AWERB Minutes June 2021

National Institute for Biological Standards and Control

Animal Welfare and Ethics Review Body

Minutes of a meeting held on Tuesday 8 June 2021 at 2:00 pm

1. 

Accepted without amendment.

3. Matters arising from 16 March 2021 Minutes – see Action Log

August 2020

20-12: CLOSED

October 2020

20-16: Comment from additional staff member was added to the report by HOLC; report will be discussed at next meeting of HOLC and PELH. CLOSED

February 2021

21-02: work on questionnaire ongoing. Item will be put on the agenda for the next AWERB meeting

The PPL Holder presented an oral update against the report. Highlights:

• The PPL supported two projects namely a PhD project on immunotherapeutic antibody conjugates for targeted delivery of nucleic acid adjuvants to the tumour tissue and a collaborative project on the adjuvant activity of microspheres and their potential for inducing anti-tumour immune responses.
• Protocol 1 was used less than expected and Protocol 2 was not used at all; the PPL application was written before the details of the projects that would be persued were agreed; the project that was eventually persued by the PhD student required the use of Protocol 3 rather than 1 or 2, since tumours had to be present before the immunotherapeutic intervention was applied; the collaborative project on microspheres started in January 2020 and work on this was paused due to the pandemic, so only a very limited number of pilot experiments for this project were performed under this licence.
• Protocols 3 & 4 were used in line with the proposed mouse numbers, however, mouse numbers would have been higher if the project work had started at the beginning of the PPL being granted and if work on this project and the microsphere collaborative project had continued throughout the pandemic in 2020.
• Protocol 5 was not used since there was no requirement to breed genetically modified mice to support the projects.
• No unexpected effects were observed for any of the procedures performed under this licence
• 3Rs – for the project on antibody conjugates for targeted delivery of adjuvants, luciferase expressing tumour cells were generated in order to refine the B16 melanoma pseudo-metastasis model. The aim was to use whole-body imaging for assessing tumour growth rather than endpoint enumeration of lung tumour nodule counts in order to reduce the number of mice required per group. However, while the tumour growth curves obtained from whole-body imaging correlated well with the endpoint enumeration of tumour nodules, whole-body imaging did not support a reduction in group size. The difference between treatment groups was smaller for the whole-body imaging read-out than for the endpoint tumour nodule enumeration read-out. Hence, endpoint tumour enumeration for this model can not be replaced with whole-body imaging.
  
  The PPL Holder pointed out that this may be different for other tumour models and has to be assessed for each tumour model separately.
• Regarding amendments – three amendments were made for this PPL, two of which were for whole-body imaging. The use of luciferase as a reporter rather then fluorescent reporter genes such as mCherry required to include intraperitoneal injection of a suitable substrate for the whole-body imaging step in Protocols 1-4. In order to be able to follow tumour growth by whole-body imaging for longer, the number of times mice may undergo whole-body imaging was increased from 5x AB + 1x AC to 10x AB for Protocols 1-4.
  
  In addition, another amendment was made to allow the perfusion of mice under terminal anesthesia (AC) in order to wash out blood from the perfused tissue such as the lungs. This amendment allowed the immune cells infiltrating the lungs to be investigated post mortem excluding the immune cells from the blood from the analysis.
• Regarding a follow-on licence – The PPL Holder declared that a follow-on licence is already under preparation in ASPeL. The aim is to have the new licence ready for AWERB review in the autumn. Work under the new licence is unlikely to start before the beginning of 2022 due to the pandemic and hence it is unnecessary to have the new licence in place earlier than that.

No questions were raised regarding the end of term review of this licence.

A general question was raised with regard to the review of amendments for project licences. It was noted that in most cases amendments were reviewed via the fast-track route. It was discussed whether amendments should be discussed by the AWERB committee if the PPL Holder seeks approval for more than two amendments for a specific licence. Several amedments to the same PPL may alter the licence significantly and may make it necessary for the AWERB committee to discuss the impact that all of the amendments have on a licence. It was discussed how the AWERB committee could be involved in assessing the impact of amendments. One suggestion was to discuss amendments that were approved via the fast-track route at the next AWERB committee meeting. It was agreed that this issue will be discussed as a separate agenda item at the next AWERB committee meeting.

Action: HOLC/chair to put the item on the agenda of the next meeting & HOLC to provide the rules for fast-tracking amendments to the AWERB committee for discussion at the next meeting.

The HOLC explained that the PEL Holder reports are drafted by the NACWOs, NIO, NTCO and HOLC for the quarterly meetings of the HOLC with the PELH. Since these quarterly HOLC/PELH meetings are not aligned with the AWERB committee meetings, the PEL Holder reports can be somewhat outdated by the time the report is discussed at the next AWERB committee meeting. It was suggested that the HOLC/PELH meetings could be better aligned with the AWERB committee meetings, however it is unclear if this is feasible since it depends on PELH availability.

HOLC update: 2 PEL amendments, 1 new PPL, 3 PPL amendments and 3 PIL amendments had been submitted and granted by the HO during this 4 month period. A recent virtual HOLTIF meeting was attended where the HO gave updates including the continuous development of ASPeL.

