Cell-cultivated products: assessing growth media and toxicology

This document outlines the scientific requirements for evaluating growth media components and toxicological hazards of cell-cultivated products when seeking market authorisation as novel foods in Great Britain (GB). In GB the Food Standards Agency (FSA) and Food Standards Scotland (FSS) carry out risk assessments for regulated products. This document is supplemental guidance to the 2016 European Foods Safety Authority (EFSA) technical guidance. It supports you through Regulation (EU) 2017/2469, which details administrative and scientific requirements for novel food applications under Article 10 of Regulation (EU) 2015/2283 for novel foods. 

This guidance forms part of a series of technical supplementary guidance publications as part of the Cell-Cultivated Product Sandbox Programme (February 2025-February 2027). 

• The aim of the Cell-Cultivated Product Sandbox Programme is to enable FSS and the FSA to accelerate the application and insights gained through our work on cell-cultivated products and translate this into practical supplemental guidance for industry. This guidance will address a range of topics relevant to cell-cultivated product development and production, helping businesses understand how to manufacture products safely and demonstrate compliance with regulatory requirements. Drawing on the findings from the Cell-Cultivated Product Sandbox Programme, alongside expert elicitation and literature reviews, FSS and the FSA are developing and publishing these supplemental guidelines to:
• provide greater clarity
• support innovation
• help businesses navigate a clearer pathway towards authorisation   

This supplementary guidance gives detailed scientific considerations for assessing the growth media components and toxicological hazards of cell-cultivated products, supporting the general requirements of Regulation (EU) 2015/2283 and 2016 EFSA technical guidance. It describes tailored information for the safety assessment process you should follow where relevant when preparing a cell-cultivated product dossier for regulatory review. 

This supplemental guidance helps you: 

• understand key safety considerations
• ensure their submissions are comprehensive
• support efficient regulatory evaluation

The goal is to support the development and authorisation of cell-cultivated products that are safe, accounting for hazards linked to the growth media components and toxicological risks.

This supplemental guidance applies specifically to cell-cultivated products regulated as novel foods in GB. Cell-cultivated products are defined as food products produced by culturing animal cells, including those from meat, seafood (fish and shellfish), fat, offal, fertilised eggs or embryos in a controlled environment, without the use of traditional farming or animal slaughter. This supplemental guidance is inclusive of products derived from both invertebrate and vertebrate animal cells such as: 

• mammalian
• fish
• shellfish
• avian cells, particularly those intended to replicate the appearance and characteristics of conventional meat or seafood

You should comply with Regulation (EU) 2015/2283 when applying for market authorisation for cell-cultivated products. This requires evidence to identify and characterise hazards and demonstrate effective mitigations are in place to ensure consumer safety.

This supplemental guidance addresses hazards associated with growth media components and provides considerations for the toxicological assessment of the cell-cultivated products as novel foods. 

The guidance is not intended to prescribe a single approach or provide an exhaustive account of all methodologies. As scientific understanding and risk assessment approaches continue to advance, alternative approaches may be appropriate, provided they are: 

• scientifically justified
• generate reliable and supportive data
• comply with the applicable novel food regulatory requirements

All safety assessments should be supported by appropriate scientific evidence, with analyses conducted by competent facilities using nationally or internationally recognised and appropriate accredited methods. A full description of the methods employed should be provided within the application and test materials used in any studies should be representative of the product intended to be marketed. Copies of the certificates of analysis should be provided. 

You should adhere to and provide evidence of using official guidelines and quality systems such as Organisation for Economic Co-operation and Development (OECD) test guidelines or Good Laboratory Practise (GLP). Testing should utilise accredited methods where available. Where not available, testing should be conducted in an accredited facility fit for the purpose of the methods. Where neither an accredited method nor facility are available, the applicant may consider ‘in-house’ methods. These should be fully described standardised internal methods with appropriate controls in the with the application justifying the use of these methods. 

Use this guidance alongside: 

• Regulation (EU) 2015/2283;
• the 2016 technical guidance from EFSA for novel food applications;
• other cell-cultivated product-specific supplementary guidance published by FSS and the FSA.

FSS and the FSA review all applications to ensure compliance with regulatory standards. We may request additional information during the approval process to address any gaps or uncertainties identified in the application review.

This section details the scientific and regulatory requirements for assessing the safety of growth media components used during cell-cultivated product production, as part of a novel food application. The guidance supplements Regulation (EU) 2015/2283. Use it in conjunction with the 2016 EFSA guidance for novel foods. 

Some growth media substances are commonly found in conventional foods. Others may have no prior history of consumption. To support the safety assessment of these components, you should use a structured and proportionate framework. For example, prioritised assessment based on the differing risk profiles of the components from existing safety data.

You should consider the potential for growth media components to bioaccumulate within cells and assess whether this could contribute to the toxicological profile of the final novel product.

