pnadel/npi_all_transcripts · Datasets at Hugging Face

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45,700	320	QUESTION: Yes. ANSWER: Um ... maybe in some -- I don't -- I don't know how to answer that question.
45,701	320	QUESTION: No smoke and mirrors here, that's the -- ANSWER: That's the question.
45,702	320	QUESTION: If you're in the circumstances where it is unlikely that this will ever be made into a -- ANSWER: Well, it was made at the bio products laboratory, t hat product. So they must have thought something posit ive about it at that stage, in spite of the difficultie s that we had with it. So maybe they thought that th ey should check that it would work, because it was a different entity. So, maybe, you know, things might -- things might work out. Maybe I was being too negative about it. Maybe it was possible to make i t work. But the other question that needed to be answered is would it actually work in the circulati on? Never mind whether the -- you know, because if you can 170 get the production process to work, which I couldn' t, but other people might have got it to work, would Factor
45,703	320	QUESTION: Do I take it from your answer that you were trying now to help us by looking back and thinking what the thinking might have been, but you weren't actually -- you're not able to say what you yourself thought at the time? ANSWER: Yes.
45,704	320	QUESTION: I should say, out of fairness, that we looked at th e 1983-1985 business plan and, as we discussed during the presentation, the door was not being closed absolutely on Factor VIII through polyelectrolyte fractionation, although there were concerns about h ow feasible it was going to be. ANSWER: Mm.
45,705	320	QUESTION: We know that the initial application was turned dow n, and I referred to a meeting that you attended on 2 June 1983. If we could have that on screen, plea se, Soumik. It's IPS -- ANSWER: That wasn't the same product.
45,706	320	QUESTION: Ah. If we bring it up on screen, perhaps you can assist us with it. IPSN0000165_109, please. ANSWER: Yeah. 171
45,707	320	QUESTION: So this is a meeting on 2 June 1983. ANSWER: Yeah.
45,708	320	QUESTION: Then "source of cryoprecipitate"? ANSWER: Which was this Alpha cryoprecipitate, which was bei ng bought in 100-kilo lots -- was it 100-kilo lots -- in large lots, as a frozen cryoprecipitate, to make -- to try to make Mono Factor
45,709	320	QUESTION: Yes, I think we're at slightly cross purposes. ANSWER: Oh right, okay.
45,710	320	QUESTION: So the paper I referred you to earlier, which you co-wrote with Dr Lane, et cetera, et cetera, and Dr Tuddenham, that was a product that was made in Elstree -- ANSWER: In Elstree, yes.
45,711	320	QUESTION: -- and that was used, as you said, on three patients -- ANSWER: And one von Willebrand's.
45,712	320	QUESTION: -- with haemophilia A and one von Willebrand's patient. ANSWER: Yes. 172
45,713	320	QUESTION: This is different. This is the application for the clinical trial -- ANSWER: Yes.
45,714	320	QUESTION: -- which was made at some point in 1982? ANSWER: Yes.
45,715	320	QUESTION: That was what I was discussing with you a moment ag o? ANSWER: Yes, yes.
45,716	320	QUESTION: Why it was that there was an attempt to have a clinical trial at that stage. ANSWER: Oh, from this -- yes.
45,717	320	QUESTION: The idea was that the material -- the cryoprecipitate would come up in from Alpha, and th en you would fractionate it -- 73 ANSWER: It was a frozen paste that you re-suspended. We did -- I did do some work with it. It was a frozen paste that was re-suspended and then put over the polyelectrolyte.
45,718	320	QUESTION: I'd like to just look at what was to said at this meeting. There was you and Anne Walton from Speywo od? ANSWER: Yes.
45,719	320	QUESTION: The note is by -- the initials are EAW. Is that An ne Walton? ANSWER: Yes.
45,720	320	QUESTION: Who was Anne Walton? ANSWER: She was -- she did some marketing but she also focu sed in on regulatory affairs.
45,721	320	QUESTION: Was she a scientist? ANSWER: Yes.
45,722	320	QUESTION: The participants from the DHSS, a Dr Fowler and Dr Purves. ANSWER: Yes.
45,723	320	QUESTION: And if we could just look at the note and I'll read it through to you. "1. Dr Fowler was of the opinion that, despite the controversy surrounding US imports as a result of AIDS, our application will not be judged prejudicia lly by the CSM if we pursue it with Alpha cryo cited as source material. There have been suggestions in 174 certain quarters about the banning of importation o f all US blood products but the impracticality of thi s is recognised by those who were well informed in th is area and a ban does not, therefore seem likely. An application based on Alpha cryo would (or should) b e judged solely on its scientific merit. "2. The possibility of leaving an application open-ended with respect to source material was discussed and dismissed as unacceptable. "3. We were advised that if a change in source material is desired, the application might proceed more easily if the licensing of the import or the c ryo were included in the CTC application. The responsibility wore the quality of the raw material would then be entirely Speywood's and in addition, the cryo would then be licensed for importation only fo r the purpose covered by the CTC." If we go over to the next page, the possible courses of action are discussed. I won't go thorou gh that, but it says: "In conclusion it appears that the use of US cryo will not prejudice our case with the licensing authorities and therefore our choice of source material can be based on commercial and scientific grounds." 175 A couple of points about that. Paragraph 1, the discussion of the potential ban on US blood product s, and the recognition that that was impractical. Are you able to help us with who was saying that it wou ld be impractical to ban US blood products? ANSWER: No.
45,724	320	QUESTION: Would you or Anne Walton have been in a position to make that observation? Do you think it's more like ly to have come from the DHSS officials? ANSWER: I think it's more likely to have come from the DHSS officials.
45,725	320	QUESTION: But the references to the source material choice be ing "based on commercial and scientific grounds", as opposed to what other grounds? ANSWER: Um ... as opposed, presumably, to citing the source of the raw material. So in other words, it's coming f rom the US. I don't know what else.
45,726	320	QUESTION: Are you able to assist us any further now about the contents of that meeting and what was discussed at it? Can you remember it at all? ANSWER: I can't remember it. I can't remember it very well at all, no.
45,727	320	QUESTION: Do you know why it was that you were asked to go fr om Speywood? ANSWER: Well, Anne would have set it up, and I would have g one 176 along because of being -- whenever that meeting was , still being chief scientist of Speywood. The most experienced for the human Factor VIII.
45,728	320	QUESTION: Can you help us with whether or not a further application was made for a clinical trial certifica te on that product? ANSWER: I don't think it was.
45,729	320	QUESTION: Do you know why it wasn't pursued? ANSWER: No -- well, yes, I probably do, because I don't thi nk there was anywhere to make it.
45,730	320	QUESTION: The facility that had been planned wasn't built? ANSWER: No. And I think at one stage it might even have be en thought you could share the facility with porcine, but that became a no-goer when -- because of virus concerns, and it had to be separate.
