Minutes of Meetings - October 1999

1. Apologies for absence

1.1 Apologies from Professors Anderson, Broom, Stephen Clark, Dunbar, Holland and McNeilly, Mr Baker and Mr Ward.

1.2 The Chairman welcomed Mr Martin Walsh, who has taken over from Mr Wilkes as head of Animal Procedures Section in the Home Office.

2. Minutes of the previous meeting (8 September)

2.1 The minutes were agreed subject to a change to para 6.8.

3. Matters arising

3.1 Primate application (para 3.3) The Home Office expected to ask the Animal Procedures Committee (APC) to consider a revised version of the primate application which it (the APC) had looked at during its June meeting. This would come up for discussion at the APC's November or December meeting.

3.2 Ferrets and gerbils (para 3.5) The Home Office had issued a consultation letter on the draft code of practice. This covered a revised version of the code which took in all the points the APC had made except for the one about an increased minimum cage size for ferrets. The Home Office had included the Committee's suggestions about that in its covering letter, asking consultees for their views on it.

3.3 The Home Office was asking for comments by 29 October.

3.4 BUAV judicial review (para 3.8) The Home Office was about to make a public announcement on this issue.

3.5 Mr McCracken asked whether he could have access to the legal advice which the British Union Against Vivisection (BUAV) had submitted to the Home Office on animal procedures licensing and the LD50 test. The Secretariat would look into this.
Action: Secretariat

3.6 LASA overbreeding report (para 4) The September meeting had agreed to set up a small group to discuss the report with LASA. The Secretariat were setting up a meeting of this group. Paper INF(99)3, circulated, contained responses to the Home Office letter seeking views on whether overbreeding should be reported, and the Chairman noticed a marked divergence of opinion among the respondents.

3.7 Tobacco applications (para 7.5) The Committee discussed this subject later in the meeting (para 5 below) but two members pointed out that the arrangements for notifying comments on these applications to the sub-group which was set up at the last meeting had not been entirely clear. The Secretariat agreed to ensure that such arrangements were clearer in future. Action: Secretariat
3.8 Revocation of a personal licence (para 9) The Home Office reported that the personal licence in question had been revoked, at the request of its holder. The Inspectorate awaited a report from the establishment about the steps they were taking to prevent a recurrence. The Committee would return to the revocation of this personal licence when the report on it had been received, and also at some point to the general topic of lone working.

4. Draft codes of practice - pigs used as xenotransplantation source animals - APC(99)38, 39

4.1 Professor Banner explained that the Home Office and the United Kingdom Xenotransplantation Interim Regulatory Authority (UKXIRA) had issued public consultation documents on the codes of practice they had drafted for the use of pigs in xenotransplantation work. The Home Office code (APC(99)38) was about the welfare of the animals. UKXIRA's (APC(99)39) was about ensuring that their microbiological and health status was suitable for them to be used as organ sources for humans.

4.2 The two documents arose from the Kennedy report on 'Animal Tissue into Humans'. They were closely linked and the Home Office and UKXIRA had collaborated on producing them. In preparing their respective documents the Home Office and UKXIRA had relied on expert groups which contained representatives from main organisations and experts, including Dr Jennings.

4.3 The Home Office group had looked at the full range of welfare questions and provided guidance on suitable standards. The issues they had examined included keeping animals in isolators, human/animal contact, surgical procedures including surgical derivation, and the problems which are associated with keeping pigs in specific pathogen free (SPF) environments - for example the provision of material to satisfy behavioural needs such as rooting.

4.4 The Home Office and UKXIRA sought the Committee's views on these documents. That did not however preclude members from offering comments to UKXIRA and the Home Office on an individual basis - the deadline for comment was 10 December. Members discussed a number of aspects of the two draft codes, in particular:

training - the wording of the documents should be reinforced so that licence holders were told that staff were expected to attend appropriate training courses where they existed. Which courses would be appropriate would be a matter for the certificate holder and the inspector to decide;

vocabulary used in parts of the Code was not as respectful as it could be, and should be amended. For instance, references to 'harvesting pigs' should be changed to 'surgical removal of piglets'.

maximum tolerance levels - the issue was whether the Codes of Practice should set maxima for (for instance) the noise and transit time to which animals should be subjected. On the whole members agreed that there was not enough scientific information available to do this, and that the codes should propose general principles and not be over-prescriptive, which might be too restrictive and ultimately counter-productive. The Chairman suggested that the Committee could discuss the character, form and content of codes of practice on another occasion, if this was thought to be useful;

primates - the Kennedy report, from which the two documents had arisen, concluded that primates should not be used in transplant work. Members thought that if this was nevertheless to happen there should be a separate Code of Practice for primates. The Home Office view was that this was not necessary at present;

multiple use of the same animal - members expressed concern about possible repeat use of animals. The Home Office said that this was not anticipated, but it is possible that such a request might need to be considered in the future;

transport - the Committee discussed the benefits and disadvantages of transporting pig-organs (with the bio-contamination risks that that entailed) or transporting the source pigs, to the operation site prior to xenotransplantation. There were arguments in both directions, both in medical terms and in terms of the welfare of the animals.

