National Institute for Biological Standards and Control
Animal Welfare and Ethics Review Body
Minutes of a meeting held on Tuesday 14 September 2021 at 2:00 pm
REDACTED (BSD Head; NACWO)
REDACTED (primary NVS)
REDACTED (Scientist; PILH)
REDACTED (Scientist, PPLH)
The HOLC will amend the minutes regarding the HOLC report and minutes will be distributed for final approval by AWERB members.
21-02: A questionnaire was drafted, but will have to be discussed at an AWERB committee meeting. ONGOING
21-06: The NHPs were used in a study. CLOSED
21-07: The fast-tracking of PPL amendments was discussed as agenda item 4 (see below). CLOSED
21-08: Engaging the PELH with regard to agenda item 12 (AOB: size & shape / BSD staffing levels) has a higher priority. The chair will invite the PELH to the next AWERB committee meeting. ONGOING
21-09: One new PPLH and one NHP scientist accepted the invitation to join the AWERB committee. CLOSED
Currently, the decision whether or not to fast-track PPL amendments is made by the AWERB chair after the NACWO, the NVS and the NTCO perfom a paper-based review of the amendments (see What to expect document). The documents in connection with a fast-tracked amendments are saved on the shared AWERB drive to which all AWERB committee members except the external lay member have access, however, the fast-tracked amendments are not discussed at AWERB committee meetings nor are the AWERB members informed about specific ongoing or completed fast-track amendments, aside from the information provided in the PELH update reports and the HOLC update summaries.
It was discussed that all AWERB committee members should have an opportunity to review and comment on fast-track amendments irrespective of how urgent such amendments are in order to enable the start of studies under the new amendments ASAP. In order to allow all AWERB committee members to review and comment on fast-tracked amendments it was decided to implement a new process. In future, the chair will distribute the documentation associated with fast-track amendments after NVS/NACWO input to all AWERB committee members by e-mail and will give the committee members 48h in urgent cases and one week in cases that are not urgent to review and comment on the amendments. The comments from all AWERB committee members including the NACWO, NVS and NTCO will be collected and forwarded to the PPLH. When all comments have been satisfactorily addressed by the PPLH, the chair will approve submission of the amendment request to the HO.
Action: HOLC/chair to initiate revision of What to expect document to reflect the agreed changes. The revisions should be reviewed by the AWERB committee at the next meeting.
This retrospective assessment was the first PPL which was assessed in the new ASPeL format. The committee felt that the new format may make it easier to assess PPLs retrospectively since the original non-technical summary is provided and since the 3Rs are addressed for the whole PPL and not individually for each protocol as in the old format.
The PPLH was present at the meeting and gave an overview of the work performed under the licence. The PPLH explained that three of the four original objectives of the licence were addressed. The one objective that wasn’t addressed was dropped in order to avoid duplication of work since another study on the subject had been published. The three objectives that were addressed by the PPL were the following:
Two scientific papers were published describing the studies performed under the PPL. The studies on Zika infection clearly showed differences between the protective activity of antibodies in the mouse versus the NHP model. The mouse model was found to be not suitable for assessing the protective activity of antibodies against Zika infection highlighting the importance of NHP models for studying particular viruses.
One aspect of Zika infection models that was initially discussed at the time of PPL submission was the pathogenesis of infection regarding the foetus. Because of the many challenges associated with such a study including the ethical implications, this aspect of the Zika infection model was not addressed. The PPL was sufficient to cover all the other planned studies on Zika infection except for one additional study on protective antibody levels. This last study was cancelled due to the SARS-CoV2 pandemic and the associated re-prioritisation of work. The PPL for Zika infection studies will not be renewed since Zika infections are no longer a public health concern in South America after natural immunity against the virus has been established within the population.
While the PPL on Zika infection studies will not be renewed, the PPLH mentioned their intention to submit a PPL which is more generic and could cover any new emerging viral pathogens. The SARS-CoV2 pandemic demonstrated that time is of essence during a pandemic and that having a generic PPL in place would allow the institute to mount a more rapid response to new emerging viruses. The AWERB committee discussed that it would be important to ensure that animals wouldn’t be purchased and kept for long time periods “on the shelf” under such a generaic licence without being used. The PPLH pointed out that NHP would be purchased as required for studies under other PPLs requiring NHP and would only be transferred to the generic PPL in case a new emerging virus was identified. The PPLH also pointed out that the generic PPL on virus infection models would not exclusively work on NHP models, but would also include other species. As has been shown in the recent pandemic for SARS-CoV2, animal models other than NHP may be very valuable in studying new emerging viruses.
