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From: TSS (216-119-129-71.ipset9.wt.net)
Subject: [Docket No. 04-116-1] USE of veterinary biological products on the topic of Transmissible Spongiform Encephalopathies (TSS SUBMISSION)
Date: November 5, 2004 at 10:05 am PST

-------- Original Message --------
Subject: [Docket No. 04-116-1] USE of veterinary biological products on the topic of Transmissible Spongiform Encephalopathies (TSS SUBMISSION)
Date: Fri, 05 Nov 2004 11:49:49 -0600
From: "Terry S. Singeltary Sr."
To: CVB@aphis.usda.gov
CC: Nicole.L.Ruffcorn@aphis.usda.gov, Questa.R.Glenn@aphis.usda.gov, BSE-L


> Meeting topics and proposed presentation titles should be submitted
> to Steven A. Karli, director, CVB, APHIS, Veterinary Services, 510
> South 17 St., Suite 104, Ames, IA 50010-8197; phone (515) 232-5785,
> fax (515) 232-7120 or e-mail CVB@aphis.usda.gov. For registration
> information contact Nicole Ruffcorn at the same address and fax number
> or via phone dial (515) 232-5785 extension 127 or e-mail
> Nicole.L.Ruffcorn@aphis.usda.gov.


http://a257.g.akamaitech.net/7/257/2422/06jun20041800/edocket.access.gpo.gov/2004/E4-3008.htm

I wish to kindly submit the following to Mr. Steven A. Karli for the
13th public
meeting to discuss regulatory and policy issues related to the manufacture,
distribution, and use of veterinary biological products on the topic of
Transmissible Spongiform Encephalopathies (all of them).

[Docket No. 04-116-1]


Greetings APHIS/USDA et al,

INOCULATION of the TSE agent is the most effected mode
of transmission, or so it seems.

MOST people have forgotten the medicines act of 1968 where
they state not to use scrapie associated fibers SAF for any
pharmaceuticals for animals in vet products;

June 1983
MEDICINES ACT 1968

''Unless there is a risk from a heat-resistant pathogen such as the
scrapie agent,
no restrictions are placed on substances sterilized by autoclaving
provided that the
complete mass is held at a minimum of 115°C for at least 15 minutes''...

http://www.bseinquiry.gov.uk/files/yb/1983/06/00001001.pdf

PLEASE do not forget the infamous 'Louping-ill vaccine' incident;

III.3.1 VACCINES
Reference has already been made to the occurrence of at least several
hundred cases of scrapie in British sheep as a direct result of the use
of a vaccine against the tick transmitted, viral disease, louping-ill
(Gordon, Brownlee and Wilson, 1939, Gordon, 1946 and Greig, 1950). This
occurrence resulted from the accidental use of scrapie-infected source
material and processing methods that did not inactivate the scrapie
agent that was unknowingly present. A more recent possible occurrence of
possible iatrogenic scrapie has recently been reported in Etna Silver
crossbred goats in Italy by Cappucchio et al., (1998). The goats were
kept at grass and concentrate rations were not fed, thus eliminating a
source of infection from feed via mammalian proteins. Animals over two
months old were annually vaccinated against contagious agalactia caused
by Mycoplasma agalactiae. The vaccine included central nervous system
from pathogen-free sheep. The mortality rate in the goats reached
28% in 1 herd, 60% in the second and 5.5% in a third herd. About half
the 56 goats were between 2.5 - 3 years old. Only 1.15% of sheep that
were kept with the goats developed scrapie. Scrapie was confirmed by
microscopic examination of the brain and by detection of PrPSc including
by immunocytochemistry. PrPSc was widespread in the brain and beyond
sites of vacuolar change. The high mortality, severe loss of weight and
simultaneous appearance in the three herds were distinctly unusual
features in this outbreak. The source of infection remains uncertain and
unproven but iatrogenic transmission must be considered.
A larger epidemic involving 20 outbreaks of scrapie in sheep and goats,
also in Italy, has been even more recently reported by Agrimi et al.,
(1999). The annual incidence ranged from 1% to 90% with a mean incidence
for goats of 26% and for sheep of 10%. The total number of cases in
sheep and goats together was 1040. The clinical disease was confirmed by
microscopic examination of the brain and PrP immunocytochemistry or
Western blotting. The high incidence in goats, the high
within-flock/herd incidence, the temporal clustering, absence of
commercial concentrate feeding in eight flocks and association with the
use of a sub-cutaneously administered M. agalactiae vaccine, prepared
locally using brain and mammary tissue from clinically healthy sheep,
strongly suggests an iatrogenic origin. Scrapie appeared between 23 and
35 months after the vaccine was administered. A third outbreak in
southern Italy attributed also to the same vaccine has been described by
Caramelli et al, (2001) in a mixed flock of Comisana sheep and half-bred
goats in an upland area of southern Italy. High crude mortality and
scrapie incidence occurred in both species and a large proportion of
aged animals were affected. The neuropathology was similar to that in
other sheep in Italy with iatrogenic disease but different from
conventional natural scrapie. Affected sheep were all of the most
susceptible genotype (Codon 171 QQ). It is stressed that the vaccines
incriminated in the transmission of scrapie in all these incidents are
not commercially produced. They have been prepared and distributed
locally within the country. Dr Subash Arya has repeatedly drawn
attention to the possible risk of transmitting CJD to humans vaccinated
with sheep-brain derived vaccines in India, e.g. Arya, (1994). However,
neither Dr Arya nor any of his colleagues has yet found any such case.
The episodes of scrapie resulting from the use of vaccines prepared from
infected sheep tissues emphasises the need for caution and mandatory
selection of safe sources for starting materials used in the manufacture
of vaccines. Such vaccines could theoretically at least, be used in
cattle thus creating a potential risk, though it is most unlikely that
they would be licensed for this purpose in Europe. Vaccines have not
been incriminated in the transmission of BSE (Wilesmith et al., 1988,
J.W.Wilesmith, personal communication). Furthermore, large numbers of
doses of commercially produced vaccines that have used bovine starting
materials, have been inoculated by parenteral and oral routes into
cattle throughout the world and a substantial proportion have been
produced in Europe, but no incident of BSE has been attributed to their
use. This is important because, since there is no species barrier, any
chink in the armour protecting vaccines from contamination would have
been revealed, but none has.

III.3.2.OTHER MEDICINAL PRODUCTS DERIVED FROM TSE-SUSCEPTIBLE SPECIES

Animal sources of material used in medicinal products vary, but mostly
are derived from cattle. There is thus at least a possibility that
unless strict precautions are taken, disease could be transmitted in
this way. It cannot be ruled out that no case ever arose by this means,
but it is clear that the majority did not, even at the very beginning of
the BSE epidemic before publication of information on BSE, and before
any legislation was in place (Wilesmith et al., 1988). The highest risk
tissue is bovine brain from a clinically affected animal or one in the
immediate pre-clinical phase. Posterior pituitary extract (now prepared
biosynthetically), was available and used in veterinary practice mainly
in adult female cattle at the time of parturition, to assist treatment
of retained placenta or to assist in milk let down. However, no
association was found between its use and the occurrence of BSE
(Wilesmith et al., 1988).

http://europa.eu.int/comm/food/fs/sc/ssc/out236_en.pdf

1: Indian J Pediatr. 1991 Sep-Oct;58(5):563-5.

Acquisition of spongiform encephalopathies in India through sheep-brain
rabies vaccination.

Arya SC.

Centre for Logistical Research and Innovation, Greater Kailash, New Delhi.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1813404&dopt=Abstract

THERE have been concerns about using drugs to super-ovulate cattle
abroad and
in the USA. How much (if any) of this product is still used in the USA,
I do not know,
but if any is used and or has been used in the past, should be stopped
ASAP for
risk of TSE;

Super-ovulate cattle. (Not to forget about the potential for some BSE
cases to come from vaccinations containing pituitary-derived SRMs.)
TWA LITTLE minute

2. We have identified one problem over where we are unable to act and
this is
the use of gonadotrophins in embryo transfer work. Some veterinary surgeons
are quite legally using this exemption from the Medicines Act contained in
Section 9(2) to prepare gonadotrophins from pituitary glands from various
species, including cattle. These hormones are used to stimulate
superovulation in
donor cows.

3. The extraction is from a pool of pituitary glands collected from
abbatoirs and the
process used is unlikely to have any effect on the BSE agent. Hormones
extracted
from human pituitary glands have been responsible for a small number of
cases of
Creutzfeldt Jacob disease in man.

http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/14006001.pdf
COMMERCIAL IN CONFIDENCE

Medicines Act - Veterinary Products Committee

Minutes of the Biologicals Committee meeting held on Tuesday 6 September
1988,
at 10:00 am in the Old Library, Central Veterinary laboratory, Weybridge.

