EN   EN 
 
 
 EUROPEAN  
COMMISSION   
Brussels, XXX   
SANTE/12040/2020  
[…](2021) XXX  draft  
ANNEXES 1 to 2  
 
ANNEXES  
to the  
Commission Regulation (EU) .../...  
amending  Regulation (EU) No 283/2013 as regards the information to be submitted for 
active substances and the specific data requirements for micro -organisms     EN 1  EN ANNEX I  
‘Introduction  
Information to be submitted, its generation and its presentation  
A dossier shall be submitted in accordance with Part A if the active substance is:  
(a) a chemical substance (including both semiochemicals and extracts from 
biological material), or  
(b) a metabolite produced by a micro -organism w here: 
– the metabolite is purified from the micro -organism; or  
– the metabolite is not purified from  a producing micro -organism which is 
no longer  capable of replication or of transferring genetic material . 
A dossier shall be submitted  in accordance with Part B if the active substance is :  
(a) a micro -organism, either as a single strain or as a qualitatively  defined 
combination of strains , or 
(b) a micro -organism , either as a single strain or as a qualitatively defined 
combination of strains , and one or more metabolites produced by the micro -
organism that are claimed to be part of the plant protection action (i.e. when the 
application of the metabolite (s) purified from the micro -organism would not 
cause   the claimed plant protection action ). 
1 For the purposes of this Annex, the following definitions apply:  
(1)  ‘efficacy ’ means  a measure concerning  the overall ef fect of the application of a 
plant protection product on the agricultural system in which it is used  (i.e. 
which includes positive effects of treatment in performing the  desired plant 
protection activity  and negative effects such as development of resistance ); 
(2) ‘relevant impurity ’ means a  chemical impurity  that is of concern for human 
health, animal health or the environment ; 
(3)  ‘effectiveness ’ means the capacity of the plant protection product to produce a 
positive  effect regarding the desired  plant protection activity ; 
(4)  ‘toxicity ’ means  the degree of injury or damage in a n organisms  caused by a 
toxin or a toxic substance;  
(5)  ‘toxin’ means  a (organic) substance that is  produced in nature and is  able to 
injure or damage a  living  organism.  
The information submitted shall meet the requirements  set out in points 1.1  to 1.14. 
1.1.  The information shall be sufficient to evaluate the foreseeable risks, whether 
immediate or delayed, which the  active substance may entail for humans, including 
vulnerable groups, animals and the environment and contain at  least the information 
and results of the studies referred to in this Annex . 
1.2.  Any information including any known data on potentially harmful effects of the 
active substance, its metabolites and  impurities on human  and animal health or on 
their potential presence in groundwater  shall be included.  
1.3.  Any information including any known data on potentially unacceptable effects of the 
active substance, its metabolites and impurities on the  enviro nment, plants and plant 
products shall be included.  EN 2  EN 1.4.  The information shall include all relevant data from the scientific peer reviewed open 
literature on the active substance, relevant metabolites, where relevant , breakdown or 
reaction products and pl ant protection products containing the active substance and 
dealing with side -effects on  human and animal health, the environment and non -
target species. A summary of this data shall be provided.  
1.5.  The information shall include a full and unbiased report of the studies conducted as 
well as a full description of  them. Such information shall not be required , where a 
justification is provided showing that : 
(a) it is not necessary owing to the nature of the  plant protection  product or its 
proposed uses, or it is not scientifically necessary;  or 
(b) it is technically not possible to supply.   
1.6.  The simultaneous use of the active substance as a biocide or in veterinary medicine 
shall be reported. If the applicant for the active substance in the plant protection  
product is identical to the one responsible for the notification of the active substance 
as a biocide or as a veterinary medicine, a summary of all relevant data submitted for 
approval of the biocide or the veterinary medicine shall be submitted. Where 
relevant, th at summary shall include toxicological reference values and MRL 
proposals, taking into account any possible cumulative exposure due to different uses 
of the same substance based on scientific methods accepted by the competent 
authorities of the U nion, together with a summary of the residues and toxicology data 
and information on the use of the plant protection product. If the applicant for the 
active substance in the plant protection product is not identical to the one responsible 
for the notifica tion of the active substance as a biocide or in veterinary medicine, a 
summary of all available data shall be submitted.  
1.7.  Where relevant, the information shall be generated using test methods, which are 
included in the list referred to in  point 6.  
In the absence of suitable internationally or nationally validated test guidelines, test 
protocol discussed with and accepted by  the competent authorit ies of the Union  shall 
be used. Any deviations from test guidelines shall be described and justified.   
1.8.  The information shall include a full description of the test methods used.  
1.9.  The information shall include a list of endpoints for the active substance , where 
relevant . 
1.10.  Where relevant, the information shall be generated in accordance with Dire ctive 
2010/63/EU of the European  Parliament and of  the Council1. 
1.11.  The information on the active substance, taken together with the information 
concerning one or more plant  protection products containing the active substance and 
together, if appropriate, with the information concerning  safeners and synergists and 
other components of the plant protection product, shall be sufficient to:  
(a) permit an assessment of the risks for humans, associated with handling and use 
of plant protection products  containing the active substance;  
(b) for chemical active substances: permit an assessment of the risks for human 
and animal health, arising from residues of the active substance  and its relevant 
                                                 
1 Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the 
protection of animals used for scientific purposes  (OJ L 276, 20.10.2010, p. 33).  EN 3  EN metabolites , impurities  and, where relevant, breakdown and reaction products 
remaining in water, air, food and feed;  
(c) for active substances that are micro -organisms: permit an assessment of the 
risks for human and animal health, arising from residues of the metabolites of 
concern in water, air, food and feed;  
(d) for c hemical active substances:  predict the distribution, fate and behaviour in 
the environment of the active substance and metabolites,  breakdown and 
reaction products  where they are of toxicological , or environmental 
significance, as well as  the time courses involved;  
(e) permit an assessment of the impact on non -target species (flora and fauna), 
including the impact on their  behaviour, which are likely to be exposed to the 
active substance, its relevant metabolites and, where relevant , breakdown and 
reaction  products, where they are of toxicological , pathogenic  or environmental 
significance. Impact can result from single,  prolonged or repeated exposure and 
can be direct or indirect, reversible or irreversible;  
(f) evaluate the impact on biodiversity and the ecosystem;  
(g) identify non -target species and populations for which risks  arise because of 
potential exposure;  
(h) permit an evaluation of short and long -term risks for non -target species, 
populations, communities and  processes;  
(i) classify the chemical active substance as a hazard in accordance with 
Regulation (EC) No 1272/2008 of the European  Parliament and of the 
Council2; 
(j) specify the pictograms, the signal words and relevant hazard and precautionary 
statements for the protection  of human  and animal health , non -target speci es 
and the environment, which are to be used for labelling;  
(k) establish, where relevant, an acceptable daily intake (ADI) level for humans;  
(l) establish , where relevant, acceptable operator exposure levels (AOEL);  
(m) establish, where relevant, an acute reference d ose (ARfD) for humans;  
(n) identify relevant first aid measures as well as appropriate diagnostic and 
therapeutic measures to be followed  in the event of poisoning or infection  in 
humans;  
(o) for chemical active substances: establish the isomeric composition and t he 
possible metabolic conversion of the isomers, whe re relevant;  
(p) establish residues definitions appropriate for risk assessment , where relevant ; 
(q) establish residues definitions appropriate for monitoring and enforcement 
purposes , where relevant ; 
                                                 
2 Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on 
classification, labelling and packaging of substances and mixtures, amending and repealing Directives 
67/548/EEC and 1999/45 /EC, and amending Regulation (EC) No 1907/2006 (OJ L 353, 31.12.2008, p. 
1). EN 4  EN (r) permit a ri sk assessment of consumer exposure, including, where relevant, a 
cumulative risk assessmen t deriving from exposure to more than one active 
substance;  
(s) permit an estimation of the exposure to operators, workers, residents and 
bystanders including, where  relevant, the cumulative exposure to more than 
one active substance;  
(t) establish , where relevant,  maximum residue levels and concentration/dilution 
factors in accordance with Regulation (EC) No  396/2005 of the European 
Parliament and of the Council3; 
(u) permit  an evaluation to be made as to the nature and extent of the risks for 
humans , animals (species normally  fed and kept by humans or food producing 
animals) and of the risks for other non -target vertebrate species;  
(v) identify  measures necessary to mitigate the  risks identified for human  and 
animal health , the environment and /or non-target species;  
(w) for chemical active substances: decide whether or not the active substance has 
to be considered as persistent organic pollutant (POP),  persistent, bio 
accumulative an d toxic (PBT) or very persistent and very bio accumulative 
(vPvB) in accordance  with the criteria laid down in  Annex II to Regulation 
(EC) No 1107/2009;  
(x) decide whether or not the active substance is to be approved;  
(y) for chemical active substances: decide wh ether or not the  active substance has 
to be considered as a candidate for substitution in accordance  with the criteria 
laid down in Annex II to Regulation (EC) No 1107/2009;  
(z) decide whether or not the active substance has to be considered as a low -risk 
active substance in accordance  with the criteria laid down in Annex II to 
Regulation (EC) No 1107/2009;  
(aa) specify conditions or restrictions to be associated with any approval.  
