Volume 7: Medicines and Cosmetics
4. Initial response on human medicines
Discussion
The communication gap between MAFF and DH prior to March 1988
Dr Little's attendance at the CSM/BSC meeting in September
After the meeting
CSM/BSC discussion of Mr Sloggem's paper
The Medicines Division response after March 1988
The response of Medicines Division to the CMO's concerns
Communication between Medicines Division and MAFF

4.82 At the end of the previous chapter we noted the limited flow of information about BSE from medicines licensing officials in MAFF to those in DH prior to January 1989. We discuss below the events surrounding the mistaken impression Dr Little gained, when attending the CSM/BSC meeting on 9 September 1987, that Mr Sloggem's investigations were part of a wider DH Medicines Division response to the emergence of the disease. We also look at what was actually discussed as a result of Mr Sloggem's paper.

4.83 We go on to consider the adequacy of the initial response by Medicines Division after the MAFF formal approach to the CMO in March 1988 and his identification of biologicals used in human medicines as a specific concern.

4.84 We conclude with discussion of the general state of communications about BSE between the two licensing divisions at this time.

The communication gap between MAFF and DH prior to March 1988

4.85 We discuss in vol. 3: The Early Years, 1986-88 our concern about the failure of those in MAFF dealing with BSE to involve DH in discussion of the risks it posed to human health generally, prior to March 1988. This delay affected the speed with which potential routes of infection were identified and measures could be considered to block them. Had there been better communication between MAFF and DH, one of the matters that might have been recognised earlier is that the concerns emerging within CVL about bovine material in veterinary medicines had similar implications for human medicines.

4.86 In theory, the links that operated between the professional staff in the two licensing authorities might have acted as a channel for informal communication about BSE. For example, although the CVL had their own unit for testing materials, they relied on DH toxicologists. DH professional staff also regularly attended both the Scientific Secretariat and the VPC meetings. Their main interest was in the effect that veterinary medication, including hormones and antibiotics in feedstuffs, might have on humans who ate animal products, or handled them. Dr Little told us that although CVL received CSM/BSC agendas there was not the same veterinary interest in human products and he did not normally attend the corresponding DH meetings: 'Medical products have very little interest to veterinarians because there is no immediate connection.' ¹ We discuss those links in greater detail at the end of this chapter. However, they did not lead to sharing of information about BSE prior to September 1987, when Dr Little did find something of interest in the agenda of the CSM/BSC meeting: the discussion of a product containing human dura mater.

Dr Little's attendance at the CSM/BSC meeting in September

4.87 As we have already noted, Dr Little's attendance at this meeting left him with the mistaken impression that DH knew about BSE and was considering it in relation to human products.

4.88 Dr Little told us that he went to the meeting with BSE in mind. He wanted to see how the CSM conducted its safety assessment of a product using human brain, given the risk of CJD. This was his first attendance at the CSM/BSC as an official observer. His thinking on BSE at that time was still highly tentative. Given his awareness that the topic was being handled with kid gloves by his senior officers (see Volume 3) and the fact that there had as yet been no referral to the VPC, we think it was natural that he adopted a low profile at the meeting. Indeed had he wished to notify his counterpart in Medicines Division about the disease and the concerns it raised, an unscheduled contribution at an advisory expert committee on human health would not have been the appropriate way of doing so.

4.89 It appears his contribution was, however, so low key that it failed to register with any of those present. This in itself might not have mattered, since it was open to him to contact Medicines Division thereafter through regular channels. However, his unexpected conversation with Mr Sloggem at the close of the meeting intervened. Given the apparent extent of Mr Sloggem's knowledge of BSE, obtained via the NPU in Edinburgh, and the nature of the product that Mr Sloggem was assessing, it was not unnatural, though extremely unfortunate, that Dr Little concluded that professionals in DH now knew about the disease and were considering it more widely than was in fact the case.

After the meeting

4.90 Dr Little told us that his responsibility after the meeting was to report relevant information to his senior officer, Dr Watson, or directly to the CVO Mr Rees. In this instance he reported back to Dr Watson what he perceived he had learnt at the BSC meeting.

4.91 Should Dr Little, believing as he did that DH knew about and was considering the disease, also have taken steps to follow up his contact with Mr Sloggem or with his opposite number at DH to establish what was happening next? Dr Jefferys told us what he would have expected: 'If mention was made of an emerging problem in the margins of the meeting one would still have expected this to have been followed up with a formal letter.' ² Alternatively Dr Little might have raised the matter with the DH Medical Assessors, with whom he met at least twice a month at the VPC or Scientific Secretariat meetings.