45,731	320	QUESTION: That is something we saw with the business plan abo ut the DHSS no longer allowing a multi-purpose site. ANSWER: Yes.
45,732	320	QUESTION: Looking back on human Factor VIII and polyelectroly te fractionation, was this always a project that was ultimately bound to fail, given the knowledge and equipment and availability of material in the early 1980s, or were there any missed opportunities to ha ve developed it further? ANSWER: Sorry, do you mean with respect to human Factor VII I? 77
45,733	320	QUESTION: Yes. ANSWER: I don't think it was going to fly. It worked very nicely for porcine Factor VIII.
45,734	320	QUESTION: But not for human? ANSWER: But not for human.
45,735	320	QUESTION: On recombinants -- I'm going to take this very briefly, if I may -- your role was important but limited in helping to provide the purified -- the first step of the purification process? ANSWER: Yes.
45,736	320	QUESTION: And then passing that on to Dr Tuddenham and his te am to work on thereafter? ANSWER: Yes.
45,737	320	QUESTION: Mr Heath's view that we heard earlier was that this was something of a tragic failure by the UK to capitalise upon the work that was done, because the -- ultimately the work was taken forward by Genentech, an American company, and subsequently by other American pharmaceutical companies as well? ANSWER: Yes.
45,738	320	QUESTION: Could I ask for your opinion on that view from Mr Heath, and in particular upon the question of whether, if other steps had been taken, it would ha ve led to a quicker development of recombinant product s or just a development by a British firm as opposed to 178 an American firm? ANSWER: I think what happened with the recombinant Factor V III was that, as I understood it, the -- there was a certain amount of money brought forward by Prutec and BTG, and that was sort of -- that money was dispersed around various Oxford facilities to try t o clone the gene, to sequence it -- sequence it first , purify it, et cetera -- and none of that programme really worked out. The only bit of that programme that worked out was Ted Tuddenham's purification. The UK didn't really have the technology at the time. In a paper that Ted wrote, Ted Tuddenham wro te, he said that they had, and I recall that they did, they interviewed Genentech, Genetics Institute, with -- another American company, and Celltech in t his country, after Ted had presented his work on purification. And Celltech in this country was at the stage of making protein -- I think it was rennet -- in bacteria. Factor VIII was a big protein. Nobody k new what the structure was. It needed to be done in mammalian cells. David had actually written into the original agreement that if it was mammalian cells then the U K manufacturing rights would stay here. So he was astute enough to realise that, and they realised th at 179 it was never going to be a bacteria. And the Oxfor d people, who were working on the project, were worki ng in yeast, which was not terribly much better for a big protein like Factor VIII. There was not much known about the structure either. I do recall that after some had been purified, it was sent to ICRF, but Mike Waterfield, who was going to do some sequencing, couldn't get time on t he sequencer. So when it went over to Genentech, they had a whole department with several people, sequences dedicated to the project. It was just completely different. So going back to your original question, which I've probably not answered, I don't know, but it ca me down to the fact that I think the funding from Prut ec and BTG was not used in a very constructive way, an d that goes back to what I said originally about Davi d, that he gave responsibility to people for doing things, and the person that stood out was Ted Tuddenham. The rest of them didn't really have the technology to do it. And Prutec and BTG got a bit upset about that, and that's when the trouble came, and David was removed and put to one side. He wasn't terribly popular with a lot of people 180 because of his, sort of, rather -- what shall we say -- his sort of -- his energetic sort of -- I ca n't think of the right word, but he wanted -- he was passionate about what he wanted, but that passion tended to make him promise too much and achieve -- not achieve it, and I don't think that made him a very good source for somebody to invest in. I don't thi nk they were very happy with it.
45,739	320	QUESTION: Ms Middleton, a few questions from some of the Core Participants that I've been invited to ask you . This means we're going to jump rather from one topi c to another. ANSWER: Yes, okay.
45,740	320	QUESTION: Starting with your time still in Scotland, and the reference that you made to a colleague sadly dying of hepatitis B, were any changes made to the way you operated in response to that death? ANSWER: Um ... immediately, yes, we did become much more aware, I think, of the potential problems with the plasma we were dealing with. The person that had t he accident, it was a known infected patient that caus ed 182 the problem there. And that was in a lab, which wa s a separate lab, where they were doing studies with th e hepatitis virus. But as far as PFC was concerned, obviously we -- I suppose we did become much more aware of the potential.
45,741	320	QUESTION: Do I understand from that answer that the colleague was somebody who worked within the Edinburgh Royal Infirmary rather than within the PFC? ANSWER: Yes, she wasn't in the PFC, she was in the Royal Infirmary. But in the same sort of department, blo od transfusion.
45,742	320	QUESTION: Do you know if the accident and the death was notif ied to any public health body? ANSWER: I'm sure it was. It was a prick. It was an accidental prick with a needle, which was, you know , tiny, but yeah, that's what happened.
45,743	320	QUESTION: Staying with your time in Scotland, and moving to Glasgow, do you recall if the blood that you were dealing with, which was taken from patients with haemophilia, was marked as being high risk? ANSWER: I don't think it was.
45,744	320	QUESTION: Do you remember if any particular procedures were i n place for how you dealt with and handled that blood ? ANSWER: No, I don't think so. 183
45,745	320	QUESTION: I am going to -- this is a document that you haven' t seen and I don't think is on our system, so I'm jus t going to read a short passage to you. It comes fro m a meeting in May 1985, a meeting in Scotland of the Scottish National Blood Transfusion Service. And i t refers to a request that has come from you to the SNBTS -- and forgive me, I've just lost my place temporarily. What is recorded in the minutes is this you have asked: "... to obtain from the SNBTS about 50 litres per annum of fresh frozen plasma from which to developed a range of reagent biodepleted plasmas." You had approached SNBTS because of "concern that the haemophiliac plasma substates in use at present might be contaminated with HTLV-III or hepatitis". ANSWER: Yes.
45,746	320	QUESTION: First of all, do you have any recollection of makin g such a request? ANSWER: I don't, but I do remember the project, so ...
45,747	320	QUESTION: Could you explain what that project was? ANSWER: The project was to use monoclonal antibodies, the o nes developed at the Royal Free, to make a Factor VIII-deficient plasma. Factor VIII-defici ent 184 plasmas from haemophiliacs were used as reagents to test for the potency of a Factor VIII concentrate. So rather than use -- these obviously became much more potentially risky -- that was thought to be the cas e, as reagents. And therefore, we decided to use norm al plasma, and deplete it of Factor VIII using monoclo nal antibody column to deplete it.