1.12.  Where relevant, tests shall be designed and data analysed using appropriat e statistical 
methods.  Details of the statistical analysis shall be reported  transparently.  
1.13.  Exposure calculations shall refer to scientific methods accepted by the European 
Food Safety Authority, where available. Additional methods, when used, shall  be 
justified.  
1.14.  For each section of this Annex , a summary of all data, information and evaluation 
made shall be  submitted. This shall include a detailed and critical assessment in 
accordance with  Article 4 of  Regulation (EC) No  1107/2009.   
2. The requirements set out in this Annex constitute  the minimum set of data to be 
submitted. Member States may set out a dditional requirements at national level to 
address  specific circumstances, specific exposure scenarios  and specific patterns of 
use other  than those taken into account for approval. The applicant shall pay c areful 
attention to environmental, climatic and agronomic conditions when tests are set up 
                                                 
3 Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February 2005 on 
maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending 
Council Directive 91/414/EEC (OJ L 70, 16.3.2005, p. 1).  EN 5  EN subject to the approv al by the Member State where the application has been 
submitted . 
3. Good l aboratory practice (GLP)  
3.1.  Tests and analyses shall be conducted in accordance with the principles laid down in 
Directive 2004/10/EC of the  European Parliament and of the Council4 where testing 
is done to obtain data on the properties or safety with  respect to human or animal 
health or the environment.  
3.2.  By way of derogation from point 3.1: 
(a) for active  substances that are micro -organisms, tests and analyses done to 
obtain data on the  properties and safety with respect to other aspects than 
human heal th may be conducted by official or officially  recognised testing 
facilities or organisations which satisfy at least the requirements set out in  
points 3.2 and 3.3 of the  Introduction of the Annex to Commission Regulation 
(EU) No  284/20135; 
(b) for tests and analyses made to obtain data for mi nor crops required under 
points 6.3 and 6.5.2 of Part A:  
– the field phase may have been conducted by official or officially 
recognised testing facilities or organisations  which satisfy the 
requirements as laid down in poin ts 3.2 and 3.3 of the Introduction of the 
Annex to  Regulation (EU) No  284/2013;  
– the analytical phase, if not realised  in accordance with the principles of 
good laboratory practice (‘ GLP principles’) , shall be conducted by 
laboratories  accredited for the re levant method in accordance with the 
European standard EN ISO/IEC 17025 ‘General  requirements for the 
competence of testing and calibration laboratories’ ; 
(c) studies conducted before the date of application of this Regulation, although 
not fully compliant wit h GLP principles or with current test methods , may be 
integrated into  the assessment  if carried out in accordance with scientifically 
validated  test guidelines , thereby avoiding  repeating animal tests, especially for 
carcinogenicity and  repro -toxicity stud ies. This derogation from point 3.1 shall 
apply in particular  to studies with vertebrate species.  
4. Test material  
4.1.  A detailed description (specification) of the test material used shall be provided. 
Where tests are done using the active  substance, the test material used shall comply 
with the specification that will be used in the manufacture of plant  protection 
products to be authorised, except for radio -labelled chemicals  or the purified 
chemical active substance.  
                                                 
4 Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 on the 
harmonisation of laws, regulations and administrative provisions relating to the ap plication of the 
principles of good laboratory practice and the verification of their applications for tests on chemical 
substances ( OJ L 50, 20.2.2004, p. 44).  
5 Commission Regulation (EU) No 284/2013 of 1 March 2013 setting out the data requirements for plant 
protection products, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and 
of the Council concerning the placing of plant protection products on the market  (OJ L 93, 3.4.2013, p. 
85). EN 6  EN 4.2.  Where studies are  conducted using an active substance produced in the laboratory or 
in a pilot plant production  system, the studies shall be repeated using the active 
substance as manufactured, unless the applicant shows that  the test material used is 
essentially the same,  for the purposes of toxicological, pathological, 
ecotoxicological, environmental and  residue testing and assessment. In cases of 
uncertainty, bridging studies shall be submitted to serve as a basis for a  decision as to 
the possible need for repetition of the studies.  
4.3.  Where studies are conducted using an active substance of different purity or which 
contains different impurities or  different levels of impurities to the technical 
specification or where the active substance is a mixture of  components, t he 
significance of the differences shall be addressed either by data or scientific case. In 
cases of  uncertainty, appropriate studies using the active substance as manufactured 
for commercial production shall be  submitted to serve as a basis for a decision . 
4.4.  In the case of studies in which dosing extends over a certain period (for example , 
repeated dose studies), the same  batch of active substance shall be used, if stability 
permits. Whenever a study implies the use of different  doses, the relationship  
between dose and adverse effect shall be reported.  
4.5.  For chemical active substances, w hen tests are conducted using a purified chemical 
active substance (≥ 980 g/kg) of stated specification, the purity of  such test material 
shall be as high as can be achieved using the best available technology and shall be 
reported. A  justification shall be provided in cases where the degree of purity 
achieved is less than 980 g/kg. Such justification  shall demonstrate that all 
technically feasible and reasonable poss ibilities for the production of the purified 
chemical active  substance have been exhausted.  
4.6.  For chemical active substances, w here radio -labelled test material of the chemical 
active substance  is used, radio -labels shall be positioned at sites (one or  more as 
necessary) to  facilitate elucidation of metabolic and transformation pathways and to 
facilitate the investigation of the distribution of  the active substance and of its 
metabolites, reaction and breakdown products.  
5. Tests on vertebrate animals  
5.1.  Tests on vertebrate animals shall be undertaken only where no other validated 
methods are available. Alternative  methods shall include in vitro methods , in-silico 
methods. Reduction and refinement methods  for in vivo testing shall also be 
encouraged t o keep the number of animals used in testing to a minimum.   
5.2.  The principles of replacement, reduction and refinement of the use of vertebrate  
animals shall be taken into account in the  design of the test methods, in particular 
when appropriate validat ed methods become available to replace, reduce  or refine 
animal testing.  
5.3.  Study designs shall be carefully considered  from ethical point of view , taking into 
account the scope for reduction,  refinement and replacement of animal tests. For 
example, by including one or more additional dose groups or  time points for blood 
sampling in one study, it may be possible to avoid the need for another study.  
6. For purposes of information and of harmonisation the list of test methods and 
guidance documents relevan t to the implementation of this Regulation shall be 
published in the Official Journal of the European Union . That list shall be regularly 
updated. ’ EN 7  EN ANNEX II 
‘PART B  
ACTIVE SUBSTANCES THAT ARE MICRO -ORGANISMS  EN 8  EN TABLE OF CONTENTS  
INTRODUCTION  TO PART B  
1. Identity of the applicant, the active substance and manufacturing information  
1.1.  Applicant  
1.2. Producer  
1.3. Identity, taxonomy, and phylogeny of the micro -organism  
1.4.  Specification of the microbial active substance as manufactured  
1.4.1.  Content of the active substance  
1.4.2.  Identity and quantification of additives, relevant contaminating micro -organisms, and 
relevant impurities  
1.4.2.1.  Identity and quantificatio n of additives  
1.4.2.2 . Identity and content of relevant contaminating micro -organisms  
1.4.2.3 .  Identity and quantification of relevant impurities  
1.4.3.  Analytical profile of batches  
1.5.  Information on manufacturing process and control measure s for the active substance  
1.5.1.  Production and quality control  
1.5.2.  Recommended methods and precautions concerning handling, storage, transport or 
fire 
1.5.3.  Procedures for destruction or decontamination  
1.5.4.  Measures in case of an accident  
2. Biological properties of the micro -organism  
2.1.  Origin, occurrence, and history of use  
2.1.1.  Origin and isolation source  
2.1.2.  Occurrence  
2.1.3.  History of use  
2.2.  Ecology and life cycle of the micro -organism  
2.3.  Mode of action on the target org anism and host range  
2.4. Growth requirements  
2.5.  Infectiv ity 
2.6.  Relationship to known pathogens  
2.7. Genetic stability and factors affecting it  
2.8.  Information on metabolites of concern  
2.9.  Presence of transferrable antimicrobial resistance genes  
3. Further information  
3.1.  Function and target organism  
3.2.  Field of use envisaged  EN 9  EN 3.3.  Crops or products protected or treated  
3.4.  Information on possible development of resistance of the target organism(s)   
3.5.  Literature data  
4. Analytical meth ods 
4.1.  Methods for the analysis of the MASAM  
4.2.  Methods to determine the density of the micro -organism and quantify residues  
5. Effects on human health  
5.1.  Medical data  
5.1.1 .  Therapeutic and first aid measures  
5.1.2.  Medical surveillance  
5.1.3.  Information on sensitisation/ allergenicity  
5.1.4.  Direct observation  
5.2.  Assessment on potential infectivity and pathogenicity of the micro -organism to 
humans  
5.3.  Infectivity and pathogenicity studies on the micro -organism  
5.3.1.  Infectivity and pa thogenicity  
5.3.1.1.  Oral, infectivity and pathogenicity  
5.3.1.2.  Intratracheal/ intranasal infectivity and pathogenicity  
5.3.1.3.  Intravenous/ Intraperitoneal or subcutaneous single exposure  
5.3.2.  Cell culture study  
5.4.  Specific infectivity and patho genicity studies on the micro -organism  
5.5.  Information and toxicity studies on metabolites  
5.5.1.  Information on metabolites  
5.5.2.  Additional toxicity studies on metabolites of concern  
6. Residues in or on treated products, food and feed  
6.1.  Estimat ion of consumer exposure to residues  
6.2.  Data generation on residues  
7. Environmental occurrence of the micro -organism, including fate and behaviour of 
metabolites of concern  
7.1.  Predicted environmental density of the micro -organism  
7.1.1.  Soil 
7.1.2.   Water  
7.2.  Exposure to micro -organisms known to be pathogenic either for plants or for other 
organisms  
7.3.  Refined exposure assessment  
7.3.1 .  Qualitative exposure assessment  EN 10  EN 7.3.2 .  Experimental exposure data  
7.4.  Fate and behaviour of metabolite(s)  of concern  
7.4.1.  Predicted environmental concentration  
7.4.2 .  Qualitative exposure assessment  
7.4.3 .  Experimental exposure data  
8. Ecotoxicological studies  
8.1.  Effects on terrestrial vertebrates  
8.2.  Effects on aquatic organisms  
8.2.1.  Effects on fish 
8.2.2.  Effects on aquatic invertebrates  
8.2.3.  Effects on algae  
8.2.4.  Effects on aquatic macrophytes  
8.3.  Effects on bees  
8.4.  Effects on non -target arthropods other than bees  
8.5.  Effects on non-target meso - and macroorganisms in soil  
8.6.  Effects on non-target terrestrial plants  
8.7.  Additional studies on the micro -organism  
8.8.  Information and toxicity studies on metabolites  
8.8.1.  Information on metabolites  
8.8.2.  Additional toxicity studies on metabolites of concern  EN 11  EN INTRODUCTION  TO PART B  
(i) This Introduction to P art B  complements the Introduction to this Annex with points 
which are specific for active substance s that are micro -organism s. 
