additional potentially risk-reducing
measures that FDA should consider at this time.


Appendix I


History of FDA Policy Making

Regarding Risk of Transmitting CJD and vCJD by Transfusion

In Aug 1983, FDA learned that a US blood donor had been diagnosed with
CJD; in-date components and plasma derivatives were voluntarily
withdrawn. Over the next 12 years there were nine other CJD-related
voluntary withdrawals of US blood products. In Nov 1987, FDA, aware that
TSE infectivity had been found in animal blood and concerned about a
growing number of iatrogenic cases of CJD among people treated with
injections of human cadaveric pituitary growth hormone (pit-hGH), issued
a memorandum recommending precautionary deferral of blood donors
previously treated with pit-hGH—acknowledging a concern about potential
transmission of CJD by products from blood of clinically normal at-risk
donors [28]. In subsequent years, FDA recommended deferral of other
donors thought to be at increased risk for CJD: recipients of dura mater
grafts and people with a family history of CJD. In Aug 1995 [29], FDA
also recommended—in addition to donor deferrals—precautionary withdrawal
of blood, blood components, and plasma derivatives [30] from donors
recognized post-donation to have CJD or to be at increased risk for
iatrogenic or familial CJD.

After a public announcement in Sept 1998 (and in guidance published in
Aug 1999 for immediate implementation with a request for comment and in
revised form in Nov 1999 [31]), FDA no longer recommended withdrawal of
plasma derivatives from donors at increased risk for most forms of CJD,
for several reasons: (1) epidemiological studies failed to find that
transfusion with human blood or components or treatment with plasma
derivatives was a risk factor for sporadic CJD (summarized most recently
at the 15th meeting of the FDA TSE Advisory Committee [32](2) the very
large pools of plasma used to prepare derivatives have a high
probability of containing a contribution from a donor incubating CJD
33], because CJD has a lifetime risk of one in nine thousand persons
with long silent incubation periods, sometimes exceeding 38 years [34],
and it is not possible to identify those donors; (3) in experimental
spiking studies, the processes used to fractionate plasma have
demonstrated a substantial capacity to reduce if not eliminate the
infectivity of TSE agents from most final products [35] (though only
modestly effective for factor VIII ), and (4) withdrawals, while
possibly reducing a theoretical risk of transmitting CJD, were thought
to contribute to shortages of some plasma derivatives. However, FDA has
continued to recommend deferring donors at increased risk for all forms
of CJD and to retrieve in-date components when post-donation information
revealed that donors either developed CJD or should have been deferred
because they had an increased risk for CJD [27].

While no longer recommending withdrawal of plasma derivatives from
CJD-at-risk donors, FDA has continued to recommend withdrawals of all
plasma derivatives prepared from pools to which any donor later
diagnosed with vCJD contributed; fortunately, that has never been
necessary in the US, although donors who later became ill with vCJD have
contributed to pools used in the manufacture of plasma derivatives in
other countries [36]—thus far without evidence of transmission. (Some
recipients of plasma derivatives in the UK [15] were recently notified
of the results of an assessment exercise to estimate the potential risk
[37].)

FDA was more concerned about the theoretical possibility of transmitting
vCJD than other forms of CJD via plasma derivatives because vCJD has an
age distribution, clinical presentation and course of illness,
histopathology and pathogenesis substantially different from those of
other forms of CJD [20], and experience with vCJD is much more limited.
Hence, the reassuring epidemiological studies that failed to implicate
blood products as a risk factor for other forms of CJD might not be
predictive for vCJD. For those reasons, FDA concluded that additional
precautionary steps were justified to reduce the risk of transmitting
vCJD by transfusion of blood components or injection of plasma
derivatives. In Aug and Nov 1999 [31] following discussions in TSEAC on
Dec 18, 1998 [38]] and using information from a travel survey of blood
donors [39, 40], FDA recommended that blood establishments defer blood
donors who had spent six months or more in the UK from the start of 1980
(estimated to be a probable earliest date when a significant number of
cattle were infected with the BSE agent in the UK) and the end of 1996
(when UK fully implemented a variety of measures to control BSE and
prevent human exposure to the BSE agent [41]. That geographically based
policy was estimated to reduce exposure to the BSE agent (as total days
spent by blood donors in UK) by about 87%, while predicted to defer
about 2.2% of US blood donors [40]).

