Volume 7: Medicines and Cosmetics
1. Introduction and overview
Animal and human medicines

1.6 Chapters 2-7 describe the arrangements covering the safety of medicines and medical devices and tell the story of the response to BSE over the period 1987-96.

1.7 The UK pharmaceuticals industry is one of the largest in the world, accounting for around 12 per cent of the world export market and with 1997 exports worth £5.5 billion. There are over 400 pharmaceutical manufacturers and research organisations in the UK, although the market is dominated by multinationals such as Glaxo Wellcome, SmithKline Beecham and Zeneca. ¹

1.8 Although the licensing system was rigorous and elaborate, the BSE measures that were taken under it to exclude doubtful raw materials were much less prescriptive and time specific than those on diseased animals and on animal products intended as food. Not until 1992 was the main action on medicines - compliance with guidance about permissible materials in products injected or applied to the skin and eyes - fully implemented on existing products.

1.9 Chapter 2 describes the parallel licensing regimes covering veterinary and human medicines, and how matters on medical devices were handled. To illustrate the range of items that had to be considered, the chapter annexes a table setting out information provided to us by the Medicines Control Agency (MCA) about the main pharmaceutical uses of bovine products. It also annexes a description of the process of making vaccines and allergens. These, as injected products, were regarded as being of particular concern. Although vaccines did not directly use bovine ingredients, bovine material was widely used in their production to grow cells and viruses. The material did not form part of the final product, but it was not known whether its use at the earlier stages could transmit infection.

1.10 The comprehensive regulation applied to medicinal products reflected the importance attached to ensuring their safety, quality and efficacy. However, unlike animal health and food safety legislation, these powers could not be used to require destruction at source of raw materials deemed unsafe for medicinal use.

1.11 With a view to keeping licensing decisions demonstrably untainted by other departmental and political considerations, the system rested heavily on recommendations from advisory committees of outside experts established under section 4 of the Medicines Act. Appeals could be made against individual decisions and legal challenges mounted. Before refusing a licence the Licensing Authority had to consult the expert committees. Fuller details of the legislative framework and institutional arrangements can be found in Volume 14.

1.12 After describing the system in place, the chapter looks at how well it was working at the time BSE emerged. It sets out findings about workload, administrative weaknesses and poor databases in the licensing divisions of both the Ministry of Agriculture, Fisheries and Food (MAFF) and the Department of Health (DH) identified in management reports by Mr Cunliffe and Dr Evans in 1987-88. The subsequent restructuring into Executive Agencies was intended to rectify some of these defects but itself caused some inevitable transitional turmoil. The chapter also explains briefly how UK licensing interacted with EU-wide ² licensing of medicines and medical devices.

1.13 Chapter 3 traces the action taken within MAFF to review and deal with the risks of BSE transmission through veterinary medicines up to January 1989. This was undertaken in a timely way but with little or no reference to parallel issues affecting human medicines. Only in January 1989 did the licensing officials in the two Departments meet to discuss a common policy and handling. The chapter traces MAFF's independent preparation by July 1988 of draft guidelines and of advice on hormone products and its discussions with manufacturers of veterinary products.

1.14 Chapter 4 covers the corresponding period in DH. It reviews the state of knowledge there about BSE prior to the MAFF approach to the Chief Medical Officer (CMO), Sir Donald Acheson, in March 1988 and the action Medicines Division officials took between then and January 1989. It discusses the unfortunate misunderstanding in MAFF about the extent to which Medicines Division officials were actually considering the implications of the epidemic and notes the effect this had on the speed with which the Division came to grips with the issues.

1.15 Chapter 4 goes on to review the response of DH officials after the CMO was informed about BSE and expressed his concerns about biological materials used in human medicines, and the time that elapsed before advice was sought from the relevant section 4 advisory committee, the Committee on Safety of Medicines (CSM). It considers the interest taken by the Southwood Working Party in this issue and their correspondence with the CSM, as well as that Committee's consideration of the implications of BSE for human medicines in November 1988.

