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Chapter 19

Production of Blood Products - Facilities


19.1 This chapter deals with the provision of facilities for the production of blood components and blood products, and in particular with the assumptions made as to process capacity in the development of plans for capital projects in the 1970s.


19.2 As noted in Chapter 17, Blood and Blood Products Management, large-scale production of blood products in Scotland started with government-led initiatives in the 1940s leading to the establishment of facilities, first, for the preparation and storage of plasma to secure supplies to hospitals and the military, and then for the preparation of freeze-dried human plasma. The most significant developments were:

  • The establishment of blood banks in the principal centres of population.
  • The setting up of regional centres in Dundee, Edinburgh, Glasgow, Aberdeen and Inverness.
  • The organisation of plasma filtration units in Edinburgh and Glasgow to process raw material collected locally and from other regions of Scotland.
  • The installation of a Blood Products Unit (BPU) for the production of dried plasma in Edinburgh at the beginning of 1943, to meet all Scottish needs.
  • The provision of a 'saline infusion fluids centre' for the preparation of saline glucose and other solutions used for intravenous injection at Glasgow, later relocated to Law Hospital, Carluke.

19.3 The wartime facilities at the Royal Infirmary of Edinburgh (RIE) rapidly became overcrowded and unsuitable, and the centre was developed and expanded throughout the late 1940s and early 1950s, with new premises located at the RIE being opened in 1950. The BPU there began to produce a range of fractionated plasma products, beginning in 1952 with immunoglobulin and an early version of Factor VIII (Cohn Fraction I).[1] Despite a major reconstruction and extension of the centre in 1961 the facilities soon proved to be insufficient for the expanding operation. By early 1965, planning for a new centre (to become the new Protein Fractionation Centre (PFC) at Liberton, Edinburgh) was under discussion at government level.

19.4 By the beginning of the reference period, the scope of the operations planned for the new PFC had changed considerably from anything that could have been envisaged in 1941, largely in response to changing demand for blood products. Cryoprecipitate had become a mainstay of haemophilia therapy, and factor concentrates were beginning to have an impact on the market. Two facilities were established in England, the Blood Products Laboratory, Elstree, (BPL) and the Plasma Fractionation Laboratory, Oxford (PFL). Planning for the Scottish facility proved to be a tortuous process, most aspects of which are of little relevance to the Inquiry. There are, however, a few matters that were important when planning was completed and the construction and commissioning of the plant began.

19.5 Two of those matters were the planned territorial scope of the PFC's operations, and the production volume targets for which the facility was to be designed. From the beginning there appears to have been uncertainty about both. It appears that from the outset the premises at the PFC, as designed, were more than large enough to accommodate a production plant sufficient to service local Scottish demand well into the 1980s. How that came about is less than completely clear. But it was to have a major impact on the ability of Scotland to meet demand for factor concentrates in this country as compared with the capacity of the BPL and the PFL to service demand in England and Wales.

19.6 By February 1965 planning for a new centre was being discussed at meetings between the Scottish Home and Health Department (SHHD) and the Blood Transfusion Services of England and Wales and of Scotland.[2] It was initially estimated that the new facility required in Scotland to manufacture plasma products should be capable of processing up to 1000 litres of plasma per week, including plasma from England.[3] It appears that demand from Northern Ireland was to be serviced from Scotland.[4] Processing of plasma from England reflected a decision that would have required continuing cooperation between the Blood Transfusion Service in England and Wales on the one hand and in Scotland on the other, while managed by separate administrative agencies and subject to policy direction by separate government departments. On a practical level, it implied that a manufacturing capacity of 1000 litres of plasma per week was specified so that it would be sufficient to service demand in Scotland, Northern Ireland and in a northern part of England that still had to be defined.

19.7 The projected capacity of the Scottish facility was amended in discussion. In May 1968, at a meeting at the RIE between SHHD, the Department of Health and Social Security (DHSS) and the Blood Transfusion Services of England and Wales and of Scotland it was anticipated that the PFC would be commissioned in June 1972 with an initial capacity of 1500 litres of plasma per week but capable of being increased to 3000 litres per week.[5] It was agreed that the PFC should be prepared to cope with the requirements of a larger part of England than originally intended. It was agreed that requirements for labile coagulation products (concentrates) needed to be revised.

19.8 At a meeting in November 1968, at the BPL, between the SHHD and the Blood Transfusion Services, it was noted that approval in principle had been given for the new PFC.[6] It was also noted that commissioning of the new BPL extension was expected to be completed by mid-1971. It was anticipated that commissioning of the PFC would be completed early in 1973. It was hoped to start building the extension at the BPL in September 1969 with commissioning expected early in 1972. Procurement of the new centre was eventually approved in November 1969. Meantime, a new pilot plant for fractionation was established at the BPU at the RIE in 1968.[7]

19.9 At a meeting on 14 March 1969, attended by representatives of the SHHD, the BPL, and the Scottish National Blood Transfusion Service (SNBTS), the need for standing arrangements for coordinating policy matters at departmental level was discussed, and a committee structure was proposed.[8] It was agreed that the SHHD should contact the DHSS with proposals to form a coordinating committee. The Medical Research Council (MRC) had a reference laboratory at Elstree, and might be involved in any new standing arrangements. Cooperation on professional and technical matters was expected to continue throughout the service, but within a formal relationship with the proposed coordinating committee. At this stage, it was agreed that the BPL should process two thirds of the plasma collected from England and Wales with the remainder being processed in Scotland.

19.10 On 27 June 1969, a meeting took place at the BPL between the SHHD and the Blood Transfusion Services of England and Wales and of Scotland.[9] The discussion was largely confined to technology. Total production targets were not resolved. On the basis of the information available, it would be difficult to form the view that the planning of production was firmly established, on a UK or on a Scottish basis at this stage.

19.11 In April 1970 the BPU was renamed the Scottish Protein Fractionation Centre (PFC). Mr John Watt was appointed Director of the BPU in 1967, and became the first Scientific Director of the new purpose-built facility in 1971 when building operations commenced.[10] In 1974 the PFC relocated to Liberton in Edinburgh.

Demand for blood products for coagulation disorder patients

19.12 There was considerable, and growing, uncertainty about levels of demand for haemophilia therapy in the UK as a whole. At 5 April 1971, it was recognised that the total ideal requirement of material for treating patients with coagulation defects was not known.[11] In 1969, the material used for treatment of 1032 haemophilia and Christmas disease patients at the 30 centres from whom records were received by the UK Haemophilia Centre Directors' Organisation (UKHCDO) then located in Oxford, was derived from 84,906 donor units, an average of just over 82 donor units per patient. The products used were:[12]

Amounts used
Material No of Donor Units % total
Plasma 11,435 13.46
Cryoprecipitate 59,715 70.34
Concentrates 13,756 16.20
TOTAL 84,906 100.00

19.13 This was said certainly to provide an underestimate of requirements. By way of example, it was observed that there was a waiting list of haemophilia patients requiring non-urgent surgery at Oxford and that it would require material from 10,000 donors to carry out the operations.[13] And the introduction of home treatment was expected to increase the amount of material used. It was noted that a record of total use year by year would give an estimate which would level off to ideal requirements. The annual figure could form a basis for an estimate of the amount of concentrate that might be required.

19.14 Dr Rosemary Biggs and colleagues reported numbers for 1969-71 in a report prepared for the MRC.[14] Over that period 1608 different patients attended haemophilia centres. On their calculations, taking account of other sources of information, the minimum total number treated was estimated at 2434. That was rounded up to 3000, as an estimate of the number of haemophilia patients in the UK, a rate of about five to six per 100,000 of the population, which was reasonably in line with other estimates. The report estimated the demand for Factor VIII concentrate at 35,779,800 to 50,000,000 international units for on-demand therapy.[15] Making allowance for major surgery and dental extractions, the total material required was likely to lie between 38,327,800 and 53,000,000 units of Factor VIII, requiring 547,540 to 750,000 blood donations per year. Home treatment would be in substitution for hospital treatment, and would not generate additional demand. Prophylactic treatment was thought to be impractical at that stage.

