Minutes of the 97th ACAF meeting held on Thursday 3rd April 2025

These minutes are subject to confirmation by the Committee. 

Members are required to declare any personal interest in matters under discussion. Where Members have a particularly close association with any item, the Chairman will limit their involvement in the discussion. In cases where an item is to be discussed in their absence, a Member may make a statement before leaving. 

This meeting was held online using Microsoft Teams.

Attendance

Committee Chair

Nick Wheelhouse

Committee Members

Martin Briggs

Emily Burton

Katrina Campbell

Nick Jonsson

Hannah Kane

Susan MacDonald Chris McAlinden

Donald Morrison

Derek Renshaw

Mike Salter

Adam Smith

Christel Wake

Helen Warren

FSA members

Nathan Allen

Krystle Boss

Aaron Bradshaw

Emily Davies

David Evans 

Emily Hudson

Michelle Hutchinson 

David Kovacic

Kaila Lee

Francisco Matilla

Barry Maycock

James Metcalfe

Shila Sultana

Johann Trotter

Alba Ureña Rusillo 

1. Apologies 

No apologies were received.

2. Welcome

The Chair welcomed members of the Committee, Secretariat and observers from the Devolved Administrations.

3. Risk Assessment update

The Regulated Products Team Leader Francisco Matilla-Garcia provided an update, informing members that a substantial number of applications have been put through risk assessment across Regulated Products in the last financial year. Members were thanked for their significant contribution to this output, highlighting that ACAF itself has been very positively recognised. Confirmation was given that there will be seven meetings this year, with the plan to have a face-to-face meeting in October. More details will be provided when confirmed. Members were also informed that following recent discussions regarding antimicrobial resistance and coccidiostats, this question will be taken through the risk analysis process.

4. Policy update

Senior Policy Manager, Rebecca Greenaway, provided an update, highlighting that the first two legislative reforms to the market authorisation process came into force on April 1^st, these being the removal of renewals and the removal of the requirement for Statutory Instruments (SIs). The GB register has undergone the phase one update and is also now live. Members were reminded that expiry dates have now been removed from those products that are authorised on the register and that the register is an ongoing piece of work, with phase two expected in the future.

Emily Burton provided members with a brief update in relation to the Science Council.

5. Minutes from 96th Meeting

The Committee reviewed the minutes from the 96^th ACAF meeting and provided feedback to be reviewed by the Secretariat.

6. RP1605 Titanium dioxide

The Secretariat introduced the item to provide clarity to Members on the function of the document. Members were reminded that this is not a market authorisation and instead is a risk assessment of the safety of titanium dioxide as a feed additive for the purposes of aiding policy decisions. It was brought to Members’ attention that the COM and COT have already reviewed the safety of titanium dioxide as a food additive and that COM had concluded that there was insufficient evidence to conclude on a genotoxic risk of titanium dioxide. Due to the little evidence in the literature to suggest that there is a health concern related to in vivo genotoxicity induction by TiO2, the COT were subsequently able to establish a health-based guidance value (HBGV); the Secretariat further added that this is not in line with EFSA’s conclusions on the literature. 

Members highlighted that they had further questions following their initial offline review of the risk assessment. As such the item was devoted to questions from the Committee to the Secretariat rather than a discussion of the paper contents and conclusions.

The Secretariat reiterated that this was a draft paper for discussion and the Secretariat sought the opinion of the ACAF which would be incorporated into a Statement Paper that reflected their views.

Following this, the discussion primarily focussed on two concerns of Members: the genotoxic potential of titanium dioxide and the potential contribution of nanoparticles to the toxicity of the compound. Members were unsure how, based upon the same literature, different conclusions could be drawn by COM and EFSA regarding the genotoxic potential. Furthermore, Members determined that clarity was required regarding the nanoparticle fraction of food/feed grade titanium dioxide (E171) and how this affects the toxicity of the additive. The Secretariat reminded Members that E171 is not classified as a nanomaterial and therefore, no nanospecific considerations were given to the risk assessment for the use of titanium dioxide in feed.