As diagnosed cases of vCJD continued to increase in the UK and former UK
residents in other countries and several cases were reported in
residents of France (currently seven) and Italy (one), affecting persons
who had not visited the UK, FDA, on advice of TSEAC, issued a second
Guidance for Industry reducing the recommended time that suitable donors
might have spent in the UK to three months and broadening the range of
countries considered to pose a risk of exposure to the BSE agent
sufficient to justify deferring donors who had spent substantial time
there [27]. The acceptable maximum times that otherwise suitable donors
might have spent in those other countries were adjusted to reflect risks
relative to that in the UK, where the both BSE and vCJD epidemics were
the largest: (1) US military bases in Europe were estimated to have
about one-third the risk of UK during periods when up to a third of the
beef used there was procured from UK. (The recommended acceptable time
spent on affected military bases was six months, to provide an
additional margin of safety.) (2) France was estimated to have about 5%
of the UK risk, because at least 5% of beef products consumed in France
until the early 1990s were thought to have been imported from UK, and,
at that time, the number of cases of vCJD in France was about 5% of
those in UK, while both countries had roughly similar populations. (3)
Other European countries were assigned a nominal BSE risk based on BSE
surveillance data from Switzerland, estimated to be about 1.5% of UK
risk; although it seemed likely that a number of countries might have
actual risks lower than that of Switzerland, the quality of their BSE
surveillance was uncertain.

In addition, FDA, concerned about UK blood donors who might be
incubating vCJD and a theoretical possibility of further adaptation of
the BSE agent to replicate in humans after a transmission by blood, also
recommended deferring anyone who had received a blood transfusion in the
UK after 1979. No deferrals of donors transfused in France other BSE
countries were recommended, however, because the risk of BSE infections
of humans was so much lower there. FDA also recommended deferring donors
who had been treated with bovine insulin from the UK in or after 1980.
(Those and other CJD/vCJD-related policies recommended for donors of
Whole Blood are summarized in Table 1 of the Jan 2002 Guidance Document
[27].)

The policies recommended for donors of Source Plasma (apheresis plasma)
were somewhat different from those for blood (Table 2 [27]). FDA did not
recommend deferring donors of Source Plasma for any period of residence
in BSE countries other than in the UK and France. (FDA recommended that
recovered plasma be treated like all other components so as to
discourage the intentional collection of Whole Blood from deferred donors.)

The modified donor deferral policy was estimated to reduce the overall
BSE-related risk by 91% (72% of the risk remaining after implementation
of the 1999 policies), with a final overall donor loss of 4.6-5.3%;
however, considerable geographic variation was expected, including
potentially higher donor losses in coastal states and near military
bases. (If blood establishments were to be more aggressive in their
deferral policies, then both overall donor loss and risk reduction might
be higher.) Implementation was recommended in two stages, to be
completed by Oct 21, 2002. Because of normal variability in blood
donations, probable self deferrals by some donors, encouragement of
increased donations by repeat donors, and active recruitment of new
donors by blood programs, it has not been possible to evaluate the
actual effects of the new policies on the blood supply, except to
conclude that obvious shortages have not resulted.

In a joint meeting of the TSEAC and Blood Products Advisory Committee
(BPAC) on Jan 17, 2002 [42], FDA solicited advice on whether food chain
controls to prevent human exposure to BSE implemented in the UK since
1996 were sufficient to obviate a need to defer blood and plasma donors
based on their subsequent travel or residence there. The reason for
review was that a major US blood program had begun to defer blood donors
based on time they spent in UK not only after 1980 through 1996 but also
after 1996 to the present. The measures thought to be effective in
protecting humans from food-borne exposures to BSE agent in the UK were
BSE control in ruminantsa

and a number of steps to reduce the likelihood that infectivity present
in cattle with unrecognized BSE would enter the food chainb
.

In subsequent meetings of the TSEAC, FDA has acknowledged that three
other countries had BSE in native-born cattle: Canada (two cows, one
resident in USA at time of diagnosis), Israel (one cow), and Japan (12
cows). The FDA was unable to estimate either the potential risk
reduction or the effect on the blood supply of deferring residents in
those countries, and the TSEAC did not suggest deferring donors for any
period of residence in those countries; therefore the FDA did not
recommend deferring donors who lived in or spent time in those countries.


Appendix II.

TABLE 1 (From Reference [27]): Donor Deferral, Product Disposition,
Recipient Notification for Whole Blood, Blood Components Intended for
Transfusion, Source Leukocytes, and Other Cellular Blood Components
Intended for Further Manufacture

Risk

Deferral

Disposition of Product

BPDR
(21 CFR 606.171)
if previously distributed product

Recipient Tracing/Notification

Diagnosed with vCJD, or suspected vCJD, CJD, or CJD and age <55 years

Permanent

Immediately retrieve, quarantine/notify consignees for all in-date
products and all out-of-date cellular blood components intended for
manufacturing into injectable products.