4.6 The Chief Inspector was asked about the thoroughness of the twice-daily check on pigs referred to in 3.3 of the Home Office code of practice. He stated that an informed visual inspection would suffice. Conditions described as 'comfortable' in the guidance, would refer to something other than concrete, for example a rubber mat.

4.7 The Home Office confirmed that the weaning period set out in their code of practice conflicts with MAFF welfare codes. But early weaning is commonly adopted by veterinary surgeons to improve the health status of commercial pig units and would only be used where it is a demonstrable need to eliminate particular micro-organisms.

4.8 The Committee was unclear as to where the Code Of Practice offered guidance on the use of anaesthesia, referred to in section 4.3 of the guidance notes. Home Office ABCU would raise this with UKXIRA. Action: Home Office ABCU

5. Two applications involving tobacco - APC(99)31A & B, 40, 43, 44, 45, and INF(99)32

5.1 Professor Banner reminded the Committee that the Minister had asked it to advise on these two project licence applications because they would involve the administration of tobacco smoke to conscious animals. After the September meeting he had written to the Minister asking for a statement of the Government's view as to whether the two applications were ruled out by the November 1997 Home Office announcement on tobacco experiments. His letter was tabled as paper INF(99)32. The Minister's reply (copy attached to these minutes) had arrived just before the meeting.

5.2 The Minister's view was that these applications were not ruled out by the 1997 announcement. That had aimed at stopping the use of tobacco in animal tests to develop tobacco products, but the current applications were to use tobacco smoke as a research tool for medical research work to develop new drugs to help people with chronic obstructive pulmonary disease (COPD).

5.3 Members were agreed that it was not for the APC to interpret the Government's policy or to confirm that the Minister was interpreting it in the way the Government had meant. But that should not constrain the Committee's advice in any way. The Committee's task in considering the two applications was to determine whether there were any weaknesses or defects in them and advise whether licences should be granted, with or without further conditions.

5.4 In discussing the detail of the two applications the Committee were helped by the Inspectorate, who sought to provide information and answer questions about them on the basis of the extensive dealings they had had with the applicants.

5.5 Papers APC(99)31A & B were the two applications (respectively, nos PPL/70 04972 and PPL/70 04956). At the September meeting Professor D Clark had agreed to collate comments on them via a small sub-group, and to devise questions to be put to the applicants. The group's questions (in which some members said their points had not been included) and the applicants' answers to them were in papers APC(99)40, 43, 44 & 45. Paragraph 7.6 of the September APC minutes had posed two other questions to one of the applicants and their response (APC(99)43) took in these points also.

5.6 Professor Clark reported that the sub-group had picked out the crucial questions to put to the applicants. The detailed protocols did not say how the subject animals were to be exposed to the tobacco smoke, but there were well-tried ways of doing this, via smoking machines.

5.7 Some members said that they had important questions which had not been answered. The applications should be of concern irrespective of how they had come to be put to the APC. Smoking research had been going on for 30 years or more and there was discussion of why both research teams had to establish new animal models for their work. It was curious also that two applications such as this had both come up to the Committee at the same time.

5.8 Other members replied that the research teams were planning to use molecular markers in ways that would not have been possible until recently and for which there was no relevant archive material. These recent advances in molecular biology explained why the APC was seeing these two applications now - they might in the near future expect to see other similar applications for tobacco work, either on COPD or on other smoking-related disorders. Some members however remained unconvinced that this work justified the use of animals.

5.9 There was a big difference between the two applications, in that 4956 would take the work only up to the 'proof of concept' stage of developing potential new drugs while 4972 would go further, up to the stage of testing a new drug. The Inspectorate confirmed that the applicants in 4956 would look for another licence if and when it came to testing their new drug or chasing up other leads they had come across as a result of their work.

Application PPL70/04956

5.10 Members turned to discussing application PPL 70/04956. This would use rats as well as mice and guinea-pigs, whereas the other set of applicants has said they would not do that since 'expert opinion' was that rats were not a good model. The Inspectorate agreed that there was a consensus to that general effect, but there was a degree of uncertainty and rats were thought to have potential uses in particular applications. Other members pointed out that COPD was a complex of diseases into which a variety of species could offer insight. Rats, or particular strains of rat, could be useful if they exhibited disease in circumstances where other species did not. The application documents also mentioned using hamsters; their use had been removed from the final application after negotiation with the Inspectorate.

5.11 The Inspectorate confirmed that animals which died during work on 04956 would not be replaced by others. The work would use spasmogens. The Inspectorate confirmed that making an animal go into spasm 40 times, as proposed, would be distressing. They would make sure that researchers were there to observe and take the right action.