19.15 Mr Watt, the Scientific Director of the PFC, proceeded on a different basis when calculating need at June 1973.[16] He calculated the need for Plasma Protein Solution (PPS - a product of the final stage of Cohn fractionation, Fraction V), and concluded that the volume of plasma required for the preparation of antihaemophiliac globulin (AHG), at Cohn stage I, would be readily achieved if his PPS target was met. He assumed that the population of the UK was 60 million, and the population of Scotland 5 million. The number of haemophilia patients in the UK was assumed to be 3000 (5/100,000). He calculated that the Scottish need for fresh frozen plasma for processing to meet the needs of the haemophilia population was 15,000 donations per million of population (45,000 donations) to provide 4.8 million plasma units per million population, or 20,000 plasma units per haemophilia patient per year. Extrapolated first to England and then to the UK as a whole (on the basis that there should be little difference in community need and that therefore the Scottish figures of need could be applied), he concluded that English need for AHG would be 48,000,000 plasma units, and total UK need would be 53,000,000 plasma units.

19.16 In Mr Watt's view, the English facilities could not achieve the necessary level of production and the PFC would require to process material for England. He argued that development of the site at Liberton would be the most economic and rapid means of achieving adequate fractionation capacity for the UK. He said:

B.P.L. and P.F.C. are each specified for 70,000 - 80,000 litres of plasma per year. It is my opinion that B.P.L. production could be increased to about 150,000 litres but further increase would appear impossible on the present site and could hardly be justified. The difference of more than 250,000 litres includes 35,000 to 40,000 which the P.F.C. must process for Scotland.

19.17 He noted that there was a risk of a dual standard of clinical availability as between Scotland and England, an intolerable situation which, he thought, could not be maintained.

19.18 At this stage, in the early 1970s, as Dr Biggs' report indicates, the Haemophilia Centre Directors recognised that the pattern of demand was changing, and that data for actual demand would be required to form a view of ideal requirements. In the event, data returned for 1970 and 1971 saw the volumes used increase, in terms of blood donations used, to 105,531, and then to 132,743 donations. In 1971, 1100 patients were treated at the 35 centres which reported, at a rate of 120.7 donations per patient per year, not including donations used in elective surgery or dental procedures. The comparative figure for 1969 was 84.9 donations per patient per year.[17] As indicated later, by early 1973 it was recognised generally that considerably more concentrate was required than the output of the UK facilities if the needs of haemophilia clinicians were to be met.

19.19 These changes in perception of the likely levels of demand were taking place as construction of production facilities was at an advanced stage of planning or had already begun in England and Scotland. In November 1969, there was a meeting at the RIE between the SHHD and the Blood Transfusion Services of England and Scotland.[18] It was reported that it would be about one year before contractors could move onto the site of the new Scottish fractionation centre, and it was estimated that commissioning would be completed in the latter half of 1974. Tenders for the work had been received by July 1971. Building of the new extension at the BPL had begun in November 1969 and was expected to be completed in September 1971.[19] Having gone to tender, and on to concluded contract, flexibility to respond to changing demands was necessarily limited, in the short term at least.

19.20 In this period of change, those planning developments appear to have depended on the Haemophilia Centre Directors for information about demand for Factor VIII and IX (cryoprecipitate or concentrates). The 1969 data referred to above were not available until 1973, still less the 1970 and 1971 figures. None of these data provided a reliable basis for forecasting growth, and they could not have provided a rational basis for projecting UK demand based on donor units. Furthermore, planning for the size and capacity of the new UK fractionation facilities coming on stream in the early 1970s had been carried out at a time when there had been no clear idea whatever of possible future demand for Factor VIII and Factor IX products.

19.21 Later analysis of data would have further undermined the reliability of the 1969 figures as a basis for projecting demand. Between 1969 and 1973, new demands were placed on suppliers by clarification of the numbers of patients needing treatment, and developments in the forms of treatment, such as home treatment of coagulation disorder patients and, to a lesser extent, prophylactic treatment, increasing the difficulties inherent in projecting demand. Further research was required. But the facilities already planned proceeded and were duly commissioned against a background of insufficient production to meet UK requirements as a whole.

Changing demand and the development process

19.22 In July 1971, there was a further meeting at the RIE between the SHHD and the Blood Transfusion Services of England and Scotland.[20] It was agreed that discussions on central processing of Factor VIII and Factor IX concentrates were imperative because of major effects on production planning. Work began at Edinburgh with a planned commissioning date for the new PFC in January 1974,[21] which coincided, in the event, with the start of the reference period for this Inquiry.

19.23 However, the wider context for these discussions changed early in 1973. The first UK licences for the US commercially produced Factor VIII concentrates Hemofil and Kryobulin were granted on 19 February and 22 March 1973 respectively.[22] On 6 March 1973, the Chief Medical Officer (CMO) for England and Wales wrote to all Senior Administrative Medical Officers.[23] He said:

The production of the human concentrate in the UK is at present insufficient to meet the stated needs of clinicians who care for patients requiring surgical, including dental, treatment or who have episodes of severe bleeding. The indications are that considerably more of this preparation would be used if it were available.

19.24 The DHSS assembled a group of experts to advise generally on the likely trends in treatment of haemophilia and, more specifically, to make proposals on which realistic planning for the future could be based. The group met on 20 March 1973.[24] It was recognised that the scale of the problem had been underestimated and that UK production was less than required to meet anticipated demand.

19.25 An updated version of Dr Biggs' report was available, still based on data for the period 1969-71.[25] On broadly the same assumptions as before, Dr Biggs estimated total demand for all types of therapy, excluding prophylaxis, at between 400,000 and 750,000 donor units per year. It was agreed that 400,000 donations would be required to treat UK sufferers, and more if strenuous efforts were made to clear surgical waiting lists and if home treatment or, eventually, prophylactic treatment were to become acceptable forms of therapy. Those planning for demand now had information from the haemophilia directors of their expectations for future demand. But it was recognised that a broader membership was required, including Regional Haemophilia Director, and Transfusion Director, representatives, the National Medical Director of the SNBTA and Mr Watt of 'the Edinburgh BPL'.[26]

19.26 The expert group's views on the development of domestic facilities at March 1973 were:

It is essential the production and distribution of the therapeutic agents concerned should be considered as a U.K. exercise.


Close co-operation between England (including Wales and N. Ireland) and Scotland will be required in order to co-ordinate and optimise blood collection and transport, the fractionation processes, distribution of the therapeutic agents, and utilisation of other blood fraction by-products.[27]

19.27 Recommendations of the group included that the UK should aim to become self-sufficient as soon as possible by increasing home production of freeze-dried concentrate. It would have been anticipated at the time that production would take place at the new PFC facility in Liberton in Scotland, still to be commissioned, and at the BPL and at the PFL in England.

19.28 On 27 March 1973, there was a meeting at the BPL between the SHHD and the Blood Transfusion Services of England and Scotland.[28] The BPL facility was by that stage taking in plasma at its planned capacity of 1500 litres per week.[29] Good progress was reported in the construction of the Edinburgh fractionation centre, with commissioning expected to start in April 1974. The work was in fact completed at the end of 1974.[30] The total cost was expected to be just over £1 million. But there was still a degree of uncertainty about the scope of the plant's operations. There was concern that planning for annual requirements was inadequate. The processing of time-expired plasma had been provided for. But the Scottish facility did not have the capacity to process English fresh plasma. That was still to be considered for the UK as a whole. At this stage, when the use of coagulation factors was increasingly seen as of central importance in the treatment of haemophilia patients, the final planning of processing of raw material and production was still incomplete.

19.29 The policy context for development took a change of direction when, on 20 June 1973, the first meeting of a Joint Steering Committee on Blood Products Production was held, bringing together DHSS and SHHD officials, representatives of the production facilities and Regional Transfusion Directors.[31] The policy implications of the entry of commercial producers into the market were acknowledged:

The first meeting of the Steering Committee had been precipitated by the fact that product licences had been granted to two firms to import antihaemophilic globulin concentrate which might entail large sums being spent by NHS authorities on these products.[32]

19.30 Full-scale production had been achieved at the BPL. Mr Watt provided information on the programme and timetable for commissioning the PFC. Production targets were explained, as were limitations on plasma supplies. The PFC's capacity could be expanded, but it was urgent for the facility to know what volume of plasma it would be asked to process for England. The views that emerged included: (a) adopting the lower of Dr Biggs' estimates of demand for plasma at 400,000 donations as a first target, with her upper estimate of 700,000 donations as the ultimate target; (b) an initial aim of processing 250,000 donations by 1975; (c) preparation of 90% of total output as intermediate potency concentrate, and 10% as high potency product; and (d) self-sufficiency for the UK by 1975. DHSS indicated that a system of call- off contracts for imported material was under consideration. Other developments were set out as possibilities.[33] It was noted that Scotland had apparently nearly reached and might exceed its proportion of the target for donations for the treatment of haemophilia suggested by Dr Biggs.

