Dr. Pool later goes on to develop a method for determining the concentration of Factor VIII in human plasma.

He discovers that the freezing and thawing of blood plasma enables him to obtain a layer rich in factor VIII, resulting in the first highly purified dried concentrate of factor VIII.

"West Germany introduced a surrogate test in 1965."

Note: Whilst the main thrust of this entry is to draw attention to the fact that West Germany introduced a surrogate test in 1965, we dispute the reference in the submission that a specific test for HCV was discovered in 1989. We firmly believe that the Chiron Corporation discovered, cloned and sequenced the Hepatitis C virus - the causative agent of Non-A Non-B Hepatitis (NANBH) two years earlier, in 1987. (see related entries link below.)

Allen also claims that he has been told that neither the National Research Council nor the Government Regulators have inspected the labs, and that there is evidence there that they are not performing within industry standards.

"An Advisory Group has recently been set up by the Department of Health under Dr Maycock's chairmanship to make recommendations on the testing of blood donations for the presence of Hepatitis Associated Antigen (HAA) and it's antibody."

The agent is associated with widely reported deaths in renal failure units.

Note: The screening of donated plasma for hepatitis B, (HBV) is introduced by BPL in November 1971.

The paper, entitled "Haemophilia Treatment in the United Kingdom from 1969 to 1974" by Rosemary Biggs, goes on to state that:

"It has been shown that such commercial blood has been 10 times more likely to transmit hepatitis than blood collected from unpaid donors by National Transfusions services." (Maycock 1972).

"Product licences have very recently been granted to two firms which enable them to market foreign human AHG concentrate to hospitals and haemophilia centres in the UK. It has come to the notice of the Department that one of the firms is already engaged in active promotion of the very expensive product." (paragraph 3)

"Product licences have very recently been granted to two firms which enable them to market foreign human AHG concentrate to hospitals and haemophilia centres in the UK." (page, paragraph 2)

"It has come to the notice of the Department that one of the firms is already engaged in active promotion of this expensive product. The firm has indicated that they can supply large quantities of human AHG concentrate and this could result in very significant expenditure if amounts were bought in excess of immediate needs." (page 2, paragraph 2)

"The Department hope to let you have a further statement soon. Meanwhile, in view of the impending availability of foreign human AHG concentrate and its very high cost, you may like to let all concerned with the treatment of haemophilia in your region know what is happening." (page 2, paragraph 6)

Note: There is no mention of safety concerns, only the usual emphasis on cost.

"At the same time the U.K. should aim to become self-sufficient as soon as possible by increasing home production of freeze-dried AHG concentrate." (page 4, point 3)

David Owen announces in the House of Commons that several million pounds has been allocated - but the initiative does not follow through as there is considerable resistance in the Department of Health against putting in the money.

Commercial Factor IX is currently available for purchase in the United Kingdom, but there is enough NHS Factor IX, and only small amounts of commercial Factor IX are required.

US prisoners are associated with SGOT levels of over 60 IUs per ml, a level that increases the risk of non-A non-B hepatitis (later known as hepatitis C transmission) by a factor of 6.

Despite knowledge of this risk, the US Pharmaceuticals (allegedly) actively recruit PRISONERS for plasma to be used to manufacture Factor VIII and IX, whilst concealing or failing to disclose the risk to hemophiliacs (plaintiffs), their physicians, or the FDA.

Centre Directors (consultants) sign up to receive products for trials.

Fifth Disease (Erythema Infectiosum)
Fifth disease is a mild rash illness with a red, patchy, "slapped cheek" rash on the face. The rash may appear on other parts of the body, such as arms, torso, buttocks, and thighs. Other symptoms such as fever, headache, body ache, sore throat, congestion, runny nose, cough, nausea, or diarrhoea may come before the rash.

Arthritis
Parvovirus B19 can lead to a seronegative arthritis and joint pains in adults and possibly in children.

Foetal Anaemia in Pregnancy
"Parvovirus infection in pregnant women is associated with hydrops fetalis due to severe foetal anaemia, sometimes leading to miscarriage or stillbirth. The risk of foetal loss is about 10% if infection occurs before week 20 of pregnancy and especially between weeks 14-20, but is minimal after then. This risk may be reduced with correct diagnosis of the anaemia (by ultrasound scans) and treatment (by blood transfusions). Once the baby is born, there is evidence to suggest no developmental abnormalities due to B19 infection during pregnancy."

Chronic Anaemia in the Immunocompromised
In people with a compromised immune system, the B19 parvovirus can manifest clinically as chronic anaemia or pure red cell aplasia.

Astonishingly, the government stopped funding the only research facility that could have developed heat-treatment and a screening test for Non-A Non-B hepatitis by as early as 1978.

"Cutter's source of blood is 100 percent from Skid-Row derelicts (Transfusion: May/June, 1974)."

Note: It is sad to read of the detrimental consequences of the UK purchasing commercial Factor VIII and IX upon the USA's attempts to form their own volunteer donor programs.

Dr David Owen: "As I told my hon Friend the Member for Sowerby on 17 February, I have authorised the allocation of special finance of up to £0.5m (about half of which would be recurring) to increase the existing production of AHG concentrate within the National Health Service with the aim of the NHS becoming self-sufficient as soon as possible" (final paragraph)

Note: This demonstrates government maladministration as the £500,000 was in fact used by the RTC, leaving BPL Elstree short-changed. The DHSS should have insisted on the extra money being allocated to its intended purpose - which was to fight this threat to public safety.

"In England and Wales the view is taken that in law the activities of health authorities attract Crown Exemption so that the provisions of the Medicines Act are not binding on them. Arrangements are being made whereby health authorities will be brought within the licensing provisions of the Act in a manner analogous to that which applies to commercial pharmaceutical manufacture."

• 18 out of 20 patients receive commercial factor VIII
• 9 patients become ill out of a total of 18
• there are 4 cases of hepatitis B within 6 months of product use
• there are 7 cases of non-B hepatitis
• 2 of the patients contract both types of hepatitis

We know from the witness testimony of a former pupil who was in his second year at the school in 1975, that the epidemic down in Alton concerned hepatitis B infections and the outbreak involved around ten boys from the school. One of them was in his dormitory and, by coincidence, the morning the outbreak was registered was the same morning of the school medical, and he woke up looking yellow-faced. The boys involved were informed that it would take around 6 months for them to fully recover.

Note: It is disconcerting to learn that all of the infected boys were forced to endure the stigma of having small red spots (as markers) put on their meal plates and were required to specifically hand their marked plates in to canteen staff, in person, in order for them to be sterilised.

• 371 patients are transfused with the commercial product
• There are 78 cases of hepatitis affecting 66 patients (17.7%)
• 1 patient dies after contracting Hepatitis B
• 12 patients contract 2 types of hepatitis: Non-B hepatitis, then HBV later on

In 1976, only a few years after the factor concentrate products of Bayer, Baxter, Armour & Alpha Therapeutic go on the market, the United States Food and Drug Administration (FDA) Bureau of Biologics holds a Conference entitled "Unsolved Therapeutic Problems in Hemophilia."

The research articles compiled from the Conference discuss the high incidence in patients using these products of disorders such as liver dysfunction, enlarged spleen, Hepatitis B, and Non-A Non-B Hepatitis. The articles conclude that these disorders were tied to the patients' use of factor concentrates, and emphasized the risks entailed in producing such concentrates using plasma from paid donors.