It was reported that some replies had been received from Companies using
pituitary glands in their products...(rest are 4 blank pages...TSS)

http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/10/06005001.pdf
NOT FOR PUBLICATION
http://www.bseinquiry.gov.uk/files/yb/1988/11/01012001.pdf
http://www.bseinquiry.gov.uk/yb/1988/11/04003001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/04/00007001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/07/00007001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/09/00004001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/10/00003001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/01/04001001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/01/26007001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/01/30001001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
snip...
I was quite prepared to believe in unofficial pituitary hormones, also
in the 1970's, whether as described by Dr. Little, or in other
circumstances, for animal use.
snip...
The fact that there were jars of pituitaries (or extract) around on
shelves is attested by the still potent 1943 pituitaries, described in
Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at
Mill Hill. Having taken the trouble to collect them, they were not
lightly thrown out...
http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf
more on the 1968 medicine act, they forgot to follow
http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf
Draft cover letter to product licence holders (considered by Human and
Vet Medicines including deer)
http://www.bseinquiry.gov.uk/files/yb/1989/02/22008001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf
(It was noted with concern that hormone extracts could be manufactured
by a veterinary surgeon for administration to animals under his care
without any Medicines Act Control.)
http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
PITUITARY EXTRACT

This was used to help cows super ovulate. This tissue was considered to
be of
greatest risk of containing BSE and consequently transmitting the disease...

http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
(pages blank...TSS)

http://www.bseinquiry.gov.uk/files/yb/1988/06/07010001.pdf
TWA LITTLE STATEMENT 331

The BSE Inquiry / Statement No 331
Dr TWA Little
(not scheduled to give oral evidence)
THE BSE INQUIRY
STATEMENT OF DR T W A LITTLE
1. This statement is given by Dr Thomas William Anthony Little (TWAL). I am
currently Chief Executive of the Veterinary Laboratories Agency (VLA) and my
professional address is New Haw, Addlestone, Surrey KT15 3NB.
2. In 1966 I joined the Central Veterinary Laboratory (CVL).3. In the
period 1973 -
1996 I held the following posts:
· 1973 - 1982 Senior Research Officer
· 1982 - 1985 Deputy Regional Veterinary Officer (Tolworth)
· 1985 - 1986 Veterinary Head of Section (Tolworth)
· 1986 - 1990 Deputy Director of the CVLThis included responsibility for the
Veterinary Medicines Unit and the Biological Products and Standards
Department
most of which became part of the Veterinary Medicines Directorate in
April 1989.
· 1990 - 1996 Director and Chief Executive of the CVL which become the
Veterinary Laboratories Agency on merger with the Veterinary Investigation
Service in 1995.
4. When I returned to the CVL in 1986 as one of two Deputy Directors I
took over
specific responsibility for veterinary medicines. This involved fairly
frequent contact
with the Veterinary Medicines Division and the Animal Health Groups in
Tolworth. The
Veterinary Medicines Division dealt with the policy and administration
side of veterinary
medicines. I also briefed the Chairman of the Veterinary Products
Committee (VPC)
before meetings and attended meetings of the VPC. I chaired the meetings
of the
Scientific Secretariat of the VPC and the Biologicals Committee of the
VPC. I also
attended meetings of the Medicines Commission and various other
committees which
dealt with human medicines when necessary. This included the Committee
on Safety of
Medicines (CSM) Sub Committee on Biological Products. I also attended
occasionally
meetings of the Committee of Veterinary Medicinal Products (CVMP) in
Brussels.
5. Within CVL I had responsibility for:-
· The Medicines Unit - headed by Alastair Kidd
· The Biologicals Products and Standards Department - headed by Dr Denise
Thornton

Progressively during 1987 staff at CVL become aware of and
discuss
informally the potential of BSE to contaminate immunological
products. Such
concerns were discussed with administrators in the Veterinary
Medicines
Division. Following Wells et al publication TWAL discussed with
Prof J
Armour, Chairman VPC.
November 1987 As a result of informal discussions, Peter
Luff was asked to produce a paper on BSE - implications for
biologicals products.
6 January 1988 Biologicals Committee of VPC. Peter Luffs paper
tabled (Annex 2 )(YB 88/01.06/1.1-1.5) detailed discussion at next
meeting.
3 February 1988 Biologicals Committee of VPC (chaired by A Kidd)
(Veterinary Medicines Division represented by Mr Muriel and Mrs
Buckler)
Detailed discussion of Mr Luffs paper. (YB 87/12.00/1.1-1.3)
Report to senior officers in MAFF (CVL, VMD and AH Division)
further consideration of whether certification of cattle for freedom
from BSE was possible. (Annex 3) (YB 88/02.03/1.1-1.2)
During the next few months, discussions were held with staff of the
National Institute for
Biological Standards and Controls (NIBSC) leading to arrangements for a
meeting at
NIBSC by Dr P Minor.
16 May 1988 Meeting at NIBSC attended by Mr J Wilesmith CVL,
Drs R Ridley and H Baker MRC, Dr Schild, Minor and Ferguson
NIBSC and Drs Beale and Garland Wellcome
Laboratories.Recommendation of this meeting (Annex 4)(YB
88/08.00/2.1 ; YB 88/07.11/13.1 ; YB 88/05.16/2.1-2.12) sent to
Julymeeting of Biological Sub committee of CSM.
7 June 1988 Biologicals Committee of VPC
Agreed to a set of guidelines for pharmaceutical industry produced
by Geoff Wood.
Further internal meeting to be arranged between CVL staff to
progress the guidelines and any urgent matters relating to products.
(Annex 5) (YB 88/06.07/10.1-10.6)
8 June 1988 Internal CVL meeting to discuss the implications of
BSE to Biologicals Products containing bovine extracted material
(Annex 6). (YB 88/06.08/11.1-11.2) Following a detailed review
of situation the following recommendations were made:1.
Specific concern over use of pituitary gland
products by veterinary surgeons and companies. Paper to
be produced for Tolworth (Veterinary Medicines Division).
2. Urgent review of all products both immunological
and pharmaceutical for possible inclusion of ingredients of
bovine origin.
3. Draft guidelines to be presented in full to the
National Office of Animal Health (NOAH), the trade body
representing the Veterinary Medicines part of the
pharmaceutical industry, at next meeting on 11 July 1988
5 July 1988 Biologicals Committee Meeting
Detailed discussion of Geoff Wood's draft guidelines (SP3875.2)
(Annex 7) (YB 88/07.05/6.1-6.4)Major concern over pituitary
gland products and a letter being sent to all licence holders.
Amended paper to be presented to NOAH on 11 July and sent to
NIBSC and DHSS.
11 July 1988 Meeting with NOAH. (Annex 8) (YB
88/07.11/12.1-12.4)Dr Little briefed the meeting on the emergence
of BSE and showed the MAFF Video.Mr Wood presented the
proposed guidelines which were discussed. Mr Cook on behalf of
NOAH agreed to comment as soon as possible and agreed to
obtain information on pharmaceutical products which contained
bovine material of UK origin.
6 September 1988 Biologicals Committee of VPCSome replies
from companies using pituitary glands in their products received.
Copies of draft guidelines have been sent to NIBSC and DHSS.
(Annex 9) (YB 88/09.06/5.1-5.4)
8 November 1988 Meeting with NOAH. (Annex 10)(YB
88/11.25/5.1 ; YB 88/11.08/5.1-5.6)
Dr Little briefed the meeting on the current BSE situation. Some
problems with implementing the guidelines were discussed but
NOAH were keen to see them published quickly.
20 December 1988 Letter from Sir Richard Southwood asking what
detailed consideration had been given to this issue and asking for
views on whether some form of guidance to industry might be
useful. (Annex 11) (YB 88/12.20/2.1)
3 January 1989 Meeting between Medicines Division of
DHSS (Dr Adams, Dr Jeffreys and Dr Purves) and MAFF (CVL)
(Dr Little, Mr Kidd and Mr Bradley) Detailed review of the
situation and the need to 'keep in step'. A further meeting to be
held after MAFF guidelines have been reviewed by the VPC at its
January meeting. (Annex 12) (YB 89/01.03/2.1-2.2)
19 January 1989 Veterinary Products Committee
The draft guidelines to assist manufacturers of biological products
containing materials of bovine origin was provided for members'
comments. Mr Ray Bradley provided members with an extensive
briefing on the BSE problem. Written comments on the guidelines
were requested before the February meeting. (Annex 13) (YB
89/01.19/6.1 ; YB 89/01.00/2.1-2.3)
26 January 1989 Reply sent to Sir Richard Southwood
(Annex 14) (YB 89/01.26/2.1-2.4)
1 February 1989 Meeting between MAFF officials (Dr Little,
Mr Kidd, Mr Bradley) and D of H (Drs Jeffrey and Adams) from
Medicines Division) plus representation from NIBSC and
Biologicals Committee of CSM.The meeting agreed the text of
what were now joint MAFF/DH guidance for manufacturers plus a
timetable for clearance by various advisory committees to enable
publication in MAIL before Easter.
15/16 February 1989 Veterinary Products Committee Meeting (Annex 15)
(YB 89/02.15/6.1 ; YB 88/02.15/7.1)VPC (89) 38 containing the
revised CSM/VPC guidelines for industry were presented for
comment together with the correspondence with Sir Richard
Southwood.Subject to some minor changes the Guidelines were
agreed.
22 February 1989 Human and Veterinary Medicines Briefing
Group on BSEThe meeting was called to consider the DH/MAFF
draft guidelines to advise CSM. The meeting consisted of members
of the Biologicals Sub Committee of CSM, invited experts,
representatives of the Department of Health Medicines Division,
the Department of Health and MAFF prior to the publication of the
Southwood Report (Annex 16) (YB 89/2.22/11.1-11.8)
7 March 1989 Biologicals Committee of VPCA joint set of
guidelines had been agreed with D of H. A separate (MAFF)
questionnaire had been prepared asking for details of all products
had been sent out to all licence holders for reply by May 1989.
(Annex 17)(YB 89/03.07/2.1-2.5)
21 March 1989 Meeting with NOAH (Annex 18) (YB
89/03.21/13.1-13.4)Dr Little outlined the current situation and
explained why members had received the guidelines from both D
of H and MAFF. He explained that the guidelines set a very high
standard but indicated that manufacturers may present equivalent
methods to obtain the required standard.
1 April 1989 VMD establishedColleagues from Veterinary
Medicines Division, the Medicines Unit and part of BP&S join up
to become the VMD as recommended by the Cunliffe Review. Dr
Rutter was appointed as Chief Executive designate. I moved on to
take over the Agency Project Team for CVL.
Contact with the Department of Health
9. I have been asked specifically about my attendance at the Biological Sub
Committee of the CSM. (Annex 19) (YB 87/09.09/1.1-12)
10. On 9 September 1987 I attended a meeting of the Biological
Sub-Committee of
the CSM. This Sub-Committee is made up of independent experts. The
function of the
Sub-Committee is to advise the Committee on Safety of Medicines, which
is also made
up of independent experts. A number of officials, mainly from the
Department of Health,
attend both committees. Both committees advise on the safety of human
medicines,
including vaccines, but do not normally address matters relating to
animal health.
11. The 9 September 1987 was (I believe) the only time I attended a
meeting of the
Biological Sub-Committee. On this occasion, I attended in place of the
usual MAFF
representative, Dr Brinley-Morgan who retired in 1986.
12. A copy of the minutes of the meeting is Annexed to this statement. (YB
87/09.09/1.1-1.12) The meeting was chaired by Professor Collee, who had
lectured to me
in Edinburgh when I was an undergraduate. Dr Paul Adams was also at the
meeting. I
knew him as we both attended as officials the Veterinary Products
Committee meetings
and were both members of that Committee's Scientific Secretariat. I do
not believe I
knew any of the other attendees at the meeting personally.
13. One of the products discussed during the meeting was composed of
human dura
mater. This was under review at the meeting because of a case of CJD
associated with its
use. The official from the Department of Health presenting the case was
Dr Adams.
14. Although the minutes of the meeting make no reference to it, I made
a mention at
the meeting of the occurrence of BSE in cattle. I believe (although I
cannot now be sure)
that I mentioned BSE during the course of the formal meeting. I can
remember that a
discussion of scrapie resulted from my mention of BSE. Professor Collee
impressed me
with his knowledge of scrapie. It may be that my mention of BSE and
Professor Collee's
comments on scrapie arose during discussion on Dr Adams's paper on the
dura mater
products.
15. Although I am uncertain about the precise context in which I raised
BSE, I am
certain that Professor Collee and Dr Adams were present when I mentioned
BSE.
16. I also believe that Dr Adams introduced me to a number of his
colleagues from
the Department of Health after the meeting, although I cannot remember
who they were.
We most probably informally discussed BSE in relation to the use of
bovine material in
medicinal products, both human and veterinary.
17. I am not aware of any action taken by the Department of Health or
the Biologicals
Sub-Committee as a result of my mention of BSE at this meeting. I have
seen a minute
from Dr Watson to Mr Rees of 10 September 1987 (YB 87/9.10/1.1)
18. I believe the minute accurately reflects what I told Dr Watson. It
was my
understanding that someone from the Department of Health would be writing or
otherwise getting in touch with MAFF.
19. There was frequent contact between myself and other senior CYL staff
with the D
of H Medical Assessors who attended the VPC meetings and the Scientific
Secretariat.
Normally either Dr Paul Adams, Dr Geoffrey Diggle or Dr Kevin Woodward
attended.
20. There was a good working relationship. As can be seen from the
chronology there
was also contacts with NIBSC which performed a role for D of H which was
similar to
that which CVL carried out for MAFF.
21. At this stage it is difficult to determine when BSE was first
discussed in these
informal discussions. Formal meetings are listed in the chronology.
Southwood Committee Recommendation - 24 February 1989
22. One of the Southwood recommendations (8.2) was "the attention of the
Licensing
Authority, the CSM and the VPC be drawn to the emergence of BSE so that
they can take
appropriate action".
23. From the chronology it can be seen that the Biologicals Committee of
the VPC
were alert to this problem from November 1987 and had commissioned
papers and the
draft guidelines which were made available to the Southwood Committee.
24. The full VPC considered the guidelines in January 1989.
Contacts with the Pharmaceutical Industry
25. As can be seen from the chronology, the draft guidelines were first
given to
NOAH in July 1988 for their comments and contact was being made with
product licence
holders in June 1988 regarding some specific products.
26. The industry started searching for alternatives to UK bovine
products at an early
stage and were anxious to protect the safety aspect of their products.
27. Meetings with NOAH also took place in November 1988 and March1989.
28. The Consultative Committee chaired by Dr Tyrrell recommended in its
Interim
Report (June 1989) that there should be more detailed investigations
into the fate of
bovine and ovine tissues which might lead to the spreading of infection.
29. Urgent activity on the veterinary aspects of inclusion of bovine
material in
vaccines and other drugs (mainly hormones) commenced in June 1988 and a
detailed
questionnaire was circulated in May 1989.
30. There was similar activity by the medical assessors of the CSM.
31. Dr Tyrell was a member of the Biologicals Sub Committee of the CSM
at this
time.
Diagnosis of Scrapie and BSE by the Veterinary Investigation Service
32. I have been asked to comment on this matter. Between 1982 and 1985 I
was a
Deputy Regional Veterinary Officer based at Tolworth in the Veterinary
Investigation
Section which managed the VI Service. I was a frequent visitor to VI
Centres and was
particularly concerned with project work. In 1995, the VI Service merged
with the CVL
to form the VLA of which I am currently Chief Executive and Director.
33. At the time of the first cases of BSE (in the mid 1980s) there were many
veterinarians in the VIS with experience in general histopathology. This
experience was
promoted and encouraged through regional, informal meetings of the
Histopathology
Study Groups, at which participants from Veterinary Investigation
Centres ("VIC"), the
CVL and Veterinary School Pathology Departments would discuss cases.
34. Although not every Veterinary Investigation Officer ("VIO") was
trained in
histopathological diagnosis, and not every VIC had the capacity to
process tissue samples
for histopathology as a routine, all VIOs considering a clinical
differential diagnosis of
neurological disease would have collected material for histopathological
examination and
referred it to a colleague with the necessary expertise. The colleague
could have been
within the VICs or the in the Pathology Department at CVL or at the Lasswade
Laboratory. Some of these VIOs with an interest and experience in
histopathology would
also have had formal training in pathology, but very few would, at that
time, have
claimed complete confidence in making histopathological examinations of
brain or other
nervous system tissues.
35. If the indication, particularly from the case history, was that an
unusual
neurological problem was occurring, the VIO usually referred the whole
fixed brain,
intact, direct to the Consultant Pathology Unit ("CPU") at CVL. The
exception to this
would have been the examination, by VIOs in some instances, of brains of
sheep for
diagnosis of scrapie and ruminants generally, for diagnosis for
listeriosis. However, brain
material from some scrapie cases was passed to the CPU, CVL sometimes
for primary
diagnosis or for second opinions.
36. Very few cases of neurological disease in adult cattle were
presented to VIOs for
post mortem examination and thus the examination of cow brains by any
pathologist at
that time was a relatively rare event.
37. The original cases to be diagnosed, of the disease which later
became known as
BSE, were referred to by Mr Carl Johnson a VIO at Wye VIC, Kent, to Mr
Gerald Wells
at CVL but, as Dr Matthews statement indicates, another case was
diagnosed at a VIC.
The transcript of Dr Matthews statement states: "Roger Hancock, who I
think first picked
[it] up down in the south west."
38. Roger Hancock was a VIO working at the Truro VIC who had experience
of the
histopathological diagnosis of scrapie. He was thus able to recognise
similarities between
spongiform changes in scrapie and those found in a brain of a cow
submitted to him. In
view of this highly unusual finding, tissues from the case were
submitted to Mr Wells at
CVL for a second opinion.T W A Little
Issued on behalf of the witness by:
The BSE Inquiry Press Office
6th Floor Hercules House
Hercules Road
London SE1 7DU
Fax: 0171 803 0893
Website: http://www.bse.org.uk
Email: inquiry@bse.org.uk
OTHER DOCUMENTS ANNEXED TO DR LITTLES STATEMENT CAN
BE FOUND AT THE FOLLOWING YEAR BOOK REFERENCES
YB 89/1.9/3.1-3.3
YB 90/11.00/5.1-5.2 attaching YB 89/03.15/4.1-4.4
YB 88/11.02/5.1
YB 88/12.07/1.1
YB 88/11.14/2.1