19.31 In an undated report prepared for the MRC's Transfusion Research Committee, and made available for a meeting of Haemophilia Centre Directors on 31 January 1974, Dr Biggs and her colleagues set out a comprehensive review of the position based on studies of the period 1969-72.[34] The report again included an attempt to estimate the total amount of therapeutic materials containing Factor VIII activity that was likely to be needed in the UK together with the amount of fresh whole blood required for processing to meet that target.[35]

19.32 Making allowance for haemophilia patients attending general hospitals, and extrapolating from accurate data for the Oxford Haemophilia Centre, the report estimated that, while they had information on 1100 patients attending 35 haemophilia centres in 1971, the number of haemophilia patients treated in 1971 in the UK as a whole was between 2434 and 3000.[36] Using data for donations used for cryoprecipitate and freeze-dried concentrate production and taking account of yield, the report concluded that for all types of bleeding (spontaneous, during surgery and for dentistry) the total demand required was between 547,540 and 750,000 blood donations per year. Home treatment would require 250,000 donations, as an alternative, but not cumulative, form of therapy. Prophylaxis would add further demand, but that approach to therapy was not recommended. At the time, 1.7 million blood donations were collected annually by the Blood Transfusion Services for all uses, including transfusion in surgery and medical procedures.

19.33 Subsequently, Dr Biggs published information relating to the period 1969-74,[37] and the Haemophilia Centre Directors supplemented that for 1975.[38] In her publication covering 1969-74, Dr Biggs summarised the effect of earlier data:

[I]t was concluded that: 'An assessment of the total amount of factor VIII likely to be required for all types of treatment puts the total in excess of 500,000 blood donations annually or about 40 million factor VIII units'.[39]

19.34 It was still not known how many blood coagulation disorder patients were treated at hospitals not designated as haemophilia centres, but it was thought that the previous estimate of total demand was unlikely to be excessive. The balance had shifted towards concentrate use, however, and it was now thought that 60% of Factor VIII should be freeze-dried[40] in order that home therapy could be instituted on a reasonable scale.[41]

19.35 The estimate was at the lower level in the MRC report. This series of reports by Dr Biggs and her colleagues reflects a more or less consistent application of a methodology developed by her team at Oxford. Individually, and in total, the reports show a movement towards a data-based assessment of demand that was not available previously to those planning the BPL and the PFC. As noted above, Mr Watt had a different view of total demand: he thought that demand could be higher. But the differences were not great in the overall scheme of things at this time.

19.36 The comparison with the 1969 assessment is stark: by 1974, estimated use was over four times the use reported for 1969. Later papers showed dramatic growth in demand, reported generally in terms of international units, though falling short of the estimate of 40 million units within the period in question. By 1974, total demand had increased to 20,548,060 units of Factor VIII and 4,866,380 units of Factor IX (roughly equivalent to 300,000 blood donor units), amounts still far in excess of the 1969 estimate.[42] For 1975, the amounts increased to 24,886,218 units of Factor VIII, and 4,914,643 units of Factor IX.[43]

19.37 It seems likely that a number of considerations affected the 1969 data. One matter affecting its reliability was exposed in the report prepared by Dr Biggs for the MRC in 1974, and repeated with reference to a later period in a report on behalf of the Haemophilia Reference Centre Directors published by Dr Biggs and Dr Rosemary Spooner in May 1978.[44] The 1978 report noted that data from 1974 implied that patients with haemophilia were attending hospitals which were not recognised as haemophilia centres under the designation scheme that had been in place since the mid-1950s. A survey was carried out. It disclosed a significant number of cases of treatment in hospitals that were not designated. The report observed that all severely affected patients would require frequent anti-haemophilic treatment each year, most of the moderately affected patients would require treatment two or three times a year, and that many of the mildly affected patients would require treatment at least once a year. The directors were concerned that large numbers of patients with Haemophilia A or B were not seen at a haemophilia centre to establish a diagnosis. In their opinion any patient who had a coagulation defect should be seen at a haemophilia centre for that purpose. To ensure a suitable supply of therapeutic material and the highest standard of treatment available, the care of these patients should also be coordinated by a haemophilia centre.

19.38 The authors' primary concern was for the welfare of the patients. But the information required to prepare a valid projection of overall need for therapeutic material was deficient. That deficiency continued to be as significant in 1974 as it had been when assessing demand several years earlier.

19.39 Other workers commented on factors that were creating increasing demand at about this time. Home treatment increased demand for factor concentrates in 1975 and 1976.[45] Dr Peter Jones and his colleagues at Newcastle examined data from all UK haemophilia centres and provided a picture of growth, from very early cases in 1960, and from the introduction of cryoprecipitate in 1964, but more particularly in 1975 and 1976. Over those two years, the number of patients on home treatment, or in training for home treatment, rose from 267 to 488. In addition, the directors of the centres estimated that 280 additional patients were awaiting entry to the scheme in 1975 and 241 in 1976. The products used included cryoprecipitate and factor concentrates, and the latter included a wide range of commercial products. Dr Jones and colleagues reported a significant rise in demand due to the number of patients involved; the variables in assessment of effective dosage; the use of prophylaxis; and the adequacy of supply. They commented that the demand in the UK as a whole could not have been met without recourse to commercial Factor VIII concentrates. About 55% of the blood product used for home treatment was imported, and in England and Wales necessarily so, because of the continued shortfall in production of NHS concentrate from voluntary donations.

19.40 Dr Jones continued to promote the benefits of home therapy well after this period. In 1980, he edited a handbook for those involved in treatment, and for patients, that was published by Pitman: Haemophilia Home Therapy.[46] Home treatment was to continue to be a major element in total demand.

The position in 1974 - the beginning of the reference period

19.41 By 1974, the PFC was manufacturing a wide range of products: fibrinogen, human albumin, anti-vaccinia immunoglobulin, anti-D immunoglobulin, prothrombin complex (Factors II, VII, IX and X) concentrate, anti-tetanus and anti-rubella immunoglobulin. In 1974, production began of a new-generation intermediate-purity Factor VIII concentrate ('NY' Factor VIII). Manufacture of this range of products was impaired in 1974 and 1975 by the move to Liberton. Dr Peter Foster, who specialised in biochemical engineering and who was to play a major part in scientific developments at the PFC, joined the service in 1973. The new plant was in routine operation from 1976.

19.42 Production targets and the scope of operations continued to be open for discussion. There was no concluded policy as to the extent of the facility's use, especially in relation to the processing of material from England and Wales. However, the lack of a formal policy at that time became more or less irrelevant. The Annual Report of the SNBTS for the year ended 31 March 1976 noted that the plant had been designed to accommodate material from England and that staff had been recruited and trained on the basis of shift-working.[47] But opposition from the trade unions, allied with demands relating to terms and conditions of employment which the employers found unacceptable, had made shift-working impracticable. In the result, the PFC could cope with Scottish needs on a day-staff only basis, but the absence of the other shifts decreased cost-effectiveness and precluded acceptance of plasma from furth of Scotland. At the beginning of the reference period, therefore, there was considerable doubt about the levels of demand that ought properly to be anticipated, and this necessarily affected the efficiency of planning of the production facilities required. Since the PFC had been conceived as one element in the total UK production capacity, its planning was directly affected.

19.43 Some English plasma was dispatched to Edinburgh. On 11 April 1977, Mr Watt reported to the SNBTS that he held 10,000 litres of plasma from England, but did not have any arrangement in place for processing it.[48] By July, the quantity had increased to 20,000 litres. The minutes of a meeting of the SNBTS Directors on 12 July 1977 noted that a system for handling English material that was acceptable both to BTS England and Wales and to the SNBTS would have to be evolved.[49] That had not been achieved by mid-1977.

