Volume 7: Medicines and Cosmetics
5. Issue of guidelines
Discussion
The message contained in the Southwood Report
Was it appropriate to issue non-binding guidelines?
The scope of the guidelines
Did the covering letters convey the appropriate message?
Should existing stocks have been withdrawn immediately?
Ministerial involvement

5.78 We turn now to discuss a number of issues arising out of the preparation and finalisation of the guidelines.

The message contained in the Southwood Report

5.79 The view of the Southwood Working Party was inevitably going to be influential in determining the response of MAFF and Medicines Division on medicines. Indeed, those who met as the HVMBG on 22 February expressed the view that only the publication of the Southwood Report removed the option of advising the CSM, as normally would be done where there was as little knowledge as in the case of BSE, to take no action but to monitor the situation. ¹

5.80 It was therefore important that the view of the Southwood Working Party was clearly expressed. We discuss in vol. 3: The Early Years, 1986-88 the wording of paragraph 5.3.5 of the Working Party's Report, and our view that this did not, on a natural reading, convey the real concerns of the Working Party.

5.81 It seems to us that those who formed the HVMBG, when they first met on 1 February, were under the impression that the Working Party's view was that the risk from medicinal products was remote, even before the taking of any precautionary measures. The working draft of paragraph 5.3.3 of the Working Party's Report, which they had in front of them at that meeting, highlighted the steps that might be taken to destroy or remove infectious agents from medicines. However, as described above, there was among the HVMBG 'general dismay at the drafting, which tends to highlight the (theoretical) risk via medicines and to relegate the qualification that the risk is remote'. ²

5.82 Dr Pickles told the Southwood Working Party of these concerns, and reassured them that the Licensing Authority, as she fairly believed, had appropriate action in hand. As a result paragraph 5.3.3 was amended to include a simple reference to the fact that the Licensing Authority had been informed and would take account of BSE.

5.83 This, it seems to us, led unfortunately over time to a further lack of understanding. The HVMBG had brought about a change in the wording of the Report, on the basis of their mistaken, but in our view reasonable, understanding of the Working Party's view. In the months and years to come, the circumstances leading to the change in wording naturally faded into the background. Similarly, although the Working Party had in correspondence communicated the importance of taking action, over time this too faded into the background, and it was the actual wording of paragraph 5.3.5 that took precedence. This was reinforced by the wording of the CSM statement of 23 February, and by the covering letters to manufacturers interpreting the Report.

Was it appropriate to issue non-binding guidelines?

5.84 We have discussed in some detail the joint guidelines issued to manufacturers of medicinal products. They were described as 'a standard . . . deemed to be "best practice" for the future'. ³ Was issuing such guidelines the appropriate step to take, rather than taking formal licensing or regulatory action? We have concluded that it was.

5.85 In reaching this view, we were assisted by evidence from a number of those involved. Professor Asscher explained in a written statement to us the considerations in play:

My own experience of the licensing of medicines is that it is advisable to avoid regulatory action if it is possible to do so. As Chairman of the CSM, my policy was always to attempt to use negotiation and recommendations rather than legal action. Formal regulation was only to be used in cases of extreme urgency or where the pharmaceutical industry had indicated an unwillingness to accept the CSM's recommendations.

Informal action is invariably both quicker and cheaper than regulatory action. The pharmaceutical industry is highly professional and is normally content to accept the recommendations of the CSM. It is not in the interests of pharmaceutical companies to promote products which are being questioned on safety grounds.

I believe that in the case of BSE, the issuing of non-binding recommendations achieved a result that could not have been obtained through taking regulatory action. Licences cannot generally be revoked merely on the basis of a remote and theoretical risk. Such a revocation would very probably be overturned if legally challenged and we would never advise Ministers to take formal regulatory action in such circumstances. The risk posed by BSE was regarded as remote and theoretical and as such formal regulatory action could not have been scientifically justified. However, it was possible to achieve the same result through the issuing of recommendations because the industry wished to receive advice and was willing to accept it. As far as I am aware, no companies declined to follow the recommendations of the CSM on BSE and medicinal products. ⁴