Yes

Consignee notified, consignee informs responsible caretaker for
discretionary recipient notification, counseling

Risk factors for CJD: Receipt of pituitary-derived growth hormone, or
dura mater transplant

Family history of CJD in >1 family member

Permanent

Indefinite; reentry if genetic testing does not reveal CJD-associated
prion protein allele

Immediately retrieve, quarantine/notify consignees for all in-date
products and all out-of-date cellular blood components intended for
manufacturing into injectable products.

Yes

Consignee notified, consignee informs responsible caretaker for
discretionary recipient notification, counseling

CJD in only 1 family member

Indefinite; reentry if genetic testing does not reveal CJD-associated
prion protein allele

Immediately retrieve, quarantine/notify consignees for all in-date
products and all out-of-date cellular blood components intended for
manufacturing into injectable products.

Yes

No


TABLE 1 (From Reference [27]): Continued

Risk

Deferral

Disposition of Product

BPDR
(21 CFR 606.171)
if previously distributed product

Recipient Tracing/Notification

Phase I Geographic donor deferrals (U.K.>3 months 1980-1996; France >5 years 1980-present; military in Europe as specified, transfusion in
U.K. since 1980)

Indefinite

Immediately retrieve, quarantine/notify consignees for all in-date
products and all out-of-date cellular blood components intended for
manufacturing into injectable products.

No - if prior to deferral implementation

No

Yes - if after deferral implementation

Phase II Geographic donor deferrals (Europe >5 years 1980-present)

Indefinite

Collected prior to deferral implementation - No retrieval, quarantine,
consignee notification

No - if prior to deferral implementation

No

Collected after deferral implemented - Immediately retrieve,
quarantine/notify consignees for all in-date products and all
out-of-date cellular blood components intended for manufacturing into
injectable products.

Yes - if after deferral implementation

Bovine insulin injection

Indefinite, donor reentry if proof of non-U.K. insulin source

Immediately retrieve, quarantine/notify consignees for all in-date
products and all out-of-date cellular blood components intended for
manufacturing into injectable products.

Yes

No


TABLE 2 (Modified from Reference [27]): Donor Deferral, Product
Disposition, and Recipient Notification for Plasma and Plasma Derivatives

Risk

Deferral

Disposition of Product

BPDR
(21 CFR 606.171)
if previously distributed product

Recipient Tracing/Notification

Phase I Geographic donor deferrals (U.K. >3 months 1980-1996; France >5 years 1980-present; military in Europe as specified, transfusion in
U.K. since 1980)

Indefinite

SP and RP: Collected prior to deferral implementation- No retrieval,
quarantine, consignee notification

No - if prior to deferral implementation

No

SP and RP: Collected after deferral implementation - Immediately
retrieve, quarantine, notify consignees of in-date SP and all RP unless
known to be previously pooled

Yes- if after deferral implementation

PD: No retrieval, quarantine, consignee notification

No

Phase II Geographic donor deferrals (Europe >5 years 1980-present)

SP

No deferral

SP: All phase I deferrals remain in place, e.g., U.K. > 3 months 1980-1996; France > 5 years 1980-present; military in Europe as specified; transfusion in
the U.K. since 1980. There is no Phase II deferral for SP.

Not Applicable

No

Phase II Geographic donor deferrals (Europe >5 years 1980-present)

RP

Indefinite

RP: Collected prior to deferral implementation- No retrieval,
quarantine, consignee notification

No- if collected prior to deferral implementation

Yes - if collected after deferral implementation

RP: Collected after deferral implementation: Immediately retrieve,
quarantine, notify consignees for all RP unless known to be previously
pooled

PD: No retrieval, quarantine, consignee notification

No

Abbreviations: SP, Source Plasma; RP, recovered plasma; PD, plasma
derivatives; BPDR, Biological Products Deviation Report


Table 2 (Modified from Reference [27]) Continued

Risk

Deferral

Disposition of Product

BPDR
(21 CFR 606.171)
if previously distributed product

Recipient Tracing/Notification

Bovine insulin injection

Indefinite, donor reentry if proof of non-U.K. insulin source

SP and RP: Immediately retrieve, quarantine/notify consignees for
in-date SP and all RP unless plasma known to be previously pooled

PD: No retrieval, quarantine, consignee notification

Yes

No

No

No

Diagnosed with vCJD, suspected vCJD

Permanent

SP and RP: Immediately retrieve, quarantine/notify consignees for
in-date SP and all RP


PD: Immediately retrieve, quarantine, notify consignees

Yes

Yes

Consignee notified, consignee informs responsible caretaker for
discretionary recipient notification, counseling

