Volume 1: Findings and Conclusions
7.
Medicines and cosmetics
Phase 2: preparing joint guidelines, January-March 1989
The final draft of the Southwood Report
The continuing concern on vaccines
CSM and VPC approval and the issue of the guidelines
Was the action taken adequate?
898 On 3 January 1989 MAFF and DH officials eventually sat down together to work out a joint policy towards medicinal products. They agreed it was essential to keep in step, especially as MAFF concerns about animal vaccines would cause DH great difficulties of supply if current stock - in some cases up to five years' supply - had to be lost. Joint guidelines should be published in MAIL together with a request for information. These conclusions were relayed by Dr Jefferys and Dr Adams to Dr Harris.
899 Within MAFF, Mr F J H Scollen, who handled the policy side of veterinary medicines licensing in Animal Health Division, minuted Mr Cruickshank with his views. He saw the issue as one to be addressed 'first and foremost in the human health context' because of the risks associated with maintaining or disrupting the supply of vaccines for human health purposes. He went on: 'Judgements about what is needed and feasible on the animal medicines front can be more readily taken afterwards.' This was the line that was subsequently taken.
900 A text for draft joint guidelines was agreed by an ad hoc working group of officials from DH, MAFF and the NIBSC, chaired by Professor Collee, which met on 1 February. The group decided that further action, especially on current stocks of affected products, should be determined once the scale of the problem had been more precisely identified with the help of the manufacturers. Any such action 'would need to be based on a human health risk/benefit assessment'.
The final draft of the Southwood Report
901 Licensing officials had been keen to know what the Southwood Report would say about medicines. They were looking to it to provide reasoned grounds for any action they might take. At the 1 February meeting those present were shown the currently proposed wording of this section by Dr Pickles, and reacted with dismay.
902 Mr Scollen, who had attended the meeting, gave a graphic account in a minute to Mr Cruickshank:
There was general dismay at the drafting, which tends to highlight the (theoretical) risk via medicines and to relegate the qualification that the risk is remote.
903 After listing a number of criticisms the group had made of the draft, Mr Scollen continued:
Even if the report is modified in the light of these reactions, its appearance seems likely to trigger a need for a major public relations job which takes full account of the medicines angle. Consistency between MAFF and DH will be essential and should be achievable. The guidelines themselves could subsequently generate similar pressures since they clearly do not address the issue of current stocks and they could prompt questions - for example - on the standards applicable in the collection of animal material at slaughterhouses for biological medicinal purposes.
While I have no doubts about the Working Group's staged approach and the balance to be struck between risks and benefits to human health, this will not be the easiest position to present to a potentially critical public prone to seeing the influence of commercial interests.
904 Dr Pickles, too, got the message. The next day she wrote to Sir Richard Southwood reporting:
They have now realised that virtually none of the current essential human or animal vaccines could comply with the CSM guidelines as agreed by their November meeting and there may be several years of some vaccines in stock to make matters more difficult. Public confidence in the vaccination programme must not be put in jeopardy and yet supplies of some vaccines are very limited. After a late start, it now seems that both human and veterinary sides of the medicines business are working together and putting together a package of measures that seem sensible and workable (and indeed now incorporate all the points you raised with Professor Asscher in your earlier letters, and which I had raised with them separately).
905 She went on to suggest a revised passage for the Report on the grounds that:
This treats CSM/VPC like HSE ie the problem has been referred to the body with the statutory responsibility in that area and it is then for them to take appropriate action.
906 The Southwood Working Party went along with this line of reasoning at its final meeting on 3 February and adopted the revised wording suggested. The report as finally published said on medicines:
5.3.3 The greatest risk, in theory, would be from parenteral injection of material derived from bovine brain or lymphoid tissue. Medicinal products for 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 medicinal 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.
The continuing concern on vaccines
907 Shortly after the final version of the Southwood Report was agreed, Dr Pickles sent a copy to the CMO with a draft submission to Ministers. This draft alerted Sir Donald Acheson to the continuing concerns about vaccines. He decided to take a personal hand in matters and asked Dr Harris on 9 February to look into the matter urgently with Medicines Division. He told us that this intervention was quite contrary to his normal practice; he was trying to 'stir up more activity in the Medicines Division'.
908 Stir up activity he did. On 13 February MD officials met and agreed to carry out a telephone survey of all manufacturers of children's vaccines. They mooted a working group of officials and experts to follow matters through, and this suggestion led eventually to the setting up of the BSE Working Group.