Dr Dodsworth speaking in 1998 with reference to 1976: "Our spokesman, Dr Tovey, the Director of the Bristol Transfusion Centre, had been through a similar exercise for the World Health Organization in Geneva. He persuaded us that if we wanted to treat our patients adequately, it would be necessary to fractionate at least 80 per cent of the blood that was donated. At this point the Government decided that money was available for neither extending the fractionation unit at Elstree nor for equipping the transfusion centres to separate yet more plasma from donor units."

Dr Dodsworth speaking in 1998: "So this is really why we found ourselves buying large quantities of factor VIII concentrate from America, and why we infected so many of our patients with HIV."

"The line of reply from Oxford does not surprise me. They are correct in stating that they are a major producer of AHG without which the programme will founder, something we cannot possibly contemplate as the Minister of State has only recently reaffirmed his aim of NHS self-sufficiency in this substance. Quite apart from this, the alternative of buying the commercial product (with its higher hepatitis risk) is more costly than producing our own." (paragraph 1)

Note: The granting of this licence is one of the earliest Factor VIII product licences that we know of.

The licence documentation for this product clearly states the word "HEAT" in the description of the licence name. The word is in brackets but it appears that some text is missing, as the brackets are not closed. It is interesting to note the use of the word HEAT as early as March 1976.

Note: The Government is, however, responsible for the two earlier pledges that were given in the House. The targets are not achieved and the UK is still not self-sufficient in blood products.

"Following a special allocation of £500,000 last year substantial progress was now being made in building up production capacity in the NHS, and self-sufficiency in home-produced Factor VIII was expected to be reached in mid-1977." (paragraph 3)

Note: The half million, (intended for building up capacity within the NHS) was, in fact, NOT used for building-up production capacity for self-sufficiency and instead ended up being paid out to increase the amount of people donating blood in the UK.

"There was no shortage of concentrate in the UK. Commercial producers could meet all the requirements likely to be made on them, on demand, but at considerable cost." (page 3, paragraph 1)

"It was suggested that the money at present being spent on commercial concentrate might be better spent if it was used to increase still further the output of NHS concentrate but it was generally agreed that money was not the only limiting factor. The Chairman drew attention to the fact that expenditure on commercial concentrate was continuing to rise even though more NHS concentrate was becoming available." (page 3, paragraph 2, lines 1-6)

The Department agreed to bear in mind the following:

"Of the English and Welsh Blood Transfusion Centres only Manchester RTC distributed commercial concentrate at present." (page 6, paragraph 2)

"The view was expressed that the purchase of commercial concentrate should be a Regional rather than an Area responsibility." (page, 6, paragraph 3)

"Trial of factor VIII concentrate in prophylaxis BPL Elstree, Lord Mayor Treloar College, Alton." (page 4, paragraph 4)

Note: We have to wonder whether the pupils' or parents' consent was gained prior to a trial being conducted in a school? Using a new medicine for the sake of improved health, or improved yield of Factor VIII is one thing, but using the new concentrates as part of trials connected to a collaborative study is quite another.

"PF Laboratory has been inspected. BPL will be visited in October." (page 7, paragraph 2, line 1)

"It is not unlikely that the accommodation of both laboratories will be criticised and, in certain respects, found inadequate. Both were designed before the Medicines Act was passed and therefore several years before those responsible for applying this Act had formulated the criteria to be met." (page 7, paragraph 3)

Note: It is quite disgusting that these failings at BPL Elstree coincide with the use of their factor VIII concentrates in trials involving children at the Treloar boarding school.

"We know that in addition clinicians are buying and using or accumulating commercially produced factor VIII concentrate at the rate of 10 million i.u. per annum." (paragraph 3)

"There is some highly potent cryoprecipitate about. I understand that the Edgware product contains levels of 100 i.u. factor VIII or more consistently." (paragraph 4, lines 1 and 2)

"With the agreement of the Advisory Group, the Department had decided that the recommendation to readmit to donor panels persons with a history of jaundice would be permissive; Regional Transfusion Directors could exercise their individual clinical judgement in the matter." (page 2, line 2)

Note: It is appalling to see that in 1976, the Department allowed the readmission of people with a history of jaundice to return to donor panels. We strongly disapprove of a decision which helped expose persons with haemophilia to hepatitis B.

"The case against the Government hinges upon the time it took to build a huge blood products laboratory at Elstree, Hertfordshire, which could have provided safe supplies of Factor VIII for British sufferers."

"The Labour Government announced in 1977 that the plant would be finished by 1979, and that Britain would be self-sufficient in blood products, and would no longer have to import any from the United States."

Dr. Peter Levine: "One wonders whether our patients are suffering a sort of immune complex disease as a result of intensive bombardment with foreign antigens...."

Dr Jones is a paid consultant to Hyland Laboratories in 1977.

Professor Blackburn reports that there is a hold-up in the expansion of fractionation in the UK. Prof. Blackburn is planning to organise a meeting to look into ways of expanding the facilities for fractionating.

Prof. Stewart: "The commercial concentrates were supplied with water for solution which was an advantage." Dr. Ellis said that Elstree was looking into this problem and might in the future supply the water with the concentrate.

Dr. Waiter states that plans have been made to divert plasma from South of the Border to Liberton when Mr. Watt is ready to receive it. The Factor VIII made from this plasma would return to Centres south of the Border. Agreement in principle has already been reached between the DHSS in London and the Scottish Home and Health Department.

Dr. Rainsford (of the Lord Mayor Treloar College, Hants), asks "if England and Wales would be charged for the use of the fractionation facilities in Scotland? If so, might it be as well to continue to buy commercial concentrates?"

He wished to know if Haemophilia Centre Directors were changing their policy with regard to sending boys to the College. The comment was made that the decrease in haemophiliacs applying for admission was in all likelihood a reflection of the improvement in haemophilia treatment throughout the United Kingdom both at Centres and by home therapy.

Note: We would like to pose the question as to whether there some sort of agreement between Haemophilia Centre Directors that they would 'channel' their patients toward the school each year on behalf of Dr Rainsford?

Who, then, decided to send the haemophiliac boys to the school? Was it the Local Authorities, school headmasters, GPs or local haemophilia centre Consultants, or did the school approach families direct?

Background: Unfortunately, we have reason to believe that in some cases children were actually 'forced' to go to the school by their Local Education Authorities on the supposed grounds that it was the only way the LEA felt able to fulfil their legal obligation to provide an adequate education... and parents would have been 'forced' into it as well. Also, we would like to point out that some children with haemophilia came from unstable family backgrounds and were encouraged to be just dumped at the school.

"the Department should not on financial grounds make a loan or grant to [Lister?] and that the possible consequences of [Lister?] ceasing to produce sera and vaccines should be accepted". (Paragraph 1, lines 3-5)

"Nevertheless we should be faced with very real difficulties if [Lister?] were to be wound up" (Line 4 of paragraph 3)

"Any disruption in production during this interim period, which could well arise if we were forced to act too quickly, would probably cause clinicians to fall back on commercial suppliers of blood products, thus adding to the total cost of the NHS as well as inducing a setback for Ministers' policy of UK self-sufficiency in blood products production" (Last 6 lines of paragraph 3)

Note: This situation ended up with the Lister Institute's Elstree Lab closing in 1978 due to repeated annual deficits coupled with the need for major expenditure in order to modernise the production facilities. The Lister Institute was well-poised to possibly go on to develop heat-treatment or even a test for NANBH by as early as 1978 - if only the Government had made that loan or grant.