NIO update: The NIO pointed out that despite requesting feedback, no feedback is returned from BSD staff or AWERB committee members regarding the courses/seminars that are recommended with only one exception. In particular with regard to feedback from BSD staff this is of some concern and feedback should be followed up in the future.

NTCO update: The interim NCTO gave a brief summary and pointed out that the new NCTO has now started and is currently trained in the role.

Head BSD update: The Head BSD talked about the difficulties in connection with the repair of the BSD roof. Three rooms on the primate floor are currently out of use due to the leak. The room that houses the transponders is close by and may be affected by the repair work. Also, a recent survey discovered that the leakage is more substantial than anticipated. The repair work will have to be carefully planned and the animals may have to be moved to other rooms on the primate floor. However, it is currently still unclear what work will have to be undertaken and how the repairs can be approached.

Similarly, the cage washer on the primate floor will probably be repLaced towards the end of the year. Again, the work will have to be planned carefully, but the risks associated with this work is manageable.

The Head BSD pointed out that there are currently 50 hamsters within the BSD and that this will increase to 100 soon. The protocols associated with the hamster work are time-consuming and additional staff members are trained to work with hamster in order to support the three staff members currently performing the hamster work.

Staff working on site are still kept to a minimum and starting times are still staggered to avoid crowding in the changing rooms. Staff overtime policy has been transferred over to MHRA overtime policy, which provides better conditions to staff members.

A concern was raised about a more pathogenic strain to be used for a study. This was communicated well between the PPL Holder and the BSD team and everything worked out well.

PF

In February the second former normal bleeder (macaque) became sick, recovered briefly before becoming unwell again. The animal was humanely euthanised and the post mortem analysis revealed that the animal had suffered pacreatitis and subsequently constipation.

Since it was the last AWERB committee meeting that the current NVS participated in, the committee members thanked the current NVS for all the hard work and agreed that we will greatly miss the contributions from the current NVS. Everyone expressed their best wishes.

The last meeting was in May 21. Finally, confirmation was received that information could be published on Insite for promotion of 3Rs. This represented a huge step forward.

Also a talk at a meeting at the London School of Hygiene and Tropical Medicine was given by a BDS staff member. The talk described the tunelling of mice for replacement of tail handling and was well received.

Unfortunately, tours in BSD are still not possible due to the pandemic.

AWERB committee members were wondering when 3Rs stories could be shared with the public on the NIBSC website. The attitude towards sharing information more widely may change with the changing membership of the board. It was also suggested that the COVID animal work at NIBSC could used to test how more openness about animal experiments could be achieved and be perceived.

NACWO – the rat towers used for housing of the hamsters made a very positive difference. Also, housing male hamsters from the same litter in pairs upon weening reduced the incidence of aggression and in particular injuries significantly. These refinements had a very positive impact.

Also, male hamsters do not recover well upon receiving injectable anaethetics. However, gaseous anaesthetics seem to work fine for male hamsters and this is now the preferred method.

The AWERB committee members wondered how these 3Rs success stories could be shared with the public or published. Maybe preparing these stories to be included in the QQR will then facilitate their publication.

The AWERB committee members suggested that these great examples of the 3Rs should be communicated with the openness board and the PELH.

9. AWERB membership

Eight staff members had expressed interest in joining the AWERB committee after the Chair presented a call for new members at the last NIBSC townhall meeting on 24^th March 21. Several of these staff members expressed an interest in observing an AWERB committee meeting and two had joined the meeting today (up until discussion of agenda item 9).

In terms of expertise, the committee needs to replace one PPL Holder and in addition needs to invite a scientist involved in NHP work to join. It therefore was decided that the Chair will invite the PPL Holder from Bacteriology who expressed an interest to join the committee after the townhall meeting. In addition, the chair will invite a previously identified staff member to join the committee to cover expertise in NHP work.

Action: Chair to invite the two specified staff members to join the committee.

Furthermore, the committee agreed that we could invite two additional lay members plus one scientist to join the board. With regard to the scientist, it would be good to take into consideration what area the scientist works in and the areas/divisions without representation should be favoured over areas/divisions with good representation on the committee.

It Was agreed for the chair to wait for the responses of the two staff members that will be invited to join the committee and for the feedback of the two staff members who joined the meeting as observers. Depending on these outcomes, further actions with regard to AWERB membership would then be agreed by e-mail with the committee members.

10.1.  QQR has been postponed to end of July, but the date has not been confirmed. It is very likely that it will be postponed once again.

10.2.  Regular BSD facility visits by the PELH. During the discussions it was noted that no regular visitis of the PELH have been scheduled despite this having been suggested in previous meetings. It was also pointed out that the Home Office Inspector expressed disappointment over the failure of the PELH to inspect the situation on the primate floor with the leaking roof. The AWERB committee members agreed that the committee should keep trying for better engagement with the PELH.

Action: Chair to e-mail PELH and to invite PELH to one of the next AWERB committee meetings and also to suggest regular visits to the BSD facility.

The meeting concluded at 16:22 pm.

END

These Minutes have been viewed and approved by the Establishment Licence Holder (Director of NIBSC).

Signature: REDACTED

Date: 29^th March 2022