(ii) For the purpose of Part B, the following definitio ns apply:  
(1)  ‘strain ’ means  a genetic variant of an organism in its taxonomic rank (species) 
that is made up of the descendants of a single isolation in pure culture and 
usually is made up of a succession of cultures ultimately derived from an initial 
single colony ; 
(2)  ‘non-viable  micro -organism ’ means a  micro -organism that is not capable of 
replication or of actively transferring genetic material . However, it may still be 
able to transfer g enetic material passively ; 
(3)  ‘colony -forming unit ’ (‘CFU ’) means  a measurement unit used to estimate the 
number of bacter ial or fungal cells in a sample, which have  the ability to 
multiply under controlled growing conditions , with the consequence that one or 
more cells reproduce and multiply to form a single visible colony ;  
(4)  ‘Internationa l Unit ’ (‘IU’) means a  quantity of a substance that produces a 
specific effect when tested in accor dance with  an internationally accepted 
biological procedure ;  
(5)  ‘Microbial Active Substance  as Manufactured ’ (‘MASAM’) means the  
outcome of the manufacturing process of the micro -organism (s) intended to be 
used as active substance in plant protection products , consist ing of the micro -
organism(s) and any additives, metabolites (including metabolites of concern ), 
chemical impurities  (including relev ant impurities) , contaminating micro -
organisms (including relevant contaminating micro -organisms) and the spent 
medium/rest fraction  resulting from the production process  or, in case of a 
continuous  manufacturing  process es a strict separation between the 
manufacturing of the micro -organism (s) and the production process of the plant 
protection product  is not possible , a non -isolated intermediate ; 
(6)  ‘additive ’ means a  component added to the active substance that is a micro -
organism  during its  manufactur ing, to preserve microbial stability and /or 
facilitate handling ; 
(7)  ‘purity ’ means  the content of the micro -organism  in relevant unit in the  
MASAM and the maximum c ontent of substances of concern  in case they are 
identified ; 
(8)  ‘relevant contaminating micro -organism ’ means a  pathogenic/infective 
micro -organism  unintentionally present in the MASAM;  
(9)  ‘seed stock ’ means a  microbial strain starter culture used to manufacture the 
MASAM or the final plant protection product ; 
(10)  ‘spent medium/rest fraction ’ means  the fraction of the MA SAM, excluding 
the micro -organism (s), metabolites of concern, additives, relevant 
contaminating micro -organisms, and relevant impurities consisting  of 
remaining  or transformed starting materials ; 
(11)  ‘starting materi al’ means  substance s used in the manufacturing process as 
substrate and/or buffering agent for the production process of the MASAM;  EN 12  EN (12)  ‘ecological niche ’ means an  ecological function and actual physical space s 
occupied by a particular species within the  community or ecosystem ;  
(13)  ‘host range ’ means  the range of different biological host-species that can be 
infected by a microbial species or strain ;  
(14)  ‘infectivity ’ means  the ability of a micro -organism  to cause an infection ;  
(15)  ‘infection ’ means  the non-opportunistic introduction or entry of  a micro -
organism  into a susceptible host, where the micro -organism is able  to 
reproduce to form new infective units  and persist in the host, whether or not the 
micro -organism causes pathological effects or disease ;  
(16)  ‘pathogenicity ’ means  the non-opportunistic ability of a micro -organism  to 
inflict injury and damage to the host upon  infection ; 
(17)  ‘non-opportunistic ’ means a condition under which a micro -organism exerts 
an infection or inflict s an injury or damage when the immune system of the 
host is not impaired by an unrelated cause;  
(18)  ‘virulence ’ means  the degree of pathogenicity that a pathogenic micro -
organism  is able to exert in  the host ;  
(19)  ‘virulence factor ’ means a  factor that enhance the  pathogenicit y/virulence of  a 
micro -organism;  
(20)  ‘metabolite of concern ’ means  a metabolite produced by the micro -organism 
under assessment, with known toxicity or known relevant antimicrobial 
activity , which  is present in the MASAM at levels  that may present a risk to 
human  health , animal  health  or the environment , and/or for which it cannot be 
adequately justified that in-situ production of the metabolite is not relevant for 
the risk assessment ; 
(21)  ‘in-situ production’  means the production of a metabolite by the micro -
organism after application of the plant protection product containing that 
micro -organism;  
(22)  ‘background level of a metabolite ’ means a  level of a metabolite that is likely 
to occur in relevant E uropea n environment s (including also sources different 
than those of plant protection) and/or in food and feed (e.g. plant edible parts), 
when the micro -organisms are in conditions to grow, reproduce and to produce 
such metabolite in presence of a host or availa bility of carbon and nutrient 
sources, under consideration of high host densities and nutrients;   
(23)  ‘antimicrobial resistance ’ (‘AMR ’) means  the intrinsic or acquired  ability of 
a micro -organism to multiply in the presence of an antimicrobial agent  at 
concentrations  which are relevant for therapeutic  measures in human or 
veterinary medicine , making that substance therapeutically ineffective ;  
(24)  ‘antimicrobial agent ’ means any antibacterial, antiviral, antifungal, 
anthelmintic or antiprotozoal agents  that is a  substance of natural, semi -
synthetic, or synthetic origin that at in vivo  concentrations kills or inhibits the 
growth of micro -organism s by interacting with a specific target ;  
(25)  ‘acquired antimicrobial resistance ’ means  a non-intrinsic and  acqui red novel 
resistance enabl ing a micro -organism  to survive or multiply in the presence of 
an antimicrobial agent at concentrations higher than that which inhibits wild 
type strains of the same species ;  EN 13  EN (26)  ‘intrinsic antimicrobi al resistance ’ means  all inherent properties of a 
microbial species that limit the action of antimicrobial agents thereby allowing 
them to survive and multiply at relevant therapeutic concentrations of an 
antimicrobial agent . Inherent properties of micro -organism s are considered not 
transferable and can include structural characteristics like lack of drug targets, 
the impermeability of cellular envelopes, activity of multidrug efflux pumps, or 
metabolic enzymes. An antimicrobial resistance gene is co nsidered intrinsic if 
it is located on a chromosome in the absence of mobile genetic element  and 
shared by the majority of wild type strains of the same species ; 
(27)  ‘relevant antimicrobial activity ’ means the  antimicrobial activity caused by 
relevant an timicrobial agents;  
(28)  ‘relevant antimicrobial  agent s’ means  all antimicrobial agents important for 
therapeutic use in humans or animals , as described in the  latest  available  
version s at the time of submission of the dossier :  
– in a list adopted by means  of Commission Regulation (EU) 2021/17606 
in accordance with Article 37(5) of Regulation (E U) No 2019/6 of the 
European Parliament and of the Council7, or 
– by the World Health Organisation8  in the  lists of Critically Important 
Antimicrobials , Highly Important Antimicrobials and Important 
Antimicr obials for Human Medicine ; 
(29)  ‘viroid ’ means a ny of a class of infectious agents consisting of a small strand 
of RNA not associated with any protein. The RNA does not code for proteins 
and is not translated ; it is replicated by host cell enzymes . 