http://www.bseinquiry.gov.uk/files/ws/s331.pdf


Minutes of the Biologicals Committee Meeting Held on Wednesday 6 January
1988, at 10.00am in the Old Library, Central Veterinary Laboratory,
Webridge.

http://www.bseinquiry.gov.uk/files/yb/1988/01/06001001.pdf

Minutes of the meeting held on 6 January 1988 in the 19th floor
Conference room , Market Towers at 10.30am

http://www.bseinquiry.gov.uk/files/yb/1988/01/06002001.pdf

BOVINE SPONGIFORM ENCEPHALOPATHY - IMPLICATIONS FOR
BIOLOGICAL PRODUCTS

snip...

There are two special cases to consider - hormones and similar extracts, and
cell cultures.

HORMONES etc,: Although the extraction of processes involve the use of
various
organic solvents, which tend to have a deliterioius effect on scrapie
infectivity,
extracts must be considered to be potentially contaminated - indeed
Creutzfeldt-
Jakob disease has been transmitted by the use of human growth hormone
extracted
from cadaver pituitaries. It is therfore not possible to regard bovine
gland extracts
as deserving special consideration: they must be autoclaved as above.
Such products
are not likely to be effective after such treatment. The use of
pituitary extracts for super-ovulation is not apparently controlled
under the Medicines Act. This is an
anomaly which requires urgent consideration...

http://www.bseinquiry.gov.uk/files/yb/1987/12/00001001.pdf

Greetings again USDA/APHIS et al,

I VOICED my concerns of the potential risk from this mode of transmission on
more than one occasion on the BSE-L which is full of Government and Industry
officials for years (see below), but my concern today has grown due to
the new
TSE in cattle called (BASE) ;

THE new findings of BASE in cattle in Italy of Identification of a
second bovine amyloidotic spongiform encephalopathy: Molecular
similarities with sporadic Creutzfeldt-Jakob disease

http://www.pnas.org/cgi/content/abstract/0305777101v1

PLUS, we have new atypical TSEs in sheep and goats, with the new findings
of BSE in a GOAT;

THE recent discoveries of previously unidentified strains of
Scrapie such as 221C44 and the Nor9845;

FULL TEXT APPRX. 91 PAGES

UK Strategy for Research and
Development on Human and Animal
Health Aspects of Transmissible
Spongiform Encephalopathies

2004-2007

http://www.mrc.ac.uk/pdf-uk_strategy_v5.2.pdf

Commission submits French Research Findings on TSE in a goat to
Expert Panel
------------------------------------------------------------------------
Reference: IP/04/1324 Date: 28/10/2004
HTML: EN

IP/04/1324

Brussels, 28 October 2004


Commission submits French Research Findings on TSE in a goat to Expert
Panel

Following the findings by a research group in France that they suspect
the presence of a TSE infection in a goats brain which tests cannot
distinguish from BSE, the European Commission has submitted data
received from the French authorities to the Community Reference
Laboratory (CRL) for TSEs based in Weybridge, England, for an evaluation
by an expert panel. TSEs are transmissible spongiform encephalopathies,
namely BSE affecting cattle, and scrapie affecting goats and sheep. The
expert panel will evaluate, over the next two weeks or so, the
scientific evidence to see if it indicates the presence of BSE in the
goat. This isolated incident does not present a risk to public health as
the goat and its herd did not enter the food and feed chain...

snip...

http://europa.eu.int/rapid/pressReleasesAction.do?reference=IP/04/1324&format=HTML&aged=0&language=EN&guiLanguage=en

Approved-By: "Terry S. Singeltary Sr."
Message-ID: <389B5176.FA244CC1@wt.net>
Date: Fri, 4 Feb 2000 16:23:50 -0600
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: Bovine Pituitary Injections * USA

######### Bovine Spongiform Encephalopathy
#########

Greetings list members,

I was curious if any U.S. or other Vets. would know of the use in the
U.S., if any, of Pituitary hormones in cows in the U.S. I will throw a
few names at you, maybe some may recognize, maybe not.....