In "Blood Transfusion for Clinicians" (1977), Dr John Wallace writes about the advantages of cryoprecipitate over Factor VIII concentrates:

"The one great advantage which cryoprecipitate has over the other concentrates of factor VIII is that it can be prepared quickly. With an average daily intake of 500 donations it is possible to maintain a daily production of 100 single donations of cryoprecipitate, and the processing of donations to the finished product takes only 24 hours. On the contrary, the complete processing of large batches of fresh frozen plasma to provide intermediate concentrate of factor VIII may occupy two to three months from start to finish. The total yield of the respective products may be virtually the same over the long period of months, but limited amounts of cryoprecipitate may be produced literally overnight."

Note: Although this entry relates to 1977, the situation with regard to cryo production is pretty much the same in 1984 (see Related Entries link below).

As soon as even the slightest warnings over AIDS started to emerge, it is clear that between the DH and Transfusion Centres (RTCs), they could have mustered up sufficient cryoprecipitate to treat only the most serious of bleeds, and they could have done this much more quickly than we have ever been led to believe...

The tragedy that unfolded was compounded (even caused) by a terrible decision made by the Committee on Safety of Medicines in July 1983, where those present dismissed the possibility of withdrawing clotting factor concentrates from the market and replacing them with cryoprecipitate. The reason cited was that it was not feasible in the UK on grounds of supply.

"Biggs in her recent paper (B.Journ.Haemat. 1977,35,487) estimates the clinical demand for factor VIII at 50 million I.U. per annum in the UK of which at least half, and preferably all should be in the form of the concentrate." (Page 1, point 3.)

It is stated in the report, that this new type of hepatitis virus appears to be the most common form occurring after blood transfusion - in some areas. (Page 3, paragraph 4)

"...In view of these facts which, I am sure are well known to everyone, I am surprised that we are exercising our minds towards the improvement of a product which is destined for obsolescence..."

"Failure to do this is just delaying the inevitable. Probably, time and money would be better used in convincing the health departments to enlarge production facilities to obviate the use of foreign currency for purchase of commercial factor VIII."

The Institutes' list of achievements are unprecedented in the field of medical science.

"A final possibility is that, since the blood products would be emanating from the U.K. they would carry the cache of our good manufacturing practice. No product licence is required for the export of blood (unlike immunological products) but this subtle distinction between the holding of a manufacturers licence and the holding of a product licence would doubtless be missed by the purchaser overseas." (point C, line 3)

"It is my own view that assuming the company elect to go for the manufacture of blood products within the UK followed by export one should make it clear that inspection of the premises established in the UK would be very likely combined with inspection of the premises from which blood was obtained since these are part and parcel of the whole operation. This would certainly be so if product licenses were involved since blood as a raw material is caught under S.I. 1971 No. 1200." (page 2, lines 6-12)

"If this produces alarm and despondency in the hearts of Cutter Laboratories then it would appear that my suspicions are not unfounded and that the firm are trying to dodge tighter requirements in the interests of making a PROFIT disregarding safety." (page 2, from line 12)

Note: What on earth were Medicines Division doing even considering the exportation of blood products overseas when the UK hadn't got anywhere near enough for their own haemophiliacs? This is hard to comprehend in light of the DOH press release of April 1976 where they re-affirmed the aim of the UK to become self-sufficient in the supply of blood products by mid-1977. (see related entries link below)

It's a great shame the DHSS couldn't have concentrated on getting the UK self-sufficient before looking into the idea of exporting blood products.

"The Working Party has been informed of 3 cases of hepatitis in haemophiliacs who had previously received treatment with concentrates which included (amongst others) Armour "Factorate" Batch R8212."

"The non-A non-B agent has not yet been purified from the livers of infected individuals or animals, or from the stool."

"Most recently it has been reported that the non-A non-B agent has been transmitted to chimpanzees. There is a preliminary report that the non-A, non-B agent has been visualized by electron microscopy in the livers of chimpanzees. This, however, needs further documentation. While the chimpanzee is a clumsy experimental animal, this will provide new opportunities for characterization of the agent."

Note: It is disconcerting to read of such a lack of respect for research animals that would eventually give their lives to such experiments. Also, in such a context, it is worrying to see mention of the livers of "individuals" ploughed straight into in the same sentence as "animals" or "from the stool".

"He felt that, at present, chimpanzees were the only possible source of reliable antigens and antisera. These animals were, however, expensive, their supply was limited, and maintenance costs were high." (Page 2, Paragraph 5)

"[Deleted Name] pointed out that it remained uncertain whether non-A non-B hepatitis virus was present in the British population and asked whether blood products of British origin were causing non-A, non-B hepatitis." (Page 3, paragraph 3)

Note: On the last page, reference is made to how few infections British Blood was causing. This clearly shows why self-sufficiency should have been achieved. The bottom line is that we all know how research is the only way to progress with any Public Health safety issue, but if the will and money had been made available, we could have achieved the same information via British donations and reduced total infections by at least 80%.

Patrick Jenkin is appointed Secretary of State for Health and Social Services on 5 May.

Gerald Vaughan is appointed Minister for Health in 1979 at the DHSS.

Dr Aronstam strongly disagrees with the PHLS suggestion:

"We have not had any cases of hepatitis following N.H.S. Factor VIII. As far as your suggestion about transfusing mild haemophiliacs with this material is concerned, I totally disagree with this concept. I do not wish any of my mild haemophiliacs to develop hepatitis in any form and therefore adopt the policy of either using D.D.A.V.P. or Cryoprecipitate."

Note: It should be pointed out that the Lord Mayor Treloar College was in fact a boarding school for children. It is disturbing to read that the PHLS were trying to persuade the school to adopt some other type of Factor VIII material which would have caused the pupils to develop hepatitis.

What on earth was the PHLS doing contacting a school to 'promote' hazardous medicines?

Dr. Shanbrom describes the implementation of this process to be "as easy as washing your hands."

"Some patients who have received commercial factor VIII since 1.1.80 will already have contracted HTLV-3 infection from other infected batches."

Here's a quick summary of the main aspects of our concerns about Cryosan:

• Cryosan Ltd., a blood-broker, obtained blood from Russian cadavers [1]
• They re-labelled the blood as having originated from Swedish donors [1,12]
• Cryosan Ltd. repackaged out-of-date blood & exported it to Europe [13,16]
• They ran a 'vampire operation' in Bogata & sourced from Haitian slums [12,13]
• Cryosan Ltd. also shipped contaminated Arkansas prison blood [12,19,21]
• Cryosan pleaded guilty to false re-labelling and was fined in 1980 [1,13]
• Cryosan shipped huge quantities of plasma to Travenol in Belgium [14,15,17]
• Over 11 million i.u. of Travenol's Hemofil and Interhem Factor VIII were imported into the United Kingdom between 1980 and 1981 [18]

NOTE: Taintedblood would like to know the exact origin of the source-plasma for this factor VIII...