5.86 Dr Jefferys and Dr Rotblat echoed these views in their written statements. ⁵ Dr Rotblat told us that the climate at the time was such that the industry was very willing to comply with informal guidelines. To the best of her knowledge, no manufacturer refused to comply with the CSM/VPC guidelines on bovine material. ⁶

5.87 We have also noted that even issuing informal guidelines was going beyond what would normally have been done in such a situation. The notes made by Mr Burton, from PD, of the discussion at the HVMBG meeting on 22 February 1989 indicate that this decision was not taken lightly, and that some were concerned that issuing guidelines was going too far. ⁷

5.88 These are persuasive arguments, on the basis of which we concluded that it was entirely appropriate to issue non-binding guidelines to address concerns about BSE and medicinal products. We discuss in Chapter 6 the action taken to achieve compliance with those guidelines.

The scope of the guidelines

5.89 Under the heading 'Scope' the joint guidelines read:

It is recommended that all products licensed under the Medicines Act 1968 for human or veterinary use, that are administered parenterally or to the eye or to open wounds, should in general conform to this guidance if they contain material from a bovine source, or if bovine material has been used during their manufacture. ⁸

5.90 All were agreed that parenterals posed the greatest cause for concern, and that action should be taken to safeguard them. Was it appropriate that the guidelines did not apply to medicinal products administered orally, and that, in the case of topical products, they appeared to apply only to those administered to open wounds or to the eye?

5.91 It is worth setting out what the Southwood Report said about the relative risks of administration by the parenteral, topical and oral routes:

5.3.2 Information from several spongiform encephalopathies suggests that parenteral inoculation is much more efficient in transmitting disease than oral or topical exposure and that neural, and to a lesser extent, lymphoid tissue carry the infection whilst the risk is far less with other tissues. The theoretical routes of transmission from cattle to humans can be presented in 'risk' order to help clarify whether action is appropriate or research worthwhile.

5.3.3 The greatest risk, in theory, would be from parenteral injection of material derived from bovine brain or lymphoid tissue. Medicinal products from injection or surgical implantation which are prepared from bovine tissues, or which utilise bovine serum albumin or similar agents in their manufacture, might also be capable of transmitting infectious agents. All medicinal products are licensed under the Medicines Act by the Licensing Authority following guidance, for example from the Committee on Safety of Medicines (CSM), the Committee on Dental and Surgical Materials (CDSM) and their subcommittees. The Licensing Authority have been alerted to potential concern about BSE in medical products and will ensure that scrutiny of source materials and manufacturing processes now takes account of BSE agent.

. . .

5.3.5 In these, as in other circumstances, the risk of transmission of BSE to humans appears remote. Nevertheless, because the possibility that BSE could be transmitted orally cannot be entirely ruled out, known affected cattle should not enter the human food chain and action now taken ensures this. ⁹

Products administered orally

5.92 In their paper for the BSC/CSM meeting in November 1988, Dr Rotblat and Dr Purves suggested that consideration might need to be given to the risks associated with parenteral, topical and oral administration, should the product be contaminated by the BSE agent. They recommended that no action should be taken with regard to oral products 'in view of the widespread consumption of beef by the population at large'. ¹⁰

5.93 Dr Rotblat explained to us that their reasoning was that it would have been inconsistent to take action against such products when no action was proposed against food containing bovine material. ¹¹ Dr Purves agreed. ¹²

5.94 The CSM/BSC recommended that no immediate licensing action should be taken against oral products in which bovine material had been used. Professor Collee explained to us the reasoning that led to this recommendation:

We faced considerable uncertainty at this time. I was aware from my knowledge of other models of infectivity that parenteral delivery of similar agents was likely to be more effective than other potential routes of transmission, such as an oral challenge. I was also aware that infection could 'home onto' particular organs or tissues; that brain was likely to be such an organ and that there might also be risks from the use of nervous tissue. The Purves/Rotblat paper had additionally drawn attention to possible risks from lymphoid tissue; I believe that I was unaware of the possibility of lymphoid tissue posing a particular risk before reading this paper. However, I believe I was alive to the concept of sub-clinical infection.

