Amendments to EU General Food Law are coming. What will change?

Amendments to EU General Food Law are coming. What will change?

On Friday, 6 September 2019, a Regulation amending the General Food Law from 2002 was published in the EU Official Journal. The initiation to amend the Regulation has its roots in the heated arguments around the safety of glyphosate and the claims about the lack of transparency in the risk assessment. Besides plant protection products like glyphosate, the amendment now covers also genetically modified organisms, food and feed additives, food enzymes and flavourings, smoke flavourings, novel foods and food contact materials.

To increase transparency, applications for authorisation submitted to EFSA for scientific evaluation will be made public. This includes all non-confidential information and studies supporting the application. This is not, in fact, an entirely novel procedure. The Food Standards Australia New Zealand (FSANZ) has already had this practice at least for food enzymes. Thus anybody interested has had a possibility to scroll through, even download, an over 1000-page application if (s)he so wishes. The data requirements by FSANZ and EFSA are not much different so one can have a pretty good idea about the content of applications submitted in the EU. FSANZ has also a consultation procedure for the submitted applications.

 

What is clearly new is that applicants and laboratories carrying out studies will have a notification obligation, basically meaning that studies with undesirable outcome cannot be hidden anymore by excluding them from the application. Further guidance is obviously needed how to fulfil this obligation. How is this accomplished with applicants coming from ouside the EU? There will be a grey area between studies carried out in the R & D phase, and those carried out with the final product.

For the applicants, the Regulation brings a very welcome improvement in that EFSA will provide pre-submission advice on the required content of an application dossier. Currently all legislation and guidelines are available as well-organised packages in EFSA homepage. The new approach must then go clearly further than that. The more innovative the applications are, the more there will be a need to consult EFSA to achieve an optimal outcome from both applicant’s and EFSA’s point of view.

For the laboratories, perhaps the major change will be the Commission fact-finding missions to ensure the compliance of laboratories/studies with appropriate standards. This has a good chance of improving the quality of the studies. However, this should not cause extra financial burden to the laboratories.

The amendment becomes applicable by the end of March 2021. Hopefully this one and a half year is sufficient to ensure that not only Commission and EFSA but also all other parties down the line, Biosafe Ltd included, will be fully prepared to the changes needed.

Updated guidance from EFSA on environmental risk assessment of feed additives

Updated guidance from EFSA on environmental risk assessment of feed additives:
Relevance for microorganisms as feed additives or production organisms

On 5 April 2019, the EFSA FEEDAP Panel published updated guidance on environmental risk assessment (ERA) after examining the 133 comments from stakeholders. The guidance is part of the process of considering new scientific developments and experience gained in the assessment of dossiers under the remit of the Panel. The 78-page ERA guidance replaces the corresponding 2008 guidance.
According to the guidance, if a microorganism is included in the EFSA QPS list (Qualified Presumption of Safety) and meets all qualifications, including the absence of acquired antimicrobial resistance genes, no ERA is required. On the other hand, microbial strains carrying such AMR genes are presumed to pose an environmental risk.

EFSA guidance on environmental risk assessment of feed additives

If the microorganism is not included in the QPS list, ERA is required on a case-by-case basis. ERA is not required if the microorganism is naturally present in the soil, plant or gastrointestinal tract. If the microorganism is not naturally present in those environments, ERA may be required. For such cases, the FEEDAP Panel provides two references: 1) OECD guidance to the environmental safety evaluation of microbial biocontrol agents; and 2) EFSA GMO Panel guidance 2011 on the risk assessment of genetically modified microorganisms. Most of the EFSA GMO Panel guidance 2011 is replaced by the FEEDAP Panel guidance 2018 on the characterisation of microorganisms used as feed additives or as production organisms. What remains valid in the 2011 guidance is the evaluation of products belonging to Category 4, i.e. products consisting of or containing genetically modified microorganisms capable of multiplication or of transferring genes. Furthermore, when the additive is genetically modified, the requirements of Regulation No 1829/2003 on genetically modified food and feed should be fulfilled.
All feed additives, including those isolated from production microorganisms, should be assessed through Phase I to identify those additives that do not need further testing. Reference can be made to published studies to support the safety of the additive. The guidance provides details on how to carry out a literature search and report the outcome.