(iii)  The information from scientific peer -reviewed literature as provided for under  point 
1.4 of the Introduction  shall be provided at the relevant taxonomic level  of the micro -
organism (e.g. strain, species, genus). An explan ation  on why the chosen taxonomic 
level is considered relevant  for the addressed data requirement  shall be provided . 
(iv)  Other available sources of information, such as medical reports, may a lso be 
provided and submitted in a summary.  
(v)  Where appropriate or specifically indicated  in the data requirements , test guidelines 
as described in Part A shall be used also for this Part, upon  adapt ation  in such a way 
that they are appropriate for  chem ical compounds present in the MASAM.  
(vi)  Where testing is done, a detailed description (specification) of the material used and 
its impurities, in accordance with point  1.4, shall be provided. Where studies are 
conducted using micro -organisms produced in the laboratory or in a pilot scale 
production system, the studies shall be repeated using the MASAM, unless it can be 
demonstrated that the test material used is essentia lly the same for the purposes of 
the testing and assessment.  
                                                 
6 Commission Delegated Regulation (EU) 20 21/1760 of 26 May 2021 supplementing Regulation (EU) 
2019/6 of the European Parliament and of the Council by establishing the criteria for the designation of 
antimicrobials to be reserved for the treatment of certain infections in humans  (OJ L 353, 6.10.20 21, p. 
1). 
7 Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on 
veterinary medicinal products and repealing Directive 2001/82/EC ( OJ L 4, 7.  1.2019, p.43 ). 
8 https://apps.who.int/iris/bitstream/handle/10665/312266/9789241515528 -eng.pdf?ua=1 . EN 14  EN (vii)  If the active substance is a genetically modified  micro -organism , a copy of the 
evaluation of the data concerning the risk assessment, as stated in Article 48 of 
Regulation (EC) No 1 107/2009, shall be submitted.  
(viii)  The assessment of pathogenicity/ infectivity of micro -organisms shall be based on a 
weight of evidence approach, taking into account that :  
– tests on animals may not always be suitable for extrapolation to humans due to  
differences between humans and test animals (e.g. immune system, 
microbiome) , and  
– micro -organisms might have narrow host range, as a result of which it cannot 
always be assumed that a micro -organism that does not cause disease in the 
animals tested has t he same result in humans, and vice -versa.  
(ix)  The information on the micro -organism shall be sufficient to permit an evaluation to 
be made as to the risk concerning  to anti -microbial resistance . 
(x)  Until  validated methods for testing dermal and respira tory sensitization of micro -
organisms  become available , all micro -organisms shall be considered as potential 
sensitizers .  EN 15  EN 1. IDENTITY OF THE APPLI CANT , THE ACTIVE SUBSTANC E AND MANUFACTURING 
INFORMATION  
1.1. Applicant  
The name and address of the applicant shall  be provided, as well as the name, 
address, telephone number and e -mail address of a contact point.  
1.2. Producer  
The following information shall be provided:   
(a) the name and address of the producer of the active substance ;  
(b) the name and address of each manufac turing plant in which the active 
substance  is produced  or will be produced;  
(c) a contact point (preferably a central contact point ), includ ing name, telephone 
number and e -mail address .  
Where, following approval of the micro -organism, there are changes in the address  
or number of producers, the information required shall again be submitted . 
1.3. Identity, taxonomy and phylogeny of the micro -organism  
The information provided shall allow an unam biguous identification and  
characterisation of the micro -organism . 
(i)  The micro -organism shall be deposited at an internationally recognised culture 
collection.  The contact details of the culture collection and accession number 
shall be submitted . 
(ii)  The micro -organism shall be identified  as unequivocally belonging to a certain 
species, based on the latest scientific information, and named at strain level, 
including any other designation which may be relevant to the micro -organism 
(e.g. isolate level, if relevant for viruses).  Its scientific name and taxonomic 
grouping shall be stated . This includes traditional Linnean taxonomy 
(kingdom, phylum, class, order, family, genus, species, and strain) as well as 
established rank -free phylogenetic taxa in betwe en these Linnean ranks and 
any other denomination relevant to the micro -organism (e.g. serovar, pathovar, 
biovar).  
(iii)  All known synonymous, alternative, superseded  names shall be provided. If 
code names have been used during development these shall also be provided.  
(iv)  A phylogenetic tree including the micro -organism shall be provided. The scale 
of the phylogenetic tree shall  be selected to include relevant strains and species 
(e.g. in case of use of read-across  among related strains  or species to address 
data requirements). Superseded names of included micro -organisms or 
taxonomic groupings may be indicated in the phylogen etic tree.  
(v)  It shall be indicated whether the micro -organism is a wild type, a mutant (either 
spontaneous or induced)  or whether it h as been genetically modified . If the 
micro -organism  is a mutant or has been modified, all known differences  in 
properties , including genetic differences, between the modified micro -
organism  and the parent  wild strain shall be provided.  The technique used for 
the modification shall be reported.  EN 16  EN 1.4. Specification of the microbial active substance as manufactured  
1.4.1.  Content of the active substance  
The minimum and maximum content of the  micro -organism in the MASAM shall be 
derived from the analysis of five representative batches  as indicated under point  1.4.3 
and reported. The content shall be expressed in :  
– where possible, the dry weight of the pure micro -organism ( if this value cannot 
be determined, a conversion factor shall be proposed to convert the  unit of 
MASAM to the unit of dry weight of pure micro -organism) , and  
– appropriate microbial unit  that most accurately reflects plant protection action, 
such as number of active units, colony forming units , or international units per 
volume or weight or any other manner that is relevant to the risk assessment on 
the micro -organism . A rationale for the relevance of the microbial unit used in 
the context of the tests to be conducted  shall be provided . The use of such unit 
shall be consistent along studies and literature data provided. In case of 
provision of literature data with different units, recalculation based on the units 
used shall  be provided . 
In case  it is claimed that  one or more metabolites present i n the MASAM are part of 
the plant protection action, the content of these metabolites shall be indicated as 
provi ded for in point  1.9 of Part A .  
1.4.2.  Identity and quantification of additives, relevant contaminating micro -organisms and 
relevant impurities  
Data  on additives, relevant contaminating micro -organisms, relevant impurities and 
metabolites of concern, present in the MASAM shall be directly derived from the 
analysis of five representative batches as indicated under  point  1.4.3 and reported.  
1.4.2.1.  Identity an d quantification of additives  
The identity, minimum and maximum content in g/kg of each additive in the 
MASAM shall be provided.  
1.4.2.2.  Identity and content of relevant contaminating micro -organisms  
The identity and maximum content of relevant contaminating mi cro-organisms in the 
MASAM, expressed in the appropriate unit, shall be reported.  
1.4.2.3.  Identity and quantification of relevant impurities  
The identity and maximum content of chemical impurities present in the  MASAM  
and which are relevant due to undesirable tox icological, ecotoxicological or 
environmental properties , shall be reported in g/kg , including also metabolites of 
concern produced by the micro -organism as impurities in the manufacturing batch.  
1.4.3.  Analytical profile of batches  
At least five representative b atches from recent and current production of the micro -
organism shall be analysed. All of the representative batches shall bear a date within 
the last five years of manufacture. Manufacturing dates of the representative batches 
and batches size shall be re ported.  
Where the active substance is produced in different manufacturing plants, the 
information required under this point  shall be provided for each of the plants 
separately.  EN 17  EN Where the information provided relates to a pilot manufacturing plant productio n 
system, the information required shall again be provided once industrial scale 
production methods and procedures have stabilised. Where available, industrial scale 
data shall be provided before approval under Regulation (EC) No 1107/2009. Where 
data on i ndustrial scale production are not available, a justification shall be provided.  
1.5. Information on manufacturing process and control measure s for the active 
substance  
1.5.1.  Production and quality control  
Information on how the micro -organism  is produced in bulk sh all be provided for all 
the steps of the manufacturing process. Such information shall include relevant 
descriptions of:  
– starting materials,  
– culture media sterilisation (e.g. autoclave),  
– initial inocula level for the culture media (e.g . number of conidia/g of dry 
culture media),  
– culture and media conditions (e.g. pH, temperature, water activity (a w)), 
– phase of the growth curve and growth stage of the micro -organism  during the 
production process,  
– ratio vegetative cells / (endo)spores,  
– fermentation process,  
– purification and cellular dehydration,  
– other technical parameters (e.g. centrifugation protocols).  
The type of manufacturing process (e.g. continuous or batch process ) shall be 
indicated.  
Both production method/process and product shall  be subject to a continuous quality 
control, and the quality assurance criteria shall be submitted. In particular, the 
possible occurrence of spontaneous changes of characteristics of the micro -organism 
shall be monitored. It shall be indicated where in th e process the quality assurance 
steps are implemented and it shall be describe d how the samples for quality 
assurance screening are taken.  