45,748	320	QUESTION: In order to create assays? ANSWER: To use for assays.
45,749	320	QUESTION: So everybody has the reference, it's PRSE0004075, a nd the minutes record that it was considered not appropriate to provide the material because there w as no surplus at the time. ANSWER: Right.
45,750	320	QUESTION: Do you know if you were able to obtain an equivalen t material from elsewhere? ANSWER: I did get some from somewhere. I bought some from somewhere. But it wasn't the United States. I'm n ot quite sure. It can't have been English, British -- I don't know where it -- (overspeaking) --
45,751	320	QUESTION: Because it was commercial? ANSWER: It must have been commercial.
45,752	320	QUESTION: And your desire was to avoid the material coming fr om the United States because of perceived risk of HTLV-III? 85 ANSWER: Well, it was to come from -- there was no point in doing it unless it came from a clean source. And I can't recall now where it did come from, but we d id use that technology, and subsequently it was -- the assay was developed and was sold commercially by an organisation called Diagnostic Reagents who were ba sed in Oxford and who supplied -- probably still do -- reagents for coagulation factors.
45,753	320	QUESTION: Moving on to a different topic, was there any discussion about proposed research concerning AIDS, HIV, HTLV-III, at Speywood during your time there? ANSWER: Not AIDS, no. I think AIDS and HIV were only reall y identified -- started to be identified in '82, '83.
45,754	320	QUESTION: But Speywood wasn't involved in any -- ANSWER: No.
45,755	320	QUESTION: Specific projects that tried to address the risk of -- ANSWER: No.
45,756	320	QUESTION: -- HIV, HTLV-III, et cetera? ANSWER: No.
45,757	320	QUESTION: Further question. How much of your work, either at the PFC or at Speywood, informed by a knowledge of the different severities of haemophilia in patients, mi ld, moderate and severe haemophilia? ANSWER: Um, I'm not sure I understand the question. We wer e making concentrates to treat haemophilia, whatever the 186 level, however severe or mild it was.
45,758	320	QUESTION: But were you aware of the distinctions between -- ANSWER: Yes.
45,759	320	QUESTION: -- mild, moderate and severe? ANSWER: Yes.
45,760	320	QUESTION: Does it come back to the fact that your role as a scientist was to seek to make the product -- ANSWER: Yes.
45,761	320	QUESTION: -- and not to decide how it should be used by the clinician -- ANSWER: Yes.
45,762	320	QUESTION: -- and the patient? ANSWER: Yes, yes. Although in discussions with the clinicians -- because we were very close to the clinical use, particularly in the UK -- we did get to learn about what people were doing, what clinicians were doing for treatment, et cetera.
45,763	320	QUESTION: Ms Middleton, with all of our witnesses, we ask at the end if there is anything else that you wish to say in your evidence. ANSWER: Um, no, I don't think so. Thank you.
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45,769	326	QUESTION: MS SCOTT:ANSWER: MS SCOTT:
45,770	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,771	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,772	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,773	326	QUESTION: SIR BRIAN LANGSTAFF:ANSWER: MS SCOTT:
45,774	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,775	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,776	326	QUESTION: SIR BRIAN LANGSTAFF:ANSWER: MS SCOTT:
45,777	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,778	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,779	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,780	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,781	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,782	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,783	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,784	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,785	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,786	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,787	326	QUESTION: MS SCOTT:ANSWER: SIR BRIAN LANGSTAFF:
45,788	326	QUESTION: MS SCOTT:ANSWER: CSA:
45,789	326	QUESTION: "The Management Committee does not have within, 83 or available to , it, such independent specialist and other advice as was available within its predecessor , the Executive Committee of SNBTANSWER: This lack of professional expertise and clinical user involvement is considered by the Transfusion Directors to be a retrograde step in the management of the service. "5. For some years before 1974 it had been planned that a small B T S Headquarters should take over the duties of the part-time officers of SNBTA and the medical secretary and administrative officer provided by SHHD. In the event the head quarters was not established until nearly 1974 at the time of transfer to CSA, when a CSA headquarters office was also established , apparently to undertake on behalf of CSA Divisions duties hitherto carried out within the Divisions themselves. The resultant duplication of effort, made worse by the recruitment of inexperienced staff to CSA headquarters, has been expensive , unrewarding to all concerned and detrimental to effective management. The Transfusion Directors are now in no doubt that the appropriate place for BTS central administration is in its own headquarters aided by financial and management containing and internal audit . This arrangement would be cost effective. Interposing CSA headquarters as a tier 84 between the Directors of CSA Div isions and the Management Committee to which they are accountable has been most unfortunate." Then it goes on at paragraph 6 , over the page , after the quote there: "After [ two and a half ] years ' experience and following careful consideration it is the view of the Transfusion Directors that BTS should be administered as a National Service and that its nature renders it unsuited to management by a committee composed entirely of Health Board members and officers and officials of SHHD within the framework of CS
45,790	326	QUESTION: A.ANSWER: A.
45,791	326	QUESTION: This lack of professional expertise and clinical user involvement is considered by the Transfusion Directors to be a retrograde step in the management of the service. "5. For some years before 1974 it had been planned that a small B T S Headquarters should take over the duties of the part-time officers of SNBTA and the medical secretary and administrative officer provided by SHHD. In the event the head quarters was not established until nearly 1974 at the time of transfer to CSA, when a CSA headquarters office was also established , apparently to undertake on behalf of CSA Divisions duties hitherto carried out within the Divisions themselves. The resultant duplication of effort, made worse by the recruitment of inexperienced staff to CSA headquarters, has been expensive , unrewarding to all concerned and detrimental to effective management. The Transfusion Directors are now in no doubt that the appropriate place for BTS central administration is in its own headquarters aided by financial and management containing and internal audit . This arrangement would be cost effective. Interposing CSA headquarters as a tier 84 between the Directors of CSA Div isions and the Management Committee to which they are accountable has been most unfortunate." Then it goes on at paragraph 6 , over the page , after the quote there: "After [ two and a half ] years ' experience and following careful consideration it is the view of the Transfusion Directors that BTS should be administered as a National Service and that its nature renders it unsuited to management by a committee composed entirely of Health Board members and officers and officials of SHHD within the framework of CSANSWER: " Then the proposal that's made for the future is set out at paragraph 7: " It is suggested that the service should transfer to a Management Committee responsible to the Secretary of State and having the following membership : " Chairman, appointed by Secretary of State ... " Transfusion Service National Medical Director ... " Transfusion Directors ... " Donor interest ... " User interest ... " Health Board interest ..." 