Numbered sources listed above are available from the following link: Cadaver Blood - Clotting Factors from the Dead

"There was a problem of non-A, non-B hepatitis related to freeze-dried factor VIII and IX, both of NHS and commercial types imported from Austria and the USA. ...[Deleted name] described a recent study at the Royal Free Hospital of 11 selected patients of whom 8 received commercial concentrate, 2 NHS concentrate, and 1 cryoprecipitate." (page 2, paragraph 4, lines 1-6)

"Experiments so far showed that there were probably 2 types of non-A, non-B hepatitis associated with factor VIII. The second type had been produced by the same batch of 'HEMOFIL' which was associated with the Bournemouth outbreak in 1974." (Page 3, point 4)

Note: These minutes also show that Factor IX was being made by Immuno Ltd. in Austria; which would therefore constitute a commercial import with regards to Factor IX. (Page 3, point 3.4)

Note: We would like to draw attention to the fact that the Immuno is listed here as manufacturing a Factor VIII product under the trade name Kryobulin. As we are aware that Immuno Ltd. was a commercial company, we can safely describe 'Kryobulin' as a commercial product. (See the additional source and the related entries link below).

The Under Secretary of State for Health, Sir George Young, responds: "The laboratory at Elstree was not designed to meet today's standards of pharmaceutical manufacturing".

"It is vital to recognise that these products carry an inherent risk for the recipient which is quite independent of any system of quality control of the manufacturing process. The acceptability of this risk is the basis of modern, life-support therapy, which enables doctors to treat previously fatal conditions."

In the case of the use of imported commercial blood products the source plasma was not given freely, but paid for, so physicians and the Blood Transfusion Service could not enjoy their usual exclusion from any liability. Also, consultants who were using the commercial Factor VIII concentrates were able to by-pass the public bodies set up to protect the patient.

Note: In trials involving infrequently treated patients, doctors could loose their protection under the rules of "Life-support therapy" if the majority of the patients included were not severe haemophiliacs.

Background: When a doctor treats a patient (without consultation) on the basis that they meet the criteria of research such as previously untreated patients "PUPs", we would suggest that they contradict, or even compromise their Hippocratic Oath by letting the research dictate clinical need.

"On the question of the use of foreign plasma members agreed that because of the risk of contamination, imported plasma from paid donors should not be processed in [the] same plant as UK plasma. However, if industry were to function at ECONOMICAL capacity there might be no alternative but to allow it to fractionate imported plasma from overseas unpaid donors such as that which might be provided by voluntary transfusion services."

"The two types of plasma and finished product would have to be kept separate at all stages and there might have to be separate quality control arrangements. It was thought that monitoring such an arrangement would not be easy." (page 3, paragraph 5)

Note: These comments make it abundantly clear exactly how much the DHSS knew about the risk of contamination from imported plasma from paid donors. They knew about the risks in 1980. In fact, we know that they were warned in January 1975 about the dangers of sourcing commercial blood from paid donors. Now we have it documented, complete with names of attendees, that they knew for sure in 1980 - so there should be no more denials and pathetic statements about 'no wrongful practices' and no more excuses about being caught unawares by the ensuing AIDS crisis.

Under the heading 'Technology' on page 2, we learn of further evidence of an early awareness of the possibility of genetic engineering: "The method of fractionation should be negotiable; (in 5-8 years' time, fractionation by genetic engineering could be the more effective technology.)"

Note: It never ceases to amaze us as to exactly how far back in time the awareness within industry and the DHSS of the process of genetic engineering of synthetic factor concentrates actually goes. We are now able to trace this knowledge right back to March 1980.

"The alternative will then be to import NHS requirements if such supplies are indeed available, and there are also grave doubts whether quality of overseas production will be acceptable. My experience of overseas plants generally leads me to believe that quality standards will be no better than those at BPL. Some of the Elstree staff told us that on recent visits to the USA they had visited fractionation plants in which the manufacturing conditions were worse than those at BPL." (pages 2, paragraph 1)

"The cleaning specifications which we agreed was the best that could be achieved in an unsatisfactory building. It is false and dangerous to imply that the revised cleaning programme has produced a safe system." (page 2, final paragraph)

The following was recorded in writing by Dr Walford in 1980: "I must emphasise that 90% of all post-transfusion (and blood-product infusion) hepatitis in the USA and elsewhere is caused by non-A, non-B hepatitis viruses which (unlike Hepatitis B) cannot, at present, be detected by testing donor blood."

NOTE: We would like to draw attention to the level of knowledge that the DHSS possessed in 1980. This is the knowledge they had then; the very same information that the haemophiliac community are only discovering now. However, this is not a question of government only having the ability to understand the situation with regard to fatalities from viral hepatitis after they had happened, this letter of 1980 demonstrates full comprehension by the DHSS of the gravamen of such infections from commercial imports. Therefore, we must ask why any preventative action wasn't taken by the DOH and why was it that a complete myth was somehow propagated that NANBH was "mild and often asymptomatic"?

• There is mould growing on a glycol line that serves one of the vessels.
• The cold freezer does not have any kind of temperature recording apparatus.
• There is water dripping from overhead metal panels and again mould growth is noticeable.
• There is plaster cracking in many parts of the building, resulting in bits of plaster breaking off.
• The autoclaves in the autoclave area have not been validated. The necessary commissioning using a multi channel recorder has not been done.
• In Room 13, paper is taped to improve the wooden benches where Factor 8 initial phase processing chromatographic work is carried out, and there are still openable windows present in what should be an aseptic area used for sterilising solutions.

Dr Peter Jones: "What should have been put in is something more in the region of £25 million..." (page 4, paragraph 2)

Reporter [with reference to hepatitis]: "Research has shown that haemophiliacs are TEN times more likely to contract the disease if they use commercial imports, rather than National Health Service material." (page 11, paragraph 6)

Reporter's Closing Comment: "The Department says there's no money available. That means hospitals will spend millions more on imports, patients will risk the consequences of skid row blood and Britain will become increasingly dependent on the world blood market." (page 16)

There have been two major lines of work toward this end: "One has drawn on recombinant DNA techniques to construct bacteria capable of producing "human proteins". The alternative has been to change the characteristics of animal, including human, cells to make them more amenable to large-scale cultivation in vitro.

"It is necessary to decide whether the principal plasma proteins could be generally available at a competitive cost and of proven safety in a time-scale which bears upon the development of BPL. If so it is important to decide whether the technology arising from genetic manipulation is one which BPL would logically become engaged in." (page 27, para 3)

"Given prompt action on the redevelopment of conventional fractionation facilities, the return on investment will have been achieved before genetically engineered products can have a major impact. Nevertheless failure to take account of them may lead to a crisis shortly after the new plant has commenced operation." (page 30, final para)

Note: From 1981, it took 13 years for recombinant clotting factors to be licensed for use within the UK (i.e. in 1994). We believe that this could have been done in far less time, like Hyland, who were running human clinical trials of their recombinant in 1987. We would also like to point out that it took Government until 2006 to fully 'roll-out' recombinant factor concentrate to all adult haemophiliacs across the UK.

From 1981, that's a grand total of 25 years of deferment.

Sir George Young's warning was reported the following month in the Sunday Telegraph (on 01.02.81) in an article entitled: "10 Sick After Factor 8 Doses". The article goes on to say:

"Imports worth an estimated £10 million of Factor 8, the missing factor in a haemophiliac's blood, come from America, Germany and Austria in powdered form to supplement the limited amount made in Britain."