4.92 We explored the question of follow-up with Dr Little when he gave oral evidence. ³

Q: Did you, Dr Little, think at all about whether anybody should follow up the question of whether the Department of Health had written to MAFF or the CVL?

A: Well, that would have been my view on 10th September, but when Dr Watson returned -

Q: Sorry your view was that they would be writing?

A: Yes. When Dr Watson returned from Edinburgh, from the NPU, and told me they were already in correspondence with the NPU, I was no longer concerned, because they were actually contacting the very group of experts that I would have put them in touch with, i.e. the people who dealt with scrapie inactivation and the growth hormone problem. So if someone, say, John Sloggem had written to me, I would have said, 'Yes, and have you contacted David Taylor at the NPU?' I mean, they had, if you like, leapfrogged that process; they had already got to the right place. Not surprising really, when you consider the history.

4.93 Dr Little explained that he did not think at the time that it might be useful for him to see whether the Department of Health was considering the matter on a general level, because he and his colleagues at the CVL dealing with biologicals had not yet produced their own internal documentation: 'They would immediately have wanted to ask a great deal of questions we would not have had answers to.' ⁴ Nor did he think at the time that it would be particularly useful to raise the matter with the chairman or members of the BSC. He told us that he understood that they were dealing with this in a proper manner, and therefore did not see any need to raise it with them: 'Sure enough it went through the process, as you can see from the minutes. They discussed it at the full meeting in January.' ⁵

4.94 We accept that once Medicines Division had recognised the potential risk from the use of bovine materials in the manufacture of medicines, as Dr Little believed, responsibility for considering how that affected human medicines rested with Medicines Division. It was not for Dr Little to check up on what they did.

4.95 However, it seems to us that even if it appeared that Medicines Division was in touch with the NPU, it would have been highly desirable to establish and maintain close communication on BSE directly between MAFF and the Division. Indeed, the fact that the NPU had been approached independently by the two Departments for advice was a clear signal that direct liaison was needed. The question of how best to ensure the safety of medicinal products in the light of the emergence of BSE raised similar issues in relation to human and animal health - for example, which were the most infective parts of the animal? Was it possible to certify herds as BSE-free? Was the disease transmissible via foetal calf serum? Consideration of common measures to deal with these was likely to be appropriate. These were questions on which each of the Departments, including the scientists in the CVL who had been working on BSE, might have had valuable expertise that could be brought to bear. In our view, this called for liaison between those responsible for considering the safety, efficacy and quality of all products, both human and veterinary, covered by the Medicines Act.

4.96 As we have indicated, Dr Little reacted promptly and appropriately in addressing the implications of BSE for veterinary medicines. Two months after the September meeting, Mr Luff was commissioned to write a paper on the subject. This was discussed by the BC, a MAFF committee, on 6 January. ⁶ In our view this would have been an ideal early opportunity for joint consideration of the issues raised by BSE on the part of MAFF and Medicines Division. There would have been much to be gained by inviting the Division to attend the meeting, and sending them a copy of Mr Luff's paper.

4.97 Dr Little told us that if DH staff had concerns there were plenty of opportunities to discuss them with him at the VPC and Scientific Secretariat meetings every month. Indeed, he added: 'I am sure there were further discussions on BSE with the Medical Assessors outside formal meetings, but I cannot recall them now.' If there were such discussions during this period they apparently made as little impact on Medicines Division thinking as did Dr Little's reference to BSE at the September CSM/BSC meeting. It is a pity that no record appears to have been made of any communication between CVL and Medicines Division officials. This might have ensured that there was a clear understanding in each Department of the activities of the other in relation to BSE.

4.98 We do not think that Dr Little is to be criticised for not doing more - his response was not unreasonable - but we do think it regrettable that the opportunity was lost for joint consideration of BSE at an early stage by those responsible for the safety of human and veterinary medicines.

CSM/BSC discussion of Mr Sloggem's paper

4.99 The position in Medicines Division was wholly different, given that DH had not been formally notified of the existence of BSE. At the time of his conversation with Dr Little in September 1987, Mr Sloggem, in his role as a pharmaceutical officer, had for his part been carrying out an admirably thorough investigation of a specific bovine brain extract in order to offer pharmaceutical advice on an application for a CTC. He had learnt about this new bovine disease only by chance during August. He perceived it as a 'slow virus'. In our view it was not incumbent on him to share the information more widely at that stage.