The techniques used to ensure a uniform product, and the assay methods for its 
standardisation, maintenance and purit y, to prevent the presence of  relevant  
contaminating micro -organisms and relevant impurities  in the MASAM shall be 
described and specified.  
Information on possible loss of activity of starting cultures shall be provided along 
with corresponding methods to assess it. If relevant, any method aiming at 
preventing the  micro -organism  from losing its effects on the target organism shall be 
described.  
1.5.2.  Recommended methods and precautions concerning handling, storage, transport or 
fire 
A safety data sheet pursuant t o Article 31 of Regulation (EC) No 1907/2006 shall be 
provided for the MASAM.  EN 18  EN 1.5.3.  Procedures for destruction or decontamination  
Methods to dispose safely of the MASAM or, where necessary, to render  the micro -
organism non-viable prior to disposal of the MASAM a nd methods to dispose of 
contaminated packaging and other materials shall be described (e.g. chemical 
methods or autoclaving).  
Information that makes it possible to establish the effectiveness and safety of these 
methods shall be provided . 
1.5.4.  Measures in cas e of an accident  
Information on procedures for  rendering the MASAM  harmless in the environment 
(e.g. water or soil) in case of an accident shall be provided.  EN 19  EN 2. BIOLOGICAL PROPERTIES  OF THE MICRO -ORGANISM  
2.1. Origin, occurrence and history of use  
2.1.1.  Origin and isolation source  
The geographical location and environmental compartment (e.g. substrate, host 
organism s), from which the micro -organism was isolated, shall be stated. The 
method of isolation and the selection procedure of the micro -organism shall be 
repor ted.  
2.1.2.  Occurrence  
The geographical distribution  of the micro -organism  shall be described . 
The environmental compartment(s) where the micro -organism  is already expected to 
occur shall be described (e.g. soil, water , rhizosphere, phyllosphere, host organism) . 
When relevant, food or feed commodities where the micro -organism  is already 
expected to occur shall  be described.  
The information referred to in this point shall be provided at the most relevant 
highest taxonomic level (e.g. strain, species, genus) and the choice of the relevant 
highest taxonomic level shall be justified.  
2.1.3.  History of use  
Previous and current known uses of the micro -organism (e.g. research, commercial, 
uses evaluated for recommending the Qualified Presumption of Safety9 status)  shall 
be described. The description shall include both plant protection and other uses (e.g. 
uses and/or assessments under other regulatory frameworks, bioremediation, uses in 
food and feed).  
The information referred to in this point shall be provided at  the most relevant 
highest taxonomic level (e.g. strain, species, genus). The choice of the relevant 
highest taxonomic level shall be justified.  
2.2. Ecology and life cycle of the micro -organism  
The known life cycle(s) of the micro -organism (e.g. parasitic, sap rophytic, 
endophytic, pathogenic) and its ecological niche(s) shall be described , along with  all 
forms that may occur  and the type of reproduction.  
For bacteriophages, information shall be provided on, if applicable, lysogenic and 
lytic properties.  
For fu ngi and bacteria, information shall be provided, if applicable, on:  
– external conditions for resting stages, information on resistance of spores 
against adverse environmental conditions, survival time of the spores and 
conditions for germination , and/or  
– formation of biofilm.  
2.3. Mode of action on the target organism and host range  
All available information on modes of action against the target organism(s) shall be 
described.  
                                                 
9 https://zenodo.org/record/3336268#.X5mJIdBKg2z . EN 20  EN The type of intended biological control (e.g. inundative or inoculative) shall be 
specified.  
In case of a pathogenic or parasitic mode of action on the target organism, 
information on the site of infection and mode of entry into the target organism, the 
infective dose and the susceptible stages of  the target organism shall be given.  The 
results of any experimental studies shall be reported.  
In case of a toxic or antimicrobial effect on the target organism caused by a 
metabolite of concern produced by the micro -organism  under assessment and 
identified as required by point  2.8, information on exposure route to the target 
organism and the mode of action of the metabolites of concern shall be described.    
All known host organisms of the micro -organism shall be listed at the relevant 
taxonomic level. Available information on possible density of ho st organisms , 
supporting the indication on natural occurrence of the micro -organisms , shall be 
provided.  
2.4. Growth requirements  
The conditions required for growth and proliferation of the micro -organism shall be 
described (e.g. host, nutrients, pH, osmotic po tential, humidity). The minimum, 
optimum and maximum temperature required for growth and proliferation shall be 
reported. The generation time under favourable growth conditions shall be reported.  
2.5. Infectiv ity 
In case any pathogenic mode(s) of action is desc ribed under  point  2.3, virulence 
factors and (if applicable) environmental factors affecting them shall be indicated 
and described. The results of any relevant experimental studies and/or 
data/information from the existing literature at the relevant taxonomic level shall b e 
reported.  
2.6. Relationship to known pathogens  
Where  the micro -organism is closely related to any known pathogens to humans, 
animals, crops or other non -target species, the applicant shall:  
– list the pathogens and the type of known diseases caused,  
– describe th e known virulence factors belonging to the pathogens,  
– describe the known virulence factors belonging to the micro -organism which is 
the active substance , 
– describe the phylogenetic relationship between the micro -organism and the 
related pathogen s identified ,  
– describe the way or means to distinguish the active micro -organism from 
pathogenic species.  
2.7. Genetic stability and factors affecting it  
Where  the micro -organism is a non -virulent variant of a plant pathogen virus, the 
likelihood of regaining virulence through mutation after application under the 
proposed conditions of use shall be reported , including the information on measures 
that can be taken to reduce the likelihood of this occurrence and the effectiveness of 
such measures.  EN 21  EN 2.8. Information on metabolite s of concern  
The applicant shall identify  and list under this point the metabolites of concern 
produced by the micro -organism , including a summary of the information submitted 
under points 5.5.1, 8.8.1, 6.1, 7.4.1 and 7.4.2  used to identify or to exclude 
metabolites as being of concern , unless the micro -organism is a virus . 
Metabolites of concern may be identified based on the scientific literature, or on 
observation of toxicity, ecotoxicity or antimicrobial activity in studies conducted 
with the micro -organism and closely related strains.  The absence of the gene(s)  
encoding the identified metabolite(s) of potential concern evidenced by employing 
appropriate genomics methods (e.g. whole genome sequencing), shall be considered 
to prove  the absence of such hazard for that metabolite(s).  
All the available information (e.g. scientific literature, experimental studies) on the 
metabolites and the related identified hazards (e.g. the toxicological characterization) 
and, where relevant, the ex posure to the metabolite shall be submitted under the 
relevant point s of the dossier (i.e. point s 5.5, 6.2 and 7.4.3  if relevant for human and 
animal health and point s 7.4.3 and  8.8 if relevant to the non -target organism for 
which a hazard due to a metabol ite was identified).  
2.9. Presence of transferrable antimicrobial resistance genes  
Where  the micro -organism is a bacterium, information  on any resistance to relevant  
antimicrobial  agent s shall be reported at strain level , and i nformation on whether the 
antimicr obial resistance gene s are acquired, transferrable and functional shall be 
reported.  The information provided shall be sufficient to perform an evaluation as to 
the risks for human and animal health due to a possible transfer of relevant 
antimicrobial resi stant genes.  
  EN 22  EN 3. FURTHER INFORMATION  
3.1. Function and target organism  
The biological function shall be specified  as:  
– control of bacteria,  
– control of fungi,  
– control of viruses,  
– control of insects,  
– control of mites,  
– control of molluscs,  
– control of nematodes,  
– control of plants,  
– other ( shall  be specified).  
3.2. Field of use envisaged  
The field(s) of use, existing and proposed, for plant protection product containing the 
micro -organism  shall be specified from among the following:  
– field use, such as agriculture, horticulture, forestry and viticulture,  
– protected crops (e.g. in greenhouses),  
– non-cultivated areas,  
– home gardening,  
– houseplants,  
– stored food/feed items,  
– other ( shall be speci fied).  
3.3. Crops or products protected or treat ed 
Details of existing or intended use in terms of crops, groups of crops, plants or plant 
products protected shall be provided.  
3.4. Information on possible development of resistance of the target organism(s)  
Available information on the possible occurrence of  the development of resistance or 
cross -resistance of the target organism(s) shall be provided. Where possible, 
appropriate management strategies shall be described.  
3.5. Literature data  
A summary on the systematic review of the scientific peer -reviewed literat ure shall 
be provided, including indication on bibliographic databases employed, criteria for 
relevance and reliability assessment in relation to the data requirements and search 
strategies , etc.  
The summary shall list the references used for the dossier compilation and for which 
points the respective references are relevant.   EN 23  EN 4. ANALYTICAL METHODS  
Introduction  
Analytical methods shall be used in the context of the generation of data for the risk 
assessment on human toxicology or ecotoxicology. Analytical me thods shall also 
support post -approval stages, for instance , in monitoring quality of the 
manufacturing process and compliance of manufacturing batches with the agreed 
specification , where relevant (Section  1), by monitoring residues on crops (Section  
6), if applicable. The method used  shall be justif ied.  