Abbreviations: SP, Source Plasma; RP, recovered plasma; PD, plasma
derivatives; BPDR, Biological Products Deviation Report


Table 2 (Modified from Reference [27]) Continued

Risk

Deferral

Disposition of Product

BPDR
(21 CFR 606.171)
if previously distributed product

Recipient Tracing/Notification

Diagnosed with CJD

and age <55 years

Permanent

SP and RP: Disposition decided case-by-case depending upon investigation
results


PD: Disposition decided case-by-case depending upon investigation results

Yes

Decided upon case-by-case

Case-by-case recommendation, depending upon investigation results

Diagnosed with CJD

(and age >55 years)

Permanent

SP and RP: Immediately retrieve, quarantine/notify consignees for
in-date SP and all RP unless known to be previously pooled


PD: No retrieval, quarantine, consignee notification

Yes


No

No


No

Risk factors for CJD: Receipt of pituitary-derived growth hormone, or
dura mater transplant


Family history of CJD in >1 family member

Permanent


Indefinite

SP and RP: Immediately retrieve, quarantine/notify consignees for
in-date SP and all RP unless known to be previously pooled


PD: No retrieval, quarantine, consignee notification

Yes


No

No


No

CJD in only 1 family member

Indefinite; reentry if genetic testing fails to reveal CJD-associated
PrP allele

SP and RP: Immediately retrieve, quarantine/notify consignees in-date SP
and all RP unless known to be previously pooled


PD: No retrieval, quarantine, consignee notification

Yes


No

No


No

Abbreviations: SP, Source Plasma; RP, recovered plasma; PD, plasma
derivatives; BPDR, Biological Products Deviation Report; PrP, prion protein


References

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Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products, revised
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40. United States Food and Drug Administration, Department of Health and
Human Services. Transcripts of the FDA Transmissible Spongiform
Encephalopathies Advisory Committee 5th Meeting, June 2-3, 1999

41. Soul P. Food chain protections in the UK with respect to TSE. In:
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Encephalopathies Advisory Committee, 11th Meeting, Jan 17, p. 159-97

42. United States Food and Drug Administration, Department of Health and
Human Services. Transcripts of the FDA Transmissible Spongiform
Encephalopathies Advisory Committee, 11th Meeting, Jan 17, 2002


------------------------------------------------------------------------

a

Ruminant feed ban (prohibition of the feeding of ruminant-derived
meat-and-bone meal—and most other mammalian proteins—to cattle, sheep
and goats), a national BSE surveillance program (including prion protein
testing of appropriately selected brain tissues from cattle at increased
risk of BSE) compliant with the requirements of the Office International
des Epizooties (OIE) to which the USA is signatory, prompt condemnation
and destruction of animals with signs of BSE, preventive culling of
animals at increased risk, and adequate compensation to owners of
condemned cattle in order to encourage compliance

b

Age-based slaughter schemes (meat from cattle more than 30 months old no
longer considered edible in UK), separation of high-risk bovine tissues
(specified-risk materials [SRM]) from edible meat and prohibition of
slaughter methods that embolize brain tissue into meat, e.g.,
intracranial air injection and “pithing”, application of the same
controls to imported and domestic meat products

http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4075B1_06.htm

Bibliography (HTM
)
(PDF
)
(Word


(DRAFT)

FOOD AND DRUG ADMINISTRATION

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

ADVISORY COMMITTEE

Hilton Hotel

8727 Colesville Road

Silver Spring, MD 20910

DRAFT AGENDA (revised 10/4/04)


Thursday, October 14, 2004

8:00 a.m. Administrative Remarks,

William Freas, PhD, Executive Secretary

8:10 a.m. Opening Remarks

Suzette Priola, PhD, Acting Chairperson

Introduction

Dr. Jesse Goodman, Director,

Center for Biologics Evaluation and Research, FDA

Presentation of Plaques to Retiring Committee Members

Dr. Jesse Goodman

8:25 a.m. Informational Presentation #1: USDA BSE Licensed Tests and
Enhanced Surveillance Program (15 minutes), Lawrence Elsken, DVM, USDA
(confirmed)

Informational Presentation #2: USDA Review of Worldwide BSE Situation
and USDA Responses (15 minutes), Lisa Ferguson, DVM, USDA (confirmed)

Informational Presentation #3: New CFSAN BSE-Food Safety Rules (15
minutes), Rebecca Buckner, Ph.D., CFSAN/FDA

Informational Presentation # 4: Update on Animal Feed Rulemaking (15
minutes), Burt Pritchett, DVM, CVM