The committee further discussed that it would be advisable for the PPLH to draft a justification for such a generic licence before embarking on drafting such a PPL.
The PPLH pointed out that the Zika work was funded by external grants which also contributed to BSD staff costs. The committee pointed out that correct costing of future studies will be vital and that the costing matrix used in the past was not entirely sufficient to fully fund the work and will need revision.
The AWERB committee approved the rstrospective assessment without any revisions required.
The PPLH was present at the meeting and gave an overview ofthe work performed under the licence. Work under this licence was not affected by the pandemic and proceeded as planned. The PPL supported the implementation studies of novel polio vaccines including a new non-infectious polio vaccine developed at the institiute. These vaccines are developed for the global market.
The PPLH pointed out that the PPL is a unique resource (the transgenic mice used under the licence plus the know-how to perform the procedures) which is not available anywhere else and that the work is in part funded by external grants.
Less than 1% of mice used under the licence have experienced a severe severity outcome. A number of refinements were implemented over the life-time of the PPL. The renewed PPL for the transgenic mouse model for poliomyelitis will further explore the feasibility to replace the mouse model with an in vitro model based on genomic analysis. This work is funded by an external grant for the next two years.
The PPL had to be amended to increase the number of mice used under the licence. This was necessary since one of the transgenic mouse strains bred and used under the PPL had to be re-derived. The breeding of the colony had become more difficult and inefficient and a new colony was derived from frozen embryos since the mouse strain is not available elsewhere. The new colony was compared side-by-side to the old colony to ensure that both colonies performed equally well in the assay. The rederivation of the strain had not been factored in when calculating the required mouse numbers for the initial PPL application.
The AWERB committee approved the end of term review without any revisions required.
The Chair suggested that in the interest of time, the PELH Update report will not be discussed in detail at AWERB committee meetings. Instead, the Chair will ask the AWERB committee members whether they would like to comment or ask questions about specific aspects of the PELH Update report.
The committee had no objectitions against this approach. Furthermore, the committee had no questions or comments regarding the PELH Update report from June 21.
The HOLC went through the HOLC update report pointing out the number of PPLs which will expire in 2022 and which will require a continuation of work. The committee discussed how the current restructuring of NIBSC (size & shape) will affect the animal work and whether or not the AWERB committee will know which PPL will be required in the future. In addition, it was discussed how the recent QQR and the recommendations of the QQR review panel would feed into the decision making on what animal work will be perfomed at the institute in the future. Furthermore, it was noted that in the proposed structure that is currently under consultation, BSD would lose 4 staff members. It is currently entirely unclear whether or not the suggested staffing levels will be sufficient to support the animal work that will be performed under the new structure. The AWERB committee felt that it couldn’t approve PPL licences and work programmes for which it is unclear whether sufficient resources will be available. If staffing levels are too low for the planned work programmes, animal welfare can only be ensured at the expense of staff welfare.
The uncertainilty in connection with the restructuring process has already led to the resignation of one recently recruited staff member (new NTCO). It is feared that other resignations may follow which will have a negative impact on the workload of remaining staff members. This is very frustrating for staff members especially since working conditions have only improved very recently with new staff being recruited and being trained.
It was decided that due to the uncertainty associated with the restructuring and the currently unknown workload that BSD will be expected to undertake in the future, the committee should contact the PELH to voice their concerns about the proposed structure in connection with the in vivo work at the institute. In addition to engaging the PELH in a discussion on these concerns, the committee also felt that the concerns should be raised as part of the formal consultation process.
Action: Chair to draft a letter to the PELH that summarises the concerns of the AWERB committee regarding the proposed structures and the reduction in BSD staff members. The draft letter will be distributed to AWERB committee members for revision and upon agreement will be sent to the PELH.
Action: Chair to draft feedback for the formal consultation process based on the concerns outlined in the letter to the PELH.
There was no time to discuss the NVS report.
There was no time to discuss openness.
11. 3Rs / welfare initiatives
There was no time to discuss the 3Rs or welfare initiatives.
The meeting concluded at 16:04 pm.
These Minutes have been viewed and approved by the Establishment Licence Holder (Director of NIBSC).
Date: 29th March 2022