Members stated that more time would be required to look at the risk assessment provided by the Secretariat in conjunction with the COM and COT opinions than what was required prior to the meeting as this entailed a lot more work than what was achievable in the week before the meeting. The Secretariat suggested that an additional meeting of the Secretariat and toxicologists of the Committee could be held to talk through any additional questions regarding the process and the risk assessment ahead of the next meeting so that full discussions on the paper content and conclusions could begin during the June meeting.

The Secretariat provided links via the assessment template to the EFSA guidance on determining and assessing nanoparticles.

7. Dossier for assessment: RP1592 Interban^®

No conflicts of interest were declared for this item.

In this meeting, the Committee assessed the remaining studies that were not assessed during ACAF 96. The Committee reviewed the tolerance study conducted in chickens for fattening provided for assessment, concluding that at the recommended dose the additive was tolerated by the target species. Based on the data available, Members were unable to conclude on the safety of the additive at the overdose levels investigated. The applicant would be made aware of this conclusion and notified that in the absence of histopathology data a conclusion at the overdose levels cannot be reached.

Members reviewed the residue studies provided, noting that studies on eggs were not required for assessment as residue levels following any withdrawal period would be negligible. The Committee concluded that extrapolation from the residue studies performed in chickens for fattening to chickens reared for laying is acceptable under the guidance. It was noted during the assessment that the proposed label does not contain a statement regarding the additives use with other coccidiostats, the applicant would be asked to provide an updated label containing a statement on uses of the additive with other coccidiostats.

The Committee discussed the proposed withdrawal period for the additive, noting that the applicant stated a storage stability study was ongoing at the time of assessment. In the absence of this data, Members were unable to conclude on the proposed withdrawal period for the additive. The applicant would be asked to provide the storage stability data that was ongoing at the time of submission.    

8. Dossier for assessment: RP2245 GalliPro Fit

Martin Briggs declared an indirect conflict of interest for this item but stayed in the meeting for this discussion. 

The Committee assessed an application for the additive GalliPro Fit 10, which is a microorganism product that contains spores of active substances Bacillus subtilis DSM32324, Bacillus subtilis DSM32325 and Bacillus amyloliquefaciens DSM25840. This additive falls under the category ‘zootechnical,’ functional group ‘gut flora stabiliser.’ The applicant is seeking authorisation for use in feed and water for laying hens and other birds kept for egg production or breeding, plus modification of a 10-fold increase in the content of the active substances.

The Committee discussed the references to existing documentation, concluding that supporting documentation is necessary for the ACAF to conduct a full risk assessment. The applicant would be asked to submit all relevant studies for the assessment of the application. The Committee also noted that the applicant had not stated how the microorganisms are enumerated or mixed during the manufacturing process. The applicant would be asked to provide the data on the total Bacillus spp. counts, the Bacillus amyloliquefaciens DSM25840 counts and the ratio in which the strains are mixed with the carrier during manufacture of the final product.

Members raised concerns regarding subsampling on the homogeneity test and concluded that this may not be representative of the whole batch. They also stated that the applicant failed to demonstrate homogenous distribution in water. The applicant would be asked to provide homogeneity studies for the additive, including homogeneity in water. In addition, the applicant would be asked to clarify their statement relating to how homogeneity can be inferred from the stability in drinking water. The applicant would also be asked to provide studies demonstrating the stability of the additive in water, including data on presence of excipients. 

It was also noted that data evidencing pelleting stability and molecular techniques used are missing from the application. The applicant would be asked to provide a pelleting stability study including retention time. The applicant would also be asked to provide information on the molecular techniques used to ensure strain integrity.