Descriptions of methods shall be provided and include details of equipment, 
materials and conditions used. The applicability of any internationally recognised 
method shall be reported.  
As far as practica ble, these methods shall be as simple as possible, involve a 
minimum cost and require commonly available equipment. Data on specificity, 
linearity, accuracy and repeatability, as laid down  in point s 4.1 and 4.2 of Part  A, are 
also required for analytical c hemistry methods used to analyse relevant impurities, 
metabolites of concern and additives included in the MASAM.  
On request by the rapporteur Member State, the following shall be provided:  
(i)  samples of the MASAM;  
(ii)  if technically possible, analy tical standards of metabolites of concern and all 
other components included in the residue definition (in case of non -provision 
of such a sample  a justification  shall be provide d);  
(iii)  if available, samples of reference substances for the relevant impurities.  
4.1. Methods for the analysis of the MASAM  
The following methods  shall be describe d providing validation data:  
(a) methods for the identification  of the micro -organism  required in accordance 
with point s 1.3(ii) and 1.3(iv), including the most appropriate molecular 
analytical and phenotypic methods , based on unique identifier s to distinguish 
the strain from other strains belonging to the same species ; with  information on 
appropriate test procedures and criteria used for identification (e.g. 
morp hology, biochemistry, serology and molecular identification ); 
(b) methods for the characterisation of the micro -organism, including the most 
appropriate molecular analytical methods and phenotypic methods, as required 
by Section  2 with information on  appropria te test procedures and criteri a used 
for identification (e.g. morphology, biochemistry, serology and molecular 
identification ); 
(c) methods for providing information on possible variability of seed stock/active 
micro -organism and its storability (including los s of activity and methods to 
assess it), as required by Section  1; 
(d) methods to differentiate a mutant of the micro -organism from the parent wild 
strain , e.g.  including the most appropriate molecular analytical methods as 
required by Section  1; 
(e) methods for the establishment of purity of seed stock from which batches are 
produced and methods to control that purity , e.g.  including the most 
appropriate molecular analytical methods as required by Section  1; EN 24  EN (f) methods to determine the content of the micro -organism in the manufacturing 
batch, and methods to detect and enumerate relevant contaminating micro -
organisms, as required in Section  1, to allow verifying  the compliance of the 
material/batch with a maximal threshold of relevant contaminating micro -
organism ; 
(g) methods for the determination of relevant impurities , metabolites of concern , 
and additives, in the manufacturing material as required by Section  1. 
4.2. Methods to determine the density of the micro -organism and quantify residues   
The methods  used to determine an d quantify:  
– the density of the micro -organisms , where relevant , as required in point s 5.3, 
5.4, 6.1, 7.3.2 and 8 , 
– the residues of metabolites of concern, where relevant , as required in point s 
2.8, 5.5 , 6 and 8.8 , 
– the residues of relevant impurities and additives, where relevant ; 
on and/or in crops, foodstuffs , feeding  stuffs, animal and human body tissues and 
fluids  and in relevant environmental compartment s shall be described.  
  EN 25  EN 5. EFFECTS ON HUMAN HEAL TH 
Introduction  
(i) The information provided, taken t ogether with that provided for one or more 
plant protection product s containing the micro -organism, shall be sufficient to 
perform  an evaluation as to the risks for human  and animal (i.e. species 
normally fed and kept by humans or food -producing animals)  health : 
(a) directly and/or indirectly associated with the handling and use of plant 
protection products containing the micro -organism ; 
(b) handling treated products ; and 
(c) arising from residues or impurities remaining in food and water.  
In addition, the informatio n provided shall be sufficient to:  
– permit a decision to be made as to whether or not the micro -organism is 
to be approved , 
– specify appropriate conditions or restrictions to be associated with the 
approval , 
– specify risk and safety phrases for the protection  of human  and  animal  
health  and the environment to be included on packaging (containers ), 
– identify relevant first aid measures as well as appropriate diagnostic and 
therapeutic measures to be followed in the event of infection or another 
adverse effect in  humans.  
(ii)  All adverse effects found during investigations shall be reported. Investigations 
which may be necessary in order to evaluate the probable mechanism involved, 
and to assess the significance of these effects shall also be performed.  
(iii)  For all studies actual achieved dose of the micro -organisms or of the metabolite 
of concern in appropriate units per kg body weight (e.g. CFU/kg), or in any 
other appropriate units shall be reported. Justification for the chosen unit shall 
be provided.  
(iv)  Available information on the identity and biological properties of the micro -
organism (Sections 1 and 2) as well as health and medical reports may be 
sufficient for an assessment of the infectivity and pathogenicity potential of the 
micro -organism.  
 (v)  Further studies may be required to complete the evaluation o f the  effects on 
human health, and the type of these additional studies shall be decided on  a 
case-by-case approach based on expert judgment , depend ing on the available 
information provided in par ticular as regards the biological properties of the 
micro -organism. Pending the acceptance of specific guidelines at international 
level, the information required shall be generated using available test 
guidelines.  
(vi)  Additional studies (see point  5.4) shall be conducted if available information 
(see point  5.2) or tests under point  5.3 require further investigation or have 
shown adverse health effects. The type of study to be performed depends on 
the effects observed.  EN 26  EN 5.1. Medical data  
5.1.1.  Therapeutic and first a id measures  
Therapeutic regimes and first aid measures for use in the event of ingestion, 
inhalation or contamination of eyes and skin shall be described. Available 
information based on practical experience or on theoretical grounds shall be 
provided.  
Wher e available and without prejudice to Article 10 of Directive  98/24/EC10, 
practical data and information relevant to the recognition of the symptoms of 
infection or pathogenicity and on the effectiveness of therapeutic measures shall be 
submitted.  
For micro -organisms excluding viruses, antimicrobial agents with effectiveness 
against the micro -organism shall be listed. In case of identification of metabolite(s) 
of concern, as required in point  2.8, the effectiveness of known antagonists of such 
metab olite(s) shall be reported.  
5.1.2.  Medical surveillance   
Available reports of occupational health surveillance programmes shall be submitted. 
These reports may refer to the strain under assessment , to closely related strains or to 
metabolites of concern, and sh all be supported with information on the design of the 
programme, on use of appropriate protective measures including personal protective 
equipment, on exposure to the micro -organism  or the metabolites of concern.  These 
reports  shall, where available, incl ude data on effects on individuals  exposed to the 
micro -organism  or the metabolites of concern  in manufacturing plants or after 
application of the micro -organism (e.g. agricultural or research workers). These 
reports shall, where available, also cover sens itisation and/or allergenic responses.  
In the case of adverse effects, attention shall be paid to whether the individual’s 
susceptibility may have been affected by any pre-disposing conditions, e.g. 
underlying disease, medication, compromised immunity, pre gnancy or breast -
feeding.  
5.1.3.  Information on sensitisation/ allergenicity  
Due to the unavailability of an adequate method to assess sensitising potential of 
micro -organisms, they shall be considered as sensitizers until a validated test is 
available and the po ssible absence of sensitising potential is demonstrated on a case-
by-case basis . 
5.1.4.  Direct observation  
Available reports from the open literature on the micro -organism or closely related 
members of the taxonomic group and relating to clinical cases of infecti ons in 
humans shall be submitted together with reports of any follow -up studies undertaken. 
Such reports are of particular value and shall contain descriptions of the nature and 
level of exposure, as well as the clinical symptoms observed, first aid and th erapeutic 
measures applied and measurements and observations made.  
In the case of adverse effects, attention shall be paid to whether the individual’s 
susceptibility may have been affected by any pre-disposing conditions, e.g. 
                                                 
10 Council Directive 98/24/EC of 7 April 1998 on the protection of the health and safety of workers from 
the risks related to chemical agents at work (fourteenth individual Directive within the meaning of 
Article 16(1) of Directive 89/391/EEC) (OJ L 131, 5.5.1998, p.  11). EN 27  EN underlying  disease, medicati on, compromised immunity, pregnancy or breast -
feeding.  
5.2. Assessment on potential infectivity and pathogenicity of the micro -organism to 
humans  
Studies to determine the potential infectivity and pathogenicity of the micro -
organism shall be performed as set ou t in point s 5.3.1 and 5.4, unless the applicant 
demonstrates, by following a weight of evidence approach, that no such effects are to 
be expected. The weight of evidence approach may be based on the information 
provided under point s 2.1, 2.3, 2.4, 2.6 and 5.1, and/or be retrieved from any other 
reliable sources (e.g. Qualified Presumption of Safety11). A summary shall be taking 
into consideration this information to demonstrate absence of infectivity and 
pathogenicity to humans, in order to justify the non -submission of the studies 
required in point s 5.3.1 and 5.4.  