4.100 The CTC application came before the BSC on 6 January 1988. On that occasion, nobody from MAFF was present. Mr Sloggem's paper, based on his diligent research, referred to the emergence of the new slow virus syndrome in cattle. Dr Rotblat told us that Dr Taylor's letter to Mr Sloggem was included in the material before the BSC. ⁷ This prompted some discussion of the subject at the meeting. Should this have led officials in Medicines Division who were present at the meeting to instigate action in relation to the use of bovine materials in medicinal products generally following the meeting?

4.101 We raised this question with Dr Purves and Dr Jefferys, respectively the Pharmaceutical and Principal Medical Assessor to the CSM/BSC, both of whom were present at the meeting on 6 January 1988.

4.102 In a written statement to us, Dr Purves explained that he did not now believe that the tentative quality of the information in Mr Sloggem's paper and Dr Taylor's letter about the new 'slow virus syndrome in cattle' could be said to form a proper basis for instigating action of any type in respect of the use of bovine material in medicines. He pointed out, as we have already noted, that no information had been supplied to Medicines Division by the VPC or MAFF. ⁸ Dr Purves added: ⁹

The information contained in Mr Sloggem's paper was placed before the Biologicals Sub-Committee, whose breadth of experience and expertise was much greater than mine and who would be expected to address any issue of wider significance to which a particular product application gave rise. The sub-committee made no recommendation that any action should be instigated in relation to the use of bovine materials in medicinal products generally.

4.103 Dr Jefferys agreed with this point. ¹⁰

4.104 We have noted that none of the leading experts present at the meeting suggested, during the course of it or afterwards, that the information in Mr Sloggem's paper had broader general implications that called for action. We do not consider that those experts are to be criticised for that. They advised that the CTC in question should be refused in part because of the concern about slow viruses and it was reasonable that they went no further.

4.105 Given that the advisory committee did not raise any wider considerations, and that they were unaware of MAFF's actions on veterinary medicines, our view is that it was not unreasonable for Medicines Division officials not to have raised any wider implications either.

4.106 Nevertheless, although we do not consider that any individuals are to be criticised, it was unsatisfactory that the information discovered by Mr Sloggem was lost from sight, and that its broader implications were not spotted. There was an element of circularity in the system - the officials did not take action because the experts had not raised concerns, but the experts advised only on the matters officials identified. We believe that had there been a system in operation in Medicines Division at that time for identifying, reviewing and recording information which raised concerns of potentially broader application, Mr Sloggem's information about the new bovine disease would have found a natural home there. Establishing such a system was certainly not part of Mr Sloggem's remit. We note that at the time the Medicines Division database was in disarray. Our understanding is that, despite the improvements that have been made to the Division's databases, it is still the case that no such system exists.

4.107 We consider that a working database of concerns and queries not arising from adverse reactions should be established. It might be rather like the Adverse Drug Reactions On-Line Information Tracking (ADROIT) database (see Chapter 2), but would record information provided by, and be accessible to, both the MCA and the VMD. The database would include all materials used as ingredients in, and during the manufacture of, medicinal products. Any new concern identified in the course of the licensing procedure in relation to any such material would be recorded in the database, and the relevant official would be responsible for drawing this and its implications to the attention of all who needed to know. We believe that this would assist the Licensing Authorities and their advisory committees in addressing any issues of potentially wider significance to which a particular licence application gave rise. Queries and doubts from advisory committees about a material might also be logged in for future reference. A shared data series of this sort would facilitate early identification where a range of existing products needed examination, or general guidance might be required.

The Medicines Division response after March 1988

4.108 When the CMO, Sir Donald Acheson, received Mr Andrews's letter of 3 March 1988 he not only understood the concern of MAFF about the potential human food threat, but also immediately perceived that there might be a risk from contaminated medication. He was unaware that this was already being considered by Dr Little and his team in relation to veterinary medicinal products. His immediate reaction was that an urgent expert assessment of the safety of biological human medicinal products should be carried out. He was particularly concerned about material used in preparing vaccines. No doubt he had vividly in mind his own knowledge of the tenacious infectivity of CJD and the disastrous story of contaminated human growth hormone. He promptly set the wheels in motion to secure advice.

4.109 At the meeting with MAFF on 17 March, called by Sir Donald, it was agreed that the use of bovine material in manufacturing vaccines would be a priority issue for the proposed expert group (which became the Southwood Working Party). The minutes of the meeting do not record any mention by the MAFF representatives, Mr Cruickshank and Dr Watson, of the consideration given so far to this by veterinary medicines licensing staff. Dr Harris, the CMO's deputy, who had extensive experience in medicines licensing, undertook to take up the biologicals aspect with the NIBSC. Ministers were told in Sir Donald's submission of 21 March that although the risk to human health through the use of bovine tissue-based biologicals in the pharmaceutical industry was likely to be low, in view of the lethal nature of the virus and its uncertainties, he felt further expert advice was needed as soon as possible. Medicines Division was brought into the picture by being sent copies of this submission.