The Committee noted that an MSDS required translating into English and HACCP documents were missing from the application. The applicant would be asked to provide MSDS for Struktol SB 509 in English and the MSDS for the final additive under current assessment. The applicant would also be asked to provide a complete HACCP plan for the production process of the additive and critical control points for all mentioned production sites (USA, Czech Republic). 

Two of the three batches tested were classed as ‘dusty’ and the fine particles would be deposited in the respiratory system. The Committee agreed that the additive is a sensitiser to the lungs, and that there is no need to classify the additive as a skin or eye irritant. It should be regarded as a skin sensitiser as it is a microbial product.

The efficacy studies the applicant provided used the lower concentration of the authorised GalliPro Fit, and not the 10x increase GalliPro Fit 10. The first two studies were dose response trials, study one had a weak positive effect, study two showed some improvements, study three replicated study one and resulted in an improved feed efficiency, study four had no effect and the Committee raised questions with regards to EU regulations. The Committee concluded that the additive has the potential to be efficacious.

9. Dossier for assessment: RP2247 Enterococcus lactis NCIMB 10415

Helen Warren declared an indirect conflict of interest but remained in the meeting for the discussion.

The Committee assessed an application for Enterococcus lactis NCIMB 10415, which falls under the category “technological additives”, functional group “silage additives”. The additive was previously authorised for use in Great Britain as a silage additive, but the authorisation expired in April 2024 and the applicant is therefore seeking a new authorisation for use in all animal species.

Members discussed the raw materials present in the additive other than the active agent and agreed that they did not pose a safety concern. It was noted that testing for impurities was conducted in-house, using internal methods; however, it was unclear which laboratory performed testing for mycotoxins and heavy metals. The applicant would be asked to clarify the organisation performing the testing and provide certificates of accreditation for all laboratories. The Committee noted that a comprehensive Whole Genome Sequence (WGS) analysis had been provided to demonstrate the taxonomic identification of the strain, and agreed with the classification as E. lactis, rather than E. faecium as it was formerly known.

The presence of virulence factors and antimicrobial resistance (AMR) determinants in certain strains of E. faecium has been well described, whereas E. lactis is generally accepted as having less pathogenic potential. However, Members noted that safety could not be presumed, referring to a recent paper in the literature which described a strain of E. lactis that carried a plasmid containing multiple AMR genes. Members noted that although the applicant had investigated the strain for the presence of a limited number of specific, known virulence factors, a full search of the WGS for virulence factors had not been performed. The applicant would be asked to perform an up-to-date search of the WGS of E. lactis NCIMB 10415 for virulence factors.

Members reviewed the manufacturing process, but it was unclear where the additive was manufactured. The applicant would be asked to clarify the manufacturing location and provide a HACCP plan and FAMI-QS certification for that site. Short-term stability of three batches of the additive in water was evaluated. Members noted that the recovery of one of the batches was quite low and therefore could not conclude on stability in water with the data provided. The applicant would be asked to provide stability data in water for an additional three batches. The applicant would also be advised that they may wish to update the conditions of use and proposed label text with the instructions for use in water.

Members reviewed the data provided for user safety, and agreed that although dusting potential was low, the additive should be considered a respiratory sensitiser and therefore any level of exposure should be considered hazardous. In vitro skin and eye irritation studies had been provided but were inconclusive and a skin sensitisation study had not been performed. The applicant would be asked to provide additional data or accept that the Committee will conclude that the additive is a potential skin and eye irritant and potential skin sensitiser. A Safety Data Sheet (SDS) had been provided for the additive but required updating. Members noted that Enterococcus spp. are classified as Hazard Group 2 biological agents on The Approved List of biological agents (published by the Health and Safety Executive), but that this was not reflected on the SDS. The applicant would be asked to update the SDS or, alternatively, provide evidence that E. lactis does not pose a risk to human health and is suitable for classification as a Hazard Group 1 biological agent. 