9:25 a.m. Questions for Presenters

9:35 a.m. OPEN PUBLIC HEARING (30 minutes)

10:05 Informational Presentation #5: Labeling Claims for TSE Clearance
Studies for Plasma Derivative Products (20 minutes),

Dorothy Scott, MD, OBRR, FDA (confirmed)

10:25 BREAK


10:45 a.m. Topic – Presumptive Transfusion Transmissions of Variant CJD
(vCJD): Consideration of Current FDA-Recommended Safeguards

A. FDA Introduction (15 minutes), David Asher, MD, OBRR/FDA (confirmed)

B. Presumptive Transfusion Transmission of vCJD (review of CJD and vCJD:
UK and EU epidemiology, case reports, surveillance and projections,
potential public health implications, and responses) (45 minutes),
Professor Robert G. Will, MD, UK CJD Surveillance Unit (confirmed).

C. Comparison of the Transfusion Risk for CJD vs. vCJD (10 minutes),
Steven Anderson, PhD, OBE/FDA (confirmed)

D. Leukoreduction and Its Failure to Remove Most Infectivity from Blood
(15 minutes), Robert G. Rohwer, PhD (confirmed)

12:10 p.m. Questions for Speakers

12:25 LUNCH

1:25

E. Changes in Canadian CJD/vCJD Blood Safety Policies (not confirmed)
(20 min), Dr. Peter Ganz, HealthCanada

F. Current Safeguards for Blood Products Recommended by FDA (15
minutes), Dorothy Scott, MD, OBRR/CBER (confirmed)

G. Possible Effects of Prior CJD-Related Blood Donor Deferrals on Blood
Supply (30 minutes), Alan Williams, PhD, OBRR/CBER (confirmed)

2:30 Questions for Speakers

2:45 OPEN PUBLIC HEARING

3:15 BREAK

3:35 Question to the Committee

3:45 Committee Discussion and Vote

5:00 ADJOURN

http://www.fda.gov/ohrms/dockets/ac/04/agenda/2004-4075A1_draft.htm


Panel Mulls Transfusion-Related Infection

By DIEDTRA HENDERSON
AP Science Writer

October 14, 2004, 4:38 PM EDT

WASHINGTON -- A second United Kingdom resident most likely acquired mad
cow disease through a tainted blood transfusion, federal health advisers
were told Thursday. A Food and Drug Administration official called the
development troubling.

Dr. David M. Asher, head of an FDA laboratory that studies contaminants
in blood and tissues, said the new information suggests that the risk of
transmission through blood should be re-evaluated.

An FDA advisory committee was considering whether safety measures are
still warranted -- or whether additional measures are needed -- to
prevent the transmission of mad cow disease through blood.

The agency already bars blood donations from people who lived more than
three months in the United Kingdom or who received transfusions there
after 1979.

In both confirmed United Kingdom infections, recipients got blood from
donors who were young and apparently healthy when they gave blood. The
chances that two confirmed infections among people who received blood
was caused instead by eating mad-cow tainted beef were remote -- 1 in
80,000 to 1 in 1 billion, the panel was told.

Getting the human form of mad cow disease through tainted blood "is a
reality. And we've got to treat it like that," said Steven Anderson, an
FDA risk assessment expert.

The new case involves an elderly woman who died from an unrelated
medical condition, according to Dr. Robert Will, a member of the U.K.
mad cow surveillance team.

Because she had received a blood transfusion in 1999 from a donor who
later died from variant Creutzfeldt-Jakob disease, the human equivalent
of mad cow disease, the woman's doctor did a more thorough analysis
after her death.

The woman had no outward signs of neurological disease and her brain,
spinal cord, tonsils and appendix were normal, Will told the panel. In
her spleen and cervical lymph nodes, however, the woman harbored
malformed, infective prion proteins.

The illness occurs when normal proteins found in the brain, known as
prions, change shape and prompt adjacent healthy prions to do the same.
When enough prions are altered, they deposit a plaque on the brain and
surround the mark with spongy holes, killing the victim.

By testing 14,964 appendices of normal surgical patients in the U.K.,
researchers learned that three were tainted with the infective proteins.
That implies 237 people per million United Kingdom residents -- or 3,808
people age 10 to 30 -- could silently incubate mad cow, Will said.

Three other countries have discovered bovine spongiform encephalopathy
-- mad cow -- in cattle: Canada, Israel and Japan. Those countries are
not yet subject to U.S. deferral of blood donations.

A Canadian-born cow infected with the disease was found in the United
States.

http://www.nynewsday.com/news/health/wire/sns-ap-mad-cow-blood,0,674091.story?coll=sns-ap-health-headlines

TSS






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