On the other hand we were conscious that scrapie, which had existed in sheep for more than 200 years, had not been shown to have any implications for human health. It was not merely that people who had eaten lamb or mutton had not developed CJD. The evidence also suggested that those who had eaten high-risk tissues (e.g. sheep brain) had not developed CJD. In addition, those who worked in high-risk occupations had not developed CJD from contact with infected sheep, including those who had worked in situations where there might have been a risk of contamination of cuts or wounds.

. . .

Recommendation (a): 'No immediate licensing action should be taken against oral products, in which bovine material has been used.'

Our approach was based on the premise that the disease appeared to parallel scrapie, which had not been shown to be transmissible to man by the oral route. In the absence of further evidence we felt that it would be alarmist to take the view that BSE could be transmitted by the oral route, particularly in the case of orally administered medicinal products where the dose involved would be much smaller than in food. We added the word 'immediate' to the recommendation to take account of the fact that the position might need to be changed if further relevant evidence came to light. ¹³

5.95 The full CSM endorsed that recommendation of the CSM/BSC. Professor Asscher explained that at the time of the November 1988 meeting, the fact that scrapie had not transmitted to man reassured the CSM that BSE was unlikely to be acquired by the oral route. ¹⁴

5.96 When the HVMBG met on 22 February, it discussed the views of the Southwood Working Party on the risk of transmission to humans, which were based on the view that the most likely cause of BSE in cattle was feeding with protein derived from scrapie-infected sheep. The minutes of the meeting note that clarification was needed on the acquisition of BSE by cattle via the oral route, which by analogy with scrapie was relatively inefficient. They suggested that there might be special factors involved, such as damage to the gut from roughage causing an 'injection' of BSE, and it was felt that the oral route for humans need not be of undue concern at that stage. The minutes also record that it was felt that to issue rules on oral products would challenge concepts on food, and cause problems with regard to gelatine capsules. ¹⁵ We note that among those present at this meeting were Dr Kimberlin, who had particular expertise in transmissible spongiform encephalopathies, and Dr Martin, of the Southwood Working Party.

5.97 The CSM endorsed the draft guidelines. In doing so, they noted the view of the Southwood Working Party 'that the risk to man of infection via medicinal products [was] remote'. ¹⁶

5.98 It seems to us that careful consideration was given to the question of oral transmission via medicinal products by the experts who sat on the section 4 committees and by the HVMBG. Nothing in the Southwood Report when it was completed was such as to change the assessments that had been made. No recommendations were made regarding sub-clinically infected cattle entering the human food chain. Indeed, we note that the Southwood Working Party had seen the CSM's November 1988 recommendations and had not dissented from their approach to orally administered products.

5.99 In our view, it was not unreasonable for the section 4 committees to reach the view that they did, and to assume that if it was safe to eat meat, it must be safe for humans to eat the minimal amount of bovine material contained in medicinal products.

5.100 This reasoning did not apply in the case of animals, particularly for cattle where there was no species barrier. However, the VPC had carefully considered the issue and we believe it was reasonable that MAFF officials took no further action on oral veterinary medicines.

Products administered topically

5.101 Dr Rotblat and Dr Purves made no specific recommendation on the appropriate course of action for topically administered products, nor was any explicit recommendation made by the CSM/BSC or the CSM itself in November 1988.

5.102 Professor Collee told us that he could not recall whether the question of topical products was discussed at the November CSM/BSC meeting, but he believed that topical products would have been thought of as very unlikely to pose a hazard to man and that they therefore did not warrant their immediate concern. ¹⁷

5.103 We consider in the next chapter the formation and work of the BSE Working Party. However, it seems to us that what Professor Collee told us about their consideration of the risks from topically administered products is of some relevance to our consideration of this issue: ¹⁸

As to topical products, one of the obvious reasons for our not being concerned about those products was the barrier provided by the skin. I regarded topical products, when applied to intact skin, as involving even less risk than products taken orally, though applications to broken skin would potentially involve a greater risk. I believe that we would also have discussed the possibility of infection being spread by the application of topical products to open wounds. However, the lack of epidemiological evidence of CJD-like illness amongst those occupationally exposed to spongiform encephalopathies (e.g. butchers and farm hands) encouraged us to regard this issue as a very low risk. In addition, the topical products involved appeared to contain low risk bovine material.