19.44 The issues remained unresolved by 17 January 1978, when again Mr Watt reported to the SNBTS Directors that the English plasma was still in store.[50] It was thought that it would require a plan drafted by the Joint Committee on Blood Products Production and agreed by Transfusion Directors north and south of the border to resolve the impasse. In the meantime, it was generally agreed that Scotland should secure its own supply of fractions before undertaking work for NBTS. Pending an agreement on shift-working Mr Watt felt he could process a limited amount of the plasma from the BPL on the basis of an extended working day, to ascertain the yield and establish costs. Directors agreed that he should do so, possibly devoting two weeks to fractionating English plasma only.

19.45 The Joint Committee on Blood Products Production involving the Scottish service and that of England and Wales did not resolve these issues. In the event, it was decided that the PFC could deal with Scottish needs only, but could not take plasma from furth of Scotland. For the time being at least, the PFC would process Scottish plasma, and service the Scottish market alone. Arrangements were made for supplying Northern Ireland later.

19.46 In retrospect, the final stages in the planning, commissioning, and initial use of the new PFC facility at Edinburgh therefore took place against the background of an underestimate of the demand for coagulation products in the UK generally, at a time when demand was increasing for a number of reasons, and without firm arrangements for the optimum use of the facilities planned for Scotland. The failure to take account of emerging demands related to new regimes such as home therapy and prophylaxis is understandable. In the initial planning stages of the PFC these treatment regimes would not have been developed as aspects of haemophilia practice. As discussed in Chapter 21, Haemophilia Therapy - Use of Blood Products, there was an element of reaction to the availability and importation of US concentrates that changed the pattern of demand. This came after the plants at the BPL and the PFC were built or in construction. And much of the latent demand for treatment could only be known when therapeutic materials became available for use.

19.47 The result, however, was that for a considerable time Scottish premises were adequate and, with the processing plant required, coagulation products could be provided to meet the demands of clinicians in Scotland, while in England and Wales there were persistent deficiencies that had to be made good by commercial purchases.


19.48 There had already been a political commitment to self-sufficiency, however. In December 1974, Dr David Owen MP, the UK Minister of State for Health, had announced exceptional government funding of £500,000 with the primary aim of making the NHS self-sufficient in blood products within two to three years, following recommendations by the World Health Organization (WHO).[51] The WHO reinforced its position in 1975.[52] The funding was to be used to provide the BPL in London with additional equipment to process the increased quantities of plasma necessary to meet the rapidly increasing demands for clotting factors for treating haemophiliacs.

19.49 So far as Scotland was concerned, it could not have been concluded at the beginning of the reference period that the country was or would be self-sufficient in Factor VIII blood products until the PFC was fully operational. The Annual Report of the SNBTS for the year ended 31 March 1976 reflects the developing position.[53] The commissioning of the PFC was almost complete, and full production to meet Scottish needs was said to be in sight, provided that appropriate supplies of plasma were forthcoming from the regions. As events were to unfold, it would be several years before the supply of plasma from the Scottish regions took up the PFC's production capacity.

19.50 Progress towards self-sufficiency depended on policy decisions, and on raw material supplies to meet processing targets that were yet to be set and implemented. However, at this time there was a lack of confidence about the future. On 8 May 1975, the SNBTS and Haemophilia Directors met with SHHD officials.[54] Officials were conscious that, in advice given on replies to parliamentary questions, ministers were constantly being informed that, when the PFC was fully commissioned, long-term supplies of Factor VIII concentrate would be assured. It was observed that it was still not clear what the timetable was for the replacement of cryoprecipitate by concentrate: so long as there was significant use of cryoprecipitate, the full demand for concentrates would not be known, and the necessary full supply of plasma might not necessarily be available. The minutes of the meeting disclose little hard information, and expose wide-ranging doubts. No firm conclusions were reached on future demands. At the following meeting on 14 November 1975, there was little progress on demand. A study group was set up, convened by Major-General H.C. Jeffrey (National Medical Director of the SNBTS), and a pro-forma prepared for the collection of data.[55]

19.51 More generally, there was explicit acknowledgement that Scotland was in part dependent on imported products prior to the full commissioning of the PFC. In England and Wales, central contracts for the purchase of commercial Factor VIII were held by the Department of Health from 1972-79.[56] On 11 June 1975, at a meeting of the SNBTS Directors, the procurement of commercial blood products was raised. It was noted that:

In response to a query from Dr Cash, General Jeffrey explained that SHHD had under urgent consideration the issue of whether commercially produced blood fractions which might be required should be purchased by the SNBTS or by Health Boards.[57]

19.52 On 30 September 1975, at a subsequent meeting of the SNBTS Directors:

It was explained that, because of the comparatively minor nature of the problem, it should be left to Directors to purchase and distribute human blood products should this prove necessary. This was an ad hoc arrangement pending full commissioning of the PFC.[58]

19.53 Commercial purchases were not centralised in Scotland, and it was left to local health boards and their officers to purchase and distribute commercially produced blood fractions as required. This became a factor in relation to the assessment of total demand, and in particular, to the assessment of the production requirements at the PFC. In one of two 'World in Action' television programmes broadcast in or around the end of 1975, Mr John Watt stated that, with sufficient plasma supplies, the PFC, Edinburgh, could supply Factor VIII concentrate for about half of the needs of those with haemophilia in Britain.[59] However, its capacity was not fully utilised: the intention to process plasma from England was never realised. Mr Watt's interview caused concern. In a letter to the British Medical Journal dated 24 January 1976, Professor John Cash commented that the programme had created a misleading impression. He wrote:

Perhaps the most important misleading feature of the second television programme was the impression given that the recent and specific injection of £500,000 into the blood transfusion services will have worked its way through by mid-1977, and by that time the necessity to purchase further supplies of factor VIII concentrates will be eliminated. Our own experience indicates that this will not occur, not least because the present NHS production target for factor VIII concentrates is too low. What seems more certain, however, is that by mid-1977 we shall begin to understand that the problems are multifactorial, a good deal more complex than hitherto appreciated, and only partly related to the haemophiliac.[60]

19.54 The failure to provide for total demand and the implied acceptance that the UK was heavily dependent on imported products were factors clearly acknowledged within the service throughout the UK. In the event, however, Scottish use of imported Factor VIII would prove to be relatively modest until about 1980.

Demand levels re-assessed

19.55 Professor Cash and Dr Mary Spencely discussed the issue of demand for Factor VIII products in Scotland in September 1976.[61] They expressed concern about forecasts based on Dr Biggs' research in 1974,[62] because of the wide range of values brought out. In their study in the south east of Scotland region based on treatment between 1961 and 1975, they had found a substantial increase in the donations required for Factor VIII production over the period. They had observed abrupt increases in demand in 1964, with the introduction of major reconstructive surgery. Subsequently, there were increases due to the gradual introduction of on-demand treatment; available to all patients. Demand increased from about 1300 donations in the period 1961-63, and reached a new plateau of about 2750 donations by 1970.

19.56 Cash and Spencely suggested that a saturation level might have been reached. Like other commentators, they had not anticipated further changes in the pattern of demand, nor, ultimately, in the number of haemophilia patients with unmet needs. Furthermore, some of their data were specific to Edinburgh and south east of Scotland. Possible concerns about the approach adopted were set out in paragraphs 5.109 and 5.110 of the Preliminary Report. The suggestion that a level of saturation might have been reached remains an odd feature of the analysis. The success of factor therapy had to be reflected in an increase in life expectancy of haemophilia patients, and the concomitant extension of the term of treatment of the average haemophilia patient. One would have expected a rising trajectory even if all other factors had remained constant: treatment years per patient had to increase. As will appear, there was also the start of home treatment, and availability of imported products had already by 1975 found a response in demand for treatment of patients who had not been catered for previously.

