Application for consent to market genetically modified organisms

1. The proposed commercial name of the product and names of the genetically modified organisms in the product, the unique identifier assigned in accordance with Regulation 65/2004, and any other name or code used by the applicant to identify the genetically modified organism.

SOURVISIAE®, Saccharomyces cerevisiae, PCT/IB2019/051682 or WO201917123OAI

2. The name and address of the person who is responsible for the marketing, whether it be the manufacturer, importer or distributor.

DANSTAR FERMENT A.G
Poststrasse 30 
CH-6300 Zug 
Switzerland

Represented by

Lallemand UK Limited (doing business as AB Vickers)
Dallow Street
Burton-On-Trent
Staffordshire
England
DE14 2PQ
 

3. The name and address of the supplier or suppliers of control samples.

DANSTAR FERMENT A.G
Poststrasse 30 
CH-6300 Zug 
Switzerland

Represented by

Lallemand UK Limited (doing business as AB Vickers)
Dallow Street
Burton-On-Trent
Staffordshire
England
DE14 2PQ

4. A description of how the product and the genetically modified organism are intended to be used, highlighting any differences in use or management of the genetically modified organism compared to similar non-genetically modified products.

Sourvisiae® is a bioengineered (GMO) strain of Saccharomyces cerevisiae capable of producing lactic acid in addition to alcohol during fermentation.

Sourvisiae® contains a single genetic modification, a lactate dehydrogenase gene from a known food production microorganism, which enables the yeast to produce high levels of lactic acid when used as a pure culture, (or when blended with another) brewing yeast strain. The brewing process is conducted without any modifications; Sourvisiae® is pitched just like conventional yeast and ferments in a normal fermentation time.

5. A description of the geographical area or areas and types of environment where the product is intended to be used, including, where possible, an estimate of the scale of use in each area.

Sourvisiae®, a genetically modified strain of Saccharomyces cerevisiae, is primarily intended for use in brewing (contained) environments across various geographical regions, especially where craft beer production and sour beer styles are popular.

6. A description of the intended categories of users of the product, such as industry, agriculture or consumer use by the public.

Sourvisiae® allows brewers to ferment and sour beers in one simple step. It is intended to be used in breweries.

7a. Information on:

i. methods for the detection, identification and, where appropriate, quantification of the transformation event,

Sourvisiae® is identified and detected using a combination of molecular and genomic techniques that ensure high specificity and traceability:

1. Whole Genome Sequencing (WGS): The primary method for identification, WGS, confirms the presence of the integrated ldhA gene from Rhizopus oryzae.

2. Polymerase Chain Reaction (PCR): Targeted PCR assays are used to detect the presence of the ldhA gene and confirm strain identity. In addition, PCR can confirm the locus of the gene. Primers specific to the integration site and the LDH cassette can be used for screening.

3. Quantitative polymerase chain reaction (qPCR) analysis demonstrates the number of ldhA gene copies that are present in Sourvisiae®.

ii. samples of the genetically modified organisms and their control samples,

Samples of the genetically modified organism (Sourvisiae®) and corresponding control samples are maintained by the applicant in Lallemand’s culture collection in Montreal, Canada.

iii. the place where the reference material can be accessed.

Reference material can be accessed at the applicant’s designated facility upon request by the competent authority, in accordance with applicable regulatory requirements.

7b. Information under sub-paragraph (a) that cannot be placed on the register for confidentiality reasons, must be identified.

Not applicable.

8. The proposed labelling which must include, in a label or an accompanying document, at least in summarised form, a commercial name of the product, a statement that “This product contains genetically modified organisms”, the name of the genetically modified organism and the name and address of the person who is responsible for marketing the product, and how to access the information in the publicly accessible part of the register.

Bioengineered Saccharomyces cerevisiae FOR SOURING DURING PRIMARY FERMENTATION/ Beer production]. Contains GMO

The proposed label is available in Appendix 12 – Sourvisiae® Label.

9. The measures to be taken in the event of the escape of the organisms in the product or misuse of the product.

Release of Sourvisiae® to the environment is not expected when used to brew sour beer (ales) due to contained use in brewery settings. In the event of unexpected spread, the food safety plan (including HACCP) and emergency response procedures should provide for immediate containment and review of procedures to lead to cessation of the spread and or brewing activities, and isolation of materials. The organism’s fitness is less than the parental strain and nutrient availability outside the brewery is limited, further reducing risk. Standard brewery sanitation protocols, including cleaning-in-place (CIP) and disinfection, are implemented to control and eliminate the organism.

10. Specific instructions or recommendations for storage and handling of the product.

Store Sourvisiae® in a dry place below 4°C.

Keep packaging intact. The product is stable for 3 years in its original sealed package.

11. Specific instructions for carrying out monitoring and reporting to the applicant and, if required, the National Assembly for Wales, which are consistent with Part C of Annex VII of the Deliberate Release Directive (as listed in Post-Market Environmental Monitoring plan A8).

Case-specific monitoring is presented in line with the conclusions of the Environmental Risk Assessment (ERA) and is designed to verify the effectiveness of risk-management measures under commercial conditions of use.

The modification in Sourvisiae® consists solely of the stable chromosomal integration of a single, well-characterised ldhA gene from Rhizopus oryzae, a food-grade filamentous fungus with a long history of safe use in fermentation. As with other enzymes, the LDH enzyme expressed in Sourvisiae® is highly specific, catalysing only the specific and characterized conversion of pyruvate to lactic acid, a normal metabolic reaction with no off target or hazardous biochemical or known side activities.