5.3. Infectivity and pathogenicity studies on the micro -organism  
5.3.1.  Infectivity and pathogenicity   
Unless the applicant can demonstrate absence of infectivity and pathogenicity based 
on a weight of evidence approach as set out in point  5.2, studies, data and 
information shall be provided and evaluated as required from  point s 5.3.1.1 to 
5.3.1.3. These sh all be sufficient to permit the identification of effects following a 
single exposure to the micro -organism, and in particular to establish or indicate:  
– the infectivity and pathogenicity of the micro -organism , 
– the time course and characteristics of the ef fects with full details of observed 
changes (clinical and behavioural) and possible gross pathological findings at 
post-mortem , 
– the relative hazards associated with the different routes of exposure , and 
– analyses throughout the studies in order to evaluate the clearance of the micro -
organism.  
If these studies are performed, the applicant shall:  
– adapt the observation period to the biological properties or the micro -organism 
administered, in particular its incubation time, rate of clearance and timing for 
observation of adverse effects , 
– estimate, during the infectivity and pathogenicity studies, the micro -organism 
clearance in the organs which is relevant for microbial examination (e.g. liver, 
kidneys, spleen, lungs, brain, blood and site of administration) , 
– take into account the potential differential species susceptibility (i.e. relevance 
of the chosen test species) of the micro -organism (e.g. based on literature) 
when the study results and their relevance for humans are evaluated.  
5.3.1.1.  Oral, infectivity and pathog enicity  
The oral infectivity and pathogenicity following a single exposure to the micro -
organism shall be reported.  
                                                 
11 https://doi.org/10.2903/j.efsa.2021.6377 . EN 28  EN A study in test animals in accordance with relevant guidelines shall be performed, 
unless the applicant can demonstrate absence of oral inf ectivity and pathogenicity 
based on a weight of evidence approach as set out in point  5.2. 
5.3.1.2.  Intratracheal/ intranasal infectivity and pathogenicity  
The intratracheal/ intranasal infectivity and pathogenicity following a single 
exposure to the micro -organism  shall be reported. Expert judgement may support the 
evaluat ion on which of the two exposure route s is the most appropriate to be 
investigated, based on biological properties of the micro -organism and available 
information described in point s 5.1 and 5.2.  
A study in test animals in accordance with relevant guidelines shall be performed, 
unless the applicant can demonstrate absence of intratracheal/ intranasal infectivity 
and pathogenicity based on a weight of evidence approach as set out in point  5.2. 
5.3.1.3.  Intravenous/ intraperitoneal or subcutaneous single exposure  
The intravenous/Intraperitoneal or subcutaneous test shall be  considered a highly 
sensitive assay to elicit in particular infectiv ity. The worst -case scenario – micro -
organism bypassing the dermal ba rrier and entering the body in a high concentration 
– may be used to assess  the results of oral and intratracheal/intranasal testing in case 
of uncertainties.  
The choice on which is the most appropriate exposure routes to be investigated  shall 
be based on  biological properties of the micro -organism and available information 
required  in point s 5.1 and 5.2.  
A study in test animals in accordance with the  relevant guidelines shall be 
performed, unless the applicant can demonstrate absence of 
intravenous/intrap eritoneal or subcutaneous infectivity and pathogenicity based on a 
weight of evidence approach as set out in point  5.2. 
5.3.2.  Cell culture study  
This information shall be reported for intracellular replicating micro -organisms, such 
as viruses, viroids or, where relevant, bacteria and protozoa, unless the information 
provided in accordance with Sections 1, 2 and 3 clearly demonstrates that the micro -
organism does not replicate in homoeothermic (warm -blooded) organisms.  
If this information is required, a cell cult ure study shall be performed in human cell 
or tissue cultures of different organs. Selection may be based on expected target 
organs after infection. If human cell or tissue cultures of specific organs are not 
available, other mammal cell and tissue cultures shall  be used. For viruses, particular 
attention shall be given on  the ability to interact with  the human genome.  
5.4. Specific infectivity and pathogenicity studies on the micro -organism  
In case, based on expert judgment, available information (see point  5.2) or effects 
observed in the single dose infectivity and pathogenicity studies (see point  5.3.1) 
require further investigation, specific  infectivity and/or pathogenicity studies shall be 
carried out, in particular in case of close relatedness to micro -organisms which are 
pathogenic to humans and animals.  
If these studies are  required, they shall be de signed on an individual basis, in the light 
of the particular parameters to be investigated and the objectives to be achieved.  EN 29  EN 5.5. Information and toxicity studies on metabolites   
5.5.1.  Information on metabolites  
All the available information (e.g. scientific literature, studies results) on the 
toxicological characterization of the metabolites and the related identified hazards to 
human and animal health , collected or generated to identify the metabolites of 
concer n listed under point 2.8 and relevant to human and animal health,  shall be 
submitted.  This information concerns metabolites for which a hazard to human or 
animal health is identified and, where relevant, other metabolites which are 
considered of no concern  and which are therefore not requiring further risk 
characterization.   
For those metabolites  for which a hazard to human or animal health is identified,  an 
estimation of human exposure shall be provided  under points 6.1 and 7.4.1.  
5.5.2.  Additional toxicity studi es on metabolites of concern  
For metabolite(s) of concern , identified based on information provided on hazard to 
(see point 5.5.1) and exposure of (see points 6.1, 7.4.1 and 7.4.2)  humans or animals  
and listed under  point  2.8, toxicological reference value(s) shall be set based on the 
available  toxicological information f or each metabolite of concern. The  reference 
values shall allow risk assessments to be performed for operators, workers, 
bystanders, residents and consume rs, as appropriate, unless a risk assessment can be 
made by other means (e.g. a qualitative assessment or using the Threshold of 
Toxicological Concern (TTC) concept).  Further exposure information may be 
required, if deemed necessary  based on expert judgeme nt. 
If reference value s cannot be set based on already existing information  or reported 
effects need further investigation, additional studies may be required and shall be 
performed on a case -by-case basis  (for example  short -term toxicity studies and 
genot oxicity studies ). If any toxicity studies on metabolites are conducted, the 
requirements set out  in Part A for the specific type of study shall be followed.  
For organisms which have not been extensively studied, i.e. where the amount of 
published informati on is not sufficient to conclude on the production of metabolites 
of concern, a repeated -dose toxicity study on relevant fractions of the MASAM shall 
be conducted in accord ance with the provisions set out  in Part A for the same type of 
study. The decision to require further studies shall be based on the type of any toxic 
effects observed and on expert judgement.  
  EN 30  EN 6. RESIDUES IN OR ON TRE ATED PRODUCTS , FOOD AND FEED  
Introduction  
Data on r esidue s as required  in point  6.2 shall be provided, unless :  
– based on a weight of evidence approach concerning the  information submitted 
in accordance with Sections 2, 3, 5  and 7, it can be justified that possible 
metabolites of concern identified (see point  2.8) are not hazardous to humans  
as a result of  the intende d use, or 
– it is possible to conclude, through estimation of consumer exposure to residues 
of metabolites for which a hazard to human health was identified  (see point  
5.5.1) that the risk for consumers is acceptable.  
6.1. Estimation of consumer exposure to res idues  
An estimation of consumer exposure shall be provided for metabolites for which a 
hazard to human health was identified based on information submitted in accordance 
with point  5.5.1, considering the intended use.  
The estimation shall include , for the metabolite s for which a hazard to human health 
was identified , a calculation of the expected residue levels of these  metabolite s on 
edible parts of treated crops using worst -case estimates, taking into account the 
critical good agricultural practic e(s), ecology of the micro -organism, such as its 
lifestyle (e.g. saprotroph, parasite, endophyte), host range, life cycle, population 
growth requirements and the conditions which trigger the production and the 
properties of the metabolite  of concern .  
The estimation of exposure to residues of metabolites , for which a hazard to human 
health was identified may also be supported by direct measurements of the 
metabolite, e.g. to show the absence of the metabolite on edible parts at time of 
harvest. When determi ning the need for direct measurements, the possibility and 
relevance of exposure to the metabolite produced after application on the edible parts 
(in-situ production) shall be taken into consideration. This may include a comparison 
between the background l evel of the metabolite and the elevated level of it due to 
treatment with the plant protection product containing the active substance. Read 
across approaches shall be justified.  
An estimation of exposure to metabolites , for which a hazard to human health was 
identified , may be supported by the direct measurements of the density of the micro -
organism on edible parts of treated crops, e.g. if it cannot be adequately justified that 
in-situ production of the metabolite is not relevant for the consumers.  Such 
measurements shall be performed under normal conditions of use and in accordance 
with good agricultural practice . 
The estimation shall take into consideration, depending on the case, the whole crop 
life-cycle (e.g. pre -harvest, and post -harvest), in order t o allow a proper assessment 
of the risk to consumers. A weight of evidence approach sh all be employed . Where 
relevant, adequate justification for read -across shall be provided (e.g. between 
different substances, members of a species, climatic conditions).  