You should provide a structured, complete list of all growth media components used during the production of the cell cultivated novel food. This requirement applies to components used at every stage of the process, including: 

• cell isolation
• proliferation
• differentiation
• harvest
• any post-harvest operations where exposure to media components could occur 

This includes, but is not limited to:

• basal media and culture formulations
• supplements, such as amino acids, vitamins, lipids, minerals, trace elements)
• growth factors, cytokines, hormones (including recombinant proteins) and small molecules
• antimicrobials and antifungals
• processing aids, surfactants, pH regulators, anti‑foam agents, chelators
• cryopreservation media and thawing solutions

If proprietary ingredients are supplied by third-party manufacturers, you should provide information about the supplier. Ensure the supplier submits complete component safety information directly to the FSA, in confidence, to support the risk assessment. 

For each component used at any stage of the production process, you should provide enough structured information to support traceability and safety assessment. The following information should be included for every component in the register:

• stages of production at which the component is used
• substance identity, including chemical name and chemical abstracts service (CAS) number
• technological properties in the production process and, where relevant, in the final novel food
• quality and quantity of component intended use, for example, food, pharmaceutical or medical, including a justification when a non-food‑safe component is used
• specification, certificates of analysis, technical data sheets and purity profile, including impurity limits and microbiological criteria
• the composition of any growth media or solutions are used at different stages throughout the process, where these vary at each stage. Include stock concentration and working concentrations at each stage
• if relevant, quantification of the levels of the substance present in the final novel product, supported by standardised analytical data
• maximum safe residual concentration justified with toxicological evidence,  applicable health-based guidance values, scientific literature, and validated safety information
• an assessment of consumer exposure to residues of growth media components in the final novel product, in relation to relevant health-based guidance values
• analytical method details, including method type, matrix validation, Limit Of Detection (LOD), Limit Of Quantitation (LOQ) and any other uncertainty information
• history of safe use and supporting references, including regulatory evaluations or published scientific evidence, where available

This list is not exhaustive. You can provide further information if it is relevant to the support safety assessment. All analytical determinations should be performed using validated, sensitive methods appropriate for the cell-cultivated product matrix. Where a substance is not detected, you should report the LOD/LOQ to demonstrate confidence in the non-detection outcome.

In some cases, cell lines may be immortalised through genetic modification. For more information on genetically modified cells and the appropriate regulatory pathway see the Identity, Production and Microbiology supplementary guidance published by FSS and the FSA. 

Where media components, growth factors or enzymes are produced using recombinant Deoxyribonucleic Acid (DNA) technology, applicants should provide additional molecular and safety information. This information should be sufficient to assess potential risks associated with the expression system and resulting product. 

The following information is expected within the application: 

• scientific name of the host organism, for example a microorganism, plant, or other expression system)
• a detailed description of the genetic modification process, including all inserted, deleted, or modified genetic elements and their functional roles
• for recombinant plants, an assessment of host plant safety, including any known toxicity or allergenicity
• for recombinant microorganisms, an assessment of organism safety and pathogenicity, demonstrating absence of virulence factors or toxin-producing pathways, absence or non-transferability of antimicrobial resistance genes and evaluation of potential for horizontal gene transfer
• confirmation of whether the host organism has a history of safe use for producing recombinant substances used in foods
• for recombinant proteins, the quantity used within production, primary sequence data, characterisation demonstrating equivalence, or near equivalence, to the native protein, and assessment of any added purification tags or sequence modifications, with evaluation of allergenicity and toxicity
• evaluation of whether the recombinant component may give rise to any additional food safety hazards
• for recombinantly produced components, evidence demonstrating the absence of viable production organisms and residual recombinant DNA in downstream materials, where relevant to the final novel product 

You should declare the grade, specification data, impurity limits, and expected maximum residual concentrations of amino acids, vitamins, minerals, and trace elements. It should be demonstrated that any residues in the final food are not nutritionally disadvantageous or present a safety concern. 

You should provide comprehensive characterisation and safety evidence for all bioactive signalling molecules and small molecules used in the production of the novel food, such as growth factors, cytokines and hormones. This includes both naturally derived and recombinant forms. 

You should provide the following information:

• identification of each bioactive substance, including its molecular identity, species of origin, production method (including the host system where recombinant), and relevant structural features such as post-translational modifications
• a description of the manufacturing and processing steps that contribute to the removal, degradation or inactivation of these substances
• data on residual levels in the final novel food, generated using appropriately sensitive and specific analytical methods, or LOD/LOQ where absence is demonstrated
• an assessment of the potential biological activity of any residual material following processing and consumption relevant conditions, for example, heat treatment or digestion. It must demonstrate that the component presents no detectable biological active in the novel food and representative final products as intended to be consumed

You should provide verifiable evidence demonstrating that source animals have complied with statutory veterinary medicines withdrawal periods, for example treatment records, veterinary certification, and residue testing data where appropriate See our Allergenicity and Nutrition guidance for more information. 