The Committee discussed the in vitro efficacy studies provided by the applicant and agreed that efficacy had been demonstrated, by means of improved production of silage from easy, moderately difficult and difficult to ensile materials. Members noted that the studies were conducted simultaneously and in-house, but agreed that this was acceptable as the substrate used in each study was different. It was noted that information on methodology was limited; for example, the order in which the silos were packed was not described. The applicant would be asked to provide more detailed information on how the substrate was transported and packed in each study.

10. Response to RFI: RP2074 FUMzyme

Adam Smith declared a direct conflict of interest and left the meeting for this item.

The Committee were satisfied with clarifications made by the applicant regarding levels of yeasts and moulds tested in FUMzyme and the identity of the test item used to perform particle size measurements. Members were also satisfied with laboratory testing certificates provided to verify that impurity testing has been conducted in accordance with approved and recognised ISO methods. A comprehensive HACCP was provided, however there were missing details, such as information on the product, the premises and the date. The applicant would therefore be asked to provide a revised HACCP plan including these details. More recent MSDS were provided as requested by the Committee, as well as accreditation certificates relating to quality control. Requested information was provided such as the type of container in which the additive will be stored, the conditions of humidity during stability testing and an example label. The applicant had indicated that homogeneity was demonstrated in Annex 26 of the original application. However, homogeneity has only been demonstrated for mash and not for pellets. The applicant would be asked to demonstrate evidence of homogeneity in pelleted feed.

Members reviewed the information provided in relation to the safety of fumonisin degradation products, concluding that the applicant should demonstrate if any new scientific information has come to light in recent years that will either alter or confirm previous conclusions on metabolites produced by fumonisin. The applicant would therefore be asked to provide a more up-to-date literature review covering the years since the original literature review (2012), and to demonstrate that the review was undertaken systematically. Regarding the bacterial reverse mutation study, justifications were provided for why 2-aminoantracene was used as the sole indicator of efficacy of the S-9 mix and also for the use of their specific positive control. An updated MSDS for the final product was provided.

The Committee reviewed information provided on the quality assurance schemes related to the efficacy trials and were satisfied quality assurance was demonstrated.

11. Response to RFI: RP2107 Availa CR

Helen Warren declared an indirect conflict of interest and remained in the meeting for this item.

The applicant proposed that the maximum extrusion temperature for stability in feed must not exceed 130°C during extrusion/pelleting and the retention time must not exceed 240 seconds. The ACAF concluded that they can only accept the minimum temperature of 112°C and retention time of 146 seconds as the information provided does not indicate how long feed was exposed to the maximum temperature. The applicant would be asked to provide more evidence to support the maximum temperature and retention time if they do not accept this conclusion.

Members were satisfied with the applicant’s literature search regarding ADME and toxicology of chromium (III) and chromium methionine for the safety for the consumer to cover aqua species. They agreed with the FEEDAP (EFSA, 2025) that the use of the additive in feed for salmonids at up to 0.6 mg Cr/kg feed (600 mg additive/kg feed) is safe for the consumers as it would not significantly increase consumer exposure to chromium. Members also concluded that due to the presence of nickel, the additive is a skin and respiratory sensitiser. The Committee stated that the Phase I assessment for the safety for the environment was adequately conducted and concluded that there is no risk, and a Phase II assessment will not be needed.

As no new additional evidence was provided to demonstrate efficacy in salmon at the maximum dose (0.6 mg/kg), members can only conclude that there is potential for efficacy at 0.2 mg/kg with a maximum dose of 0.4 mg/kg.

12. Draft safety assessments: RP1275 and RP1696

Members were presented with a draft Safety Assessment document for application RP1696.

The Committee was also presented with the final draft of the Safety Assessment document for application RP1275. The Committee provided feedback on final corrections and approved the opinion to be finalised and sent to Risk Managers.

13. Any other business

Members were asked for their advice on an application in the validation phase with regards to extrapolation of efficacy.

An update on upcoming applications was also provided.

Next ACAF meeting: 11^th June 2025 on Microsoft Teams.