Pituitary Injection (Willington) Pituitary (posterior lobe) Injection B
VET C OXYTOCIN LEO* PITOCIN* Pituitary Injection (Dales) 137 *
(Willington Medicals Ltd) Pituitary Extract (VDC) 557 Pituitary
Injection (Dales) 161 Pituitary (Posterior Lobe) Injection (Univet) 534
Pituitary (Posterior) Injection (Pharmavet) 464 Pituitary (Posterior
Lobe) Injection B vet C Posterior Pituitary Injection BVETC Pituitary
(Posterior Lobe) Injection BVetC 1965 Pituitary Extract Injection 10
i.u./ml

Or any other type, you get the picture, there are way too many to list,
but do any of the Veterinarians on the list in the U.S. know of any of
these or other type of pituitary hormones that were used in cows in the
U.S.?

Thank you, Terry S. Singeltary Sr., Bacliff, Texas USA

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html
############

Approved-By: "Terry S. Singeltary Sr."
Message-ID: <38A47737.F8C80314@wt.net>
Date: Fri, 11 Feb 2000 14:55:19 -0600
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: The Possible relationshipt between BSE and use of pituitary
hormones in cows...

######### Bovine Spongiform Encephalopathy
#########

Greetings list members,

I find this article most interesting. Might be old news to some, but
thought some might find it as interesing as I did........

Kind Regards, Terry S. Singeltary Sr., Bacliff, Texas USA
___________________________________________________________________ Dr
Anne Maddocks 16/06/99

THE BSE INQUIRY

Statement of Dr Anne C Maddocks M.A, B.M, B.Ch, F.R.C.Path

The possible relationship between BSE and use of pituitary hormones in cows

1. Introduction

1.1 It is suggested in this statement that the promiscuous use of
pituitary hormones in cows may have resulted in BSE in the same way that
treatment with pituitary growth hormone (hGH) or follicular stimulating
hormone (FSH) has been shown to cause iatrogenic CJD in humans.

1.2 The important difference between the medical and veterinary use of
these hormones being that slaughtered cattle subsequently entered the
animal food chain as meat and bone meal (MBM) creating the likelihood of
a widespread dispersal of any infectivity able to survive the rendering
process.

1.3 The use of hormones in cows has a very complex background which is
little known among ordinary farmers. Although 'published' the material
from which the findings in this paper have been drawn was only available
via several visits to the library at Wye College (University of London
Department of Agriculture), The Scientific Periodicals Library at
Cambridge, The Royal Society Library, The Royal Society of Medicine's
Library, The British Library at St. Pancras, British Library Science
Collections at Holborn and extensive use of the Aldwych branch of the
British Library Science Collections and their stock from Boston Spa.
(This search was part of wide BSE studies which do not relate to the
Inquiry).

1.4 This extensive trawl was necessary to locate both the original
experimental work and reports of cattle breeders' conferences reflecting
the later practical application of that work because there is little
direct publication of findings and outcomes by the commercial cattle
breeding sector in the UK. (The journal "Theriogenology" has
contributions from US commercial Embryo Transfer (ET) workers). Whilst
the underlying science is abstruse and reported only haphazardly it
should be noted however the 'ordinary farmers' do use the M.O.E.T.
system (see Appendix Five to this statement) to breed from their best
cows. This may involve an ET centre or may be done on the farm.

1.5 The background to this area lies in the science of Endocrinology
which is applied in both Medicine as therapy, and Agriculture as
manipulatory techniques to increase milk yield and enhance production.
This is the reason for the wide spectrum of ultra specialist journals
which has to be consulted and whose normal readership will consist
_________________________________________________________________

only of the most scientific of obstetricians, agribusiness or breeding
specialists, none of whom would be likely to read right across the
spectrums' medical and veterinary aspects.

1.6 I should like to point out that professionally, while I do not
belong to those groups, I am a very experienced control of infection
specialist, as well as a clinical microbiologist. It is professional
suicide for infection control doctors to accept as 'mere' coincidences
similar events which are close in space or time. It must be assumed that
in depth investigation may reveal links or common factors, and it is
necessary to 'hack in' to specialist areas through research. This is my
position in this instance.

1.7 Please note for clarity this account is written without the
historical background and most of the scientific detail - important
though these are to the argument. It has been thought better to put this
detail into Appendices at the end of the document where they can be
separately considered, rather than have one very detailed and lengthy
account.

2. The argument for the transmission of a TSE which became the BSE
outbreak through use of cadaveric hormones

2.1 Transmissible Spongiform Encephalopathies (TSEs) are rare diseases.
Since Kuru was described in 1957 only familial variants have been found
but suddenly in 1985 two previously unknown TSEs emerged at once, a
striking coincidence that merits attention.

2.2 The possible significance of BSE and hormone related CJD occurring
at about the same time has been obscured because:

(a) neither disease was publicised for some time and then when they were
publicised it was through articles which appeared in different
sub-speciality journals.

(b) hormone therapy related CJD (so far as it was discussed at all) was
seen as obviously an iatrogenic disease with a known origin. BSE on the
other hand was portrayed as a "mystery disease" which baffled scientists.

2.3 An in depth look at historical events gives a different perspective
on these two diseases and a possible reason why they appeared at the
same time.

2.4 The most important point to have in mind when reflecting on this
coincidence is that advances made in endocrinology are applied in both
medicine and veterinary science. Endocrinology is a "free-standing"
science rooted in physiology, with its own specialist departments and
techniques drawing on animal experiments, endocrine biochemistry and
electron microscopical ultra structure studies. As advances are made in
endocrinology they are fed across into both medicine and agriculture at
about the same time like a rising tide advancing on all fronts.

2.5 Given that the human disease is undoubtedly related to pituitary
hormone therapy, is there any possibility of a similar pituitary hormone
relationship with BSE?
________________________________________________________________

2.6 We know that use of pituitary hormones in the 1970s and 1980s
resulted in deaths from CJD throughout the world but most notably in the
UK, France, USA and Australia. Thinking about BSE has focussed
(understandably) upon the way in which the original isolated cases of
the diseases were magnified into an epidemic, less attention has been
paid to the reasons for its original emergence in different places but
at the same time. If it could be shown that cows had been given
pituitary hormones, then it would seem reasonable to look to see if:

(a) these might have been contaminated and

(b) whether this could have been responsible for the transmission of a
previously unknown TSE amongst cows.

3. Hormones

A. Human pituitary growth hormone (hGH) and Human pituitary fertility
hormones

3.1 Human pituitary growth hormone (hGH) and Human pituitary fertility
hormones had been used in treating humans, as replacement therapy and
both types definitely gave rise to CJD cases (see hGH/CJD legal case
reports - Morland Papers (M2 Tab 1) -and Allars Report) (M1 Tab 1).

B. Cows

3.2 Improvement in "production" was a constant ambition for
agriculturists in all possible ways. Embryo transfer however was in a
class of its own; it was a sort of "Grail Quest" with its origins in the
1890s (Heape at Cambridge) and with a long history of hard struggle 1949
to 1970s with a considerable emotional investment and commitment at the
Unit for Animal Reproduction (UAR) at Cambridge University.

3.3 Bovine pituitary growth hormone (bGH) was given to boost milk yield
and pituitary fertility hormones fi'om various species were given to
cows as one of the methods of stimulating Multi-Ovulation for Embryo
Transfer (the M.O.E.T. System - see Appendix Five) in order to
manipulate normal reproductive functions.

3.4 As it happened the hormone used at the UAR was non-pituitary so no
problems could emerge. It was only with the promiscuous use of various
pituitary gonadotrophins in the 1970s that the door would have been open
for prion type agents to be transmitted. Whilst growth hormones are
species specific, Follicular Stimulating Hormone (FSH) from cows,
horses, pigs and sheep were capable of being used with success in the
M.O.E.T. process; as this method moved out of the research environment
at Cambridge (having been publicised at various cattle breeders
meetings) and became a mechanism of agricultural production, whatever
hormones were available were used. It is in this promiscuity of use that
the possibility of TSE transmission arises.

C. Luteinising Hormone (LH)

3.5 Since writing the above I have been told that pituitary luteinising
hormone (LH) also was used more frequently than I had realised to
prepare recipient cows, ie on a larger number of cows than were donors.
As this was also a pituitary hormone it represents yet another possible
path. _____________________________________________________________

MIRROR IMAGES [NA...TSS] sporadic CJD cases ?sporadic BSE
____________________________________________________________

3.6 This demonstrates potential routes of spread for bovine infections
which run in parallel with human iatrogenic disease.

