Food Safety of Cultured Meat - III

Food Safety Assessment Techniques for Cultured Meat - Part I  

In the context of cultured meat processing, the toxicity testing required for cultured meat products or specific inputs in the manufacturing process and their extent are yet to be developed. The safety of the final product including cultured meat as an ingredient, additive, or whole food, is to be established through a safety assessment of the inputs and then an evaluation of the types and levels of residues, by-products, and metabolites remaining in the final product will be necessary. If deemed to have a significant novel or unique properties, an assessment of the final product itself as a whole may be needed.

 

Many existing standard toxicity testing methods can be used to assess inputs. However, any inputs into food must be of food-grade quality, meeting specifications and criteria specific to that ingredient specified in the Codex Alimentarius or such relevant standard. Thus, the development of specifications for cultured meat and additives, such as scaffold materials, may be warranted. Approaches to safety testing of ingredients and food additives are well established, using biochemical, in silico, in vitro, and in vivo methods. Globally harmonized testing standards such as those developed by the Organisation of Economic Co-operation and Development (OECD), World Health Organization (WHO), Food and Agriculture Organization (FAO), or regulatory organizations may be applied directly or modified for use in the cultured meat safety testing context. Tests and analyses under these standards are generally carried out following Good Laboratory Practice (GLP), a set of principles designed to assure study quality and integrity.

 

According to the European Food Safety Authority and U.S. Food and Drug Administration, products that have compositional, nutritional, and functional equivalency to already accepted foods are in theory as safe as the products to which they are equivalent. Hence, the comparison then relies on the history of safe use and data supporting the safety of the conventional food, where any identified differences will direct further safety testing. It is expected that some cultured meat products will not be the same as their conventional counterparts. In fact, if a cultured meat product may contain synthetic scaffold materials or other novel inputs, or the cells may be genetically modified such that new proteins are expressed or existing proteins are under- or overexpressed, and the biochemistry and composition of those proteins may vary. Thus, toxicity testing may be required to demonstrate the safety of inputs and components in the final product accordingly.

 

Thus, there are various existing technologies and analytical methods have bee already adapted or modified to synergize with current and proposed developments in the safety aspects of cultured meat. Hence, the following methods represent brief gross explanations of some of the critical analytical methods that are already in practice for the evaluations.   

 

Microbiological Analysis

Generally, microbiological limits are established for conventional livestock or aquaculture products throughout the world and guidance has been developed to help identify microbiological hazards in meat, poultry, seafood, and other animal proteins by various organizations such as the U.S. Department of Agriculture, FDA, FAO/Codex Alimentarius, WHO, etc. Bacterial and viral contamination may be detected through routine process monitoring such as physicochemical changes, pH shifts, and changes in turbidity, where compromised cell cultures can signal contamination. Theoretically, existing standards, guidelines, and specifications for microbiological characterization are mostly applicable, which employs conventional techniques such as plate counting methods or immunoassays, as well as more efficient techniques including molecular methods such as polymerase chain reaction, and enzyme-linked immunosorbent assays (ELISA). Nonetheless, biosensor technology may also be applied in real-time to screen and detect microbial contamination of meat products in case required, as well as there are commercially applicable standard methods exist to detect and quantify common microbiological hazards, such as Salmonella, Listeria, and E. coli.

 

Further guidance on the evaluation of viruses and mycoplasma in products derived from cell lines of animal origin is available for biotechnological products, where infectivity, electron microscopy, reverse transcriptase, antibody production tests, and in vitro assays using susceptible indicator cells may be used to detect viruses. In addition, mycoplasma can be assessed using nucleic acid amplification technique-based assays, DNA staining, and culture methods, but currently, it is unknown whether cultured meat product manufacturing may pose any unique microbiological hazards, as no novel pathogens are expected.

 

On contrary, microbiological challenge testing may be a useful approach to evaluate any potential hazards arising from storage or food processing. In challenge testing, pathogenic organisms are intentionally introduced to a given food, then products are treated or stored under realistic conditions and analyzed for any physicochemical changes, microbiological growth, or hazardous degradation products, which can provide information on product stability and the effectiveness of procedures designed to eliminate pathogens.