 

The guidance can be found here:
https://www.efsa.europa.eu/en/efsajournal/pub/5648

QPS, a useful concept in the safety evaluation of microorganisms

QPS, a useful concept in the safety evaluation of microorganisms

…and I do not mean Queries Per Second, which is a common measure of the amount of search traffic an information retrieval system, such as a search engine or a database, receives during one second.

The concept of Qualified Presumption of Safety was developed by the European Commission together with its scientific committees on animal nutrition, on food and on plants to facilitate the safety evaluation of microorganisms intentionally introduced into the food chain. During that time I was a member of the Scientific Committee on Plants, and my academic and Biosafe colleague Atte von Wright was a member of the Scientific Committee on Animal Nutrition.

The idea was to introduce in the EU a concept similar, but not identical, to the GRAS (Generally Recognised As Safe) system established by the FDA (Food and Drug Administration) in the USA. The main difference between the GRAS and QPS concepts is that the former is generally limited to a specific application (such as the use of a lactic acid bacterium as a probiotic), while QPS refers to generic safety of a microorganism spanning all or most of its uses.

QPS microorganisms for food or feed

QPS microorganisms for food or feed

Why is QPS concept useful?
The concept simplifies the evaluation of applications submitted to the Commission by greatly reducing the amount of studies required for an adequate safety assessment of a QPS microorganism. So, if you use a microbial species included in the QPS list to develop a product intended for human or animal use within the EFSA context, tolerance studies in target animals, studies on consumer and environmental safety and genotoxicity and subchronic toxicity studies are not required. Not only are these studies the most expensive ones, but also lead to unnecessary use of laboratory animals in cases where there are no safety concerns.

Where did this initiative lead in practice?
The European Food Safety Authority (EFSA) maintains and develops a list of QPS microorganisms for food or feed use. Currently the list contains many bacteria and yeasts but excludes e.g. filamentous fungi. Whenever a new species is introduced by an application submitted to the Commission and forwarded to EFSA, the QPS working group can assess its safety and conclude on its possible inclusion in the QPS list. The assessment is based on taxonomic identification, body of knowledge, possible pathogenicity (or other safety concerns) and the use of the microorganism.

What about the filamentous fungi, the biotechnological work horses?
Because of the often significantly more complex secondary metabolism of filamentous fungi, it has not been possible to extend the QPS concept into this group of microorganisms. However, if you develop the fungal strain stepwise, target the modifications and study the safety of strategic strains, you may well be able to justify a limited number of toxicological studies carried out along the lines of strains. This approach would be feasible in the future also for the lines developed by using the CRISPR-Cas9 and other genome editing techniques.
Sirpa Kärenlampi

Download the guide to the safety assessment of non-QPS organisms

Bioinformatics and antimicrobial resistance genes

Bioinformatics and antimicrobial resistance genes

In my work as a DNA detective (well, an R&D Manager involved in microbial bioinformatics) I see hundreds of microbial genomes yearly, most of which are bacterial. For bioinformaticians, bacteria seem the easiest targets, in comparison to eukaryotic species with huge genomes and complexity. From my point of view, however, bacterial genomes are perfect: you can get a nearly complete genomes with quite little effort, and the data never lie. This provides an amazing view on the developments of microbial biotechnology and microbial diversity.

My life as a DNA detective

Microbial bioinformatics

My job is to analyze the safety aspects of microbial genomes for companies who develop microbial products into the food chain. They may be production organisms for amino acids, enzymes or vitamins, or live micro-organisms. Many of the products will be evaluated by the European Food Safety Authority (EFSA). Whatever the purpose, safety means the absence of acquired antimicrobial resistance genes, genes for toxins and virulence factors, in some cases also describing the genetic modifications in detail. First of all, however, the genome is used for unequivocal taxonomic identification at the species level, sometimes even at the strain level. This is essential in granting the QPS (qualified presumption of safety) status for a microorganism.

The small and complete microbial genomes make the bioinformatics part relatively easy and not time consuming. What does take time, is the interpretation of the outcome of the analysis. I wanted to start this blog to give you a glance at the scientific and technical issues that must be considered when analyzing a genome. In this first post, I will scratch the surface of my favorite and at the same time my least favorite subject, antimicrobial resistance (AMR) genes.
I have a copy of the “Guidance on the characterization of microorganisms used as feed additives or as production organisms”,, (subsequently simply “guidance”) always on my desk. We actually anticipated certain aspects of the guidance – such as the requirement of whole genome sequencing – well before it was published and adopted in 2017. A safety aspect that EFSA has always emphasized if the demonstrated absence of transmissible resistances to antibiotics with clinical or veterinary importance. EFSA states in the guidance that intrinsic AMR is not considered a safety concern, “intrinsic” meaning something that is typical of “all the strains of that species”.