3.7 Because we know that pituitary derived hormones are a potentially
highly successful means of infection the use of pituitary derived
gonadotrophin to stimulate multi ovulation in M.O.E.T techniques appears
to be a likely candidate route for spread of the disease (this applies
particularly if "cottage industry" bovine hormones are used).

3.8 As to timing, human hGH and hFSH treatments were finally fully
developed in the - 6 -1970s. Indeed, the majority of the iatrogenic CJD
victims received their treatment then. M.O.E.T for cows also burgeoned
in the late 1970s.

3.9 That two new diseases both appeared in one year (1985) really is
fortuitous because of the different incubation periods and amplification
by MBM in feed but even two similar new diseases appearing within a year
or two would be significant.

3.10 My thesis is that:-

(i) Although only a relatively small number of animals might be infected
at first by pituitary hormones, acting as a "starter" event, this would
of course be hugely amplified by "cow cannibalism" - Meat and Bone meal
in feed (see Mirror Images diagram).

(ii) A suspect batch of hormone might be used in several different
geographical areas giving rise ultimately to more or less simultaneous,
dispersed outbreaks, which would all of course be of a similar type.

(iii) These outbreaks could act as a "platform" for the take-off of the
epidemic.

(iv) Choice of pituitary Hormones. (see Appendix Four: Gonadotrophins)

3.11 It must be remembered that the problem arises not from the hormonal
action as such, but because the pituitary is effectively part of the
brain and can contain TSE agents. As might be expected problems only
occurred (in growth hormone and fertility treatment) where the chosen
hormone was extracted from the pituitary.

3.12 Human fertility treatment with menopausal urine gonadotrophin was
used in Europe without problems, only the Australians using pituitary
FSH had CJD cases. In the same way Cambridge M.O.E.T research in the
1950s and 1960's used PMSG (pregnant mare serum gonadotrophin) without
problems. A TSE could only appear when pituitary FSH was used instead,
most likely when the technique was applied in the field in the 1970's.
The change back to pituitary hormone was probably due to its greater
commercial availability in the USA and possibly its action in crude
extracts. (PMSG activity was not easy to control and also repeat cycles
lead to antibody production).

3.13 It has to be pointed out that there is a missing factor in this
hypothesis which is a sporadic form of BSE in cows comparable to
sporadic CJD in humans. Such a condition is innately likely to exist
however (on the basis of the similarity of
________________________________________________________________

mammalian prion proteins) and is accepted as the basis of the "one old
cow" theory of BSE origin - of which the hormone-use theory is a variant.

4. A new event- why should BSE happen in 1985

4.1 The injection of pituitary hormones is the "new thing" that happened
not feeding meat and bone meal which had occurred for many years
(although of course feeding meat and bone meal was "cannibalism" and was
recognised (too late) as a potential route tbr recycling infections).
Once the infection was established, the MBM recycling effect would have
been a powerful route of infection.

4.2 Although any pituitary hormone could carry a TSE it seems most
likely that Embryo Transfer in the 1970's, particularly the rush to
commercial non-surgical transfer in the late 1970's was the potential
advent. A wide variety of hormones (probably including bovine FSH) was
used, but semi-commercial E.T. was not documented or controlled so we
will never know what was used in all instances (see Appendix Five on
M.O.E.T).

5. Conclusion

5.1 It seems at least possible that in the same way that
well-intentioned growth hormone replacement therapy and fertility
treatment with FSH led to CJD cases, the BSE outbreak was a tragic
outcome of an heroic effort (1890-1970s) to bring about bovine embryo
transfer.

5.2 This would not have happened had everyone continued to use the
non-pituitary gonadotrophin (PMSG) used in the original research at
Cambridge, but the potential transmission risks of pituitary extracts
were only begun to be understood in the mid 1970s as instances of
iatrogenic transmission were reported and validated. (bGH for extra milk
yield remains another possible origin, but the timing displayed favours
the FSH hypothesis).

5.3 This hypothesis is not provable but the timing appears compelling.

5.4 In the following appendices, I develop more specific aspects of this
argument and detail my sources for this submission.
_______________________________________________________________

References

"The History of Clinical Endocrinology" by V C Medvai (1993) "Controlled
Reproduction in Cattle and Bufib. lo" by Ian Gordon (1996)

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html
############

Approved-By: "Terry S. Singeltary Sr."
Message-ID: <3924296D.26CEF8D9@wt.net>
Date: Thu, 18 May 2000 10:33:33 -0700
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: human/animal medicinal products (vaccines) * Industry * T.S.E.'s
(PART 2)

######### Bovine Spongiform Encephalopathy
#########

MAFF The Central Veterinary Laboratory New Haw, Weybridge, Surrey
TELEPHONE.* BYFLEET4 I I I I j EXT,

Professor Sir Richard Southwood F.R.S. Department'of Zoology University
of Oxford Sou~h Park Road Oxford OX1 3PS

26 January 1989

Dear Sir Richard

BSE AND VETERINARY MEDICINES

Thank you for your letter of 20 December.

The Veterinary Products Committee had a very full discussion on BSE at
their last meeting On 19 January when they consided a set of draft
guidelines which had been prepared by the Biologicals Committee in
consultation with various experts at the Central Veterinary Laboratory
and elsewhere. The VPC have requested further information including a
full list of products involved, including all the old medicines, to
assess the likely effect of various control measures and their
practicality.

The Biological Committee has discussed BSE on a number of occasions over
the past year and we have met with the National office of Animal Health
(who represent the Veterinary pharmaceutical industry) in July, November
and January and have warned them of the need to introduce control
measures to avoid possible problems with material which could to be
contaminated with BSE, and we have also met many of the individual
product licence holders.

Given the difficulty of detecting the BSE agent our philosphy in
drafting guidelines for consideration by the VPC has been to concentrate
on the source and nature of the materials used in the manufacture of
veterinary products.

The experience with scrapie has led vaccine manufacturers to avoid sheep
material. One way forward with the current situation would be to
substitute tissues from other species where either cattle or sheep
material is used but this would cause widespread disruption of supplies.

89/01.26/2.1

CVO/BSE/1/2

Another way forward would be to use cattle material from a presumed BSE
free source. Manufacturers are already turning to overseas sources and
particularly Ireland but the discovery recently of BSE in Ireland
indicates the problem which may arise from this method of control.
Moreover, the presence of exotic diseases rules out tissues and sera
from many other countries. It might be possible to certify some herds in
the United Kingdom as free from BSE in the future but it will be a long
time before the full range of products used in the manufacture of
biologicals from foetal calf serum to milk casein, could be derived from
such sources.

Another way forward is to look at the constituents of each product and
assess the risk. In some cases substitution may be possible - i.e. the
use of synthetic media for Clostridial vaccines rather than cooked meat
broths or pig bile instead of ox bile. In other cases such as ox brain
for pituitary hormones we have already stopped the use, as synthetic
hormones are widely available.

Foetal calf serum poses a problem in that it will be difficult to find
an adequate substitute. Although the risk is likely to be very low, some
manufactures are looking overseas for supplies.

We are atso working very closely with colleagues in the Department of
Health to ensure we issue consistent advice to manufacturers.

I will send you a copy of our guidelines when the VPC approves them.

This certainly is a very serious problem and we look forward to seeing
your report and any other advice you may care to offer.

Yours sincerely

T W A LITTLE

Undisclosed cc: CVO Mr Cruickshank Dr Watson Mr Kidd Mr A Taylor Dr
Thornton Mr A Laurence Mr Wilesmith Dr P Adams, DOH

89/01.26/2.2

MF903/1 0532

IN CONFIDENCE

HUMAN AND VETERINARY MEDICINES WORKING GROUP ON BSE

PROPOSED JOINT CSM/VPC GUIDELINES FOR INDUSTRY

The following guidelines are addressed to product licence holders and
applicants.

It is intended that all products licensed under the Medicines Act 1968
for human or veterinary use should conform to these guidelines if they
contain material from a bovine source, or if bovine material has been
used as an intermediate in manufacture.

The guidelines apply to products that are administered parenterally or
to open wounds.

Guidelines

1. All bovine material should come from cattle, taken from a closed herd
in the female line since 1980, in which no animal bas been clinically
suspected of having BSE and which has not been fed rations containing
ruminant derived protein during that period. 2. No brain, lymphoid
tissues, placenta tissue or primary cell of bovine origin should be used
in the manufacture of medicinal products.

3. No tissue is to be used in medicinal products when collected
postmortem from a bovine animal after brain penetrative stunning.

4. All tissue collected from the bovine animal should be taken
aseptically using virgin or sterilised needles, syringes, scalpel blades
etc.

5. It is recommended that whenever possible, source animals should be
calves up to 6 months old and that the following procedures are observed.

i. For serum: all cellular components must be removed.

ii. For foetal calf serum: great care should be taken to avoid
contamination by placenta and foetal fluids. All cellular components
must be removed.

iii. For faeces: these should be collected from the rectum.

iv. For bile: this should be collected aseptically.

v. For milk or products derived from milk: Collection should be aseptic
from animals under 3 years old.

6. Sterilization procedures should be demonstrated to be capable of
inactivating scrapie-like agents - at present thought to be autoclave,
at 134°C-138°C for 18 minutes at 30 psi.

89/01.26/2.3

MF903/1 0533

DRAFT MAIL ARTICLE

CONCERN ABOUT BSE IN HUMAN AND VETERINARY MEDICINES

Bovine Spongiform Encephalopathy (BSE) is a bovine disease characterised
by rapid degenerative neurological changes culminating in death.

This disease has recently been diagnosed in the UK and although there is
no evidence to suggest that it may be transmitted to man, the Licensing
Authority considers it prudent, having taken expert advice, including
that of CSM and VPC, to advise that all manufacturers whose products
contain bovine material should conform to the guidelines set out below.

In order that the Licensing Authority may obtain accurate up-to-date
information about all such products, manufacturers are asked to supply
details of products which contain bovine material as an active or
excipient, or in which bovine material has been used as an intermediate
in manufacture.