9 November 2021 9 subcommittee. Then if we go back to page 2, it sets out the constituents -- the constitution , rather , of the Blood Service Subcommittee at subparagraph (iii) there: "Six members of the Management Committee ( one of whom would be Convener ) -- including the Chairman and Vice-Chairman as ex-officio members in terms of the Standing Orders of the Agency, Two specialists in clinical medicine , Two specialists in laboratory medicine , One medical officer from the Scottish Home and Health Department , One representative of Donor Interest s ." Then we see at (v): "... that the National Medical Director should , as a matter of course , receive the agenda and supporting paper s for each meeting of the Blood Transfusion Service Subcommittee and attend or be represented and [ over the page ] that the other Directors within the Blood Transfusion Service should also receive copies of the agenda and supporting papers of each meeting and , subject to the agreement of the Convener , attend if they so wished ... " So that was the agreement that was reached in June 1977 , and so what then happened was that that subcommittee , in turn , set up a working party in which 90 representatives of the -- in which the transfusion directors participated. There were further legislative changes in 1978 , which had the effect of reconstituting the CSA , and so members of the management committee of the CSA were appointed by the Secretary of State and that structure remained large ly unchanged , following the appointment of Professor Cash in 1978 as the National Medical Director . Again, the extent to which the regional services retained autonomy through the period will be an issue that we will -- sorry, the extent to which the individual Blood Transfusion Centres re tained autonomy through this period will be explored within the hearings. We can see from the minutes that are available to us that , through the late 1970s and 1980s the Scottish National Blood Transfusion Service Co-ordinating Group met on a regular basis , as did the SNBTS directors. I've already mentioned , when I was doing the presentation on England , that the first formal liaison , if you like , between Scotland and England and Wales came when the advisory committee to the National Blood Transfusion Service in England was formed in December 1980 , and there was -- part of the remit was to advise the Department of Health and 91 Social Security on co-ordination of the English and Welsh and Scottish Blood Transfusion Services. The first joint committee between the Scottish and the English services was the formation of the SNBTS/NBTS liaison committee in June 1990. We can also see from the minutes that there was regular attendance by Professor Cash at Regional Transfusion Director meetings in England, that Dr Cash attended the Advisory Committee on the NBTS formed in December 1980, although that Committee was dealing only with matters concerning England and Wales, and there was often an English director or a representative of the National Directorate , once that had been formed , at Scottish Regional Transfusion Director meetings. In 1990, the Scottish National Blood Transfusion Service created a General Manager position and that position was then renamed National Director in 1996 , and the National Medical Director, who was Professor Cash, became the National Medical and Scientific Director. So the regional directors and the PFC director became managerially accountable to the General Manager , who then became known as the National Direct or, and professionally accountable to the 92 National Medical and Scientific Director. The SNBTS management board at that stage compromised (sic) the General Manager , the National Medical and Scientific Director , the five Transfusion Centre Directors the Director of PFC, a National Donor Services Manager, Director of Human Resources, a Director of Finance, and a Director of Quality . Following a strategic review in 1998-1999, SNBTS was restructured to move away from regional structure towards a national structure and , since that time, all blood donor services have been managed nationally. A directorate for operations was created to manage donor services, manufacturing and logistics and the number of blood processing and testing units was reduced to two. A national quality directorate was formed along with other national support services and hospital blood banking and related clinical and laboratory functions remained distributed within the Regional Transfusion Centres. The Regional Transfusion Directors became clinical directors. In 2002 to 2003 , the Common Services Agency underwent a strategic review and , once again , the clinical directors of Scottish National Blood Transfusion Service expressed their dissatisfaction 9 November 2021 3 with the CSA , as being not qualified to manage the performance of the SNBTS , and a report authored at that time concluded that there was some justification for those concerns because of the lack of a developed system of clinical governance in the CSA and a lack of clarity about the role and purpose of the board and a lack of clarity about how the CSA and its divisions add value to each other's activities. Following that review, the governance arrangements were strengthened. The SNBTS national director became an executive director of the CSA board and the CSA board adopted the governance structure of other health boards, including a clinical governance committee and a centralisation of some of its support services. On 1 October 2008 , the National Health Service Functions of the Common Services Agency Scotland Order removed the production of blood fractions from the functions of the CS
45,792	326	QUESTION: A.ANSWER: A.
