AWERB Minutes 16 November 2021

National Institute for Biological Standards and Control

Animal Welfare and Ethics Review Body

Minutes of a special meeting held on Tuesday 16 November 2021 at 2:00 pm 

1.

The Chair welcomed the second new NVS to the AWERB committee.

3. Minute Taking during Meeting

The AWERB Chair asked for a volunteer to take the minutes of the meeting. Since no volunteer came forward, the meeting was recorded. The AWERB Chair volunteered to transcripe the minutes after the meeting with help of the recording/transcript, but pointed out a conflict of interest since the AWERB Chair is also the PPL Holder of the PPL application under discussion.

• a) Additional Revisions (Action Plan & Refinements)
  
  The Chair/PPL Holder outlined what additional revisions had been included in the document in response to a meeting of the PPL Holder, the BSD Head, the two NVSs and the HOLC/NTCO in the previous week on the 10^th November 2021. The revisions were included in order to make specific paragraphs in the action plan clearer and to adjust the table on humane endpoints for general health monitoring in a manner that will allow BSD to assess the general health of mice more easily. Furthermore, two additional paragraphs were included under refinements.
• b) The NVS asked about the need to include footpad injections as a route of application for immunotherapeutic intervention. The Chair/PPL Holder explained that footpad injections are good for experiments where the immune response in the draining lymph node is investigated in detail. Furthermore, the Chair/PPL Holder pointed out that the injected solution drains quickly from the footpad and that the mice do not show any signs of pain after footpad injection. Only one foot will be injected and with Toll-like receptor agonists used as adjuvants, the mice do not experience any inflammation at the injection site. The Chair/PPL Holder further clarified that for the footpad injections, the needle is inserted between the toes of the foot.
  
  It was agreed that the Chair/PPL Holder should make it clear throughout the protocols which routes of administration were performed with (AB) or without anesthetics (AA).
• c) The committee further discussed the weight loss cut-off for the mild and the moderate severity level specified in the general health monitoring table in the action plan. The NVS explained that the cut-off values have been refined by the Home Office and 15% of weight loss is the preferred cut-off for moderate severity. If a higher cut-off is necessary for a PPL (e.g. 20%), the PPL Holder will have to justify the higher cut-off. The Chair/PPL Holder confirmed that for this licence the cut-offs of 10% and 15% body weight loss for mild and moderate severity levels are suitable.
• d) Use of Freund’s Complete Adjuvant (FCA)
  
  Upon discussion of the use of FCA as part of the PPL, the chair/PPL Holder was asked to add that FCA would only be used as adjuvant for immunotherapeutic intervention if requested by third parties. The BSD Head mentioned that FCA often leads to nodule formation under skin and it would be good to capture this in the adverse effects. However, immunotherapeutic interventions with TLR agonist adjuvants very rarely induce adverse responses, so this step doesn’t have a section with expected adverse responses where nodule formation could be mentioned.
• e) Overlap between protocols 1-4 of the PPL application
  
  The Chair/PPL Holder was asked to what extent the different protocols of the licence overlap. The Chair/PPL Holder explained that the protocols do not overlap, but serve different objectives. The first protocol does not include transfer of tumour cells, the second includes transfer of tumour cells after the immunotherapeutic intervention and the last one includes transfer of tumour cells before immunotherapeutic intervention.
• f) It is currently entirely unclear if staffing levels will be sufficient, since staffing levels upon transformation are unknown and since the number and nature of the work programmes approved upon transformation are unknown. Should there be insufficient staffing levels upon transformation of the agency, mechanisms that allow for prioritisation of animal work will have to be put in place. This is likely to involve some sort of cross-institute committee.
  
  The AWERB committee discussed that BSD should ensure that no work on any licence is started if it is not clear that staff levels within BSD and within the scientific division are sufficient to support the work.
  
  The BSD Head also mentioned the distribution of a spreadsheet to capture the amount of planned work, which may help with the planning and prioritisation of experiments.
  
  In the future, the researchers may have to help out more with aspects of the experiments that do not require a PIL e.g. weighing of mice and measuring tumour sizes. Researchers such as PhD students who are relying on experiments to go ahead in a specific time frame may have to obtain a PIL so that they can perform experiments independently. This will require training from BSD staff, but may pay off in the long run.
• g) A NACWO again raised that the wording regarding the general health monitoring is not clear and not consistent throughout and may require more revision. The Chair/PPL Holder suggested to send in the precise, clear wording for the affected paragraphs so that the PPL application can be revised accordingly. However, all AWERB members would have to agree on the wording.
• h) The NVS had a question regarding the requirements of genetically modified mice which naturally develop tumours in protocol 1 (immunotherapeutic intervention studies) which does not involve tumours. The Chair/PPL Holder explained that in some cases mechanistic aspects of immune response initiation may be studied in these mouse strains before tumours develop.
• i) The NVS asked what imaging modalities will be used under the licence. The Chair/PPL Holder explained that they mainly used bioluminescence which is picked up very well by the in vivo imager whereas they had no success so far with picking up fluorescence from antibody that they injected.

The Chair/PPL Holder explained that the the final revisions included in the application as agreed during this meeting would be distributed to the AWERB members within the next week including the compiled revision log. The transcribed minutes of the meeting would follow and the AWERB members would have to make sure that the minutes correctly reflect the discussions.

The meeting concluded at 15:24 pm.

END

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

Signature: REDACTED

Date: 29^th March 2022