19.57 A further difficulty was that the paper depended on data peculiar to the region. No commercial products were used in south east Scotland over the period of the study. But there was extensive use of commercial products in Glasgow.[63] In the Glasgow and south west of Scotland region there was also extensive use of cryoprecipitate as the therapeutic product of choice. Apart from distinguishing the two regions' use of therapeutic materials, these two factors underline a basic issue over the definition of demand for NHS products generally. So long as haemophilia clinicians were free, in the exercise of their very considerable clinical autonomy, to elect for commercial products or for products other than concentrates in treating their patients, actual demand for NHS concentrates could never be relied on as a measure of total demand for therapeutic products generally. The position in Edinburgh and south-east Scotland over the period of study reflected the firm and apparently unwavering commitment of the then Haemophilia Director, Dr Howard Davies, to NHS material, much of it cryoprecipitate. That was not the position in Glasgow and south west Scotland, the largest region of the country. Imported material was making a significant contribution (over 90%) to the demand for Factor VIII concentrate in the period 1971-74. In both regions at that period there was significant use of cryoprecipitate, again reflecting the choices of the Haemophilia Directors at the time.

19.58 The use of cryoprecipitate for the treatment of adults in the west of Scotland was reflected in the well-established pattern of production of cryoprecipitate in that region during the periods when successively Dr John Wallace and Dr Ruthven Mitchell were the SNBTS consultants in charge. Dr Davies in Edinburgh was also an advocate of cryoprecipitate use. Professor Cash and Dr Spencely based their calculations on the assumption that 70% of the therapeutic material used would be cryoprecipitate, reflecting product choice in the east of Scotland at the time. A material shift in haemophilia practice towards use of concentrate would necessarily depend on production capacity and the supply of raw material in the form of frozen plasma.

19.59 The views set out by Cash and Spencely in this paper were clearly not accepted universally. In the paper, they commented at some length on the choice of therapeutic materials, and the efficiency of production of cryoprecipitate as against concentrate. But it is in the authors' estimation of demand that the paper is interesting for present purposes. They concluded that the Blood Transfusion Services should consider a production target of an average of 15,000 units of Factor VIII per patient per year with a total UK annual requirement of around 50 million units. Converting that into donations per million of population per year threw up a range of values from 15,000 to 20,000, with the qualification that the higher figure would rise further if the volume of fresh plasma obtained from each donation was reduced.

19.60 At the date of the Cash and Spencely paper in September 1976, the authors believed that, following the commissioning of the PFC, the south east of Scotland was already self-sufficient in therapeutic Factor VIII products. But there remained considerable issues about the rest of Scotland. It was recognised that supplies of antihaemophilic factor (AHF) (concentrate) were limited: 'What supplies of AHF there are, should be reserved for outpatient use, while cryoprecipitate is used for inpatients'. The conclusion of the paper was:

In the meantime the blood transfusion services ought to look towards improving the quality of cryoprecipitate production and procedures for the procuring of bulk fresh plasma. The plasma fractionators should look towards technical developments that will lead to improved yields, the general hospital medical staff towards a dramatic increase in the use of red cell concentrates and packed red cells in preference to whole blood, and the staff of regional haemophilia centres to the more economical and critical use of factor VIII concentrates. There is no evidence to suggest that the voluntary blood donor will not respond; indeed those in the regional blood transfusion centres know that quite the reverse is true.

19.61 It is implicit in the proposals for restricted use that there would be deficiencies in supply if there was a significant change towards concentrate use. The authors advocated the use of packed red cells as a way of releasing more plasma for production. Apart from increases in the volume of plasma for processing, any deficiencies in domestic supplies of Factor VIII concentrate could only have been made up by the purchase of commercial products, which was already happening in the west of Scotland. Of possibly greater significance, so far as developing a strategy for self-sufficiency is concerned, is the clear message that there was no settled practice governing the choice of product for well-recognised categories of application. In particular, the factors identified as relevant to the choice of product were related to the economics of manufacture, and yield, predisposing the authors to recommend cryoprecipitate in preference to Factor VIII concentrates.

19.62 An attempt to assess the resources for the adequate treatment of Scottish haemophilia patients was set out in a paper prepared for a meeting of the SNBTS and Haemophilia Directors on 4 October 1976.[64] There were 436 registered haemophilia patients. Their distribution across Scotland was: Glasgow 285, Edinburgh 95, Aberdeen 25, Dundee 17 and Inverness 14. Twenty to 22 of these required treatment three or four times a year. Eighty seven to 92 required more frequent therapy. The rest hardly ever required treatment or required it not more than twice a year. The data were not entirely reliable because of the practice of some patients of attending general hospitals. Factor VIII usage in the first six months of 1976 presented the following picture of the current position:[65]

Aberdeen Dundee Edinburgh Glasgow Inverness
Cryoprecipitate as donations 467 121 5965 8829 154
PFC Factor VIII: vials 288 111 (307,700 units)
1381 358
Commercial Factor VIII 0 0 0 (90,740 units) 0

19.63 There are obvious problems with the data. The inconsistent use of units of measurement is very confusing. An apparent problem is the absence of recorded use of commercial product outside Glasgow coupled with low use of PFC Factor VIII. Availability of the PFC concentrate at this period was affected by the transfer of production from the RIE to the new PFC. The data are not sufficiently specific to factor this into the assessment of the validity of the exercise. The impression given, as far as haemophilia treatment is concerned, is that at this time, as was clearly the case in Glasgow, most plasma was being retained locally for cryoprecipitate production, but the extent to which the disruption of the PFC supplies affected practice is unknown, and there remains a question whether the reports of commercial usage can be treated as wholly reliable.[66]

19.64 Nevertheless, there is a marked difference between the Glasgow data for the first six months of 1976, and for the full year 1975 (as the PFC began to come on stream). For 1975, total cryoprecipitate of 26,616 donations and PFC Factor VIII of 1023 vials were recorded as used.[67] Superficially, the rate of use of PFC Factor VIII had more than doubled. The paper listed a number of topics for discussion which highlight concerns at the time over the assessment of total demand. These included the numbers of patients with haemophilia, moderate and severe, in the community; the amount of Factor VIII (cryoprecipitate and concentrate) required for each patient; the best use of resources; patients' lifestyles; and the follow-up and evaluation required. It was suggested that a national register might be justified. Two points warrant specific reference: the effect of home therapy on total consumption and, related to that, the approach to decision-making on suitability for home therapy; and the introduction of new surgical techniques likely to make heavy demands on resources over relatively short periods.

19.65 The assessment of demand had begun to take into account factors that were to become significant within a short period. The context for the discussion had to take account of government policy to use blood from voluntary donations, in keeping with the WHO recommendations.[68]

19.66 The minutes of the meeting on 4 October 1976 note that estimating requirements for Factor VIII had been causing concern at UK level.[69] The cost of maintaining a UK-wide register was said to be a 'practical obstacle' to implementation of that proposal. Two points were noted as being of particular concern: the increasing needs for clotting factor products as a child grew older, and the increasing prospects of longevity. The wider context was reflected in two paragraphs, the first of which (paragraph 7) said:

The primary need was seen as the provision of information to help on balancing use and requirements. Use would obviously increase if patients took up and were encouraged to take part in eg skiing or other outdoor pursuits. It was becoming increasingly apparent that haemophiliacs should be advised to live within the limits of their disability and in the more severe cases this could lead to them living a more sedentary life. While it was acknowledged that this is a difficult area, impinging as it did on the question of clinical freedom, it was thought to be a realistic approach.[70]

19.67 The following paragraph (paragraph 8) proposed a UK-wide meeting with the Haemophilia Society with a view to discussing the use of the scarce resources available and other topics on a UK basis that might lead to the production of a register among other things. The importance of an agreed policy for Scotland with the support of clinicians in England and Wales was stressed.

19.68 An exploratory meeting of Blood Transfusion Directors and Haemophilia Reference Centre Directors was held in Sheffield on 22 October 1976.[71] Dr Biggs and colleagues presented the data on need, estimated at 40 million units of freeze-dried Factor VIII. International data suggested a need for England, Wales and Northern Ireland of 36,481,890 units, and for Scotland 3,741,917 units, giving 40,223,807 units in total. These figures presented a picture of spurious arithmetical accuracy, but they agreed fairly well with estimates based on UK data. They anticipated a shift from the use of cryoprecipitate to the use of concentrates, noting that five commercial companies were licensed to supply very satisfactory products which offered convenience in use.