The integration cassette contains no plasmid backbone, no antibiotic resistance markers, or any unintended genetic material, as confirmed by PCR and whole genome sequencing. The LDH enzyme introduced is a non-toxic, non-pathogenic metabolic enzyme that catalyses the natural conversion of pyruvate to lactic acid, an established food-relevant biochemical reaction. The strain shows no off-target integrations, is genetically stable over 100 generations, and exhibits no new traits linked to survival, pathogenicity, toxicity, allergenicity, or environmental persistence compared to the parental S. cerevisiae strain.

Based on the Environmental Risk Assessment (ERA) in this submission, the acceptance of Sourvisiae® as Generally Recognized As Safe (GRAS) in the United States and in Canada as a novel food, this product can be considered not to present any risk (on its use in beer production) however a case specific monitoring is suggested to further validate this.

Case-specific monitoring will be undertaken at three representative brewery sites in Wales (two small breweries and one medium-sized brewery via specific agreement contract) over 18 months as a start. Monitoring will assess viable cells in (i) spent yeast sampled immediately before and after on-site treatment and (ii) treated liquid waste. Culture-based viable counts will be used, with confirmatory identification where appropriate. Lallemand will either work directly with the breweries if confidentiality clause allow to ensure that sampling is conducted appropriately and will perform the testing required to determine the viable cells in the spent yeast and liquid waste. Where conditions require (i.e. issues of confidentiality), the breweries will be given specific directions to complete the necessary analysis and reporting to ensure that outcomes are shared with the competent authority as necessary. A specific analysis and reporting form will be devised and exchanged as part of the sales contract.

The intended case-specific monitoring will be conducted during an initial verification period of approximately 18 months following the start of commercial use at selected sites. If results demonstrate effective treatment and no issues are identified, case-specific monitoring may be discontinued after 18 months, and monitoring will continue through general surveillance. Case-specific monitoring may be reinitiated if triggered by deviations, incidents, or relevant findings from general surveillance.

The approach to General Surveillance (GS) for Sourvisiae® as well as any GMO is for a design to detect any un-anticipated adverse effects on human health, animal health, or the environment. This will be achieved by integrating existing, well-established monitoring systems with operational level reporting and regulatory oversight. Therefore, our proposed GS will operate proportionately to the extent of Sourvisiae®’s use and will draw on multiple complementary mechanisms, including routine inspections and sampling conducted under the UK Food Surveillance Program (HSE), the Lallemand internal Quality System with HACCP based controls, and ongoing compliance with UK Food Hygiene legislation (The Food Hygiene (Wales) Regulations 2006) and the associated Food Law Code of Practice (Wales) (and similar codes for England and Scotland). These established food safety management systems also provide ongoing assurance that control measures implemented during brewing are effective in removing or inactivating the production microorganism. They therefore support confirmation the condition of use, which is that no viable genetically modified microorganisms are present in the final consumed product, is consistently met during commercial operation.

Operators receive clear guidance enabling them to recognise and report any unanticipated effects associated with the GMO during its production, distribution, storage and or use with HACCP plans in place while third-party auditing schemes provide additional independent verification of safety and quality performance. GS will be maintained mirroring the monitoring applied to conventional brewing yeasts, complemented by case-specific monitoring at three sentinel brewery sites during an initial verification period. If and highly unlikely adverse indications emerge, procedures for emergency response, including notification of authorities, activation of brewery containment and decontamination measures, and documented follow-up evaluations are in place as well measures to ensure corrective actions are implemented rapidly and effectively.

Lallemand will inform the competent authority of the results of monitoring, including both case-specific monitoring and general surveillance. Lallemand will provide an annual monitoring report as required and will immediately notify the Competent Authority should any unanticipated adverse effects be identified, enabling proportionate, risk-based mitigation measures to be implemented.

Lallemand will update the PMEM plan and review, update and adapt the associated methodology as necessary. Where case-specific monitoring is discontinued after approximately 18 months based on satisfactory results, general surveillance will continue for the duration of the authorisation. Case-specific monitoring may be reintroduced if warranted by deviations, incidents, or findings from general surveillance.

12. The proposed restrictions in the approved use of the genetically modified organism, such as where the product may be used and for what purposes.

Sourvisiae® is used as a fermentation/processing aid in the production of beer and related alcoholic beverages. It is intended to provide controlled lactic acid production during fermentation, either as a pure culture or in combination with conventional brewing yeast. Sourvisiae® is intended to be used in controlled brewing environments such as commercial breweries and pilot-scale brewing facilities using standard brewing practices. The organism will be handled under standard brewing conditions ensuring containment within fermentation vessels.Disposal of spent yeast should comply with local regulations for brewery waste management to prevent unintended environmental exposure.

13. The proposed packaging.

20 x 500g vacuum-packed sachets 25 x 10g vacuum-packed sachets

14. The estimated production in and/or imports to Wales, England, and Scotland.

1000 Kg

15. Any proposed additional labelling, which may include, at least in summarised form, the information referred to in paragraphs 4 and 5 of PART I of this Schedule (above), or paragraphs 9 to 12 of PART II, as set out immediately above.

No additional labelling is proposed.