4.110 Both Sir Richard Southwood, as soon as he was appointed, and Dr Pickles, to whom Sir Donald gave the role of coordinating action within DH and assisting the Southwood Working Party, were left in no doubt about the importance the CMO attached to this matter. Having taken all these steps to secure authoritative advice, the CMO quite rightly stood back to await results. We consider Sir Donald's initial response with regard to human medicines was prompt and appropriate.

The response of Medicines Division to the CMO's concerns

4.111 We examined closely the initial response from Medicines Division in order to assess whether it reacted with sufficient urgency after the CMO had set the framework for action. We looked separately at the periods before and after Dr Pickles's minute of 21 June 1988, on behalf of the Southwood Working Party, pressing for the section 4 committees to be consulted on a number of matters. Dr Jones told us that the receipt of Dr Pickles's minute was the 'first time' Medicines Division realised it was going to be 'expected to do something'. ¹¹

4.112 We discussed in Chapter 2 the deficiencies described in the Evans-Cunliffe report, which had been published in December 1987. In particular Medicines Division was overloaded and short-staffed, the database was in disarray, and the management structure was divided and had weak lines of responsibility. These difficulties are factors we have borne in mind in considering the adequacy of the response in Medicines Division to the emergence of BSE.

Obtaining expert advice

4.113 The CMO's submission to Ministers identified the need for further expert advice as soon as possible. When we discussed the submission with Dr Gerald Jones, the Senior Medical Officer in Medicines Division, he told us that the state of knowledge about BSE in the Division at that time was 'virtually zero', although there was a steep learning curve over the next few months as its knowledge increased. By the end of June it had become clear it had 'a serious problem'. ¹²

4.114 Dr Jefferys, who was the branch head responsible for new drugs and biologicals, told us:

my scientific knowledge of BSE and other spongiform encephalopathies was at the time extremely limited - I had learnt about kuru as a medical student, had seen one patient with classical CJD during my years in clinical practice and was aware of the problems relating to dura mater and iatrogenic CJD. I believe that the other officials within Medicines Division had similarly limited knowledge about BSE and other spongiform encephalopathies and there was not available within the Division the necessary expertise to consider the issue. ¹³

4.115 Clearly then, Medicines Division was in no position to form its own judgement about the issues raised by the emergence of BSE until it obtained expert advice. We think it was a natural and reasonable reaction of the Division to await the informed advice that the CMO had commissioned from the new working group of experts. The CMO clearly envisaged that the expert advice he required would be provided by the Working Party, and it was anticipated that the Working Party would report within a relatively short period of time. Dr Jones told us that is how he read the CMO's submission:

I do not think anyone should read this as saying we need urgent action to examine medicinal products, exposure of people in abattoirs or vets. It does not say that at all. The urgency is for him to get advice to understand what the disease means. It means nothing more in fact, in my opinion. ¹⁴

4.116 However, there remained the question of what, if any, preliminary steps should be taken in the interim to ensure the Division was well informed and well placed to take action, should that be necessary.

Searching the database

4.117 Perhaps an obvious preliminary step would have been to obtain a foundation of knowledge about which products contained, or had been manufactured using, bovine materials. The principal sources available to provide such information were Medicines Division's NORSK database, and its paper files. Unfortunately, as we noted in Chapter 2, the database had severe limitations.

4.118 In addition to those limitations, there were shortcomings relevant to the issues raised by a disease such as BSE. Dr Jefferys told us that the NORSK database was theoretically intended to be able to inform users of the nature of both active ingredients and excipients (ie, non-active ingredients) in licensed medicinal products. However, it was not capable of informing them of the source of these ingredients, nor of the nature of the ingredients used merely in the manufacturing process. ¹⁵ This was a problem because bovine albumin, foetal calf serum and bovine nutrient broth were extensively used in the production of medicines such as vaccines. Dr Rotblat told us that during preparation of their paper she and Dr Purves had discovered that the database was inadequate; in particular they had no data on materials used as excipients or in the production process. ¹⁶

4.119 We also described the difficulties with the paper filing system in Chapter 2. The difficulties that would have been involved in discovering the use of bovine material in manufacture by reading the copious gold files are self-evident. Furthermore, manufacturers at that time did not necessarily keep records of sources of raw materials, which were frequently bought from specialist companies, and were not required to advise the Division of any changes in this. Files might therefore have been inaccurate in those respects. ¹⁷

4.120 In short, the Division could not rely on the information it held to identify comprehensively those products that used bovine materials at some stage in their manufacture, and the source of those materials. We recognise the difficulties to which these shortcomings must have given rise. The new database (the Product Licence User System or PLUS database) was introduced only in 1993. We have been careful to bear in mind the technological advances that have been made since 1988. However, it might be said that the very existence of these difficulties should itself have prompted early thought about what steps might be taken to address them.