45,793	326	QUESTION: " Then the proposal that's made for the future is set out at paragraph 7: " It is suggested that the service should transfer to a Management Committee responsible to the Secretary of State and having the following membership : " Chairman, appointed by Secretary of State ... " Transfusion Service National Medical Director ... " Transfusion Directors ... " Donor interest ... " User interest ... " Health Board interest ..." 9 November 2021 9 subcommittee. Then if we go back to page 2, it sets out the constituents -- the constitution , rather , of the Blood Service Subcommittee at subparagraph (iii) there: "Six members of the Management Committee ( one of whom would be Convener ) -- including the Chairman and Vice-Chairman as ex-officio members in terms of the Standing Orders of the Agency, Two specialists in clinical medicine , Two specialists in laboratory medicine , One medical officer from the Scottish Home and Health Department , One representative of Donor Interest s ." Then we see at (v): "... that the National Medical Director should , as a matter of course , receive the agenda and supporting paper s for each meeting of the Blood Transfusion Service Subcommittee and attend or be represented and [ over the page ] that the other Directors within the Blood Transfusion Service should also receive copies of the agenda and supporting papers of each meeting and , subject to the agreement of the Convener , attend if they so wished ... " So that was the agreement that was reached in June 1977 , and so what then happened was that that subcommittee , in turn , set up a working party in which 90 representatives of the -- in which the transfusion directors participated. There were further legislative changes in 1978 , which had the effect of reconstituting the CSA , and so members of the management committee of the CSA were appointed by the Secretary of State and that structure remained large ly unchanged , following the appointment of Professor Cash in 1978 as the National Medical Director . Again, the extent to which the regional services retained autonomy through the period will be an issue that we will -- sorry, the extent to which the individual Blood Transfusion Centres re tained autonomy through this period will be explored within the hearings. We can see from the minutes that are available to us that , through the late 1970s and 1980s the Scottish National Blood Transfusion Service Co-ordinating Group met on a regular basis , as did the SNBTS directors. I've already mentioned , when I was doing the presentation on England , that the first formal liaison , if you like , between Scotland and England and Wales came when the advisory committee to the National Blood Transfusion Service in England was formed in December 1980 , and there was -- part of the remit was to advise the Department of Health and 91 Social Security on co-ordination of the English and Welsh and Scottish Blood Transfusion Services. The first joint committee between the Scottish and the English services was the formation of the SNBTS/NBTS liaison committee in June 1990. We can also see from the minutes that there was regular attendance by Professor Cash at Regional Transfusion Director meetings in England, that Dr Cash attended the Advisory Committee on the NBTS formed in December 1980, although that Committee was dealing only with matters concerning England and Wales, and there was often an English director or a representative of the National Directorate , once that had been formed , at Scottish Regional Transfusion Director meetings. In 1990, the Scottish National Blood Transfusion Service created a General Manager position and that position was then renamed National Director in 1996 , and the National Medical Director, who was Professor Cash, became the National Medical and Scientific Director. So the regional directors and the PFC director became managerially accountable to the General Manager , who then became known as the National Direct or, and professionally accountable to the 92 National Medical and Scientific Director. The SNBTS management board at that stage compromised (sic) the General Manager , the National Medical and Scientific Director , the five Transfusion Centre Directors the Director of PFC, a National Donor Services Manager, Director of Human Resources, a Director of Finance, and a Director of Quality . Following a strategic review in 1998-1999, SNBTS was restructured to move away from regional structure towards a national structure and , since that time, all blood donor services have been managed nationally. A directorate for operations was created to manage donor services, manufacturing and logistics and the number of blood processing and testing units was reduced to two. A national quality directorate was formed along with other national support services and hospital blood banking and related clinical and laboratory functions remained distributed within the Regional Transfusion Centres. The Regional Transfusion Directors became clinical directors. In 2002 to 2003 , the Common Services Agency underwent a strategic review and , once again , the clinical directors of Scottish National Blood Transfusion Service expressed their dissatisfaction 9 November 2021 3 with the CSA , as being not qualified to manage the performance of the SNBTS , and a report authored at that time concluded that there was some justification for those concerns because of the lack of a developed system of clinical governance in the CSA and a lack of clarity about the role and purpose of the board and a lack of clarity about how the CSA and its divisions add value to each other's activities. Following that review, the governance arrangements were strengthened. The SNBTS national director became an executive director of the CSA board and the CSA board adopted the governance structure of other health boards, including a clinical governance committee and a centralisation of some of its support services. On 1 October 2008 , the National Health Service Functions of the Common Services Agency Scotland Order removed the production of blood fractions from the functions of the CSANSWER: The CSA remained responsible for the provision of supplies of human blood for transfusion and related services , and there was a period of wider organisational structural change in 2012-2013 resulting in consolidation of a number of CSA divisions , often called strategic business units , and the centralisation of support services , but the 94 SNBTS was considered of sufficient size and specialty to retain its own identity. In 2013, there were changes to the name . The SNBTS Board was renamed Senior Management Group and was chaired by the SNBTS national director. The medical and Scientific Committee was renamed the Clinical Governance and Safety Group and the posts of clinical directors were removed and SNBTS was organised into a number of national directorates led by associate directors. Those were donor and transport (sic) services, blood manufacturing, patient services and strategy planning and performance. There's been no significant further change to structure since that time. It appears from the documentation that the Inquiry has that the SNBTS was fun ded centrally from the Scottish Government's central budget rather than from region health budgets as was the case in my England and Wales, that until 2002/2003 the Scottish Home and Health Department provided the CSA with a ring-fenced budget for the blood service but , after this time , there was no ring-fenced budget so it was left to the CSA to allocate a budget to the SNBTS as part of its internal business planning. So, sir , that brings me to the end of the 95 presentation on the history and structure of the Blood Transfusion Services. The presentation is accompanied -- supported by a written presentation , which has been disclosed to Core Participant through their legal representatives and will be made available on the website , and that has more detail and references to other documents that , for reasons of time , I haven't been able to go to.
45,794	326	QUESTION: A.ANSWER: SIR BRIAN LANGSTAFF:
45,795	326	QUESTION: MS FRASER BUTLIN:ANSWER: SIR BRIAN LANGSTAFF:
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QUESTION: Yes. ANSWER: Um ... maybe in some -- I don't -- I don't know how to answer that question.