This information and any enquiries should be addressed, for human
medicines, to.......... at Market Towers; and for veterinary medicines
to........... at CVL by 1 July 1989. The format and information required
are as follows:
_____________________________________________________________________
PL/CTC/CTX PL/CTC/CTX Bovine State: Does this product Number Name
Ingredient Active at present conform Excipient conform to the
intermediate guidelines (Y/N)
_____________________________________________________________________
........... ........... .......... ............ ................
........... ........... .......... ............ ................
_____________________________________________________________________

The guidelines, which should be observed on all human and veterinary
medicines containing bovine material are as follows:

1. All bovine material should come from cattle, taken from a closed herd
in the female line since 1980, in which no animal has been clinically
suspected of having BSE and which has not been fed rations containing
ruminant derived protein during that period.

2. No brain, lymphoid tissue, placenta tissue or primary cell cultures
of bovine origin should be used in the manufacture of medicinal products.

3. No tissue is to be used in medicinal products when collected
postmortem from a bovine animal after brain penetrative stunning.

4. All tissue collected from the bovine animal should be taken
aseptically using virgin or sterilised needles, syringes, scalpel blades
etc.

89/01.26/2.4

MF903/1 0534

5. It is recommended that whenever possible, source animals should be
calves up to 6 months old and that the following procedures are observed.

i. For serum: all cellular components must be removed.

ii. For foetal calf serum: great care should be taken to avoid
contamination by placenta and foetal fluids. All cellular components
must be removed.

iii. For faeces: these should be collected from the rectum.

iv. For bile: this should be collected aseptically.

V. For milk or products derived from milk: Collection should be aseptic
from animals under 3 years old.

6. Sterilization procedures should be demonstrated to be capable of
inactivating scrapie-like agents - at present thought to be autoclave at
134°C-138°C for 18 minutes at 30 psi.

89/01.26/2.5

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html
############

Approved-By: "Terry S. Singeltary Sr."
Message-ID: <39A2CFCD.11EBFE00@wt.net>
Date: Tue, 22 Aug 2000 12:09:01 -0700
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: TSE's and Vaccines [continued]

######### Bovine Spongiform Encephalopathy
#########

BOVINE SPONGIFORM ENCEPHALOPATHY (BSE)

A meeting was held in Room 111 at Richmond House between the CMO and Mr
Andrews (PUS, MAFF). Mr. Heppell and Dr Walford were present. The matter
discussed was the setting-up of the Expert Working Party to give advice
on the veterinary and potential health aspects of the outbreak cf BSE.
It was pointed out by the CMO that the "worst case" on the veterinary
side would be if it become clear as the months passed that BSE is
transmissable within herds of cattle vertically from mother to calf and
laterally within herds eg by eating infected placentae. If this is so it
will not be possible to control the outbreak at this stage. However, it
is possible that the virus does not pass beyond the animal which has
been infected through feeding stuff. On the human health side tne "worst
case" situation would be that the virus could pass to man either through
milk or through meat brain etc. It was agreed that it would be necessary
for the setting-up of the Expert Advisory Group and its recommendations
to become public knowledge. MAFF, however, was reluctant to make a
formal announcement about the setting-up of the group. It considered it
extremely likely that it would need to respond publicly to press reports
of an 0utbreak of BSE in Guernsey and would refer to the setting-up of
the Southwood Expert Group's existence would be announced in relation to
such a press conference. Speed in setting-up the group is therefore
imperative.

88/4.11/2.1 ===========

ANNEX 5 COMMERCIAL IN CONFIDENCE MEDICINES ACT - VETERINARY PRODUCTS
COMMITTEE

Minutes of the Biologicals Committee meeting held on Tuesday 7 June 1988
at 10.00am in the Old Library, Central Veterinary Laboratory, Weybridge.

Dr. Little - Chairman

Mr Bousfield Miss Lucas Mr Boughton Mr Luff Dr Bracewell Dr MacOwan Mr
Gray Mr Murial Mr Harris Dr Thornton Dr Hussaini Mr Travas - Brown Dr
Lee Dr Wilkins Miss Lowe

Mrs Evans - Technical Secretary

The Chairman welcomed Mis Lowe, who had recently joined Animal Medicines
Division at Tolworth, to the Committee.

1. Apologies for absence 1.1 Apologies were received from Mr Cameron, Mr
Hartley, Mr Kidd, Dr Lamont, Mr Watson and Mr Wood.

B L A N K

88/06.07/10.1

B L A N K

88/06.07/10.2

B L A N K

88/06.07/10.3

B L A N K

88/06.07/10.4

B L A N K

88/06.07/10.5

7. Any Other Business

7.1 Bovine Spongiform Encephalopathy

It was noted that the disease would become a notifiable disease from 1
July 1988.

It was agreed that the BP&S document (SP 3663.2), first discussed at the
January 1988 Biologicals meeting, should be re-examined and a set of
guidelines drawn up for industry.

A meeting between Medicines Unit, BP&S and CVL experts on the disease
would be arranged as soon as possible to discuss guidelines. The draft
guideline would be an item on the agenda at the next Biologicals meeting.

8. Date of the next meeting

8.1 The next meeting will be on Tuesday, 5 July 1988 in the Old Library.

JUNE 1988 MEDICINES UNIT CVL, WEYBRIDGE

88/06.07/10.6 ============= ANNEX 6

MEETING HELD ON 8 JUNE 1988 TO DISCUSS THE IMPLICATIONS OF BSE TO
BIOLOGICAL PRODUCTS CONTAINING BOVINE - EXTRACTED MATERIAL

Chairman - Dr Little Mr Bradley Mr Dawson Mrs Evans Mr Gray Mr Kidd Mr
Luff Dr Thornton Mr Wilesmith

BACKGROUND

The first cases of BSE were identified in November/December 1986, but
with reviewing previous data the first confirmed clinical case was found
to be in April 1985.

The incidence of BSE was highest in the South of England but incidents
had occurred from the Shetlands down to Guernsey.

The youngest recorded age at which BSE was confirmed in a cow was 2
years 9 months, while the peak incidence appeared to be in 4 year old
cattle.

It was considered that exposure to the disease had occurred from 1982
onwards and that the incubation period ranged from 3-6+ years.

Calves appeared to be at 30x greater risk than adult cattle and
incidents were significantly more prevalent in dairy rather than beef
suckler herds.

The major source of infection was considered to be infected meat and
bonemeal feedstuffs. It was noted that meat and bonemeal feedstuffs were
exported to Europe and the third world.

BSE AGENT

Characterisation of the protein fibrils of the agent showed it to be a
spongiform encephalopathy agent and as yet no differences between BSE
and scrapie, other than host, have been found.

So far there has been no evidence on BSE transmissibility to other
species, but experiments are underway.

Discussion continued with scrapie being used as the model for BSE
distribution in lymphoid tissues and subsequent treatment.

The tissues most at risk of containing, and consequently transmitting,
scrapie were the brain, spinal cord and lymphoid tissues. Scrapie had
been found in many other tissues including the placenta, pancreas and
lung. However all routes of transmission were considered possible so use
of amy bovine derived tissues were considered to be of some degree of risk.

88/06.08/11.1

BOVINE BIOLOGICAL PRODUCTS

The bovine tissues used in biological products were outlined as:

SERUM

This was the main concern as it was included in the majority of
biological products.

Serum was considered likely to be of low risk for transmission of the
agent. However, utilization of a closed farm with no known clinical
cases would be preferable for serum production. If non-UK serum were to
be included in products it would need to be irradiated to remove any
other viruses or bacteria.

PEPTONE/MEAT DIGEST

For growth media and also used as a freeze-drying stabiliser. Autoclave
treated.

PITUITARY EXTRACT

This was used to help cows super ovulate. This tissue was considered to
be of greatest risk of containing BSE and consequently transmitting the
disease.

BEEF BRAIN AND BRAIN INFUSION BROTHS

Considered to be of great risk.

TISSUE CULTURES DERIVED PROM PRIMARY BOVINE TISSUES

Milk proteins - scrapie had not been found in milk as yet.

OX BILE

FAECES

Scrapie was suspected of being excreted in the faeces, but had not been
isolated yet.

RECOMMENDATION

The greatest concern was the use of pituitary gland products. It was
agreed that the Medicines Unit should prepare a paper to advise Animal
Medicines Division, Tolworth on the course of action to be taken.

It was agreed that B P & S should draw up a full list of all the tissues
involved in biological products. Medicines Unit would produce a list for
pharmaceutical products. A chart of risk assessment should be made for
each of the tissues in relation to the products, together with
appropriate treatments for each tissue.

It was agreed that some form of guidance should be given to companies at
the next NOAH meeting on 11 July.

MEDIClNES UNIT JUNE 1988

88/06.08/11.2 =============

ANNEX 7 COMMERCIAL IN CONFIDENCE 88/07.05/6.1--6.4

[[this seems to have some interesting data they must have forgot to
blank out (foetal calf serum, pituitary based products and other
hormones. However, the quality of the text print is so poor, i have
asked for another copy. should only be a few days before receiving. will
post this document later, will move forward for now...TSS]]

kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html
############

Approved-By: "Terry S. Singeltary Sr."
Message-ID: <39A96DCB.AD45580D@wt.net>
Date: Sun, 27 Aug 2000 12:36:43 -0700
Reply-To: Bovine Spongiform Encephalopathy
Sender: Bovine Spongiform Encephalopathy
From: "Terry S. Singeltary Sr."
Subject: BSE AND VETERINARY MEDICINES

######### Bovine Spongiform Encephalopathy
#########

Professor Sir Richard Southwood F.R.S. Department of Zoology University
of Oxford South Park Road Oxford OX1 3PS

26 January 1989

Dear Sir Richard

BSE AND VETERINARY MEDICINES

Thank you for your letter of 20 December.

The Veterinary Products Committee had a very full discussion on BSE at
their last meeting on 19 January when they considered a set of draft
guidelines which had been prepared by the Biologicals Committee in
consultation with various experts at the Central Veterinary Ladoratory
and elsewhere. The VPC have requested further information including a
full list of products involved, including all the old medicines, to
assess the likely effect of various control measures and their
practicality.

