## 2 Endophytes-Current State of the Art
### Possibilities of Using Endophytes in Agriculture-Bioproducts and Strains Used in Biofertilizers
The Commission Regulation (EU) 2022/1438 eliminates criteria irrelevant to microorganisms, such as data on isomers, and changes the approach to residue evaluation, as microorganisms themselves are not considered hazardous in this context. It also focuses on specific risks, such as toxic metabolites from certain fungi and bacteria, and clearly differentiates between chemical and biological active substances [181]. The updated rules introduce precise requirements for defining microorganism compositions, including (1) unique accession number in a recognized culture collection; (2) scientific identification at species and strain levels; and (3) information on whether the microorganism is a wild type, mutant or genetically modified [181]. Additionally, the manufacturing and analytical methods for microorganisms differ from those for chemicals. The new guidelines mandate validated analysis techniques to identify and quantify active microorganisms, detect contaminants and evaluate metabolites and impurities [181]. Regulation 2022/1438 further establishes that microorganisms must meet safety standards, demonstrating that (1) the strain is non-pathogenic; (2) any isolated virus is not infectious to humans; and (3) bacterial strains lack transferable genes for antimicrobial resistance [181]. New criteria for determining low-risk microorganisms expand the category to include additional virus species beyond baculoviruses. Substances approved as low-risk are granted a 15-year approval period instead of the standard 10 years, incentivizing the use of these safer alternatives [181]. Three related regulations refine other aspects of the approval process: (1) Regulation 2022/1439 updates data requirements for approving microorganisms as active substances; (2) Regulation 2022/1440 specifies data submission needs for PPPs containing microorganisms; and (3) Regulation 2022/1441 adjusts principles for member states' evaluation and authorization of such PPPs [181]. This regulatory overhaul supports the EU's push to reduce chemical pesticide use, promote biopesticides compatible with organic farming, and advance integrated pest management (IPM). By streamlining authorization and tailoring risk assessments to the unique nature of biopesticides, the EU aims to foster their development and market availability [181]. In summary, endophytes are environmentally friendly, non-toxic, easy to apply and cost-effective in nature, so farmers can use them as a fertilizer substitute for sustainable agriculture. The issues that influence successful commercialisation should be listed:  
* Detailed studies about the biochemical, molecular and genetic mechanisms of endophytes determining stress resistance in different crops;
* Stability of strains/consortia;
* To obtain diligent research on both the positive and negative effects of endophytes in order to gain a true understanding of their potential for use in field trials of at least three years;
* Documented biosafety of bioproducts (especially containing live strains) in agroecosystems;
* An easy way to commercially produce bioproducts.