4.121 We discussed with Dr Jefferys (to whom Mr Wilson's minute in April and Dr Pickles's first minute in May had been addressed) and with Dr Jones, the steps that might have been taken. Dr Jones explained that awaiting the deliberations of the proposed expert view was 'clearly and obviously' what they would want to do. ¹⁸ He did not consider the possibility that the proposed expert group might ask for information about the extent to which bovine tissue based biologicals had been given licences:

Before that expert group met, you are referring to Southwood, my view about what they would say can only be at one extreme they might say that this disease in cattle will have no implications whatever for human health. At the other extreme they might say we are going to face a very serious epidemic of infectious disease, or they could have expressed a view intermediate between those two extreme positions.

That was my position before, as any normal man would have towards a committee that has not started work.

4.122 We noted with interest the contrasting and commendable response of Dr Pickles prior to the first meeting of the Southwood Working Party. At the same time as she contacted Dr Jones, she also contacted Mrs Alderman, one of the information scientists in MB1, to request some information from the database. It appears that the database was not entirely uninformative: Mrs Alderman was able to supply some answers to her questions, although these were far from comprehensive.

4.123 It seems to us that this was a logical preliminary step. It might, for example, have identified any products that were of particular concern, assisted in the preparation of the paper for the BSC, or revealed the deficiencies in the information available and enabled thought to be given to the best means of obtaining the information that the database was unable to provide. If a time came when action was called for, Medicines Division might have been better placed to take it promptly.

4.124 While it would have been creditworthy if Dr Jones and Dr Jefferys had taken the initiative in the same way as Dr Pickles, we do not consider that their failure to do so ranks as a shortcoming which calls for criticism. Given their perception in April/May that the Southwood Working Party would be advising on this subject, and their other preoccupations, we think it was within the range of acceptable responses to take no such preliminary steps prior to receipt of Dr Pickles's minute of 21 June, but rather to await the views of the Working Party.

Action after Dr Pickles's minute of 21 June - advice from the section 4 committees

4.125 Dr Pickles's minute of 21 June 1988 was important in changing the Medicines Division perception. She made it clear that the Southwood Working Party were looking to the section 4 committees to consider the issue of BSE and medicinal products. In effect, the Division was expected to advise the Working Party, and not vice versa. There could be no doubt that the ball was now firmly in the Division's court; it had very little real alternative to referring the matter to the section 4 committees for advice, which it did.

4.126 However, we were concerned whether the matter was put to the section 4 committees sufficiently promptly. We considered first who was responsible for assigning an appropriate degree of priority to the matter.

Who in Medicines Division was responsible for deciding what should be done about BSE, and when?

4.127 The witnesses who gave evidence from Medicines Division told us that there was no obvious lead responsibility in the Division for a topic, such as BSE, that raised issues affecting several branches. The existing structure of the Division had evolved to handle a certain range of applications and issues relating to individual medicinal products. By contrast, BSE was an unusual problem, which had implications across all branches of the Division and potentially affected both new - and as yet unlicensed - drugs, and drugs already on the market. ¹⁹

4.128 We discussed with Dr Jones and Dr Jefferys whether in practice lead responsibility for BSE naturally fell to a particular individual or branch within the existing structure of Medicines Division. In particular, we noted that concern had been expressed by the CMO in his submission of 21 March 1988 about 'bovine tissue-based biologicals'. Was MB3A, with its responsibility for new drugs and biologicals, the natural branch to address these concerns? And was Dr Jefferys, as head of that branch and as Principal Medical Assessor to the BSC, the individual to whom lead responsibility naturally fell?

4.129 Dr Jefferys explained that MB3A was responsible for the medical assessment of new applications for medicinal products including biologicals, but not dental and surgical materials. ²⁰ He did not accept that it was for MB3A to lead on policy advice concerning the potential impact of BSE on biological products in the first phase of the Division's consideration of the issue. ²¹ Its responsibility was for assessing new drug applications. Others in the Division had responsibility for the older products and for dental and surgical materials. ²² A number of people within different branches would be involved. ²³ Dr Jones agreed that there was no particular branch with a general responsibility for biological matters, or which would be the automatic point of reference if a problem were to arise with regard to a drug with a biological component. ²⁴

4.130 Similarly, the issues raised by BSE had implications for each of the section 4 committees and subcommittees. ²⁵

4.131 We accept that responsibility for BSE did not naturally fall solely to a particular branch or individual in the existing structure of Medicines Division, but raised issues relevant to the different medical and pharmaceutical branches. Although MB3A and Dr Jefferys clearly had some relevant responsibilities, so too did other branches.