 

Residue, Contaminant, and By-product Analysis

Even though some substances are not intentionally included in the final product, there are various substances that are intended to be used during the manufacturing process that could carry residues over to the final products. Thus, the presence of any drugs such as antibiotics, additives, processing aids, and contaminants needs to be considered and analyzed. Limits and maximum impurity or residue levels for general residues such as metals, natural toxins, agricultural or veterinary chemicals, and environmental contaminants are already established for conventional livestock or aquaculture products in many jurisdictions and can be used as it is or with slight modifications. As a matter of fact, a list of antimicrobials that should not be used in animals due to their critical importance for human medicine has been already developed and adopted by the World Health Organization (WHO). Most antibiotic drugs currently approved for use in food animals are also approved for human use, but if these existing criteria for conventional products require additions or modifications for cultured meats remain to be determined.

 

If new processes or techniques are incorporated those novel inputs may need to be validated through existing or specific techniques developed to conduct analytical tests to identify any residues, contaminants, or by-products in the final product. The conventional inputs with known chemical hazards such as dissociation reagents and cryoprotectants may be screened using conventional analytical methods such as mass spectrometry, chromatography, and immunological techniques, though sample preparation may require modification for the cultured meat matrices. Bioassays that are already used to detect a wide range of residues in conventional meat products such as a multiple bioassay method designed to screen meat and poultry for common antibiotic groups (U.S. Department of Agriculture) can be easily applied and after which the specific techniques can be used for full identification and quantification. Bioassays may also be used as a screening tool for currently unknown or unexpected hazards, where determining whether the sensitivity and range of the tests are adequate for the various inputs used in cultured meat products, or whether the techniques will require modification, is an important factor in improvements for future.  

 

Biochemical, Molecular, Physical, and Compositional Analyses

Biochemical, molecular, physical, and compositional analyses are another major aspect of cultured meat products which can be used as part of a comparative approach to assess the similarity to existing products. Hence, GE food and feed and cloned animals intended for food are analyzed using specific safety assessment techniques that can be anticipated to apply to cultured products, whether the given product is genetically modified or not.

 

the extent of any differences in the genome and confirmation of intentional effects or identification of unintentional expressions of products not normally seen in meat or seafood can be determined using molecular and biochemical analysis of cultured meat products. Any differentiated expression of products found can be compared to conventional products to identify any new or increased hazards related to consumption. For example, a safety assessment of a GE fish, AquAdvantage salmon, and a GE pig, GalSafe pig, determined that the introduced DNA was safe for the resulting GE animal and its offspring and that the animals are safe to eat. The safety assessments relied on determining the health of the animal, as a healthy animal is likely to be safe to eat, where phenotypic characterization, as well as compositional and nutritional analysis of the edible tissues, must be performed to ensure that there were no biologically relevant differences between the GE animals and comparator conventional animals.

 

Methods already exist to characterize GE animals intended for use as food, where the genome sequence is evaluated to determine whether the inserted genetic material changes essential gene function, as part of this analysis it is intended to identify whether there are new and unintended open reading frames or not and to ensure that no genes code for known toxins or antinutrients. The biochemical and proteomic analyses already exist to assess the expression of new products and identify differences in protein, peptide, amino acid, and metabolite levels as compared to conventional meats, where any newly expressed or altered proteins may affect product stability or physical properties and alter their toxic or allergenic potential. The assessment of a novel protein may focus on amino acid sequence similarity to known toxins or allergens and an if significant homology is found, then further testing may be performed to understand stability or digestibility in the human body and toxicity testing of that protein.

 

The cells themselves are typically monitored throughout the process for quality control measures, which can provide an indication of cell health. For example, physicochemical properties, proliferation potential, differentiation capacity, karyotype stability, and the expression of specific cell markers to validate identity can provide valuable safety information and identify any unwanted physicochemical transformations.

 

A compositional analysis is mainly considered to be a key element of a comparative safety assessment, which may include an assessment of macro- and micronutrients, bioactive compounds, toxins, and allergens that can provide a baseline to compare cultured meat with a conventional product. Because products that are similar to conventional meat products are more likely to be processed and metabolized similarly and may rely on the safety assessment of their conventional counterpart.

 
References:
https://ift.onlinelibrary.wiley.com/doi/full/10.1111/1541-4337.12853
https://www.foodincanada.com/features/the-food-safety-advantages-of-lab-grown-meat/
https://www.frontiersin.org/articles/10.3389/fnut.2020.00007/full
https://www.centerforfoodsafety.org/blog/6458/is-lab-grown-meat-healthy-and-safe-to-consume
https://www.mdpi.com/2304-8158/10/12/2922