1.16 It became plain to Medicines Division officials following that meeting that advice was needed from officials at MAFF about the veterinary aspects of the CSM's proposals, for instance regarding its recommendation that material should be sourced from certified healthy herds. Towards the end of 1988 this prompted officials in the Division to contact their counterparts in MAFF.

1.17 Chapter 5 reviews the intense period of joint activity by MAFF and DH officials and their ad hoc and statutory advisory committees between January and March 1989. During this period the Southwood Report was finalised, discussed by Ministers and published. The Report's findings and their reassuring interpretation for medicines licensing purposes were crucial to the action taken then and subsequently.

1.18 Joint guidelines were agreed about bovine material in injected veterinary and human medicinal products and those applied to open wounds and eyes. A questionnaire was drawn up to establish which existing products used bovine materials either as ingredients or in the process of manufacture. A formal statement approved by the CSM said that it agreed with the Southwood Report assessment that the risk of harm through medicines was remote and that the measures being taken were precautionary. In March, the guidelines and questionnaire were sent to veterinary and human medicines manufacturers under cover of a letter that relayed the line taken in the CSM statement and stated that the action was 'purely precautionary'. The same phrase was used in a DH Parliamentary Answer.

1.19 The prime concern of DH officials and their expert advisory committees during this period was to avoid a 'vaccine scare' that might reduce take-up of vaccinations, with consequent deaths or serious illnesses. They were also concerned to avoid shortages of essential products. This dominated their reactions during the final drafting stages of the Southwood Report and led them to object to the way it was proposed in that Report to treat the risk through medicines. They preferred a more reassuring approach. They postponed decisions about how to deal with existing licences and stocks of material pending receipt of the replies to the questionnaires. However, that was to prove a protracted process.

1.20 Chapter 6 carries the story forward from March 1989 to 1996 in both MAFF and DH. The licensing divisions were being restructured into two new Executive Agencies, the Medicines Control Agency (MCA) and Veterinary Medicines Directorate (VMD) from April 1989 onwards. At the same time they were engaging in the large-scale administrative exercise, spread over the next 18 months, of collecting 100 per cent of responses to the thousands of questionnaires and analysing those of concern.

1.21 Concerns about presenting a reassuring message continued during this period. We discuss how the public presentation that resulted then affected the perceptions of those following up the questionnaire responses.

1.22 We look at the part played in the story by the special expert advisory committee set up by the CSM - the BSE Working Group - and its interaction with officials. The Working Group had the remit of providing advice on BSE risk to all the section 4 advisory committees involved with human medicinal products. Its membership included the chairmen of all those committees as well as the Chairman of the Spongiform Encephalopathy Advisory Committee (SEAC), Dr Tyrrell.

1.23 The chapter reviews the action taken to ensure that newly manufactured products complied with the guidance and existing stocks were eliminated. Only a small number of products that gave cause for concern were identified from the responses to the questionnaires. These were products that used high-risk material from a UK source and were administered by a high-risk route. The main items were sutures and some vaccines. We review the action taken on each of these and what is known about when existing stocks of them were used up or withdrawn. A small number of items that had used foetal calf serum (FCS), bovine serum albumen (BSA) or other bovine material in the production process may have continued in use until 1991 or 1992, and some stocks of animal vaccines may not have been exhausted until even later.

1.24 Chapter 7 looks at the fate of the recommendation to investigate the infectivity of FCS and BSA contained in the Interim Report of the Tyrrell Consultative Committee on Research into Spongiform Encephalopathies (the Tyrrell Report) in June 1989. The previous chapter indicates that those taking decisions on vaccines did not have firm evidence on whether BSE could be transmitted through these media. While MAFF put the work in hand through the NPU, DH took the view that the work was no longer necessary because of the steps already being taken by the pharmaceutical industry.