Dr Charles Rizza: "There might be a greater degree of risk from commercial products."

"The National Institute for Biological Standards and Control, [NIBSC] which tests all foreign blood products imported by Britain, rejects a "small amount," believed to be about 5%, of the millions of bottles of Factor 8 brought in each year."

They were only children, aged between 9 and 14.

Note:
In the USA, blood collectors refuse to take blood donations from GI's until at least 2 years have elapsed since visiting the Far East and then only after blood tests have been completed.

Note: Other manufacturers are reluctant to adopt this technique over concerns regarding:

• 50-90% loss of yield,
• factor supply could be in jeopardy
• pasteurized factor will cost ten times more
• concerns over the effectiveness of inactivating non-A non-B hepatitis
• patients might develop inhibitors.

In February 1981, 10 children at the Treloar specialist school in Alton, Hampshire are infected with hepatitis from contaminated Factor VIII in what we believe to be a second outbreak of hepatitis B. There then follows a warning regarding infected Factor VIII supplies being imported from the USA.

The Department of Health admitted at the time that they knew there was a risk of infection and the then Health Minister, Dr Gerard Vaughan, claimed that the £1.29m being invested in the BPL Elstree would resolve the problem.

Note: We have to wonder if this second outbreak of hepatitis was as a direct consequence of an approach made by the Public Health Laboratory Service (PHLS) two years earlier on 14th May 1979? We can determine from documentation that there was the intention from the PHLS of transfusing mild haemophiliacs with a Factor VIII 'material' which would have caused mild haemophiliac children to go on to develop hepatitis.

In a reply letter of May 1979 to the PHLS from Dr A. Aronstam of the Lord Mayor Treloar Hospital, we read that Dr Aronstam totally disagreed with the PHLS' suggested concept and he adamantly stated that he did not wish any of his mild haemophiliacs to develop hepatitis in any form.

Note: We believe this article to be Conrad ME. Diseases transmissible by blood transfusion: viral hepatitis and other infectious disorders. Semin Hematol 1981; 18:12246.

Factor VIII: "It has been decided to make special arrangements for one unit only - the Lord Mayor Treloar Hospital in Wessex whose residential 'school' caters for 40 severe haemophiliac pupils drawn from all over the country. The Hospital will receive an allocation of 300,000 international units of Factor VIII per annum calculated on the basis that the Blood Products Laboratory (BPL) currently produces approximately 7,500 units per severe haemophiliac." (point 2.)

BPL aims initially to return to Regions 80% of the notional gross yield. This equates roughly with the present production levels. The remaining Factor VIII will be used to build up a necessary reserve stock and to meet the allocation for the Lord Mayor Treloar Hospital. (point 3.)

Factor IX: "Treasurers will wish to note that since we are currently self-sufficient in Factor IX and production is expected to keep pace with demand for the foreseeable future, it has been decided to exclude this product from the pro rata system." (point 5.)

Note: This is a useful document for several reasons. Here we have written proof that the Lord Mayor Treloar School was indeed catering for severe haemophiliac pupils, therefore confirming the age-range and we are also given a figure for how many - 40 haemophiliac pupils in 1981.

We are also interested to read that BPL will supply RTCs with certain blood products, such as Factor VIII, by proportional distribution to their input of plasma and that this system excludes Factor IX.

Mr. Race Oral Question, May 1983: "As the House of Commons' favourite own-goal merchant, the Minister for Consumer Affairs, was warned two years ago by his own Department of the danger of contaminated blood supplies coming from the United States, will the Prime Minister rectify that deplorable and disgraceful mistake by immediately authorizing the necessary expenditure within the National Health Service to make Britain independent in its blood supplies?" (see first column, para 9.)

The CDC warns doctors to be alert for "opportunistic infections associated with immunosuppression in homosexual men".

Based on this evidence and the high prevalence of hepatitis in the same population, the US Pharmaceuticals (allegedly) should have known by no later than the Summer of 1981 that urban homosexual males were not "suitable donors" within the meaning of federal regulations and/or other applicable standards of care.

"Table (2) compares the figures for B and non-B hepatitis in patients receiving only one product in any year for the years 1977-9 and was presented in last years report."

"It shows that there is a 4-20 times higher incidence of overt non-A, non-B hepatitis associated with U.S. Commercial concentrate compared with NHS." (see Page 1, under A: 'Incidence of Hepatitis due to commercial versus NHS associated hepatitis')

Manufacture of Products by Genetic Engineering

"At the last meeting of the PSG it was asked whether the redevelopment of BPL would be permitted to produce genetically engineered material in direct competition with Industry."

"As a general principle Ministers are not in favour of NHS facilities engaging in activities which Industry is competent to perform. This does not preclude involvement in product development but, with certain exceptions (eg products derived from human substances) manufacture of products which are or will be available commercially is difficult to justify."

The Government is slow to implement these plans.

Dr Gerard Vaughan: "I appreciate your Society's concern about the extent to which the NHS relies upon commercial blood products. As I told you, the upgrading programme being carried out at the Blood Products Laboratory at Elstree will, at present yields, enable the Laboratory to double its output of Factor VIII to 30 million international units by the end of 1982."

Dr Gerard Vaughan: "While this will not eliminate the need for commercial products, it represents a major step forward in NHS production of the vital material."

"The targets were not achieved and we are still not self-sufficient in blood products. I was told by a Minister of the present Government that they made the decision to be self-sufficient in 1982. Was Baroness Trumpington unaware that the House had already been told in 1975 that Britain would be self-sufficient? What happened? ...."

Oxford Haemophilia Centre Letter to All Haemophilia Directors:

"Infectivity of initial batches is tested by injecting the product into Chimpanzees. However, it is stated that it is unlikely that Manufacturers would be able to ensure this form of quality control in all future batches."

Note: The letter states that it is important to find out in studies of human beings the extent to which infectivity has been reduced.

Use of Previously Untreated Patients (PUPs) that have not previously used concentrates form large donor pools is suggested.

Controlled Studies on a "named patient-basis" is deemed to be undesirable.

Professor Bloom welcomed Dr. Aronstam to the meeting and said that he felt sure that the Reference Centre Directors would benefit from Dr. Aronstam's special experience of managing adolescent haemophilic boys.

"Dr. Kernoff said that he thought NIBSC were responsible for checking factor VIII preparation for assaying the material before it was released for use in hospitals throughout the U.K."

"He had therefore heen very surprised by the letter in the Lancet describing discrepancies between the 'labelled' potency and the 'found' proteins. NIBSC allowed 20%-leeway on the assay value of the material."

"He thought that NIBSC should have been the people to have known about the discrepancies and that it should not have been necessary for the discrepancies to have been brought to light by a Haemophilia Centre. There was some discussion about the functions of NIBSC."

"The use of animal models for infectivity study purposes was discussed. Chimpanzees would cost £10,000 per animal test per 6 months. If humans were used it would not be possible to have a "known positive" control. The methods of inactivation available were heat treatment; irradiation or absorption." (Page 5, paragraph 1, line 4)

"It was agreed that infectivity was the crucial question and the dilemma over the use of chimps (an endangered species), owl monkeys (information to be supplied by Dr Sommerville when available) and humans formed the basis of a long discussion." (Page 5, paragraph 2, line 7)

Note: It is disconcerting to read of infectivity study models involving human beings. We would have said that the crucial question should have been over the use of humans in infectivity studies. Did they carry this out, or was it just a discussion of what these doctors thought their options were?