5.104 In February 1989, it was decided that products administered to open wounds or to the eye should be included within the scope of the joint guidelines. It is not entirely clear what prompted this extension. Professor Collee believed that the phrase 'or to the eye' was added as a result of concerns raised by him and others of the possibility of infection via the conjunctival route. ¹⁹

5.105 We have in mind also the views of the Southwood Working Party on the risk of topical transmission. Again, it seems to us that the views taken by the section 4 committees and the HVMBG as to the risks from topically administered medicinal products were not unreasonable, particularly given that open wounds and the eye were brought within the scope of the guidance.

5.106 We note in Chapter 6 that when further consideration was given to topically administered medicinal products by the BSE Working Group in July 1990, it appeared that the use of bovine material in such products was confined to two manufacturers, who used material from Germany. Although there might have been a case for including all topically applied products within the guidelines, it appears with the wisdom of hindsight that this would have made no difference in the event.

5.107 Again, although the position was somewhat different for animals, for the reasons given above, we do not think that this should necessarily have led to a different approach being taken in the case of veterinary medicines.

Did the covering letters convey the appropriate message?

5.108 It was important that, once the guidelines were finalised, information was obtained and compliance was secured as quickly as possible. The covering letters with which they were sent out had a part to play in achieving this. Did those covering letters convey the appropriate message to licence holders?

5.109 In considering this question we noted the difference between the letters sent by MAFF and those sent by Medicines Division. Both described the guidelines as a 'purely precautionary measure' and as representing a standard 'deemed to be "best practice" for the future'. Both indicated that steps should be taken to implement the guidance. However, the letter sent by Medicines Division said that it was realised that the guidance 'might not be fully applicable in all circumstances', while the MAFF letter read:

Where a company will find it impossible to meet the guidelines, or, where an alternative process is in use which is thought to give equivalent or better protection than the guidelines, details should be provided. ²⁰

5.110 The MAFF letter also referred to the gravity of the situation so far as farmers were concerned. Animals did face a more certain risk than humans: for animals of the same species as the material used in the medicinal product, there would be no species barrier to the transmission of a TSE. Indeed, this point was recognised at the second meeting of the HVMBG. ²¹ Medicines Division was addressing a more speculative concern that BSE might be transmissible to humans. In doing so, it seems to us that they were entitled to have regard to the views of the Southwood Working Party as they perceived them, and of the experts who sat on the section 4 committees and the HVMBG, as to the likelihood of that concern being realised.

5.111 The HVMBG were of the view that the guidelines should be seen as a 'gold standard'; they, and the CSM, approved the covering letter that was sent by DH. Professor Collee told us that there was an appreciation that they would have to be flexible as time progressed: ²²

41. It is also correct to say that the guidelines were viewed as best practice and we knew that as we progressed, we would have to be flexible . . . Products were treated on an individual basis, taking into account the considerations set out in paragraph 42 below and balancing those considerations against the benefit provided by the particular product. Action was not taken on all products that did not meet the guidelines issued in February 1989. For example, the guidelines excluded the use of all bovine material of a certain type, regardless of its source. However, it was reported to us that BSE was confined to the British Isles, save some cases which had occurred as a result of export (see the meetings of September 1989 (YB 89/9.6/10.1-10.8) and July 1990 (YB 90/7.4/1.1-1.8)) and accordingly we were able to recommend that no action be taken on certain products using the excluded material if it was appropriately sourced (see recommendation one, September 1989 Working Party meeting). In other cases, however, drawing on the responses to questionnaires, we determined that action was required.

42. The consideration of particular products in relation to BSE involved looking at a number of different questions, namely:

(a) The particular part of the bovine animal which was used in the product;

(b) The way in which that bovine material was used (whether as an active ingredient, excipient, or as part of the manufacturing process);

(c) The way in which the product was administered to the human i.e. orally; by implantation; by parenteral injection or topically.