19.69 In discussion, Dr Biggs is reported to have commented that 40 million units was too low an estimate for the future because use was increasing. Professor Cash agreed. He was alarmed by the games and sporting risks now covered and the implications for demand: he thought it was morally wrong to commit such large amounts of material.[72] Dr Wallace pressed for a common policy, but he too reflected the view that haemophilia patients should live within the limits of their disabilities.[73] In contrast to the views of these suppliers of clotting factor products, a representative of the 'consumers', the Haemophilia Centre Director Dr Jones, was of a different view, encouraging normal sporting activities such as football: if patients sat around they would need more therapy.[74] He proposed a target of 42.4 million units. Following extensive discussion, the final proposal, from Professor Colin Prentice, was that the current target should be 40 million units, rising to 50 million units over the following three years.[75] There were doubts about the usefulness of the exercise.[76] The fractionators were not in agreement about the criteria to apply and about the practical implications of working to the targets proposed. At least some haemophilia directors were apparently not according priority to the goal of UK self-sufficiency in blood products, particularly Factor VIII concentrates, and appear to have been content to continue to use increasing amounts of imported products rather than their domestic counterparts.

19.70 At a meeting of the SNBTS Directors on 26 October 1976, in discussing the supply of Factor VIII concentrates, it was noted that, in Scotland as in England and Wales, there was still a long way to go towards setting ultimate targets for the production and use of Factor VIII products, though Scotland's problem was smaller than in England and Wales.[77] It was agreed that a firm attempt should be made at the meeting of the Haemophilia Directors planned for 24 January 1977 to set interim Scottish targets.

19.71 The practitioners, in England and Wales as well as Scotland, had not resolved targets. In their paper, Professor Cash and Dr Spencely had not resolved the issue of methodology to the satisfaction of UK colleagues. Estimates of demand remained uncertain. The paper's projection of total UK demand at 50 million units exceeded Dr Biggs' estimate of 40 million, but reflected the longer-term projection for the UK as a whole. But each projection exceeded by a considerable margin the production targets on which the two major facilities in England and Scotland were planned, and constructed or developed at this time. There was little obvious collaboration between the two groups - the blood transfusionists and fractionators interested in production on the one hand, and the haemophilia clinicians preoccupied with consumption on the other. Neither group was successful in estimating demand and regulating both production and consumption in the period between 1972 and 1981 with much accuracy. A casualty of this overall lack of collaboration was the idea, or at least the practicality, of UK self-sufficiency during this period. That would become a matter of regret.

19.72 In the event, in the UK as a whole, there was an emerging shortfall in production of growing significance. The comparative positions in Scotland and England are set out in Chapter 21, Haemophilia Therapy - Use of Blood Products. In retrospect it is clear that there was a material failure, at the beginning of the reference period, in the planning of production capacity to anticipate the actual emerging levels of demand; and a correlative failure to provide production facilities in the UK as a whole with the capacity to service domestic requirements. The positions in the two parts of the UK differed. In England and Wales, there was a significant shortfall in production capacity which, in absolute terms, made it impossible in the 1970s and early 1980s to produce enough material to meet domestic demand. In Scotland, the facilities were sufficient in scale, or at least flexible enough to adapt to meet growing demand, until the end of the 1970s. However, plasma supplies, yield of concentrate, out-of-date data on use of Factor VIII, and failure to appreciate the impact on total demand of changing haemophilia clinical practice all contributed to the problem there, as in the UK as a whole.

19.73 Dr Biggs wrote a letter to The Lancet of 29 June 1974. It is quoted in the Preliminary Report, but captures the atmosphere at the time, and is worth repeating:

Those who treat haemophilic patients in the UK have in the past of necessity tolerated the chronic undertreatment of their patients and have put much time and effort into spreading the inadequate amounts of therapeutic material thinly so that deprivation should be least damaging. Essential but non-urgent operations have been postponed and are still being postponed. Economy has also been achieved by calculating the dose for each lesion for every patient to give the absolute minimum dose. In addition patients have not been put onto home therapy who would greatly benefit by this treatment .... There is, in fact, evidence that 90% of haemophilic patients in the UK receive less (and in some cases much less) than optimum treatment for their complaint. The consequences of this undertreatment include subjecting the patients to unnecessary, painful and destructive bleeding into joints and muscles. Ancillary effects of undertreatment include loss of educational time and inability to hold continuous employment.[78]

19.74 Dr Biggs proceeded to make an emotional appeal for the purchase and use of stocks of 'good quality human Factor VIII' readily available from commercial companies that were by then licensed to make supplies in this country, and dismissed, rather contemptuously, all arguments based on financial constraints. She concluded:

Whatever solutions there may be for problems of this sort in general, some immediate solution should be found for the ridiculous impasse of large available stocks of therapeutic materials locked up in stores because no-one will buy them and, on the other hand, patients in dire need of this same material.[79]

19.75 At least so far as England and Wales were concerned, her comments underline the deficiencies in domestic production. As will be seen in Chapter 21, Haemophilia Therapy - Use of Blood Products, the purse strings were loosened and imported materials were used in large quantities as time passed. The description of the commercial concentrates in stock as 'good quality human Factor VIII' would be challenged within the following decade as the likely impact of non-A, non-B Hepatitis (NANB Hepatitis) came to be appreciated.

19.76 It appears to be clear that the problems that preoccupied the medical profession and the technologists associated with blood product production in the mid- to late-1970s related to production capacity, cost, and adequacy of supply of therapeutic materials for appropriate treatment of the patient population. Awareness of NANB Hepatitis (later identified as Hepatitis C) became an emerging issue: AIDS had not yet been reported. As the 1980s progressed, the emphasis was to change dramatically.

The final chapter

19.77 The evolving history of blood product development in Scotland will be traced elsewhere in this report. At this stage, however, it is appropriate to define the end stage of the production of concentrates in Scotland, since that, incidentally, put an end finally to the pursuit of self-sufficiency and removed the scope for controversy over production targets.

19.78 In 1998 the fractionation of plasma from UK donors was banned as a precaution against the risk that variant Creutzfeldt-Jakob disease (vCJD) might be transmitted by blood products. At UK level, precautionary concerns around vCJD risk drove the decision. Historically, sporadic vCJD was not thought to be transmissible by blood components or plasma products. When vCJD was first described in about 1996, it was recognised that it was a different kind of disease and there was concern that it might prove transmissible. The risk that, because of the pooling effect, one infected individual donor might contaminate a whole batch of products influenced the UK government to take the view that it would be preferable to move away from UK plasma. There was speculation that potentially vast numbers of people might develop the disease. Though that never came to pass, it was thought to be possible at the time.[80]

19.79 It was assumed, correctly, that the risk of transmission of vCJD from blood collected in Britain was greater than the risk in source countries from which substitute supplies might be found and in which bovine spongiform encephalopathy (BSE), and hence vCJD, had not occurred. BSE was predominantly a UK-centred outbreak, with some cases in Ireland and Western Europe. Of approximately 220 to 230 cases of clinical vCJD, probably about 180 to 190 were in the UK. There had been two or three cases in the USA of vCJD but they were mainly in individuals who spent time in other countries, including the UK.[81]

19.80 In the aftermath of the ban on UK plasma, it was announced in October 1998 that the SNBTS was to undergo a major modernisation programme.[82] Processing and testing functions were terminated at all five Blood Transfusion Centres and concentrated on two sites, Edinburgh and Gartnavel (replacing the Carluke Centre). The two national laboratories were to be developed and equipped to deal with new blood tests and processing technologies for the whole of Scotland. There was to be national coordination of the collection of blood and of blood stocks. It was also indicated that additional funds were to be allocated, among other things, for 'sourcing of non-UK plasma', presumably an indirect allusion to the risks potentially associated with vCJD in the domestic blood supply.

19.81 There were factors other than vCJD, however, that affected the PFC's ability to continue functioning as a manufacturing facility. European regulatory authorities had pressed for additional viral inactivation following transmission of hepatitis and HIV during 1984 in Germany. These required changes in manufacturing processes and fresh clinical trials to obtain regulatory approval. New equipment was required. There was a decision to fund recombinant coagulation factor concentrates. At the same time, demand for human albumin fell following reports of adverse consequences for recipients.[83] These factors pointed to a further move from the PFC's established range of activities.