"It is clear that chimpanzees can be used at a much younger age than was previously mentioned (2 yrs vs. 3 years). It is also rumoured that NIH costs (contracted to a colony in U.S.) are lower than those in Liberia." (Page 4, point b)

On page 5, under the heading "Procurement of Infective Material" we read that:

"Various people were contacted in the U.K., but none had much to offer. C. Rizza in conjunction with J. Craske are running a prospective trial of "first time" haemophiliacs receiving NHS and commercial concentrates." (Page 5, point 3.)

Note: We have to ask what the reference to "first time" haemophiliacs really means in practice? We would suggest that in order to meet the criteria for trials such as this, the haemophiliac subjects should not have been exposed to large pool concentrates - which would almost certainly mean that they were either a young child PUPs (Previously Untreated Patients), or moderate to mild haemophiliacs, who were again likely to be children, but might also have been adults.

Note:
Perhaps the question should be posed as to whether the medical profession knew that haemophiliacs already had antibodies to Hepatitis B? Yet, the profession's desire to amass research through trials on PUPs (Previously Untreated Patients) prevailed.

"Doubts have been raised now about the project, triggered by difficulties with the inactivation process necessary to render any such vaccine non-infective from free virus and by recent concern over the possibility of transmission of AIDS (Acquired Immune Deficiency Syndrome) via the human plasma from which the vaccine is derived."

We can date the source document for this information, since on page 4, under the paragraph with the heading: "Present Situation" we learn that the circular was written sometime in June 1982, and that Dr. Harris, then DCMO, was considering the importation of a US vaccine.

Note: The DHSS seemed more concerned with commercial interests - like whether to continue with the financial contribution they had been making towards the development of a plasma-derived Hepatitis B vaccine which they could exploit commercially - than the safety of products made from source-plasma obtained in questionable circumstances:

"...This is due to concern which has arisen about the possible transmission of AIDS in plasma-derived products, in circumstances where the blood donors likely to be the most productive sources of hepatitis B surface antigen happen often to be individuals at risk of developing AIDS."

"....plasma taken from homosexual drug-takers contains a sort of virus which goes undetected when the plasma is tested because it is suppressed by the drugs. However, when used for Factor VIII, it becomes active again."

The DHSS letter states that information has been received from the American Bureau of Biologics (via NIBSC) indicating there may be considerable publicity in the next couple of weeks concerning the safety of American Factor VIII.

From the following comment, it appears the DHSS are complacent at this stage:

"In any case with our voluntary unpaid donor system we do not have the same problems as in the States where drug addicts are tempted to give blood simply for the money. However, about half of the Factor VIII bought from commercial companies is imported from the USA."

Note: In terms of knowledge in the United Kingdom, this is one of the earlier dates (16 July 1982) which demonstrates that the DHSS had advance "private" knowledge of the safety risks from US commercial factor VIII almost 10 months earlier than we previously thought. This DHSS letter went out 1 year prior to the infamous July 1983 CSM meeting (reported in the Guardian by Sarah Hall on Friday May 25, 2007).

Unfortunately, the Factor VIII and IX products are already in production and/or already on the shelves in US pharmacies waiting to be infused by hemophiliacs who purchase them.
(CUTTER memorandum dated August 3, 1982)

A trial is to be conducted at Oxford involving Haemophilia A patients, whereby the vaccine is to be administered by subcutaneous route.

Note: The requirement of an autopsy is applied to ALL persons with haemophilia who have died. There is nothing in the minutes which indicates that the cause of death is taken into account.

Dr Craske is tasked with looking into reports of the syndrome in 3 haemophiliacs from the United States. HCDO minutes state that: "It appeared that there was a remote possibility that commercial blood products had been involved."

Note: Despite Dr. Edward Shanbrom patenting and proposing the process to US industry in 1980, solvent detergents are not widely taken up by the leading pharmaceutical companies until 1987.

"Since there are as yet no confirmed laboratory tests available for non-A, non-B hepatitis the only sure way of assessing the risk of transfusion hepatitis associated with new brands of concentrate where attempts have been made to inactivate hepatitis viruses by heat, ultra-violet light and propiolactone or other methods, is by use of chimpanzee inoculation experiments, or TRIALS of each product compared with an UNTREATED product in a group subjects where the susceptibility to hepatitis is known to be high. We have demonstrated such a group in the patients with mild coagulation defects already studied at Oxford. (Page 1, paragraph 4)

"Some children with cirrhosis have received concentrate for 6-7 years. (Page 2, under "Complications", 16 lines from the bottom of the page.)

Note: The worst thing we are seeing here is that it is seems to be acceptable to these physicians that CHILDREN should have cirrhosis. It should be noted that this is coming from the very people who said that they weren't aware or didn't think that hepatitis was a serious problem.

On reading the circular, we discover that highly purified genetically-engineered Factor VIIIc was already being produced by a team at the Royal Free Hospital and that Genentech owned the RF method. We also read that Speywood signed a collaboration agreement with Genentech in relation to genetic engineering of FVIII.

At the end of the circular, under 'STOP PRESS', we read an alarming statement by the DHSS that they thought there could be valuable spin-off from a story in The Times. The DHSS state that they thought it should prompt the CBLA into examining its proposed investment in light of current developments in genetic engineering:

The DHSS in 1982: "I feel that the sooner this exercise is done the better in order to reassure our financial colleagues and the Treasury - otherwise each new reported 'break-through' will have them rushing to cancel the cheques!"

Note: Rather disgracefully, it took another 12 years for recombinant clotting factors (made synthetically) to be licensed for use within the UK in 1994. Compare this with Hyland running human clinical trials of their recombinant Factor VIII as early as 1987, just over 4 years from the date of this DHSS circular.

From the point of being licensed, why did Government take another 12 years (right up to 2006) to make the safe product available to all adult haemophiliacs across the UK?

From 1982, that's a grand total of 24 years of delays.

In the same meeting, some suggestion is made that cryoprecipitate might be preferable to concentrates, but no actual recommendations are made.

"...patients and parents should be aware of the potential risks."

"Manufacturers entering the trial should undertake to make positive contributions of data and financial support in return for a properly conducted trial in a well-documented community of haemophiliacs."

"It is realised that overseas producers do not have access to trial facilities of equivalent quality and veracity elsewhere." (Page 2)

Note: Again, not enough emphasis on product safety, moreover, we see only cost concerns and world market trends being placed over and above patient safety. Clearly, trials were not being conducted in the product manufacturer's country of origin, for example, the United States, because they knew all too well that such trials would not have been permitted within their law.

At the same meeting, all four US plasma companies agree to postpone submitting any request to the FDA for permission to amend their warning labels or package inserts and they agree not to apply to the FDA until the other 3 companies have agreed to make their applications and to make the warnings similar in content.

His inadequate solution reads as follows: "The problem related to the investigation of factor VIII related Acquired Immune Deficiency Syndrome (AIDS) has been satisfactorily resolved. We will report any patient detected in the U.K. who has received U.K. commercial factor VIII direct to the C.D.C. and will at the same time notify C.D.S.C. at Colindale."