The Biologidal Committee has discussed BSE on a number of occasions over
the past year and we have met with the National Office of Animal Health
(who represent the Veterinary Pharmaceutical indusyry) in July, November
and January and have warned them of the need to introduce control
measures to avoid possible problems with material which could to be
contaminated with BSE, and we have also met many of the individual
product licence holders.

Given the difficulty of detecting the BSE agent our philosphy in
drafting guidelines for consideration by the VPC has been to concentrate
on the source and nature of the materials used in the manufacture of
veterinary products.

The experience with scrapie has led vaccine manufacturers to avoid sheep
material. One way forward with the current situation would be to
substitute tissues from other species where either cattle or sheep
material is used but this would cause widespread disruption of supplies.

89/01.26/2.1 ==============

Another way forward would be to use cattle material from a presumed BSE
free source. Manufacturers are already turning to overseas sources and
particularly Ireland but the discovery recently of BSE in Ireland
indicates the problem which may arise from this method of control.
Moreover, the presence of exotic diseases rules out tissues and sera
from many other countries. It might be possible to certify some herds in
the United Kingdom as free from BSE in the future but it will be a long
time before the full range of products used in the manufacture of
biologicals from foetal calf serum to milk casein, could be derived from
such sources.

Another way forward is to look at the constituents of each product and
assess the risk. In some cases substitution may be possible - i.e. the
use of synthetic media for Clostridial vaccines rather than cooked meat
broths or pig bile instead of ox bile. In other cases such as ox brain
for pituitary hormones we have already stopped the use, as synthetic
hormones are widely available.

Foetal calf serum poses a problem in that it will be difficult to find
an adequate substitute. Although the risk is likely to be very low, some
manufactures are looking overseas for supplies.

We are also working very closely with colleagues in the Department of
Health to ensure we issue consistent advice to manufacturers.

I will send you a copy of our guidelines when the VPC approves them.

This certainly is a very serious problem and we look forward to seeing
your report and any other advice you may care to offer.

Yours sincerely

T W A LITTLE

Undisclosed cc: CVO Mr Cruickshank Dr Watson Mr Kidd Mr A Taylor Dr
Thornton Mr A Laurence Mr Wilesmith Dr p Adams, DOH

89/01.26/2.2 ===============

MF903/1 0532

IN CONFIDENCE

HUMAN AND VETERINARY MEDICINES WORKING GROUP ON BSE

PROPOSED JOINT CSM/VPC GUIDELINES FOR INDUSTRY

The following guidelines are addressed to product licence holders and
applicants.

It is intended that all products licensed under the Medicines Act 1968
for human or veterinary use should conform to these guidelines if they
contain material from a bovine source, or if bovine material has been
used as an intermediate in manufacture.

The guidelines apply to products that are administered parenterally or
to open wounds.

Guidelines

1. All bovine material should come from cattle, taken from a closed herd
in the female line since 1980, in which no animal has been clinically
suspected of having BSE and which has not been fed rations containing
ruminant derived protein during that period.

2. No brain, lymphoid tissue, Placenta tissue or cell cultures of bovine
origin should be used in the manufacture of medicinal products.

3. No tissue is to be used in medicinal products when collected
postmortem from a bovine animal after brain penetrative stunning.

4. All tissue collected from the bovine animal should be taken
aseptically using virgin or sterilised needles, syringes, scalpel blades
etc.

5. It is recommended that wheneverpossible, source animals should be
calves up to 6 months old and that the following procedures are observed.

i. For serum: all cellular components must be removed.

ii. For foetal calf serum: great care should be taken to avoid
contamination by placenta and foetal fluids. All cellular components
must be removed. iii. For faeces: these should be collected from the
rectum.

iv. For bile: this should be collected aseptically.

v. For milk or products derived from milk: Collection should be aseptic
from animals under 3 years old.

6. Sterilization procedures should be demonstrated to be capable of
inactivating scrapie-like agents - at present thought to be autoclave,
at 134°C-138°C for 18 minutes at 30 psi.

89/01.26/2.3 =============

MF903/1 0533

DRAFT MAlL ARTICLE

CONCERN ABOUT BSE IN HUMAN AND VETERINARY MEDICINES

Bovine Spongiform Encephalopathy (BSE) is a bovine disease characterised
by rapid degenerative neurological changes culminating in death.

This disease has recently been diagnosed in the UK and although there is
no evidence to suggest that it maybe transmitted to man, the Licensing
Authority considers it prudent, having taken expert advice, including
that of CSM and VPC, to advise that all manufacturers whose products
contain bovine material should conform to the guidelines set out below.

In order that the Licensing Authority may obtain accurate up-to-date
information about all such products, manufacturers are asked to supply
details of products which contain bovine material as an active or
excipient, or in which bovine material has been used as an intermediate
in manufacture.

This information and any enquiries should be addressed, for human
medicines, to.................. at Market Towers; and for veterinary
medicines to................. at CVL by 1 July 1989. The format and
information required are as follows: PL/CTC/CTX PL/CTC/CTX Bovine State:
Does this product Number Name Ingredient Active at present conform
Excipient conform to the Intermediate guidelines (Y/N)

........ .......... ......... .......... .......... ..........

........ .......... ......... .......... .......... .......... The
guidelines, which should be observed on all human and veterinary
medicines containing bovine material are as follows:

1. All bovine material should come from cattle, taken from a closed herd
in the female line since 1980, in which no animal has been clinically
suspected of having BSE and which has not been fed rations containing
ruminant derived protein during that period.

2. No brain, lymphoid tissue, placenta tissue or primary cell cultures
of bovine origin should be used in the manufacture of medicinal products.

3. No tissue is to be used in medicinal products whcn collected
postmortem from a bovine animal after brain penetrative stunning.

4. All tissue collected from the bovine animal should be taken
aseptically using virgin or sterilised needles, syringes, scalpel blades
etc.

89/01.26/2.4 =============

MF903/1 0534 0534

5. It is recommended that whenever possible, source animals should be
calves up to 6 montbs old and that the following procedures are observed.

i. For serum: all cellular components must be removed.

ii. For foetal calf serum: great care should be taken to avoid
contamination by placenta and foetal fluids. All cellular components
must be removed.

iii. For faeces: these should be collected from the rectum.

iv. For bile: this should be collected aseptically.

v. For milk or products derived from milk: Collection should be aseptic
from animals under 3 years old.

6. Sterilization procedures should be demonstrated to be capable of
inactivating scrapie-like agents - at present thought to be autoclave at
134°c-138°C for 18 minutes at 30 psi.

89/01.26/2.5 ===============

TIP740203/1 0424

CONFIDENTIAL

Mr Cunningham CMP3 From: D O Hagger MB1 Dr Salisbury MED/IMCD3 Mr Burton
PD/STB/PGIB Date: 15.02.1989 Mr Dudley PD/AD4

BOVINE SPONGIFORM ENCEPHALOPATHY 1. The purpose of this minute is to
alert you to recent developments on BSE as they affect medicines and to
invite representatives to a meeting in Market Towers on 22 February 1989.

2. The report of the Working Party on Bovine Spongiform Encephalopathy
(BSE) was submitted by the CMO to the Secretary of State for Health and
Minister for Agriculturer on 9 February.

3. The stunmary at the end of the report records, inter alia: 'we have
drawn the attention of the Licensing Authority to the potential of
transfer of BSE agent in human and veterinary medicinal products. In
paragraph 7 of his submission (Annex A), the CMO notes:

"I am also putting work urgently in hand to satisfy myself that
everything possible has been done to ensure .... that transfer of the
BSE agent in human and veterinary medicinal products does not occur."

4. The Veterinary Products Committee meets on 16 February and The
committee on Safety of Medicines on 23 February when each will be
considering a draft of some joint guidelines for manufacturers of
medicinal products which use bovine material as an ingredient or an
intermediate in the manufacturing process (Annex B}.

5. A small DH/MAFF working group met earlier this month and was involved
in the drafting of the proposed guidelines. A further meeting has now
been arranged to consider the position on medicines in the light of the
Southwood report. It will take place on Wednesday 22 February, the day
before the CSM meeting, and will be held in the 19th floor conference
room, Market Towers, starting at 10 am. It will be chaired by Professor
Gerry Collie, who is a member of the CSM and Chairman of its Biological
Sub-Committee. Other independent experts being invited for the first
time are Dr Tyrrell, Dr Kimberlin and Dr Martin. Professor Asscher,
Chairman of CSM proposes to attend as observer. Dr Shild and Dr Minor
from NIBSC will also be present as will officials from Medicines
Division and MAFF. Dr Collie will report the outcome of the meeting to
the CSM when they consider the subject the following day.

6. Although a wide range of medicines may be implicated - and the
present proposal is to write to companies for more information - an
"instant" telephone survey of manufacturer of vaccines used for children
has already been undertaken in response to a request from Dr Harris. The
results are in Dr Adams' minute of 14 February (Annex C) - the proviso
in his second paragraph, last sentence should be noted.

7. I also attach a copy of some draft briefing on veterinary medicines
by MAFF for their Minister in respect of the southwood report,
Paragraphs 1 and 4(1) in particular should be noted.

89/02.15/11.1 =============

TIP740203/1 0425

8. I think it would be helpful if those directly concerned with the
Department's vaccination programme were represented at the meeting on 22
February. I should therefore be glad if addressees would let Mr
Whitbread (MT ext 3234) know who will be attending. A sandwich lunch
will be available if necessary. Finally I should be glad if you would
observe the confidential marking while Ministers are considering the
report.

