Volume 4: The Southwood Working Party, 1988-89
8. Subsequent events
Medicinal products

8.4 On 2 November Dr Pickles had written to Mr Lawrence about medicinal products:

I hope we can persuade Sir Richard that the issue is now being looked at in depth by the appropriate experts who also have the executive power to do something about it. This means Sir Richard needs only a passing reference in his own report. ¹

8.5 The subsequent concerns about complacency on the part of the CSM led Sir Richard to write once more to Professor Asscher on 23 December 1988. He commented:

We interpret your recommendations as drafted to mean that conditions that may be impossible in practice will be demanded of new products of bovine origin, and yet other than for the insulins we see no firm commitment to look at existing products.

In my letter of 7 December I touched on one of the conditions that may prove very difficult in practice, the 'certification of healthy herds' if this is to embrace those never fed ruminant protein. In the letter of 14 November I hinted at the problems there could be in another aspect, that of ensuring manufacturing processes are capable of eliminating scrapie agent. It is also not clear if the exclusion of brain and lymphoid tissue concerns only active ingredients or intermediates and culture media also, and whether this is an absolute condition. Some flexibility may be needed in interpretation of these guidelines.

We understand that the CDSM and CRM will be informed of your recommendations and we trust they will take appropriate action. We note the recommendation to the Licensing Authority to consider bovine insulin and heparin, and would like reassurance that appropriate action would be taken against any other relevant parenteral products. This point is not clear from the CSM minutes. ²

8.6 He went on to offer Dr Pickles's assistance in drafting informal advice to manufacturers on the sourcing of products, adding:

We see that a reduction in 'risk' could result more rapidly from informal action, much of which we believe could be taken without formal licence variation, rather than relying on a formal licensing approach. ³

8.7 He concluded: 'We are now finalising the report from my working party and will make reference to our concerns about medicinal products and that we have drawn the attention of the Licensing Authority to that concern.'

8.8 Meanwhile, on 19 December, Sir Donald Acheson, who had been kept informed of developments, commented to Dr Pickles: 'The additional urgent issue is that the Report deals appropriately with the complacency regarding Biologicals of Bovine origin.' ⁴

8.9 Sir Richard wrote to Dr Little on this subject on 20 December:

I understand that the Biologicals Subcommittee of the Veterinary Products Committee has been considering the potential risk from using biological products manufactured from bovine sources in the light of the emergence of BSE in cattle.

We are pleased to hear of the detailed consideration which is being given to this issue. As you may know we have already identified the pressing need for more research in this area. It would be interesting to know what steps are being taken by the VPC in their consideration of licence applications for new products. In addition, we trust that any steps that are thought necessary to safeguard new products will also be applied to existing products.

There are of course various steps which manufacturers can take to reduce or even eliminate any possible risk of contamination by the BSE agent. Indeed some may well have taken action already. Presumably one solution would be to purchase material from abroad. Other possibilities might be to avoid the use of brain or lymphoid tissue directly or in culture media and reducing nervous tissue contamination of serum by ensuring that animals are not destroyed by brain- penetrative stunning. In this context it would be helpful to have your views on whether some form of guidance to the industry might be useful. ⁵

8.10 On 17 January 1989 Dr Pickles commented in a letter to Sir Richard that she had seen some internal papers suggesting that the DH Medicines Division 'appeared to be taking the potential problem with medicinal products seriously at last'. ⁶ On 26 January Sir Richard was sent letters from both Professor Asscher and Dr Little, informing him of discussions that had already taken place with the veterinary pharmaceutical industry and of action being proposed, including the publication of joint guidelines for manufacturers of both human and veterinary products. ⁷ Professor Asscher said:

We originally considered the problem of BSE in the light of the 43 products which our computer database showed to include bovine material as an active ingredient. We will now need to consider the possible hazard from the use of bovine material as an intermediate in the manufacture of products. This will include the use of bovine material in nutrient broths, foetal calf serum and the use of bovine serum albumin. You will be aware that these materials are used very extensively in the production of most vaccines, monoclonal antibodies and other biotechnologically derived products.

8.11 This letter ended:

We have to consider the impact on the supply of these important products whilst at the same time seeking to maintain public confidence in the vaccination programme. Many vaccines are stored for up to 5 years before being released and this will therefore have to be considered.

For all these products it will be important to ensure that our recommendations are practicable and can be scientifically justified.

Finally, I want to reassure you that CSM intends to take appropriate action in regard of products within its remit and that CRM and CDSM are being kept fully informed of our recommendations. I hope you will agree that the Secretariats and the Committees are giving considerable attention to this important issue. ⁸

8.12 On 1 February Dr Pickles attended a meeting of the Human and Veterinary Medicines Briefing Group, consisting of both the VPC and the Biologicals Subcommittee of the CSM, together with officials from DH and MAFF. She showed them, in confidence, the passage of the draft Report that dealt with medicinal products. This concluded:

5.3.3. . . . All relevant products are being reviewed by the Licensing Authority. However, the Working Party acknowledge that at least some leading pharmaceutical companies have already made appropriate changes in their production processes. There are various steps which could be considered which might reduce the chance of the BSE agent or those bovine tissues most likely to contain it ever entering into pharmaceutical manufacture. For example, only animals never fed ruminant-protein could be used; or serum only taken from animals killed other than by brain-penetrative stunning which might release nervous tissue into the circulation; and the use of brain or lymphoid tissue directly or in culture media could be avoided. In all cases only healthy animals should be used in pharmaceutical manufacture but in the case of BSE it has to be accepted that infection could be present without clinical disease. The production processes are being examined to determine how these might be modified so as to destroy or remove infectious agents; the scrapie agent must now be included in such considerations.

8.13 The reaction of the meeting was described as follows in a note by Mr Frank Scollen (Head of Animal Medicines Division at MAFF):

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. The paragraphs concerned also imply (mistakenly) that numerous licensed human medicinal products are affected; that some but not all manufacturers have taken necessary action; that various safeguards could readily be introduced into the production and processing of bovine material; and that the Licensing Authority and its advisory committees need to have their attention drawn to the problems. ⁹

8.14 This reaction led Dr Pickles to suggest to Sir Richard that the relevant passage in the Report should be modified. She wrote on 2 February:

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) . . .

If you are content that all is now in hand, a briefer version of 5.3.3 might be adequate. I attach my suggestions. 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. I also have suggestions for minor alterations to the summary sections to make it clear that the Licensing Authority has already started addressing the problem. ¹⁰

8.15 An 'informal note' of the Working Party's final meeting, on 3 February 1989, recorded that the section of the Report on medicinal products had been shortened substantially to give no details of changes that might reduce risk, since the statutory responsibility in this area lay with the Licensing Authority. Dr Pickles was able to report on the very satisfactory response now being taken by both human and veterinary sides of the Licensing Authority, but explained the potentially grave problems for the supply of essential vaccines if foetal calf serum were to be considered at risk of being infected. ¹¹

8.16 This last meeting also noted that BSE had been declared a zoonosis, thus enabling the implementation of a ban on milk from affected animals. The import and export of MBM was discussed, and Dr Pickles's 'informal note' records that the general feeling was that no comment on exports was necessary in the Report: 'No attempt was being made to conceal the risks and it was for each country so set its own standards.' ¹² (Dr Pickles, however, alerted the CMO to this decision a few days later as a 'loose end' - see paragraph 9.35) Finally, the text of the Report itself was agreed, and the Chairman and other members of the Working Party signed the accompanying letter to Ministers.