Background: On 13 September 1982, Dr Craske was tasked with looking into reports of the syndrome in 3 haemophiliacs from the United States. The HCDO minutes stated that: "It appeared that there was a remote possibility that commercial blood products had been involved." We hardly think that putting in place a simple detection and reporting protocol could be considered a satisfactory resolution to the problems surrounding AIDS and commercial factor VIII. We are appalled that more wasn't done.

Note: The reference on the letter from the PHLS of 10th January 1982, shows the letters "JC", which we believe are the initials for Dr John Craske.

• Lederman reports widespread immunity abnormalities, possibly linked to AIDS.
• Menitove states that AIDS has a 40 per cent mortality, and reports widespread cell abnormalities.
• Desforges recommends Cryoprecipitate rather than concentrate because of the risk of AIDS.

The American Association of Blood Banks, the Red Cross, and the Council of Community Blood Centres states that the use of surrogate tests is currently being evaluated in areas of the US where AIDS is most prevalent.

3 manufacturers: Armour, Cutter, and Hyland - state that they will introduce "active methods" of donor screening within the next two weeks.

BAXTER had already conducted a survey of several donor centers and determined that up to 16% of their donors would not pass the new test, additionally BAXTE'S high titered immunoglobulin donors would be eliminated.

In order to defer the NHF recommendation, Rodell tells officials that testing is currently in the "Research and Development,� stage", however, the HBc Antibody test was not in the R and D stage and it had been approved by the FDA in 1979 and was suitable for use as a screening device.
(CUTTER Memorandum dated January 17, 1983.)

"The issue of manufacturing licences for the Blood Transfusion Centres in Scotland when similar licences were not issued in England and Wales resulted, as you know, from differing legal advice in each case. Scottish law officers held that Crown Privilege did not apply and that licences were required; legal advice for England and Wales held that Crown Privilege did apply and that licences were not necessary. Licences were therefore issued for BTS Centres in Scotland but not for BTS Centres in England and Wales.

We were advised in 1979 (Mr Sutherland wrote to Mr Firstbrook) that the Scottish law officers had reviewed their original opinion and decided that Crown Privilege did apply to the CSA and Health Boards in Scotland, and that formal licensing of the Blood Transfusion Service in Scotland was no longer required. In other words from that time the BTS in Scotland was on the same footing vis-a-vis the Medicines Act as the BTS in England and Wales."

Note: The differences of opinion do seem to eventually settle on the view that Crown Immunity did apply to Scotland.

Note: At this time, there is overwhelming scientific evidence supporting the conclusion that AIDS is transmitted by blood products such as factor concentrates.

The use of pre-March 83 stocks are not banned owing to concerns that this would lead to a crisis in supply.

• failure to provide adequate details on the manufacturing process
• failure to provide adequate evidence of the product's efficacy
• failure to provide evidence that the cryoprecipitate was at least equivalent in quality to that used for the manufacture of Alpha's factor VIII
• there should be an undertaking offered that a donor list will be available to the manufacturer.

The 4 US fractionators (blood companies) are engaged in meetings with the FDA with a common goal of averting a complete recall, the only responsible option available to them.

"The object of the study will be explained to them, and their consent or that of their parents obtained, if under 16 years of age."

"You will see that the class of patients to be given these products are those who have had no previous treatment with factor VIII concentrate."

"It is likely that there are only a limited number of these patients in the U.K. who will require factor VIII therapy in any one year. We will be grateful if you notify Dr. J. Craske of any approaches from commercial firms with a proposal to evaluate their product."

Note: This is really damning evidence. It is monstrous that the PHLS are still actively looking for both Previously Untreated Patients (PUPs) and inviting approaches from commercial firms as late as March 1983 in order to expose previously untreated patients to hepatitis for the sake of their trials, especially whilst Dr Craske categorically had knowledge of AIDS from 13th September 1982; at which point, he was tasked with looking into reports of the syndrome in 3 haemophiliacs from the United States where there was the 'remote' possibility that commercial blood products had been involved.

The following is stated: "Attached are letters recently released by FDA, on or about the 17th March 1983. You will see that the US are taking steps to avoid the use of blood from high risk groups in the preparation of certain blood products."

It is reported by all Directors present that sessions were held in penal institutions in all regions.

"These observations are consistent with the hypothesis that AIDS is caused by a transmissible agent, presumably a virus, that can be included in blood products, and that some recipients of the agent have not (at least not yet) developed the complete clinical syndrome with its devastating complications."

"These alternative hypotheses might be distinguished through a study of T-lymphocyte subpopulations among similarly treated haemophiliacs in a geographical area to which AIDS has not yet been introduced. The resolution of this question by a timely investigation in some country, where cases of AIDS have not yet been reported would be an immense help to public health workers worldwide. In this situation "negative results" would be of great significance."

NOTE: Please click the 'Find Related Entries' link below to see how this Timeline entry relates to the one for 10th October 1983 regarding the Medical Research Council. It appears that Dr Gordon's letter somehow managed to engender a controlled AIDS study of UK Haemophiliacs; the Edinburgh Haemophiliac Cohort; a study which we believe to have been entirely unethical. TaintedBlood has members who have testified at the Archer Inquiry where they expressed belief that their infections where acquired as a result of this study. (see 2nd link below)

Note: This work should have been completed by approximately 1978, so it stands to reason that this construction at BPL is rather later.

From as early as 1973, Government knew that production of Factor VIII in the UK was insufficient. The aim to become self-sufficient in blood products was already in place, and by 1976 they had re-affirmed their aim to become self-sufficient by mid-1977. There had also been the World Health Organisation (WHO) resolution stating that each country should be able to supply sufficient quantities of its own blood and blood products to meet clinical needs.

Note: There was substantial evidence to justify a change in therapy and a complete recall of unscreened Factor VIII by May 1983.

Mr. Race: "As the House of Commons' favourite own-goal merchant, the Minister for Consumer Affairs, was warned two years ago by his own Department of the danger of contaminated blood supplies coming from the United States, will the Prime Minister rectify that deplorable and disgraceful mistake by immediately authorizing the necessary expenditure within the National Health Service to make Britain independent in its blood supplies?" (see first column, para 9.)

Note: This Oral Question reveals that Dr Gerard Vaughan, then Minister for Health, knew sometime in 1981, possibly from as early as May, of the threat of contaminated blood supplies which were being imported from the United States. This is one of the earliest warnings that we are aware of so far and we are astonished to learn of how early this awareness was, and that so little was done. Clearly, we are not being told everything.

We would like to comment in turn on the following statements made by Professor Bloom:

Bloom: "Haemophiliacs, their parents and doctors have always balanced the quality of life and the dangers from bleeding against the risks of treatment."

Note: TRUE regarding the balancing act. But we would have to state that we were not always informed of the risks, in fact, hardly ever, if at all. We know that trials of 'Hepatitis Reduced' Factor VIII were still being planned as late as 22nd March 1983 (after the UKHCDO suspected the link between AIDS and Factor VIII) and that the PHLS were still actively looking for Previously Untreated Patients (PUPs) and courting approaches from commercial firms in order to expose previously untreated patients to hepatitis for the sake of trials.

Bloom: "The cause of AIDS is quite unknown and it has not been proven to result from transmission of a specific infective agent in blood products."