909 Twenty-four hours later, MD had collected a useful body of information from those manufacturers identifying what they knew about vaccines that contained bovine material or which might have used it during manufacture, and about the stocks held. This suggested that in some cases considerable stocks were held, described variously as 'large', five years, and 63,000 litres.
910 An ad hoc group of experts and officials met again on 22 February. This meeting was a key precursor to discussion and advice from the CSM the following day. For this meeting the group added to its number several outside experts - Professor Asscher, Chair of the CSM, Sir John Badenoch, Chair of the Joint Committee on Vaccination and Immunisation (JCVI), Dr Kimberlin of the NPU, Dr William Martin (Southwood Working Party member) and Professor M D Rawlins, Chair of the CSM subcommittee on Safety, Efficacy and Adverse Reactions (SEAR).
911 Those present at that meeting were told of the information on vaccines collected at Sir Donald's instigation. They considered the Southwood Report, the proposed guidelines, a draft questionnaire seeking information from licence holders and a draft letter to licence holders. There clearly remained a number of concerns about the content of the guidelines and whether they ought to be going out at all. It was agreed that the guidelines should be seen as 'gold standard' and that this should be made clear.
CSM and VPC approval and the issue of the guidelines
912 The CSM met the next day and approved the various drafts, including a covering letter and also a position statement of its own. This said that the Committee had considered the safety of human medicines in the light of the Southwood Report and agreed that the risk to humans of infection via medicinal products was remote. It said the CSM and the VPC had agreed joint guidelines 'as a precautionary measure, and for the sole aim of seeking to guard against what is no more than a theoretical risk to man'. The VPC had approved the guidelines a few days earlier.
913 The main points covered in the guidelines were:
- they applied to all licensed products for injection, application to the eye or to open wounds;
- no brain, neural tissue, thymus or other lymphoid tissue, placental tissue or cell cultures of bovine material should be used in manufacture;
- collection techniques to avoid contamination should include no brain-penetrative stunning, the use of sterile and disposable equipment, calves to be under 6 months, all cellular components to be removed from serum;
- sterilisation advice; and
- the guidelines applied also to material from sheep, goats, deer and other animals susceptible to TSEs.
914 An MCA paper for the Committee drew attention to products already produced and awaiting distribution. It noted that the questionnaire asked companies about their stocks and said: 'The Committee's advice on this issue will be sought at a later date.'
915 Ministers were told on 23 February that the CSM and VPC had concluded that the risk of transmission of BSE through vaccines was remote. To ensure the safety of medicines, however, guidelines would be going out to producers in March. The Cabinet took this into account when they discussed the Southwood Report later that day.
916 The guidelines and questionnaire were issued on 9/10 March by DH. The covering letter took the wording a stage further by referring to the guidance as 'a purely precautionary measure' and said that it represented 'a standard that is deemed to be best practice for the future, and steps should be taken to implement it. However, it is realised that this guidance may not be fully applicable in all circumstances.' MAFF issued parallel documents for manufacturers of veterinary products on 15 March 1989.
Was the action taken adequate?
917 The guidelines were the single most important step taken to secure the safety of medicines. They were the only specific protection put in place to guard against BSE infection via medicines, since the SBO Regulations of November 1989 expressly excluded from staining and sterilisation the material going for pharmaceutical use. Here we consider how matters were handled between January and March 1989, looking at:
The Southwood message and how it was interpreted
918 When discussing the Southwood Report earlier in this volume, we noted that the wording the members of the Working Party finally adopted to describe the risks from bovine material in vaccines and other injected products failed to convey their true concerns.
919 The potential risks from parenteral injection had been one of the Working Party's most serious worries. They were concerned about existing products and existing stocks. Their identification of risk as remote was predicated on action being taken to address these matters.
920 Those preparing the guidelines, on the other hand, believed that the risk even before taking any precautions was theoretical and remote. Dr Martin observed to the Inquiry that his impression on attending the meeting on 22 February was that those on the human medicine side regarded BSE as an animal problem, and considered that the Southwood Working Party were being excessively apprehensive.
921 The Working Party were anxious to avoid a vaccine scare. Nevertheless, as discussed earlier in this volume, they should not have allowed their Report to give a false impression of their assessment of the risk posed by medicinal products. The message that flowed from it was that risk was remote even if no remedial measures were taken. This interpretation became the conventional wisdom both inside Departments and among medicines manufacturers and others outside government.
Were non-binding guidelines appropriate?