5.112 We recognise these pragmatic considerations, which the covering letter reflected. We note from Mr Burton's notes of the HVMBG meeting on 22 February that, given the concerns about issuing guidelines at all, a conscious decision was taken, at Mr Hagger's suggestion, to accompany the guidelines and questionnaire with a reassuring letter. One consequence of this appears to have been the use of the phrase 'purely precautionary'. In our view, the addition of the word 'purely' itself changed the emphasis, to a much less urgent tone.

5.113 We do not think that the covering letter is to be criticised. However, given its reassuring wording, it was all the more important to ensure that appropriate action was taken to follow-up the letter, and ensure that the guidelines were complied with. We consider this question in Chapter 6.

Should existing stocks have been withdrawn immediately?

5.114 If a decision had been taken to revoke or suspend the product licences of medicines containing, or manufactured with, bovine materials, immediate withdrawal of existing stocks of those medicines would have been required. ²³ The use of informal guidelines did not have the same consequence, so MAFF and Medicines Division had to make a decision one way or the other about whether to withdraw existing stocks at that stage.

5.115 We noted above our view that the line taken on orally and topically administered products was reasonable. It seems to us that the logical corollary of that approach was to take no action on existing stocks of such products. Accordingly, we focus here on the question whether existing stocks of vaccines should have been withdrawn.

5.116 We saw that in February 1989 Dr Pickles's draft submission to the Minister alerted the CMO to the fact that concerns about the safety of vaccines had not yet been resolved. This prompted an initial telephone survey of companies manufacturing children's vaccines. The information obtained indicated that considerable stocks of some vaccines had been manufactured using bovine serum of UK origin.

5.117 The CSM was told that for some vaccines there might be supplies for up to five years, and that a question on stocks of products had accordingly been included in the questionnaire. It was told that its advice on this issue would be sought at a later date. The CSM was apparently content with this approach - it approved the draft guidelines, to be issued shortly, and the setting up of a BSE Working Party. The question and answer briefing circulated by Mr Hagger the next day stated that there was no reason to question the safety of existing products.

5.118 Concerns about vaccines were also discussed by Mr MacGregor, the CMO and Mr Clarke on 23 February, and by the Cabinet later that day. It is not clear whether the question of what, if anything, should be done with existing stocks was expressly addressed. Both the Ministers and the full Cabinet were told that guidelines were shortly to be issued to manufacturers, and it seems to us that it must have been at least implicitly understood, if not expressly discussed, that existing stocks were not to be immediately withdrawn.

5.119 On 7 March 1989, Mr Mellor answered a Parliamentary Question on the dangers to human health from vaccines using material from cattle infected with BSE. He answered:

The comments in the recent report by the working party chaired by Sir Richard Southwood that there may be a remote theoretical risk of bovine spongiform encephalopathy being transmitted to patients by the use of injectable medicines derived from bovine material, have been carefully considered by the Committee on Safety of Medicines. The committee agreed with the working party that any such risk from injectable medicines including vaccines is both theoretical and remote. We have accepted this advice. As a purely precautionary measure, further guidance on good manufacturing practice in this area is about to be issued to manufacturers of all medicines including vaccines. ²⁴

5.120 A question we were anxious to explore was whether, on receipt of the preliminary information about stocks of vaccines using bovine serum of UK origin, DH should have ordered the immediate withdrawal of all affected existing stocks. We are conscious that this is a matter that has excited considerable public interest and concern. There were two principal arguments against immediate withdrawal of stocks - the difficulty of procuring sufficient 'clean' stocks to maintain the vaccination programme, and the danger of causing a vaccine scare that would deter parents from having their children vaccinated at all.

5.121 The HVMBG expressed concern at its meeting on 22 February about problems with the availability of supply of vaccines if companies could not comply with the guidelines. ²⁵ Dr Rotblat told us that existing stocks could not simply be replaced 'overnight' because of the long time scale for manufacture of new batches of the vaccines. ²⁶ Professor Asscher explained: ²⁷

When considering the question of vaccines, it is important to be aware that manufacturing vaccines is an art - it is not easy to manufacture large supplies of effective vaccines. Manufacturers tended to keep large stocks of existing vaccines which, in some cases, were likely not to be exhausted for as much as 5 years.