D O Hagger Rm 1533 Ext 3201 MT

CC:(minute only) Dr Harris Mr Wilson Dr Jones Dr Adams Dr Jefferys Dr
Wood Dr Pickles Dr Rotblat Dr Purves Mr Sloggem Mr Bewley Mr Love Mrs
Alderman Mr Whitbread [[penciled in, cannot read...tss]]

89/02.15/11.2 ================

BOVINE SPONGIFORM ENCEPHALOPATY MEETING HELD ON 21 AUGUST 1989 AT 2:15
IN ROOM 720

Present:

Miss M Duncan (Chairman) Mr W Burton Dr E Hoxey Mrs J Dhell Ms K Turner
Dr S Whittle Mr N Weatherhead 1. Apologies were received from Dr
Richardson who was represented by Dr Whittle. An invitation given to Med
ISD was not taken up.

2. A Status Report Following the Chasing of Non-Responders

Despite letters and telephone calls to the companies who have not
replied the final response was still only about 66%. The committee was
concerned about the number of UK companies who have not yet responded.
Concern was also shown about BSE products being transported around Europe.

The Committee decided that a definitive list was needed of the companies
in the UK and Europe, who have not responded. Those companies would be
sent a 2nd reminder.

ACTION: N Weatherhead

3. Of the 10 companies who were sent a further letter by Mr Burton
requesting why the company gave an affirmative answer to question number
8, only five replied, of these two changed their responses while the
other company answers were accepted. The companies who did not respond
will be chased.

ACTION: N Weatherhead

4. Results of the Additional Enquiries Made

The committee discussed the need for more information on categorisation
of Bovine Products but a decision had to he delayed until the MCA
Working Group met in September.

5. The MCA had sent 2700 questionnaires out, 1,124 had made valid
returns; of these 122 use animal material of some kind and there are 582
pcoducts involved.

6. The MCA/BSE working group will meet on 6th September. Their aim is to
review responses from professional officers in MCA who have suggested
seven categories of importance (with 1 being the most important) for
medical products:-

ID 2267/NRE/1

89/08.21/10.1 ==============

1. Products with Bovine brain/lymph tissue administered by injection.

2. Products with bovine tissue other than brain/lymph administered by
injection.

3. Tissue implants/open wound dressing/surgical materials/dental and
ophthlamic products with bovine ingredients.

4. Products with bovine ingredients administered topically.

5. Products with bovine ingredients administered orally.

6. Products with other animal/fish/insect/bird ingredients administered
by injection /topically/oral routes.

7. Products with ingredients derived from animal material by chemical
processing (eg stearic acid, gelatine lanolin ext.

The BSE working group will decide which of these are important, and
should be examined more closely, and which categories can be eliminated.

The responses by the companies were presented by Ms Turner and were
categorised by MCA standards, the products that were discussed were all
low volume usage products eg sutures, heart valves

8. As the responses included some materials of human origin it was
decided that more information should be sought about CJD. There had been
2 recent deaths reported associated with human growth hormone. These
were being investigated.

9. Re-editing of the Paper on "Incubation of Scrapie-like Agents"

It was suggested that the document could be sent out to companies with
the non-standard sterilization Document. The document could have severe
implications on the companies whose products have a high risk factor as
decided by the MCA working group. It was decided that the committee also
needed consultation on abattoir systems working within the UK. Advice
could be gained from David Taylor of the Agricultural Research Council
in Edinburgh who could give information on how Europe and the rest of
the world maintain satisfactory standards. The results of this
information may have implications for the document.

The 'introduction' in the document will be changed to include further
CJD information the document will then be given to the BGRP who will be
asked to recommend who should receive it.

10. Is MAFF Input Necessary

It was decided that MAFF will only be approached when consultation on
the Guidelines are necessary.

ID 2267/NRE/2

89/08.21/10.2 ==============

11. The Need for a List of High Priority Implantables

The commitee decided that no list is necessary as all implantables,
including ones from a human source are of high priority. Concern was
shown over Killingbeck who use human material but had not yet responded.
The company will be chased for a response.

Concern was shown over the fact that there may be other scrapie-like
organisms in other animals and further enquiries should be made.

Action N Weatherhead W Burton

12. Possible Policy Options

1. MCA should be pressed for a decision over action on the high risk
category products.

2. What action about should be taken about the limited effect of current
sterilization methods on BSE.

3. What action should be taken against companies that claim to meet the
guidelines.

N D WEATHERHEAD

ID 2267/NRE/3

89/08.21/10.3 ================

kind regards, Terry S. Singeltary Sr, Bacliff, Texas USA

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html
############

WITH all this data, plus new studies showing TSE and BSE in the non cns
tissue;

According to Nov. 2 Yomiuri Newspaper, researchers of the Prion
Disease Research Center, the National Institute of Animal Health
of Japan reported in the International Symposium of Prion Diseases
held in Sendai from October 31 to November 2., 2004, that they
detected prion in the adrenal gland and peripheral (sciatic and
peroneal) nerves of the 11th BSE case of Japan (a 94-months old
cow found dead on the farm on March 4 this year).

http://www.maff.go.jp/www/press/cont2/20041101press_7.htm
(only in Japanese)

EMBO reports AOP Published online: 11 April 2003

Widespread PrPSc accumulation in muscles of hamsters orally infected with
scrapie

Achim Thomzig, Christine Kratzel, Gudrun Lenz, Dominique KrĂĽger &
Michael Beekes Robert Koch-Institut, P26, Nordufer 20, D-13353 Berlin,
Germany

Received 13 February 2003; Accepted 13 March 2003; Published online 11
April 2003.

Abstract :

Scrapie, bovine spongiform encephalopathy and chronic wasting disease
are orally communicable, transmissible spongiform encephalopathies
(TSEs). As zoonotic transmissions of TSE agents may pose a risk to human
health, the identification of reservoirs for infectivity in animal
tissues and their exclusion from human consumption has become a matter
of great importance for consumer protection. In this study, a variety of
muscles from hamsters that were orally challenged with scrapie was
screened for the presence of a molecular marker for TSE infection, PrPSc
(the pathological isoform of the prion protein PrP). Sensitive western
blotting revealed consistent PrPSc accumulation in skeletal muscles from
forelimb and hindlimb, head, back and shoulder, and in tongue.
Previously, our animal model has provided substantial baseline
information about the peripheral routing of infection in naturally
occurring and orally acquired ruminant TSEs. Therefore, the findings
described here highlight further the necessity to investigate thoroughly
whether muscles of TSE-infected sheep, cattle, elk and deer contain
infectious agents.

http://www.emboreports.org/

Prions in skeletal muscle

Patrick J. Bosque*,dagger ,Dagger , Chongsuk Ryou*, Glenn Telling*,§,
David Peretz*,dagger , Giuseppe Legname*,dagger , Stephen J.
DeArmond*,dagger ,¶, and Stanley B. Prusiner*,dagger ,||,**

* Institute for Neurodegenerative Diseases and Departments of dagger
Neurology, ¶ Pathology, and || Biochemistry and Biophysics, University
of California, San Francisco, CA 94143

Contributed by Stanley B. Prusiner, December 28, 2001

Considerable evidence argues that consumption of beef products from
cattle infected with bovine spongiform encephalopathy (BSE) prions
causes new variant Creutzfeldt-Jakob disease. In an effort to prevent
new variant Creutzfeldt-Jakob disease, certain "specified offals,"
including neural and lymphatic tissues, thought to contain high titers
of prions have been excluded from foods destined for human consumption
[Phillips, N. A., Bridgeman, J. & Ferguson-Smith, M. (2000) in The BSE
Inquiry (Stationery Office, London), Vol. 6, pp. 413-451]. Here we
report that mouse skeletal muscle can propagate prions and accumulate
substantial titers of these pathogens. We found both high prion titers
and the disease-causing isoform of the prion protein (PrPSc) in the
skeletal muscle of wild-type mice inoculated with either the Me7 or
Rocky Mountain Laboratory strain of murine prions. Particular muscles
accumulated distinct levels of PrPSc, with the highest levels observed
in muscle from the hind limb. To determine whether prions are produced
or merely accumulate intramuscularly, we established transgenic mice
expressing either mouse or Syrian hamster PrP exclusively in muscle.
Inoculating these mice intramuscularly with prions resulted in the
formation of high titers of nascent prions in muscle. In contrast,
inoculating mice in which PrP expression was targeted to hepatocytes
resulted in low prion titers. Our data demonstrate that factors in
addition to the amount of PrP expressed determine the tropism of prions
for certain tissues. That some muscles are intrinsically capable of
accumulating substantial titers of prions is of particular concern.
Because significant dietary exposure to prions might occur through the
consumption of meat, even if it is largely free of neural and lymphatic
tissue, a comprehensive effort to map the distribution of prions in the
muscle of infected livestock is needed. Furthermore, muscle may provide
a readily biopsied tissue from which to diagnose prion disease in
asymptomatic animals and even humans. Dagger Present address: Department
of Medicine, Denver Health Medical Center, Denver, CO 80204.

§ Present address: Department of Microbiology and Immunology, University
of Kentucky, Lexington, KY 40536-0230.

** To whom reprint requests should be addressed. E-mail: vann@cgl.ucsf.edu.

www.pnas.org/cgi/doi/10.1073/pnas.052707499

http://www.pnas.org/cgi/content/abstract/99/6/3812?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=prusiner&author2=prusiner&titleabstract=prions+meat+tissue+mice&fulltext=prions+meat+tissue+mice&searchid=1024346978866_6016&stored_search=&FIRSTINDEX=0&fdate=1/1/2002

Extraneural Pathologic Prion Protein in Sporadic Creutzfeldtâ¬Jakob
Disease

Markus Glatzel, M.D., Eugenio Abela, Manuela Maissen, M.S., and Adriano
Aguzzi, M.D., Ph.D.

snip...


Conclusions Using sensitive techniques, we identified extraneural
deposition
of PrPSc in spleen and muscle samples from approximately one third of
patients
who died with sporadic Creutzfeldtâ¬Jakob disease. Extraneural PrPSc
appears
to correlate with a long duration of disease.

http://content.nejm.org/cgi/content/short/349/19/1812?query=TOC

WITH all this data mounting, there is only one logical thing to do at
this point
in time. WE must remove all animal tissue from these products...

thank you,

with kindest regards,
I am sincerely,

Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, TEXAS USA 77518





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