5.12 Members found it curious that animals were not to be subjected to tobacco smoke during researchers' weekends off. The regimen however allowed for a break period of this sort.

5.13 Members expressed concern about the distress scorings, which appeared on the face of it to treat an animal suffering from convulsions as 'normal' and not requiring any intervention. Other members pointed out that such scoring tables, though they are becoming a standard method of assessing stress levels and the need to intervene, are fraught with problems especially when, as here, the distress scores appear without the necessary amplification and weightings.

5.14 Members agreed that if the application went ahead the researchers would need to submit an early progress report to the Inspectorate setting out the scientific progress being made and comparing the actual welfare effects on the subject animals as against those that had been predicted. After a long discussion the Committee reached the conclusion, with which not all members were content, that the Chairman should write to the Minister advising that he should allow the project to go ahead on condition that

5.15 Moving to application PPL/70 04972, members asked why there were so many control animals. The Inspectorate explained the rationale for the control groups and agreed to enquire about this. The animals were subject to a restricted feeding regime because they would be kept immobile for substantial periods. Members expressed concern about duplication of this work in the applicants' plant in the United States. The Inspectorate believed that this US work was a separate programme, but this was company business and not something into which they could properly enquire.

5.16 Members expressed the concerns about the distress scoring method and the submission of an early report that they had in relation to the first application. They agreed that the Chairman should write to the Minister recommending that he should allow the project to go ahead subject to these two concerns being addressed.

Both applications

5.17 The Committee noted in discussing application 70/04956 that the stated benefits of the work included the possibility of identifying people particularly susceptible to COPD, who could then be targeted for smoking cessation programmes. Some members took the view that such a development could be seen as paving the way for an expansion of the marketing of tobacco and that granting project licences could be criticised on those grounds. The Chairman would point this out to the Minister.

5.18Members agreed that it was important for the researchers in both studies to publish as much of the results of their work as possible. It was pointed out that, though scientists are usually keen to publish, there are constraints both on what journals will carry and (for patent etc reasons) what researchers can release. Nevertheless the Inspectorate had very strongly pressed the importance of publication on both sets of applicants.

5.19 The Chairman would write to the Minister as set out above (5.14, 5.16, and 5.17). Action Chairman, Secretariat, Inspectorate

6. Work Programme 1999/2000

6.1 Professor Banner introduced the 1999/2000 work programme (APC (99)41). The paper was for information at this stage, but would be revisited and finalised at the December meeting. Mr McCracken suggested that the Committee might consider compliance with licence conditions - perhaps at some point in the first half of 2000.

6.2 The cost-benefit sub-committee might present an interim report at an event on the style of the July forum. If it did, there would need to be some thought about how public the forum should be and whether admission would be by invitation only. Action: Secretariat

7. Any other business

7.1 Professor Banner had met the Minister, Mike O'Brien MP, on 7 October. They had discussed the work programme and the profile of the Committee. The Minister said he was keen that the Committee should be seen to be consulting, and that it should take this into account when planning its work. Professor Banner asked the Secretariat to arrange a meeting of the Chairs of all the sub-committees and working groups, to help co-ordinate their activities. Action: Secretariat 7.2 As well as seeing Mr O'Brien, Professor Banner had since the last APC meeting had discussions with the Association of the British Pharmaceutical Industry (ABPI - paper INF(99) 28 gave details) and with the Farm Animal Welfare Council (report - by FAWC's secretariat- awaited).

7.3 Dr Purchase reported on the work of the newly-formed Efficient Regulation Group, which he chairs. He had written to Professor Banner about this and the Secretariat would circulate his letter. The Research Defence Society (RDS) had discussed their views about inefficient and ineffective regulation of animal procedures with the Minister, and he had welcomed the setting up of the group. The Committee agreed that it would be interested see the group's conclusions in due course.

7.4 Dr Jennings told the Committee about a claim to UKXIRA by a company engaged in primate work that it had taken this from the UK to Canada because the Inspectorate would not allow animals used in an invasive procedure to undergo a subsequent biopsy. The Chief Inspector said that the company concerned had not been refused authority for biopsy work on those grounds.

7.5 Dr Suckling asked whether it would be right for the Committee to reconsider its minuting style. It was important that the style should be suitable for a published document now that the minutes were, or soon would be, publicly available over the Internet. The Committee noted that it had agreed to publish its minutes and would review the practice in due course.

7.6 Mr Bone advised members about disposal of Committee papers. The guidance already issued to members explained about disposal of papers which were marked 'Restricted'. Members could dispose of other APC papers by returning them to the Secretariat or they could if they preferred use ordinary means of disposal as long as the papers were first torn up or (preferably) shredded. The Secretariat would amend the guidance accordingly. Action: Secretariat 8. Next meeting

November 10 1999, 10.30, room G21 Home Office Queen Anne's Gate .