4.132 But we also consider that good management called for a lead responsibility to be assigned. It would have been for Dr Jones to do this. He told us:

I think we have to get away from this idea that there was someone beneath my level who would be allocated lead responsibility across Medicines Division. That did not happen in the small number of items which did not automatically belong to one of the Medical Groups, but did involve work by all of them. At some point it would clearly emerge that somebody was going to do the work. ²⁶

4.133 That being so, it was ultimately for Dr Jones, having discussed the matter with senior staff, to decide the priority to be accorded to BSE in relation to other work within Medicines Division, and set in hand appropriate action.

Was the matter put to the section 4 committees with sufficient urgency?

4.134 The BSC was asked to consider the implications of BSE in November 1988. Dr Jefferys told us that the first available opportunity for BSE to be considered by the BSC was September. The July meeting was only days away in June 1988, and the section 4 committees did not meet in August, save in an emergency. ²⁷ We agree that the urgency of BSE was not such as to justify convening the BSC in August. However, we question whether the section 4 committees should have been asked for advice earlier than they were.

4.135 Dr Jefferys suggested that priorities were changed in order to meet the deadline. ²⁸ Dr Rotblat agreed with Dr Jefferys, although she recalled that, rather than dropping other work, she managed by working longer hours. ²⁹

4.136 In oral evidence Dr Jones indicated that Dr Rotblat was not told that BSE was a high priority matter, nor that the paper was to be prepared in time for the September meeting. If the matter had been given a higher priority it could have been put to the committees before November:

She was not told, 'This is priority, make sure it is done for the next available meeting', which I take it could either have been September . . . or October. It could have gone in October if you had insisted. Biologicals would not have met in October, as you know. We must not get caught up in bureaucracy. If the Biologicals Sub-committee does not meet, you ask the Chairman and two or three of his colleagues to come to the CSM.

The system is flexible enough to deal with anything if it is identified as of high priority. In this particular case it has obviously been done in an ordered professional way, not with low priority but in an ordered professional way, and the next meeting was going to be November, of the various committees. ³⁰

4.137 Clearly much depended on the priority given to BSE at the time. When we asked Dr Jones about this, he said that the risk from medicinal products, although a potentially very serious issue, was considered to be remote and had to be balanced against a number of other extremely urgent priorities:

On the food side we knew in June there was, whatever the words are, remote theoretical risk to human health on the food side. Our perception was the risk to human health from medicines was, if anything, even lower . . . But it was not regarded with the pressing concern of, for example manufacturing defects with medicines, that could lead to the deaths of patients overnight; serious adverse reactions which were collected by the Division at the rate of 15 to 20,000 a year. ³¹

4.138 He did not think that anybody seriously expected an infectious agent that could pose a risk to be present in a final product of a vaccine produced in culture with foetal bovine serum:

If it were a risk it would either be zero or so close to zero that it could never be detected. That was the view. ³²

4.139 Others, among them the Southwood Working Party and Dr Pickles, did not share Dr Jones's assessment. Dr Jones told us that he did not inform his colleagues of his view at that time. None the less, it is hard to avoid the conclusion that his opinion influenced his assessment of the priority to be afforded to BSE.

4.140 The evidence we have heard suggests to us that a full paper could have been prepared for the September meeting of the BSC had the task been assigned a somewhat higher priority. In our view, Dr Jones should have asked that such a paper be prepared. Two further months were allowed to elapse during which progress might otherwise have been made.

4.141 Dr Jones accepted that Dr Jefferys did not have the lead responsibility for BSE in Medicines Division, ³³ and in written communication with the Inquiry accepted that it was for him, Dr Jones, to decide the priority to be accorded to it. As such we do not think that any criticism attaches to Dr Jefferys.

Publication of a request for information in MAIL

4.142 On 2 November 1988 the CSM/BSC recommended that there should be an article in MAIL requesting manufacturers to identify products in which bovine materials had been used. No such request was issued until March 1989, in the event by means of a questionnaire rather than an article in MAIL. In considering whether Medicines Division should have acted with greater urgency in response to the emergence of BSE, we questioned whether this lapse of time was appropriate.