You should provide complete characterisation and safety justification for all processing aids used during production. Processing aids include, but are not limited to: 

• surfactants
• chelators
• solubilising agents
• anti‑foam agents
• filtration enhancers
• pH modifiers
• any auxiliary substances used to facilitate manufacturing steps 

To support regulatory assessment, you should:

• provide the chemical identity and CAS-number, along with the quality grade, for example, food-safe, pharmaceutical grade; where a non–food-grade material is used, a robust safety justification should be provided
• submit full specification data for all processing aids used at any stage of production
• provide validated analytical data quantifying residual levels in the final novel product, or supply a scientifically justified removal rationale supported by process controls, for example, washing, filtration, or centrifugation. Demonstrate that the substance is effectively removed or reduced to safe levels, with justification based on health-based guidance values

For more information on process aids and additives, see our Cell-Cultivated Product Regulatory Authorisation Guidance

You should provide comprehensive characterisation and safety assessment for all scaffolds, microcarriers or structural materials used during any stage of the production process. These materials may serve as a surface for the cellular attachment to support growth. They can influence product integrity, residual composition or safety and therefore require comprehensive regulatory scrutiny.

Edible scaffolds and microcarriers

Where the scaffold or microcarrier is intended to remain in the final product, you should provide:

• full composition and material identity
• quality grade, for example, food-safe with justification where non–food‑safe materials are used
• specifications, including physical and chemical properties, and relevant microbiological standards
• quantification of the residue level of the scaffold or microcarrier present in the final novel food, supported by validated analytical data
• a narrative demonstrating that its presence does not introduce nutritional, chemical, physical or toxicological risks

Non‑edible scaffolds and microcarriers

Where the scaffold or microcarrier is not intended to remain, you should provide:

• evidence of complete removal
• details of the process and the process controls, for example, filtration, washing, dissociation, demonstrating reliable removal

Where complete removal cannot be demonstrated, you should provide a lidated residue testing of the scaffold and its components.

Assessment of leachables, extractables, degradation products and particulates

 You should assess the potential for scaffolds and microcarriers to release:

• leachables, for example, plasticisers
• extractables under processing or digestion conditions
• degradation or breakdown products released through shear, enzymatic activity, pH shifts, or thermal or chemical processes
• particulate matter, including microplastics, generated through processing

For more information, including where additional authorisations are likely to be needed, see our Cell-Cultivated Product Regulatory Authorisation Guidance.

You should provide clear evidence that the water used throughout the production process meets safety and quality standards appropriate for food production in the (UK). This includes water used for media preparation, cell washing, cleaning, process operations, and as an ingredient. You should demonstrate control of chemical contaminants by residue testing in the final novel product. You may refer to Regulation No 1881/2006, for indicative lists of contaminants and associated maximum levels. Where relevant, you should also consider recent updates, for example, 2023 amendments under EU law.

For more information on potable water requirements and alternative washing substances, see our hygiene guidance.

Food contact materials (FCMs) are materials and articles that come into contact with food during its production, processing, storage, preparation or serving. You should provide a clear description and safety assessment of all FCMs and equipment that contact the product, culture media or intermediates during any stage of cell-cultivated product production. This includes: 

• cell isolation
• expansion
• differentiation
• harvesting
• downstream processing
• final novel product handling

Further guidance is included in the EFSA guidance on FCMs (2017). 

You should provide details of:

• an inventory of all materials and equipment that may contact cells, media, scaffolds, or final novel products
• For each material, you should provide:
  • material identity and composition, for example, polyethylene, silicone or stainless steel
  • certification or declaration of compliance with applicable FCM regulations or standards
  • intended function and stage of use in the production process

When considering the analytical strategy for all growth media components, you should include a clear, evidence-based justification in their dossier for identifying and quantifying any residual substances that carry over into the novel food. Attention should be paid to components with a higher likelihood of persistence, including substances that are lipophilic, chemically stable, or biologically active. You should:

• identify all inputs with plausible carryover into the final novel food, and target those with toxicological relevance, including cleaning agents or other processing materials with potential incidental food contact
• use validated analytical methods appropriate for cell-cultivated product matrices, for example, liquid chromatography with tandem mass spectrometry (LC–MS/MS), or gas chromatography/mass spectrometry (GC–MS)
• report LOD, LOQ, and measurement uncertainty for all analytical determinations
• provide removal or degradation data demonstrating the effectiveness of processing steps, for example, washing, filtration, heat treatments, or digestion simulations
• provide data on the impact of cooking or metabolic processing, to demonstrate the extent of inactivation of biologically active components, such as growth factors

You should demonstrate that growth media components and key process parameters do not introduce cell line instability leading to safety concerns for the novel food. See our guidance on ‘Identity, Microbiology and Production’ for more information on the impact of growth media components on cell line stability.