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QUESTION: No smoke and mirrors here, that's the -- ANSWER: That's the question.

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QUESTION: If you're in the circumstances where it is unlikely that this will ever be made into a -- ANSWER: Well, it was made at the bio products laboratory, t hat product. So they must have thought something posit ive about it at that stage, in spite of the difficultie s that we had with it. So maybe they thought that th ey should check that it would work, because it was a different entity. So, maybe, you know, things might -- things might work out. Maybe I was being too negative about it. Maybe it was possible to make i t work. But the other question that needed to be answered is would it actually work in the circulati on? Never mind whether the -- you know, because if you can 170 get the production process to work, which I couldn' t, but other people might have got it to work, would Factor

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QUESTION: Do I take it from your answer that you were trying now to help us by looking back and thinking what the thinking might have been, but you weren't actually -- you're not able to say what you yourself thought at the time? ANSWER: Yes.

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QUESTION: I should say, out of fairness, that we looked at th e 1983-1985 business plan and, as we discussed during the presentation, the door was not being closed absolutely on Factor VIII through polyelectrolyte fractionation, although there were concerns about h ow feasible it was going to be. ANSWER: Mm.

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QUESTION: We know that the initial application was turned dow n, and I referred to a meeting that you attended on 2 June 1983. If we could have that on screen, plea se, Soumik. It's IPS -- ANSWER: That wasn't the same product.

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QUESTION: Ah. If we bring it up on screen, perhaps you can assist us with it. IPSN0000165_109, please. ANSWER: Yeah. 171

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QUESTION: So this is a meeting on 2 June 1983. ANSWER: Yeah.

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QUESTION: Then "source of cryoprecipitate"? ANSWER: Which was this Alpha cryoprecipitate, which was bei ng bought in 100-kilo lots -- was it 100-kilo lots -- in large lots, as a frozen cryoprecipitate, to make -- to try to make Mono Factor

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QUESTION: Yes, I think we're at slightly cross purposes. ANSWER: Oh right, okay.

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QUESTION: So the paper I referred you to earlier, which you co-wrote with Dr Lane, et cetera, et cetera, and Dr Tuddenham, that was a product that was made in Elstree -- ANSWER: In Elstree, yes.

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QUESTION: -- and that was used, as you said, on three patients -- ANSWER: And one von Willebrand's.

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QUESTION: -- with haemophilia A and one von Willebrand's patient. ANSWER: Yes. 172

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QUESTION: This is different. This is the application for the clinical trial -- ANSWER: Yes.

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QUESTION: -- which was made at some point in 1982? ANSWER: Yes.

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QUESTION: That was what I was discussing with you a moment ag o? ANSWER: Yes, yes.

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QUESTION: Why it was that there was an attempt to have a clinical trial at that stage. ANSWER: Oh, from this -- yes.

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QUESTION: The idea was that the material -- the cryoprecipitate would come up in from Alpha, and th en you would fractionate it -- 73 ANSWER: It was a frozen paste that you re-suspended. We did -- I did do some work with it. It was a frozen paste that was re-suspended and then put over the polyelectrolyte.

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QUESTION: I'd like to just look at what was to said at this meeting. There was you and Anne Walton from Speywo od? ANSWER: Yes.

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QUESTION: The note is by -- the initials are EAW. Is that An ne Walton? ANSWER: Yes.

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QUESTION: Who was Anne Walton? ANSWER: She was -- she did some marketing but she also focu sed in on regulatory affairs.

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QUESTION: Was she a scientist? ANSWER: Yes.

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QUESTION: The participants from the DHSS, a Dr Fowler and Dr Purves. ANSWER: Yes.