On the surface it seems clear, but when do you know you have analyzed “all strains of that species”? Never, I suppose. And, AMR genes are not always necessary for the survival of the microorganism, making them dispensable. This means that they can be replaced by e.g. mobile elements in the genome, leading to susceptibility of that particular strain to the antimicrobial. Suddenly there you have one susceptible strain, although the rest of the strains still carry the AMR gene. Also, the phenotype does not necessarily tell anything about a trait being acquired or intrinsic – if there have been modifications to the regulation of the AMR gene in one strain, which then becomes susceptible, it does not mean that the rest of the strains carry an acquired AMR gene. The requirement “all strains” simply can’t be accepted – and I think this is also understood in EFSA. Perhaps the guidance could be written in a way that allows some room for interpretation.
We are advised to interpret the results of the genome investigation in the light of minimal inhibitory concentrations (MIC) for the strain. In my opinion, the interpretation is clear in only two cases: if the genome search reveals no AMR candidates, and the MIC values are below the cut-off (safe strain); and if the genome search reveals a clearly acquired AMR gene which can be directly linked to the MIC value above the cut-off (hazard). In the latter case, one of course has to identify the gene as acquired by experience or by comparing it to other genomes, if available. (So, perhaps only one clear case). In all other cases the situation is more complex, and almost all genomes carry genes that are known to contribute to antimicrobial resistance. For example, did you know that the E. coli K-12 strain (generally considered as safe lineage) has matches to more than 70 genes that contribute to AMR?
We have developed our “Biosafe” way of dealing with AMR genes and interpreting whether they are a concern or not. In practice, we have to have multidisciplinary know-how of bioinformatics and microbiology, and in-depth EFSA knowledge to survive in the regulatory jungle.

Pauliina Halimaa

New EFSA guidance on feed microorganisms into force

New EFSA guidance on feed microorganisms into force

The new “Guidance on the characterisation of microorganisms used as feed additives or as production organisms” by the FEEDAP Panel of EFSA entered into force in the beginning of September 2018. This guidance assists the applicants seeking authorization for their products in proper characterization of the microorganism, whether genetically modified or not. Compared to previous guidance, one significant change is that whole genome sequence analysis is required for bacteria and yeasts and also recommended for fungi. This serves the purpose of improved overall characterization of the microorganism, including taxonomic identification and the presence of both intrinsic and introduced antibiotic resistance genes or virulence factors. A particular attention has been paid to the antimicrobials considered by World Health Organization as critically or highly important.
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Biosafe is proud to sponsor the Feed Additives 2018 conference on 26-28 September in Amsterdam

Biosafe is proud to sponsor the Feed Additives 2018 conference on 26-28 September in Amsterdam

Feed Additives 2018 is an annual gathering for leading feed additives producers, traders and users. It is a three-day opportunity for relationship building, hearing about the latest scientific advancements from high-level speakers and getting practical guidance for improving your business.
Our Scientific Director, Professor Atte von Wright, and Research Manager, PhD Pauliina Halimaa will be available throughout the three-day conference at our stand. Please take the opportunity to ask us about feed additive regulations and how to assess microbial safety. Atte’s interview is available at https://www.feedadditives-global.com/biosafe/.

More information about Biosafe’s services regarding feed additives can be found from  http://www.biosafe.fi/en/en-biosafefeed

As a partner, we can offer discounted tickets. Subsidised tickets to Compound Feed Mills and Premixers are available at the following rates:
1 day ticket = 299€ + VAT
2 day ticket = 499€ + VAT
3 day ticket = 699€ + VAT
These rates are not available through the website. Feed mills or premixers who wants to register at this discounted rate please contact pauliina.halimaa@biosafe.fi

For any other firms, please use our unique discount code FABIOSAFE18 which allows you to book through the website with a 15% discount.

Ticket bookings can be made at https://www.feedadditives-global.com/global/registration/

Feel free to contact us directly or book a meeting via the FeedAdditives app!