4.143 When we asked Dr Jones about it, he pointed out that if urgent communication were required a letter would be sent, rather than an article being published in MAIL. This would be costly but was possible if appropriate. The very fact that the recommendation from the section 4 committees was for an article in MAIL was an indication that they did not consider this to be of that degree of urgency. ³⁴

4.144 Professor Collee explained to us, in a written statement, that the BSC and CSM did not intend that an article should be placed in MAIL immediately following the November 1988 meetings. They were consulting and progressing with necessary care. In order to determine how many and what questions should be asked, it was necessary to go through a process of careful scientific evaluation. Professor Collee explained why he did not believe it would have been possible for a comprehensive questionnaire to have been administered before March 1989. ³⁵

4.145 We ascertained that there was an issue of MAIL in November 1988, and that the next issue was not published until March 1989. In those circumstances, it seemed to us unrealistic to suggest that an article should have been included in MAIL immediately following the November meetings of the BSC and CSM. Moreover, we were persuaded by the reasoning, set out by Professor Collee and others, that it was acceptable that no general request for information was issued to licence holders before the guidelines and questionnaire were sent in March 1989.

Communication between Medicines Division and MAFF

4.146 We have discussed above some of the problems that arose because of the weight that was subsequently put within MAFF on Dr Little's incorrect impression of how matters stood in DH. Joint consideration of the implications of BSE might have prevented the misunderstanding from arising, or from persisting. However, the lack of communication between the two medicines licensing divisions of the Departments continued even after the CMO had asked for the question of bovine biologicals in human medicines to be urgently considered.

4.147 As we have noted earlier, there were arrangements for contact between those in MAFF and Medicines Division responsible for medicines licensing. There was a degree of cross-attendance at the meetings of the VPC, CSM and other section 4 committees. Dr Jefferys told us that Dr Adams and Dr Diggle from the Division were the official contact points with the VPC, who might have brought information across. ³⁶ Dr Adams explained: ³⁷

I attended these meetings on occasion between 1986 and 1988 (when I was promoted to Principal Medical Officer) as part of my responsibilities as Senior Medical Officer. My purpose in being at the meetings was to encourage consistency of approach with regard to particular drug substances in respect of which there was an application before the VPC, when those substances had already been licensed for human use.

4.148 There were no official MAFF observers at the meetings of the CSM and other section 4 committees; Dr Little told us that VMD officials were not regular attendees at human health committee meetings as 'medical products have very little interest to veterinarians because there is no immediate connection'. ³⁸

4.149 Professional staff from Medicines Division also attended meetings of the Scientific Secretariat of MAFF. In addition, Dr Little told us of the 'good working relationship' between himself and other CVL staff and the DH medical assessors who attended the VPC meetings and the Scientific Secretariat meetings. ³⁹ He elaborated: ⁴⁰

I would also note that as part of my responsibilities as Deputy Director, I met the relevant Department of Health Medical Assessors at least twice a month at either the VPC or its Scientific Secretariat meetings (see paragraphs 19 and 20 of my statement dated 18th December, 1998 . . .). If Department of Health staff had concerns, there were therefore plenty of opportunities to discuss them with me at these meetings. I am sure there were further discussions on BSE with the Medical Assessors outside formal meetings but I cannot recall them now.

4.150 However, it did not seem to us that in practice there was real and constructive communication between the two Departments about the implications of BSE for medicinal products. The narrative in Chapter 3 reveals the consideration that was given to BSE and veterinary medicinal products by MAFF from late in 1987 onwards. However, it was not until July 1988 that it was suggested that DH should be kept informed of any developments with BSE. Mr Wood's paper with draft guidelines on veterinary medicines was sent to Dr Harris in July 1988, following a suggestion from Dr Minor of the NIBSC.

4.151 For their part, Medicines Division seem to have initiated very little contact with MAFF: Mr Wood's paper was one of the annexes to Dr Rotblat's and Dr Purves's paper. In a note dated 12 October 1988 commenting on that paper, Dr Pickles said:

5. But there are also other recommendations on the MAFF list that could be looked at and easily incorporated into any recommendations of your own eg not using serum from cows killed by brain-penetrative stunning. Perhaps it would be wise to find out what has been happening in VPC before you put the problem to CSM and its sub committees (different recommendations about acceptability of non-British bovine sources could be embarrassing and would give legitimate grounds for appeal to the MC). ⁴¹

4.152 Dr Purves referred to this comment in a written statement to us:

One comment Dr Pickles made about our draft recommendations was that we should have looked at, and incorporated into our recommendations, those made by MAFF on veterinary products with bovine materials. We had most certainly considered the MAFF own recommendations and indeed had appended them as Appendix 3 to our own report. ⁴²