922 It could be argued that suspect material could have been cut off promptly and decisively had formal licensing action been initiated at once on individual items of high risk. We were, however, persuaded by the arguments put to us that guidelines were a more appropriate approach. In essence these arguments were that this approach was quicker and cheaper, and as effective. We agree that had regulatory action been attempted based on an unproven risk, a shoal of legal challenges might have resulted.
Was the scope of the guidelines adequate?
923 The question here was whether covering parenteral products and those applied to open wounds or to the eye was enough: should orally administered and all topical products - such as creams and ointments - also have been included in the guidance?
924 Oral products were carefully considered by the experts who sat on the section 4 committees. Nothing in the Southwood Report pointed to the need to alter the assessments made by them in November and sent to Sir Richard at that time. No recommendations were made by the Southwood Working Party regarding subclinically infected cattle entering the food chain. We felt that it was not unreasonable for the section 4 committees 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 oral medicines such as gelatine in capsules.
925 As for topical applications, the guidance covered the two most obvious risks, application to open wounds and to the eye. The decision not to include other topical material at this stage seemed reasonable.
Were existing stocks of injected products treated appropriately?
926 The issues that exercised us most were whether suspect stocks of injected products should have been immediately withdrawn and how this should have been handled and presented.
927 There were two principal arguments against immediate withdrawal of stocks. The first was the difficulty of procuring sufficient guaranteed 'clean' stocks to maintain the vaccination programme or provide life-preserving medication. Many of the contemporary documents and the statements we saw emphasised the difficulty of replacing stocks overnight. In particular, 'growing' batches of vaccines was a lengthy process. For this reason, stocks tended to be built up and kept for a number of years ahead.
928 The second argument was that such action risked causing a general panic that would deter parents from having their children vaccinated, as had happened on previous occasions over other 'scares'. Discussing his later concern that the proposed ban on bovine offal should not raise alarm about pharmaceuticals, Sir Donald Acheson told us:
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.
929 Professor Asscher told us he saw the risk-benefit analysis of existing stocks as comparatively easy because the risk according to the Southwood Report was remote, and because vaccines were very important in protecting 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.
930 We weighed carefully all the evidence provided to us. It is clear that the overwhelming opinion of the medical professionals at this time was that existing stocks should not be immediately withdrawn. Officials in MD accepted this advice and in our view it was reasonable for them to do so. Experience had shown that incomplete vaccination of children led to significant numbers of deaths that would otherwise have been prevented.
931 The decision not to withdraw existing stocks immediately 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 continued use of existing stocks.
932 The message in the various Q&A briefs prepared at the time of publication of the Southwood Report was that the CSM and the Southwood Working Party were agreed that the risk of transmission of BSE via medicinal products was remote, and that there was no reason to question the safety of existing stocks.
933 There was concern that publicity about the steps being taken would create the very situation that it was desired to avoid. This raised ethical as well as practical considerations, calling for judgement rather than scientific expertise. We believe that vaccine scares, like food scares, are likely to be fostered by a belief on the part of the public that the full picture is not being disclosed. A decision in an individual case not to disclose the full picture in order not to alarm the public is likely to perpetuate, in the long term, the distrust that leads to alarmist reaction. We can appreciate the short-term attraction, in the case of BSE, of not telling the public that there was a degree of concern about vaccines. Taking a long-term view, however, we believe that a policy of giving the public full information about risk is, on pragmatic grounds alone, the correct one, whether the subject matter is food, vaccines, or any other area of potential hazard. If we are correct, the ethical requirement must also be one of openness.
934 We were unable to establish in precisely what terms the decision to go on using existing stocks was brought to Ministers' attention and what express consideration they gave to it. 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 while the guidance worked its way through. However, there is no doubt that the decision was not taken at a ministerial level.
935 When we put to various Ministers the question of whether they would have expected to be consulted or informed, we received various answers. Mr Clarke, who was Secretary of State at the time, thought that if the experts were agreed, they probably need not refer it to Ministers. Mrs Virginia Bottomley and Mrs Edwina Currie, who had also served as Ministers in DH, took a different view. Mrs Currie added that she would not dream of overruling people who were on the various senior medical committees. However, she went on to say: '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.'
936 Had the decision in February 1989 about the continued use of stocks of potentially infected vaccines and its sensitivity in relation to the vaccination programme been explicitly put to Ministers, we believe they would have accepted the overwhelming advice of the expert committees, CMO and other DH officials. However, we also believe they would have taken a lively interest in how soon the doubtful material would be phased out and the steps to encourage this. Such interest would have influenced the subsequent pace of events.
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