19.82 While red cell and platelet production continued in Scotland; domestic blood, collected in Scotland (and throughout the UK), was no longer used for the production of plasma fractions.[84] As a result, the SNBTS had to import plasma or obtain it from commercial (non-UK) sources. Plasma was sourced commercially after 1999. That allowed fractionation to continue for a time.

19.83 The next significant change in the scope of the operations of the SNBTS was prompted by the implications of the first documented clinical case of transmission of vCJD early in 2004.[85] The vCJD threat, together with the move away from human blood clotting factors to synthetic alternatives, contributed to the decision in June 2006 to accept the recommendations of National Health Services Scotland that it was no longer viable to operate the PFC as part of the NHS.[86] At the time the decision was taken production at the PFC had already been suspended due to concerns about quality assurance.[87] The economics of continuing production in Edinburgh influenced the decision. The PFC closed in 2008 after attempts to find a private buyer failed.

19.84 So far as the PFC was concerned, there was a practical risk of continually recalling batches of product. The risk of recalling product carried a threat of shortages. In general terms, the PFC had become one of the smallest fractionators in the world, and was particularly small compared to large corporate commercial fractionators. But there was the added consideration that, with the end of an era of effectively free supply of plasma, the balance of economics changed in favour of purchase of products from the international commercial community.[88]

19.85 Fresh frozen plasma for clinical use is still imported for two groups of patients. One group comprises children up to the age of 16 years. For that group, plasma has hitherto been imported from the USA but in the future will be imported from Austria. That product receives methylene blue treatment, a pathogen reduction treatment which can be applied to plasma. The second group comprises patients undergoing plasma exchange, particularly for a condition called Thrombotic thrombocytopenic purpura (TTP or Moschcowitz syndrome). Methylene blue treated plasma is thought not to be the best treatment for them. So pharmaceutically cooled plasma, called 'octaplas', is used. It is again manufactured from European plasma. Albumin and immunoglobulins are also supplied commercially.[89] However, for all practical purposes, fractionation, as the definitive manufacturing process, had ceased before the decision to place the facility on the market had been taken.

19.86 With the closure of the PFC, Scotland lost many of the skill sets associated with fractionation. The technological developments that have followed since the millennium are largely irrelevant to practice in Scotland. The BPL, the English fractionation centre, remains open, but uses imported plasma.[90] The English Service has a plasma collection facility in New England, USA, from which it obtains supplies for the NHS.[91]

Discussion and conclusions

19.87 The planning and construction of the extended facility at the BPL, and the new PFC, took place at a time when there was already increasing demand generated by some known factors, for example, use of clotting factor products in major reconstructive surgery and the gradual introduction of on-demand treatment, available to all patients, in the period 1961-64. In 1976, changing policy relating to patients' lifestyles, moving from maintaining a protective environment towards encouraging sport and other potentially dangerous activities, had an impact on demand. At the meeting of Blood Transfusion Directors and Haemophilia Reference Centre Directors held in Sheffield on 22 October 1976 the views of haemophilia clinicians were made explicit: normal sporting activities such as football should be encouraged. The increasing needs for clotting factor products as a child grew older, and the increasing prospects of longevity required to be taken into account. By the autumn of 1976, also, it was appreciated that home therapy would be likely to increase demand. And it was anticipated that the introduction of new surgical techniques was likely to make further heavy demands on resources over relatively short periods.

19.88 Overall there was a changing environment in which haemophilia care would come to demand increasing quantities of therapeutic materials beyond those anticipated in the planning of production facilities. And there was the beginning of an inexorable shift towards concentrates as the product of choice in haemophilia therapy, which would become clear as the use of Factor VIII in particular grew throughout the 1970s and early 1980s.

19.89 Haemophilia clinicians' treatment policies, and the encouragement of patients to live a 'normal' lifestyle, associated with clinical independence that extended to the selection of therapeutic products thought best to suit the requirements of the individual patient, were factors beginning to affect the demand for concentrates. The lack of a centralised purchasing system for commercial products meant that purchases could be made without central monitoring. As will appear from Chapter 21, Haemophilia Therapy - Use of Blood Products, returns were made to UKHCDO of the use of commercial products. But in the absence of a haemophilia register there was not a comprehensive record of all demand.

19.90 Unless the Blood Transfusion Services and the fractionators had full knowledge of the total demand for the current groups of therapeutic products required for effective treatment of patients, and of the proportion of that demand likely to be met by commercial purchases, effective planning of the production targets and production plant and processes required by the fractionation centres was unlikely to be achieved.

19.91 Since the commercial market to which Dr Biggs referred was largely serviced by foreign pharmaceutical companies, clinical independence and a policy of national self-sufficiency in blood products were bound to come into conflict.

19.92 While that would have been the case in a static market environment, the added elements of technological change and changing patterns of demand would inevitably add to the complexity of the problem of servicing the market.

19.93 Tensions between fractionators and clinicians were also inevitable unless there was a properly coordinated policy and management framework that was effective to resolve issues and implement solutions to problems as they emerged and were identified. After full commissioning of the PFC and until the 1980s; Scottish production of concentrates largely met the demands of haemophilia clinicians for NHS factor products. However, total demand for NHS products was always lower than total demand overall, since commercial purchases reflected clinicians' preferences that involved choices that were independent of the availability of the domestic product. In the longer term, if true self-sufficiency were to be achieved and maintained, additional capital investment would have been required.

19.94 In the circumstances, it is somewhat surprising that Scottish needs were as well catered for as, in the event, they proved to be. The SNBTS's ability to meet actual demand for therapeutic products from domestic sources was sustained from 1975-76 to 1981-82, and, with the exception of the two years 1978-79 and 1979-80, when demand for clinical use exceeded the PFC's output, available supplies of PFC Factor VIII concentrate exceeded demand for concentrate estimated at average UK rates.[92] This outcome, however, was a reflection of the failure at UK level to realise the policy objectives formulated at the planning of the production facilities in England and Scotland. If the PFC at Liberton had been called on to meet the demands of a significant part of northern England, Scotland's domestic supplies of Factor VIII concentrate would have fallen short of demand.

1 Foster, 'Plasma fractionation in Scotland', Blood Letter, Spring 2008 [PEN.017.2468]

2 Planning of Plasma Fractionation in Scotland, synopsis by SNBTS of meetings February 1965-March 1973 [SNF.001.2412]

3 Ibid

4 Girdwood, Fifty Years of an Organized Blood Transfusion Service in Scotland, (undated) [SNB.010.1836] at 1840

5 Present: IS Macdonald (SHHD), Dr Thomson (DHSS), W d'A Maycock, L Vallett (BPL), RA Cumming, JG Watt (Edinburgh). See Planning of Plasma Fractionation in Scotland, synopsis by SNBTS of meetings February 1965-March 1973 [SNF.001.2412]

6 Same parties as 'the May 1968 meeting' excluding Dr Thomson. 'Planning of Plasma Fractionation in Scotland', synopsis by SNBTS of meetings February 1965-March 1973 [SNF.001.2412]

7 Maj. Gen. Jeffrey's letter of 6 January 1975 to Chief Administrative Medical Officers [SGH.007.7009]

8 Minutes of meeting [SNB.010.2066]

9 Note of meeting [SNB.010.2059] Present: DM Pendreigh (SHHD), W d'A Maycock, L Vallett, D Ellis (BPL), RA Cumming, JG Watt (Edinburgh).

10 Foster, Self-sufficiency and the supply of blood products in Scotland, SNBTS, February 2011 [PEN.013.1125]; Girdwood, Fifty Years of an Organized Blood Transfusion Service in Scotland, (undated) [SNB.010.1836] at 1840

11 Report on progress of an MRC Cryoprecipitate Working Party Survey, provided to a meeting of Haemophilia Centre Directors in Oxford on 5 April 1971 [DHF.001.1811] at 1820

12 Ibid [DHF.001.1811] at 1824

13 Ibid [DHF.001.1811] at 1820

14 Report by Dr Biggs et al, [SNB.001.4871]

15 The international unit (IU) was a measure of Factor VIII activity. The assumed level of activity in a given quantity of blood provided the conversion factor adopted, and varied from time to time.