5.122 In determining the appropriate course of action, the advisory committees had to weigh against the 'remote' and 'theoretical' risk posed by BSE the consequences of any disruption to the vaccination programme, caused by interruption to supplies of vaccines or by withdrawal from the vaccination programme as a result of a vaccine scare. Professor Asscher explained: ²⁸

Vaccines were the main group of existing products which came before the CSM for consideration. From my point of view, the risk-benefit analysis of existing stocks of vaccines was comparatively easy, principally for two reasons. The first was that the risk posed by BSE to human health was, during my time as Chairman of the CSM, always regarded as remote; that was certainly the view of the Southwood Working Party in its report. The second was that vaccines are very important to the protection of human health. The CSM's judgement was that the risks associated with interruption of the UK vaccination programme were far greater than the potential risk of BSE being transmitted. The CSM had learnt from its experience of previous vaccine scares, such as that connected with the whooping cough vaccine, that a potential consequence of any vaccine scare was refusal by the public to take part in the vaccination programme, which could lead to serious public health problems. I recall us advising the Licensing Authority of this.

5.123 Professor Collee, too, explained that in any consideration of vaccines they had also to take into account 'the obvious risk if stocks of vaccines were withdrawn'. ²⁹

5.124 Dr Jefferys spoke about the 'inevitable consequences' of 'any damage to the vaccine programme' ³⁰ and Dr Rotblat referred to the disease that 'would occur' if the vaccination programme were interrupted:

It was agreed that the benefits of the vaccination programme outweighed the theoretical risk of transmission and that the current vaccines could be used until new batches became available. The theoretical risk of transmission of BSE had to be set against the disease which would occur if the vaccination programme was interrupted. The vaccines in question had proven efficacy in protecting the public against serious diseases. The fact that low risk bovine material had been used in the manufacturing process in no way outweighed the benefit derived from these vaccines. ³¹

5.125 As we have indicated, there was concern to avoid creating a vaccine scare. Professor Asscher had referred to such concerns in his letter to Sir Richard Southwood on 26 January 1989. ³² Sir Donald Acheson had a similar concern a little later in 1989, when consideration was given to introducing a Specified Bovine Offal ban (see vol. 6: Human Health, 1989-96). When explaining that concern to us, he told us of the experience that lay behind it, which it seems to us was of equal relevance in February 1989: ³³

I had in mind a marked and extended previous reduction in the acceptance of whooping cough vaccine which had followed incorrect public allegations by a scientist that the administration of the vaccine carried a significant risk of encephalitis. On the one hand I was aware that during the period 1980-1988, due to incomplete vaccination of our population of children, there had been 123 deaths from measles and 50 from whooping cough in England, together with a many times larger burden of illness and some long-term complications. Against this I had to balance a remote risk of a fatal disease.

5.126 Of some importance was the way in which bovine sera were used in the manufacture of vaccines. We describe this in Annex 2 to Chapter 2. This underpinned the experts' evaluation of whether and to what extent vaccines might become contaminated with BSE. Professor Collee explained the process to us. ³⁴

Organisms used for vaccine production have to be grown in various nutrient media. Specifically, viruses need to be grown on host cells (tissue culture cells) which in turn are fed by nutrient media in bottles. It is this food which contains the foetal calf serum and/or bovine serum albumin. In due course, the viruses are harvested from the cells by various processes that achieve their separation and the viruses are then purified and further treated to be vaccines.

5.127 We have weighed all of this evidence carefully. It is clear that the overwhelming opinion of the medical professionals was that existing stocks should not be immediately withdrawn. This was accepted by the officials in Medicines Division, and in our view it was reasonable of them to do so. Experience had shown that incomplete vaccination of children led to significant numbers of deaths that would otherwise have been prevented. The experts attached considerable importance to the need to avoid a reoccurrence of this situation. It seemed to us that a responsible approach was adopted, having regard to this known risk and the countervailing potential risk posed by BSE, particularly bearing in mind the nature of the material and manufacturing processes involved. Again, this decision increased the importance of making efforts to ensure that sources were changed and existing stocks replaced. We discuss this in Chapter 6.