Note: We must take exception with this based upon documented evidence regarding exactly what Professor Bloom knew or strongly suspected at that time. Professor Bloom was Chairman of the UKHCDO at the 13th September 1982 meeting; which was 8 months earlier. It is minuted on page 10, paragraph 3, that Dr Craske was tasked with looking into reports of the syndrome in 3 haemophiliacs from the USA and that it appeared that there was a remote possibility that commercial blood products had been involved.

Bloom: "In addition the importation of licensed blood products has always been strictly monitored and controlled."

Note: We find this shocking statement to be both inaccurate and misleading. We know from the 11 January 1982 Oxford Letter that Professor Bloom had an excellent understanding of the 'named patient' basis and had discussed plans to request exemption from a Clinical Trials Certificate in respect of individual products in order to expedite trials.

This man had been infused with American Factor VIII.

"... I have reviewed the literature and come to the conclusion that all blood products made from blood donated in the USA after 1978 should be withdrawn from use until the risk of AIDS transmission by these products has been clarified. Appended is a paper in which I set out my reasons for making this proposal. Perhaps the subject could be discussed at an early meeting with haematologists, virologists and others concerned so that a decision may be made as soon as possible."

"In conclusion, I say that I am most surprised that the USA manufacturers of the implicated blood products have not informed their customers of this new hazard. I assume no critical warning has been received in the United Kingdom?"

Note: Why did the DHSS not agree with PHLS (CDSC)? After all, the PHLS were the people who should have had the last word.

IMPORT OF BLOOD PRODUCTS

"Imports of blood products into the United Kingdom for medicinal purposes have to be licensed under the Medicines Act 1958. Licensed products must satisfy the requirements of the Act for safety quality and efficacy."

"It is made a condition of product licences in this field that the licence holder exercises proper quality control, which involves accounting for the source and quality of the blood, its processing and final product examination. On all blood products the licensing authority imposes a "batch release" condition under which samples must be supplied for testing by the National Institute for Biological Standards and Control [NIBSC]."

"Although all medicinal products require a product licence if they are to be promoted for medicinal use, a doctor may prescribe an unlicensed product provided this is on what is known as a "named patient" basis."

Nevertheless, the DHSS appear to take little notice:

"In my view this suggestion is premature in relation to the evidence and unbalanced in that it does not take into account the risks to haemophiliacs of withdrawing a major source of their FVIII supplies".

Note: Where were the DHSS obtaining their medical advice? The HCDO had already had 9 months to consider the problem of imported Factor VIII as Dr Craske had been specifically tasked by the HCDO with looking into reports of AIDS in 3 haemophiliacs from the United States - this was in September 1982. Dr Craske, at that time, had suspected a link to commercial Factor VIII and this was minuted.

"It was agreed that there was insufficient information available from the U.S. experience to warrant changing the type of concentrate used in any particular patient. Moreover once the condition is fully developed it seems to be irreversible so that there would seem to be no clinical benefit to be gained by changing to another type of factor VIII." (page 2, paragraph 2)

"With regard to general policy to be followed in the use of factor VIII concentrates, it was noted that many directors have up until now reserved a supply of National Health Service concentrates for children and mildly affected haemophiliacs and it was considered that it would be circumspect to continue with that policy. It was also agreed that there was, as yet, insufficient evidence to warrant restriction of the use of imported concentrate in other patients in view of the immense benefits of therapy." (page 2, paragraph 3)

Prior to this meeting, physicians should reasonably have known the following:

• As early as 13th September 1982, Dr J. Craske was tasked with looking into reports of the syndrome in 3 haemophiliacs from the United States, and he suspected a remote possibility that commercial blood products were involved.
• On 15th January 1983, there had been an article in the Lancet by Dr Jones (a member of the UKHCDO) where AIDS had been linked to common cell immunity in haemophiliacs.
• By March 1983, the Directors of Haemophilia Centres were requested to report any cases of AIDS in haemophilia patients to the Oxford centre, to then be relayed to the Communicable Disease Surveillance Centre.
• On 23rd March 1983, in the USA, FDA regulations for the collection of plasma excluding donors from high-risk groups were introduced. However, use of pre-March 1983 stock was unfortunately NOT banned due to supply concerns.
• On 6th May 1983, the UK's CDSC telephoned the DHSS to inform them that a 23 year old haemophiliac patient from Cardiff was now showing symptoms of an AIDS diagnosis after having been infused with US Factor VIII.
• On 9th May 1983, the CDSC had written a crucial letter recommending that American FVIII should be withdrawn from use due to the risk of transmitting AIDS.

The only exception the Directors made was to continue with their policy of only using NHS material for children under the age of 4 and for mild haemophiliacs.

Background: Why didn't the Directors of Haemophilia Centres try and do more to ban imported Factor VIII concentrate? They appear to have ignored the following warnings:

• Dr Craske had been tasked by the HCDO with looking into reports of the syndrome in 3 haemophiliacs from the United States a whole 9 months before (in September 1982) and he suspected a link to commercial Factor VIII.
• 5 months earlier, (January 1983) there had been an article in the Lancet by Dr Jones (also HCDO), where AIDS was linked to common cell immunity in haemophiliacs.
• The FDA requirements on blood donations had already been introduced on 23rd March 1983 - this was 2 months before this decision.
• On 6th May, (1 week earlier) the CDSC telephoned the DHSS to inform them that a 23 year old haemophiliac patient in Cardiff was now showing symptoms of an AIDS diagnosis after having been infused with US Factor VIII.
• On 9th May 1983, (4 days earlier), the CDSC had written a letter recommending that American FVIII should be withdrawn from use due to the risk of transmitting AIDS. The DHSS definitely had sight of this CDSC letter by 13th May 1983.

In a DHSS Circular of 16 May 1983, we read about the fears of UK haemophilia centre directors that contaminated US Factor VIII might be 'dumped' in the United Kingdom following the 24th March 1983 FDA requirements in respect of the selection of donors with the overall aim of reducing the possibility of transmission of AIDS.

"Products manufactured from plasma taken before the new regulations were introduced have to be labelled to indicate this." "However, the UK product licenses do not contain this requirement and there are fears among haemophilia centre directors that the more "dangerous" material may be dumped in the UK."

This DHSS circular goes some way toward posing questions that, if acted upon, could have helped the situation:

• Is it possible to obtain concentrates made from American plasma which does not come from donor centres in New York (particularly) but also from San Francisco and Los Angeles....?
• Is it possible to accept only concentrates made from plasma taken after the 24th March regulations?
• Can we find out, for each manufacturer, the date of plasma collection in relation to each batch of concentrate in current use in the UK?
• Could Immuno - or other European manufacturers - produce sufficient material derived from European plasma to supply up to 30 million i.u. of FVIII concentrate should it prove necessary to withdraw some or all of the American products?

Note: Clearly this goes somewhere toward showing willing and raising questions over what action to take. So what went wrong and why were these suggestions not followed up?

• To take all necessary steps and measures in respect of AIDS.
• To avoid the use of coagulation factor products from large plasma pools, except when such a product is specifically indicated for medical reasons; this is especially important for those countries where self-sufficiency in the production of such products has not been achieved.
• To inform attending physicians and selected recipients, such as haemophiliacs, of the potential health hazards of haemotherapy and the possibility of minimising these risks.
• To provide all donors with information on AIDS, so that those in high risk groups will refrain from donating.
• To pursue rapid and full implementation of recommendations of R(80)5 and R(81)14.