16 Watt, Plasma fractionation in the United Kingdom - a personal appraisal', (Draft) 12 June 1973 [SNB.010.1991]

17 Biggs, 'Jaundice and antibodies directed against Factors VIII and IX in patients treated for Haemophilia or Christmas disease in the United Kingdom', British Journal of Haematology, 1974, 26, 313 [LIT.001.0099] at 0102

18 Planning of Plasma Fractionation in Scotland, synopsis by SNBTS of meetings February 1965-March 1973 [SNF.001.2412] at 2413

19 Ibid [SNF.001.2412] at 2413-2414

20 Ibid [SNF.001.2412] at 2413

21 Ibid [SNF.001.2412] at 2413

22 Chronology of events with relevance to 'self-sufficiency' etc [SGH.002.1313]. See Chapter 21, Haemophilia Therapy - Use of Blood Products

23 CMO's letter [DHF.001.2122]

24 Minutes of Expert Group on the Treatment of Haemophilia, 20 March 1973 [SNB.006.7631] at 7633

25 Factor VIII Concentrates and the Treatment of Haemophilia, Report by Dr Biggs [SNB.006.7775]

26 Minutes of Expert Group on the Treatment of Haemophilia, 20 March 1973 [SNB.006.7631] at 7634

27 Ibid [SNB.006.7631] at 7634

28 Note of meeting [SNB.010.2009]

29 Approximately the capacity mentioned by Mr Watt in his personal assessment of 12 June 1973.

30 Foster 'Plasma fractionation in Scotland', Blood Letter, Spring 2008 [PEN.017.2468]

31 Note of meeting [SNB.006.7767]

32 Ibid [SNB.006.7767] at 7768

33 Ibid [SNB.006.7767] at 7769-7771

34 Minute of meeting [SNB.007.2190]. The report is [SNB.001.4871]. Information has been taken from pages 4874, 4890, 4891 and 4892.

35 From its terms, it appears that in this report 'United Kingdom' was used accurately to include Scotland.

36 Biggs, 'Jaundice and antibodies directed against Factors VIII and IX in patients treated for Haemophilia or Christmas disease in the United Kingdom', British Journal of Haematology, 1974, 26, 313 [LIT.001.0099] at 0102

37 Biggs, 'Haemophilia treatment in the United Kingdom from 1969 to 1974', British Journal of Haematology, 1977, 35, 487 [LIT.001.0159]

38 Haemophilia Centre Directors' Annual Statistics for 1975, British Journal of Haematology, 1977, 36, 447 [SNB.001.7011]

39 A 'unit' is defined relative to the material involved. A 'unit' of Factor VIII is arbitrarily defined as the amount of AHF activity present in 1 ml of normal male plasma: Buchholz, 'Blood Transfusion: Merits of Component Therapy', The Journal of Pediatrics, February 1974, 84/2, Page 165 [LIT.001.0141] Col 142

40 FVIII concentrate

41 Biggs, 'Haemophilia treatment in the United Kingdom from 1969 to 1974', British Journal of Haematology, 1977, 35, 487 [LIT.001.0159] at 0174

42 Ibid [LIT.001.0159] at 0165 and 0167

43 Haemophilia Centre Directors' Annual Statistics for 1975, British Journal of Haematology, 1977, 36, 447 [SNB.001.7011]

44 Biggs and Spooner, 'National survey of Haemophilia and Christmas disease patients in the United Kingdom', The Lancet, 27 May 1978, 1143-4 [LIT.001.0352]

45 Jones et al, 'Haemophilia A home therapy in the United Kingdom 1975-6', British Medical Journal, 3 June 1978 [LIT.001.0258]

46 Jones, P., Haemophilia Home Therapy, 1980, Pitman, London.

47 SNBTS Annual Report 1 April 1975-31 March 1976 [SNB.010.3921]

48 Letter from Mr Watt to Miss Corrie, 11 April 1977 [SNB.002.1777]

49 Minutes of SNBTS Directors meeting, 12 July 1977 [SNB.002.1814] at 1816

50 Minutes of SNBTS Directors meeting, 17 January 1978 [SGF.001.0341] at 0341-2

51 Letter to Regional Administrators in England and Wales, 24 December 1974 [DHF.002.9393]

52 WHO, Twenty-Eighth World Health Assembly, Geneva, 13-30 May 1975 WHA28.72 Utilization and supply of human blood and blood products [DHF.003.0764]

53 SNBTS Annual Report, 1 April 1975-31 March 1976 [SNB.010.3921]

54 Minutes of meeting [SNB.001.4903]

55 Minutes of meeting [SNB.001.4906]

56 See briefing papers for Scottish Parliament Health Committee Meeting on 31 January 2006 [SNF.001.2449] at 2462

57 Minutes of meeting [SNF.001.0001] at 0006

58 Minutes of meeting [SGH.001.6135] at 6137

59 Transcript of 1975 World in Action programmes [PEN.013.1400] at 1421

60 Cash, 'Commercial and NHS factor VIII concentrates', British Medical Journal, 24 January 1976, 221 [LIT.001.0245]

61 Cash and Spencely, 'Haemophilia A and the blood transfusion service; a Scottish study', British Medical Journal, 18 September 1976 682 [LIT.001.0255]

62 Biggs et al, 'Factor VIII concentrates made in the United Kingdom and the treatment of Haemophilia based on studies made during 1969-72', British Journal of Haematology, 1974; 27: 391 [PEN.016.0341]. (This is the published version of the typescript paper made available to the UK Haemophilia Directors meeting on 31 January 1974 - See paragraph 19.31 above.)

63 See Chapter 23, Viral Inactivation of Blood Products for Haemophilia Therapy up to 1985

64 Resources required for adequate treatment of Scottish Haemophiliacs [SNB.001.4943]

65 Ibid [SNB.001.4943] at 4944]

66 The disruption due to the relocation of the PFC is discussed in Chapter 21, Haemophilia Therapy - Use of Blood Products, at paragraph 21.47

67 'Resources required for adequate treatment of Scottish Haemophiliacs' [SNB.001.4943] at 4944

68 Ibid [SNB.001.4943] at 4945-4946

69 Minutes of meeting [SGH.001.1320]

70 Ibid [SGH.001.1320] at 1321

71 The full list of participants sets out the major players in the field (other than DHSS, SHHD and Northern Ireland government officials, who had not been invited) at this period. Minutes of meeting [SNB.001.4953]

72 Minutes of meeting [SNB.001.4953] at 4954

73 Ibid [SNB.001.4953] at 4954

74 Ibid [SNB.001.4953] at 4954-55

75 Ibid [SNB.001.4953] at 4956

76 Dr Wallace's report to SHHD dated 25 October 1976 [SNB.001.4960]; and Mr Watt's letter to Dr McIntyre of SHHD dated 29 October 1976 [SNB.001.4958]

77 Minutes of Meeting [SGH.001.6042]

78 Biggs, 'Supply of blood-clotting-factor VIII for treatment of haemophilia', The Lancet, 29 June 1974 [PEN.016.0440]; Preliminary Report, paragraph 5.122

79 Biggs, 'Supply of blood-clotting-factor VIII for treatment of haemophilia', The Lancet, 29 June 1974 [PEN.016.0440]

80 Professor Turner - Day 7, page 35

81 Professor Turner - Day 7, pages 36-37

82 Scottish Office press notice, Improvements to blood transfusion service announced, 28 October 1998 [SGH.003.8451]

83 Foster, 'Plasma fractionation in Scotland', Blood Letter, Spring 2008 [PEN.017.2468] at 2471

84 Professor Turner - Day 7, page 33

85 Professor Turner - Day 7, pages 18-19

86 Scottish Government press notice, Changes in blood processing activities, 26 June 2006, Available: Last accessed 15 Oct 2012

87 Ibid

88 Professor Turner - Day 7, page 36

89 Ibid pages 33-34

90 Ibid pages 33-34

91 Dr Norfolk - Day 7, page 79

92 Chapter 21, Haemophilia Therapy - Use of Blood Products, at paragraphs 21.62 to 21.65

20. Haemophilia Therapy - The Period up to the Early 1980s >