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QUESTION: And if we could just look at the note and I'll read it through to you. "1. Dr Fowler was of the opinion that, despite the controversy surrounding US imports as a result of AIDS, our application will not be judged prejudicia lly by the CSM if we pursue it with Alpha cryo cited as source material. There have been suggestions in 174 certain quarters about the banning of importation o f all US blood products but the impracticality of thi s is recognised by those who were well informed in th is area and a ban does not, therefore seem likely. An application based on Alpha cryo would (or should) b e judged solely on its scientific merit. "2. The possibility of leaving an application open-ended with respect to source material was discussed and dismissed as unacceptable. "3. We were advised that if a change in source material is desired, the application might proceed more easily if the licensing of the import or the c ryo were included in the CTC application. The responsibility wore the quality of the raw material would then be entirely Speywood's and in addition, the cryo would then be licensed for importation only fo r the purpose covered by the CTC." If we go over to the next page, the possible courses of action are discussed. I won't go thorou gh that, but it says: "In conclusion it appears that the use of US cryo will not prejudice our case with the licensing authorities and therefore our choice of source material can be based on commercial and scientific grounds." 175 A couple of points about that. Paragraph 1, the discussion of the potential ban on US blood product s, and the recognition that that was impractical. Are you able to help us with who was saying that it wou ld be impractical to ban US blood products? ANSWER: No.

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QUESTION: Would you or Anne Walton have been in a position to make that observation? Do you think it's more like ly to have come from the DHSS officials? ANSWER: I think it's more likely to have come from the DHSS officials.

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QUESTION: But the references to the source material choice be ing "based on commercial and scientific grounds", as opposed to what other grounds? ANSWER: Um ... as opposed, presumably, to citing the source of the raw material. So in other words, it's coming f rom the US. I don't know what else.

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QUESTION: Are you able to assist us any further now about the contents of that meeting and what was discussed at it? Can you remember it at all? ANSWER: I can't remember it. I can't remember it very well at all, no.

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QUESTION: Do you know why it was that you were asked to go fr om Speywood? ANSWER: Well, Anne would have set it up, and I would have g one 176 along because of being -- whenever that meeting was , still being chief scientist of Speywood. The most experienced for the human Factor VIII.

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QUESTION: Can you help us with whether or not a further application was made for a clinical trial certifica te on that product? ANSWER: I don't think it was.

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QUESTION: Do you know why it wasn't pursued? ANSWER: No -- well, yes, I probably do, because I don't thi nk there was anywhere to make it.

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QUESTION: The facility that had been planned wasn't built? ANSWER: No. And I think at one stage it might even have be en thought you could share the facility with porcine, but that became a no-goer when -- because of virus concerns, and it had to be separate.

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QUESTION: That is something we saw with the business plan abo ut the DHSS no longer allowing a multi-purpose site. ANSWER: Yes.

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QUESTION: Looking back on human Factor VIII and polyelectroly te fractionation, was this always a project that was ultimately bound to fail, given the knowledge and equipment and availability of material in the early 1980s, or were there any missed opportunities to ha ve developed it further? ANSWER: Sorry, do you mean with respect to human Factor VII I? 77

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QUESTION: Yes. ANSWER: I don't think it was going to fly. It worked very nicely for porcine Factor VIII.

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QUESTION: But not for human? ANSWER: But not for human.

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QUESTION: On recombinants -- I'm going to take this very briefly, if I may -- your role was important but limited in helping to provide the purified -- the first step of the purification process? ANSWER: Yes.

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QUESTION: And then passing that on to Dr Tuddenham and his te am to work on thereafter? ANSWER: Yes.

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QUESTION: Mr Heath's view that we heard earlier was that this was something of a tragic failure by the UK to capitalise upon the work that was done, because the -- ultimately the work was taken forward by Genentech, an American company, and subsequently by other American pharmaceutical companies as well? ANSWER: Yes.

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QUESTION: Could I ask for your opinion on that view from Mr Heath, and in particular upon the question of whether, if other steps had been taken, it would ha ve led to a quicker development of recombinant product s or just a development by a British firm as opposed to 178 an American firm? ANSWER: I think what happened with the recombinant Factor V III was that, as I understood it, the -- there was a certain amount of money brought forward by Prutec and BTG, and that was sort of -- that money was dispersed around various Oxford facilities to try t o clone the gene, to sequence it -- sequence it first , purify it, et cetera -- and none of that programme really worked out. The only bit of that programme that worked out was Ted Tuddenham's purification. The UK didn't really have the technology at the time. In a paper that Ted wrote, Ted Tuddenham wro te, he said that they had, and I recall that they did, they interviewed Genentech, Genetics Institute, with -- another American company, and Celltech in t his country, after Ted had presented his work on purification. And Celltech in this country was at the stage of making protein -- I think it was rennet -- in bacteria. Factor VIII was a big protein. Nobody k new what the structure was. It needed to be done in mammalian cells. David had actually written into the original agreement that if it was mammalian cells then the U K manufacturing rights would stay here. So he was astute enough to realise that, and they realised th at 179 it was never going to be a bacteria. And the Oxfor d people, who were working on the project, were worki ng in yeast, which was not terribly much better for a big protein like Factor VIII. There was not much known about the structure either. I do recall that after some had been purified, it was sent to ICRF, but Mike Waterfield, who was going to do some sequencing, couldn't get time on t he sequencer. So when it went over to Genentech, they had a whole department with several people, sequences dedicated to the project. It was just completely different. So going back to your original question, which I've probably not answered, I don't know, but it ca me down to the fact that I think the funding from Prut ec and BTG was not used in a very constructive way, an d that goes back to what I said originally about Davi d, that he gave responsibility to people for doing things, and the person that stood out was Ted Tuddenham. The rest of them didn't really have the technology to do it. And Prutec and BTG got a bit upset about that, and that's when the trouble came, and David was removed and put to one side. He wasn't terribly popular with a lot of people 180 because of his, sort of, rather -- what shall we say -- his sort of -- his energetic sort of -- I ca n't think of the right word, but he wanted -- he was passionate about what he wanted, but that passion tended to make him promise too much and achieve -- not achieve it, and I don't think that made him a very good source for somebody to invest in. I don't thi nk they were very happy with it.