4.153 Dr Purves did not suggest that he and Dr Rotblat had been in touch with colleagues in MAFF to discuss the issue. His evidence was that Dr Jefferys and Dr Adams were responsible for such liaison:

They were in charge of liaising with those senior people in other organisations, including the lead officials for BSE in DoH and MAFF and the CMO about what was being done in Medicines Division and what could be done. ⁴³

4.154 However, Dr Rotblat thought that Dr Purves had been in contact with MAFF colleagues:

I presume that Dr Purves and Mr Sloggem framed the concept of 'healthy herds' and specifically mentioned brain and lymphoid tissue following discussions between them and MAFF. ⁴⁴

4.155 Dr Jones told us that it would have been desirable for the people dealing with the issue of BSE to communicate with MAFF. He said that if someone needed to suggest to those individuals that they should contact MAFF, it would be for the appropriate branch head to do so but not himself. He could not recall having had any contact himself with MAFF over this period. ⁴⁵ Dr Jones told us that it was a commonplace practice when preparing a paper for the CSM that was likely to have a significant effect outside the Division to check with other Government Departments. ⁴⁶

4.156 It is not clear to us what, if any, real liaison had taken place prior to November 1988. Dr Pickles's report of the discussion of the BSC meeting that month noted that further information would be sought from MAFF and other experts on how disease-free herds, procedures and countries might be identified. It seemed to us that this was the first occasion on which real consideration was given to the need to work in conjunction with MAFF. Dr Adams told us that he went to talk with Mr Bradley about this in December 1988. ⁴⁷

4.157 We wondered whether the requirements of the Medicines Act inhibited such communication. However, Dr Jones told us that the confidentiality requirements of the Medicines Act would never inhibit him or his staff from communicating across the whole branch, all the branches in DH, or indeed all Government. If they wanted to communicate something with MAFF then section 118 of the Medicines Act would not matter at all. ⁴⁸

4.158 We were surprised by the tenuous nature of the working relationships between the two Licensing Authorities at this time. Veterinary and human medicines, particularly vaccines, drew on the same or similar raw materials, sterilisation procedures and production processes. A single piece of legislation applied across the board, imposing the same assessment criteria: safety, quality and efficacy. Parallel systems of quality proofing and enforcement were operated through the licensing processes. A family of statutory committees advised under the same section of the Medicines Act. The Medicines Commission spanned both human and veterinary medicines and had an overview of the workings of the system as a whole.

4.159 Moreover, as we noted above, the question of how best to ensure the safety of medicinal products in the light of the emergence of BSE raised similar issues in relation to human and animal health on which each of the Departments might have valuable expertise that could be brought to bear.

4.160 We were therefore puzzled by the communication gap between the two Departments - both the passiveness of MAFF in relation to informing and discussing matters with DH, and the failure of Medicines Division immediately to open up discussions to ascertain what knowledge the CVL already held. The licensing authorities would appear to have shared interests, shared criteria and shared powers. One possible explanation was the perception, described in Mr Cunliffe's management report on veterinary licensing in early 1988, that animal health was the smaller 'poor relation' of human health and would usually take its cue from human health considerations. ⁴⁹

4.161 Whatever the reason, it seems to us that the lack of communication at this stage between the two Licensing Authorities contributed to a delay of several months in putting in hand action and consultations to address the potential risk to the population of the UK through medicinal products manufactured with or containing bovine materials. It meant that officials in Medicines Division were some months behind their counterparts in MAFF in beginning to address the problems, and that further delay ensued once the two Licensing Authorities began to work simultaneously on the matter.

4.162 We do not know what improvements have been made since that period in the communication arrangements between the two Licensing Authorities. We understand that the process for passing information between them is for it to be referred from one section 4 committee to another, via their respective secretariats. These matters seem to us to fall within the remit of the Medicines Commission to investigate. However, some of them may be wider than that and raise questions about the way the Medicines Commission, the Health and Agriculture Departments and the agencies that now exist relate to one another and where policy assessments, as distinct from individual product assessments, are made.

4.163 If the suggestion we have made at paragraph 4.107 above for a register of concerns is followed up, its contents at any given time would provide an obvious core topic for regular meetings.

4.164 We would also see merit in a formal concordat about information sharing between the two executive agencies that now exist to handle licensing matters. If a piece of information rings warning bells with officials on one side, it would be preferable for this to be shared freely and more speedily than through the formal processes and paperwork of the advisory committees. There also would appear to be a departmental 'need to know' on matters that might have wider repercussions. Consideration might be given to whether other aspects of the relationship between human and animal medicines licensing would similarly benefit from a concordat.