Supplementary guidance to applicants for the assessment of cell cultivated products in food: identity, production and microbiology

Applicants must ensure they are using the latest version of this supplementary guidance found on the FSS webpage alongside the Regulation (EU) 2015/2283 and 2016 technical guidance published by the European Food Safety Authority (EFSA) for novel food applications. 

All safety assessments should be supported by scientific evidence, with analyses conducted by accredited laboratories using nationally or internationally recognised and validated methods. Where a method has been used that is not internationally recognised, a full description of the methods should be provided within the application. Applicants are also encouraged to adhere to the Organisation for Economic Co-operation and Development (OECD) guidelines on Good Laboratory Practice (GLP) and chemical testing where applicable. Where this is not possible, fully validated internal methods with appropriate controls may be used, provided they are scientifically justified. Copies of the certificates of analysis (CoA) should be provided. 

The FSA and FSS will review applications to ensure compliance with regulatory standards. Additional information may be requested during the verification process to address any gaps or uncertainties identified in the review of the submission. 

The Food Standards Agency (FSA) and Food Standards Scotland (FSS) assess the food safety risks of the novel food and its production, in line with Article 11 of Regulation (EU) 2015/2283 and Article 7 of Regulation (EU) 2017/2469. This section of the supplemental guidance specifically addresses the requirements of identity. 

The identity section of the application must define clearly what the final product is. The final product is the novel food as intended to be placed on market and consumed.  The application must include a description of the physical form of the food and should include a detailed characterisation to allow it to be fully understood and assessed. The description of the novel food should define exactly what the food is, how it will be used, and what it is made from. This should include, where appropriate, any scaffolding or any other culture input that may remain within the novel food as placed on market for example, chicken cells cultured on an edible structural support. 

The following bullet points should be used as a baseline for considering what information is required to clearly detail what the identity of the novel food is. This list is not exhaustive, and applicants should consider what additional information may be required to characterise the identity of their novel food.

Applicants should provide a description of what the novel food is, as intended to be placed on market. This includes characteristics of the novel food under assessment (for example, isolated cells, cells combined with a scaffold etc). 

• Description and authenticity of the cell types used within the novel food as placed on market, including clarity on whether cells are differentiated in the final product.  This should include morphological and physical characteristics of the cells in the final product.
• Characterisation of genetic stability, including description of any genetic modification in the final product including the characteristics of intentional epigenetic modification, or epigenetic consequences of genetic modification where relevant.
• Characterisation of the stability of any additional genetic or genomic alterations.
• Proximate analysis and form of the final food for example, wet biomass. See Allergenicity and Nutrition guidance for further information. 

To understand what the food is, it is important to characterise the cell line and cell line identity used to produce the CCP product. Section 3.2 describes the information required from the starting cell line. 

An essential component of establishing the identity of the novel food is a clear understanding of the cell lines used in its production. The safety assessment relies on evidenced authenticity and identity of the cell lines used to develop the CCP product as a novel food. The cell lines should be verified using a justified approach to analytical techniques to confirm cell species and cell type. 

The process to isolate the cells from the biological source, to create the cell line, should be described in detail within the application. This should be inclusive of the steps taken to establish the cell line from the biological tissue sample, or equivalent for example, cell isolation from the cell source and processes for selection of the cell type. Where appropriate, consider the use of tables, diagrams or flow charts within the application to aid description and provide detailed narrative.   

Characterisation of the cell type should include, but not be limited to, the following: 

• Biological source of the cells, including taxonomic information for the cell source, authenticity of the cell type derived from the source animal for example, the exact cell lineage and any changes to the cells through production. Include the biological function of the cell type isolated.
• Species testing of the cell line to confirm the cell line originates from the declared species and has not been contaminated or misidentified. Note: this is of particular importance for non-farmed animals where traceability information may not be fully available.
• Confirmation of the cell type authenticity using morphological, phenotypic and molecular marker analysis.
• Verification of cell immortalisation and effect on cellular physiology, if applicable, and how this has been achieved.
• Differentiation state of the cell. This should include information regarding all differentiation stages during the production processes.
• Stability of the cell line should be demonstrated in terms of genomic stability (See section 3.3 for genomic integrity).
• Purity of the cell line, including a defined acceptance criteria and specific details of any additional cell types within the culture.
• Consideration for the absence of risk from adventitious agents including viruses and mycoplasma within the cell culture.
• Free from adventitious agents including viruses and mycoplasma within the cell culture.

An important part of the identity and safety assessment process is to have full understanding and traceability of the cell source. General Food Law (GFL) Regulation (EC) 178/2002 applies to all inputs used in the production of CCPs. For further information on hygiene requirements for CCPs see the FSA/FSS published guidance.

Whilst there are several different methods to source cells from the biological source, all methods should include the appropriate traceability information. All certification of animal health status should be independently confirmed by personnel qualified to assess animal health. 

Where cells are sourced from animals outside of the United Kingdom (UK) or the European Union (EU), there should be demonstration that UK/EU, or demonstrably comparable, best practices have been adopted. 

Where the cells are sourced from:

• Slaughtered farmed animals’ appropriate certification to show ante-mortem and post-mortem checks detailing the animal’s health status should be included within the application. This should include the certification to detail individual or herd/flock health status from the farm ( for example, animal health passport).
• Live farmed animals application must consider what additional risks may have been introduced from cells obtained through live biopsy from a live biological source.
• Wild caught animals (including seafood sources)  for example, fish or other seafood species - a risk-based approach to traceability, within the requirements of GFL, must be fully detailed within the application. There should be verified documented evidence from an independent expert that the animal is of appropriate heath and quality to enter the food chain at the point of cell isolation. The application should consider potential hazards and the mitigation steps documented.
• Established/proprietary cell lines traceability information tracing the cell line back to the source animal and appropriate information from the source animal must be included within the application. Where cells are obtained from cell suppliers, certificates of authenticity and CoAs should be provided.

Where relevant, the traceability of the source animal should also cover the traceability of any animal cells isolated from embryonic tissue or fertilised eggs. 

Where cells are sourced from multiple independent sources  for example, different starting animals, the required information should be provided for each source, as the nature and variability of the risk may differ.  

Additionally, there should be consideration and appropriate justified evidence of the absence of animal disease, zoonotic diseases and Transmissible Spongiform Encephalopathies (TSEs), also known as prion disease, when selecting the biological source of CCPs.