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QUESTION: Ms Middleton, a few questions from some of the Core Participants that I've been invited to ask you . This means we're going to jump rather from one topi c to another. ANSWER: Yes, okay.

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QUESTION: Starting with your time still in Scotland, and the reference that you made to a colleague sadly dying of hepatitis B, were any changes made to the way you operated in response to that death? ANSWER: Um ... immediately, yes, we did become much more aware, I think, of the potential problems with the plasma we were dealing with. The person that had t he accident, it was a known infected patient that caus ed 182 the problem there. And that was in a lab, which wa s a separate lab, where they were doing studies with th e hepatitis virus. But as far as PFC was concerned, obviously we -- I suppose we did become much more aware of the potential.

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QUESTION: Do I understand from that answer that the colleague was somebody who worked within the Edinburgh Royal Infirmary rather than within the PFC? ANSWER: Yes, she wasn't in the PFC, she was in the Royal Infirmary. But in the same sort of department, blo od transfusion.

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QUESTION: Do you know if the accident and the death was notif ied to any public health body? ANSWER: I'm sure it was. It was a prick. It was an accidental prick with a needle, which was, you know , tiny, but yeah, that's what happened.

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QUESTION: Staying with your time in Scotland, and moving to Glasgow, do you recall if the blood that you were dealing with, which was taken from patients with haemophilia, was marked as being high risk? ANSWER: I don't think it was.

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QUESTION: Do you remember if any particular procedures were i n place for how you dealt with and handled that blood ? ANSWER: No, I don't think so. 183

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QUESTION: I am going to -- this is a document that you haven' t seen and I don't think is on our system, so I'm jus t going to read a short passage to you. It comes fro m a meeting in May 1985, a meeting in Scotland of the Scottish National Blood Transfusion Service. And i t refers to a request that has come from you to the SNBTS -- and forgive me, I've just lost my place temporarily. What is recorded in the minutes is this you have asked: "... to obtain from the SNBTS about 50 litres per annum of fresh frozen plasma from which to developed a range of reagent biodepleted plasmas." You had approached SNBTS because of "concern that the haemophiliac plasma substates in use at present might be contaminated with HTLV-III or hepatitis". ANSWER: Yes.

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QUESTION: First of all, do you have any recollection of makin g such a request? ANSWER: I don't, but I do remember the project, so ...

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QUESTION: Could you explain what that project was? ANSWER: The project was to use monoclonal antibodies, the o nes developed at the Royal Free, to make a Factor VIII-deficient plasma. Factor VIII-defici ent 184 plasmas from haemophiliacs were used as reagents to test for the potency of a Factor VIII concentrate. So rather than use -- these obviously became much more potentially risky -- that was thought to be the cas e, as reagents. And therefore, we decided to use norm al plasma, and deplete it of Factor VIII using monoclo nal antibody column to deplete it.

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QUESTION: In order to create assays? ANSWER: To use for assays.

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QUESTION: So everybody has the reference, it's PRSE0004075, a nd the minutes record that it was considered not appropriate to provide the material because there w as no surplus at the time. ANSWER: Right.

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QUESTION: Do you know if you were able to obtain an equivalen t material from elsewhere? ANSWER: I did get some from somewhere. I bought some from somewhere. But it wasn't the United States. I'm n ot quite sure. It can't have been English, British -- I don't know where it -- (overspeaking) --

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QUESTION: Because it was commercial? ANSWER: It must have been commercial.

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QUESTION: And your desire was to avoid the material coming fr om the United States because of perceived risk of HTLV-III? 85 ANSWER: Well, it was to come from -- there was no point in doing it unless it came from a clean source. And I can't recall now where it did come from, but we d id use that technology, and subsequently it was -- the assay was developed and was sold commercially by an organisation called Diagnostic Reagents who were ba sed in Oxford and who supplied -- probably still do -- reagents for coagulation factors.

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QUESTION: Moving on to a different topic, was there any discussion about proposed research concerning AIDS, HIV, HTLV-III, at Speywood during your time there? ANSWER: Not AIDS, no. I think AIDS and HIV were only reall y identified -- started to be identified in '82, '83.

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QUESTION: But Speywood wasn't involved in any -- ANSWER: No.

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QUESTION: Specific projects that tried to address the risk of -- ANSWER: No.

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QUESTION: -- HIV, HTLV-III, et cetera? ANSWER: No.

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QUESTION: Further question. How much of your work, either at the PFC or at Speywood, informed by a knowledge of the different severities of haemophilia in patients, mi ld, moderate and severe haemophilia? ANSWER: Um, I'm not sure I understand the question. We wer e making concentrates to treat haemophilia, whatever the 186 level, however severe or mild it was.

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QUESTION: But were you aware of the distinctions between -- ANSWER: Yes.

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QUESTION: -- mild, moderate and severe? ANSWER: Yes.

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QUESTION: Does it come back to the fact that your role as a scientist was to seek to make the product -- ANSWER: Yes.

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QUESTION: -- and not to decide how it should be used by the clinician -- ANSWER: Yes.

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QUESTION: -- and the patient? ANSWER: Yes, yes. Although in discussions with the clinicians -- because we were very close to the clinical use, particularly in the UK -- we did get to learn about what people were doing, what clinicians were doing for treatment, et cetera.

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QUESTION: Ms Middleton, with all of our witnesses, we ask at the end if there is anything else that you wish to say in your evidence. ANSWER: Um, no, I don't think so. Thank you.

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QUESTION: MS SCOTT:ANSWER: MS SCOTT:

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