5.128 The decision not to withdraw immediately existing stocks gave rise to a separate but related dilemma: the question of what information should be given to the public about the risks associated with BSE and the decision that had been taken in respect of existing products and stocks. We discuss this general theme in Volume 1.

Ministerial involvement

5.129 We also gave consideration to whether the question of continued use of existing stocks of human vaccines was of such a nature that it should have been drawn specifically to the attention of the Minister, and a decision taken by him. It raised ethical and political issues as well as public health ones. We noted at paragraph 5.120 above that it was not clear in precisely what terms the issue was brought to Ministers' attention, and what express consideration they gave to it. Mr Clarke could not recall that he was aware of the 'dilemma' in relation to existing stocks. ³⁵ As we have already noted, it seems to us that it must have been at least implicitly understood, if not expressly discussed, at a ministerial level, that there was an issue regarding existing stocks of vaccines, and that a decision had been taken that they were not to be immediately withdrawn. However, there is no doubt that the decision was not taken at a ministerial level.

5.130 We asked Mr Clarke whether he thought that this decision could perfectly appropriately have taken place without any Minister being aware of it, or whether it was something he would have expected a Minister in DH to be informed of at some stage. His reaction was that where people were making a judgement on scientific risk, on which they regarded themselves as the only people, or the main people, qualified to make that judgement, there was probably no need to refer it to the Minister. The CMO was given a wide remit because Mr Clarke had great confidence in him. Where broader public interest considerations, for example the interests of the pharmaceutical industry, came into play, then Mr Clarke suggested that a Minister should be involved. ³⁶ In his view, if the clinical advisers were all agreed that existing stocks were safe, and this was the advice they could properly give to Ministers, they would not bother the Minister. ³⁷

5.131 Mrs Currie indicated that generally Ministers would be alerted if there was a problem. The experts were trusted at a very high technical level to take decisions in as objective a fashion as possible. She did not think, when we asked her, that the question about existing stocks would necessarily have gone to Ministers. She thought the experts would take a decision within their range of expertise and legal responsibilities. ³⁸

5.132 Given the uniform advice of the expert advisory committees, we think it is highly unlikely that any different decision would have been taken. Those expert advisers included the chairman of the Joint Committee on Vaccination and Immunisation, and representatives of the NIBSC and the Southwood Working Party, as well as the members of the section 4 committees themselves. Mr Clarke referred to the clear impression he gained from his various advisers: 'they were advising us that we should continue with vaccine components and so on . . . the risk was so remote that would not justify stopping it.' ³⁹

5.133 Mrs Currie told us:

I would not dream of overruling people who were on the various senior medical committees.

. . .

If it was an issue that was likely to arouse public concern, for example, a dodgy batch of vaccine, then Ministers would be alerted very quickly. ⁴⁰

5.134 She observed:

What causes alarm is the feeling that they are being sold a pup; that reassurances are being offered that something is safe when perhaps it is not. That causes alarm and that will cause wholesale withdrawal from a product. ⁴¹

5.135 In discussion with us about the vaccination programme, Mrs Virginia Bottomley, who became Secretary of State for Health at a later period, described her likely stance:

I hesitate to speak on a subject which was before my time. I think in the light of the great concern on this subject, as I understand it in the press then, I would have wanted, I think, myself, just to know steps were being taken. ⁴²

Earlier, she had described her likely position in relation to a difficult issue of this sort:

I think I would want a little bit more than a bland assurance. I think I would have wanted to know that on 14th October a minute had been sent out and that there had been some effect or that - I would want to know the date upon which there was likely to be a further report, or I might have said, 'Please send me a report at the end of the year to say what action is being taken'.

5.136 In our view, while there may have been a case for referring this decision to the Minister for approval, we do not consider that officials are to be criticised for not doing so: it seemed to us that Ministers were aware of the general concerns, if not the specific question of existing stocks, and of the different considerations at play. Moreover, the expert advice was unanimous. However, as we shall see, the fact that Ministers had not been a formal part of the decision-taking process meant that they did not ask to be kept informed about the follow-up action.