Based on the exposure estimation, an indicative consumer risk assessment shall  be 
performed to demonstrate that the anticipated exposure to metabolites , for which a 
hazard to human health was identified , does not constitute an unacceptable dietary 
consumer  risk. EN 31  EN 6.2. Data generation on residues  
For those metabolites of concern identified under point 2.8 and for which it was not 
adequately demonstrated that the risk to consumers is acceptable based on the 
information provided under  point  6.1, relevant studies of  a data package on residues 
as provided in Section 6 of Part A shall be required. The studies shall be performed 
with a representative plant protection product aiming at analysing and , if possible , at 
quantifying the different metabolites of concern identified as described in point  2.8. 
If a data package on residues is required:  
– half of the supervised residues trials shall be residue decline trials  which  shall  
includ e, unless it can be demonstrated that only non -viable micro -organism s 
are present  at the time of harvest , at least one post -harvest measurement , 
– information on levels of the micro -organism  and concentrations of the 
metabolite( s) of concern shall be provided , 
– based o n the residue trials , a consumer risk assessment shall  be performed to 
demonstrate that the exposure does not constitute a n unacceptable  consumer 
risk. 
  EN 32  EN 7. ENVIRONMENTAL OCCURRE NCE OF THE MICRO -ORGANISM , INCLUDING FATE AND 
BEHAVIOUR OF METABOL ITES OF CONCERN  
Introduction  
(i)  This Section sets out requirements that make it possible to determine  
ecological implications of the micro -organism, considering its occurrence  in 
the relevant environmental compartments and to assess the potential exposure 
of humans and  non-target organisms to the active substance, and where 
relevant to metabolites of concern. Information on the biological properties and 
ecology of the micro -organism as well as its intended use, i.e. information 
submitted in accordance with Sectio ns 1 to  6, is the main source of 
information. This may be complemented with  literature data, laboratory 
investigation or field measurements.  
(ii) The information provided for the micro -organism and one or more preparations 
containing the micro -organism shall be s ufficient to permit an assessment of 
the exposure of non -target organisms to the micro -organism. In addition, 
sufficient information shall be provided to permit an assessment of metabolites 
of concern , in case  they are identified under  point  2.8. 
(iii)  The information provided shall be sufficient to identify measures necessary to 
minimise impact on non -target species and the environment.  
7.1. Predicted environmental density of the micro -organism  
7.1.1.  Soil  
The predicted environmental density of the micro -organism in  soil following 
treatment with the product under the proposed conditions of use shall be estimated , 
unless the applicant properly justifies absence of hazard under  Section 8.  
7.1.2.  Water  
The predicted environmental density of the micro -organism in surface wate r 
following treatment with the product under the proposed conditions of use shall be 
estimated , unless the applicant properly justifies absence of hazard under  Section 8.  
7.2. Exposure to micro -organisms known to be pathogenic either for plants or for 
other or ganisms  
For micro -organisms not occurring in the relevant E uropean  environments at the 
relevant highest taxonomic level and which are known to be pathogenic either for 
plants or for other organisms (see point s 2.2 and 2. 3), the host organisms in which 
proliferation of the micro -organism is expected shall be indicated. If non -target 
organisms indicated under  Section 8 may be exposed to the host organisms colonised 
by the pathogen, information on the likelihood and, if appli cable, level of exposure 
shall be provided.  
Such information may be provided based on the biological properties (see Section  2), 
literature data and/or studies required under  Section  8. 
7.3. Refined exposure assessment  
7.3.1.  Qualitative exposure assessment  
A qualit ative assessment of the exposure to the micro -organism shall be carried out 
if:  EN 33  EN – adverse effects are observed on non -target organisms (see Section 8) after 
exposure to environmentally relevant concentrations, based on the predicted 
environmental density of  the micro -organism calculated as provided for in 
point  7.1, or information is not sufficient to conclude about it , or  
– under consideration of the information provided  for in point  7.4 a potential risk 
is identified for humans or non -target organism(s) , or information is not 
sufficient to conclude about it.  
If required  to provide supporting indications for the risk assessment , a qualitative 
assessment of the exposure to the micro -organism shall be provided employing a 
weight of evidence approach. Such qual itative assessment shall take into 
consideration the predicted environmental densities calculated under  point  7.1, and 
may be based on the ecology of the micro -organism, such as its lifestyle (e.g. 
saprotroph, parasite, endophyte), host range  and possible host densities , life cycle, 
population growth requirements or available monitoring data at the relevant highest 
taxonomic level. Adequate justification for using read -across shall be provided (e.g., 
among strains of the same  species).  
7.3.2.  Experimental exposure  data 
If under consideration of the information provided under  point s 7.1, 7.2, 7.3.1 and 
7.4 a potential risk is identified for humans or non -target organism(s) or information 
is not sufficient to conclude about it, the population density of the micro -organism 
shall be determined in relevant environmental compartment(s) (e.g. soil, water, plant 
surfaces).  
The experimental data shall include population densities measured in a time course 
including pre -application and immediately post -application, aiming at demonstrating 
the potential decline of population density.  
7.4. Fate and behaviour of metabolite(s) of concern  
7.4.1.  Predicted environmental concentration  
In case of identification of metabolites which are present in the MASAM  and for 
which a hazard to human health or non -target organisms was identified (see points  
5.5.1 and 8.8.1 ), the predicted environmental concentration of the metabolite in the 
relevant environmental compartment (i.e. soil, surface water, groundwater or air) 
shall be provided. If the applicant cannot adequately demonstrate  that in-situ 
production of the metaboli te is not relevant for the risk assessment, provisions set out  
in point  7.4.2 shall be followed.  
No predicted environmental concentration calculations are needed for metabolites for 
which a hazard to human health or non -target organisms was identified  that are 
produced in situ  but are not present in the MASAM . 
7.4.2.  Qualitative exposure assessment  
In case of identification of metabolites for which a hazard to human health or non -
target organisms was identified (see points  5.5.1 and 8.8.1 ), a qualitative exposure  
assessment shall be performed on such metabolites  where the information provided 
under  point  7.4.1 is not sufficient to conclude on acceptable risk to non -target 
organisms or on no -risks to human health.  
If required, the assessment may be based on existi ng knowledge on the ecology of 
the micro -organism, such as its lifestyle, host range, life cycle, population growth EN 34  EN requirements, available monitoring data at the relevant highest taxonomic level and 
the conditions , which trigger the production of the meta bolite, and on the properties 
of the metabolite. A weight of evidence approach shall  be employed. Adequate 
justification for using read -across shall be provided (e.g. between different 
substances, members of a species, climatic conditions).  
7.4.3.  Experimental ex posure data  
Experimental exposure data shall be provided for the metabolites of concern 
identified under  point  2.8 for which the information provided under  point s 7.4.1 and 
7.4.2 is not sufficient to conclude on acceptable risk to non -target organisms, or on 
no-risks to human health.  
In such cases, sufficient information on the concentration of the metabolite of 
concern in the relevant environmental compartments (e.g. soil, surface water, 
groundwater, air, flowers, leaves, roots, host  organisms) shall be pr ovided to permit 
an assessment.  The study shall be conducted in accord ance with  the relevant 
provisions of Part A for the relevant  type of study .  EN 35  EN 8. ECOTOXICOLOGICAL STUD IES 
Introduction  
(i)  This Section sets out requirements for the data t o allow :  
– for the assess ment of  potential adverse effects on non -target organisms 
likely to be exposed to the micro -organism and relevant associated 
metabolites of concern , and  
– for the identification of the relevant tests to be carried out on specific 
non-target or ganisms, based on information regarding intrinsic 
properties, so as to limit testing to what is necessary to conclude the risk 
assessment . 
Attention shall be paid to microbiological species which are not known to 
occur in the relevant E uropean  environment s. The information provided shall 
be sufficient to determine the physiological and ecological host range (in 
conjunction with the analysis of key biological traits  of the micro -organisms ) 
in order to assess impacts on non -target organisms.  
 (ii)  The infor mation provided  at the most relevant highest taxonomic level , taken 
together with that for one or more preparations containing the micro -organism, 
shall be sufficient to permit an assessment of the impact on non -target species, 
likely to be at risk from ex posure to the micro -organism. When submitting this 
information the applicant shall take into account that the  impact on non -target 
species can result from single, prolonged or repeated exposure and can be 
reversible or irreversible. The information provide d shall be sufficient to:  
– decide whether or not the micro -organism can be approved ,  
– specify appropriate conditions or restrictions to be associated with any 
approval ,  
– permit an evaluation of short - and long -term risks for non -target species 
populations,  communities, and processes , as appropriate , and 
– specify any precautions deemed necessary for the protection of non -
target species.  
(iii)  In general, the duration of experimental studies shall be long enough to permit 
time for incubation, infection and manifestation of adverse effects in non -target 
organisms depending on the biological properties of the micro -organism.  The 
provided studies shall take into consideration the maximum recommended 
application rate or the expected environmental concentration, the exposure that 
may arise from the intended uses and the potential of the micro -organism to 
proliferate in the environment or in the host.  
In order to distinguish between pathogenicity of the living micro -organism and 
toxic effects triggered by its meta bolites of concern, appropriate controls shall 
be included in addition to the no -dosed control group, such as inactivated 
forms of the living micro -organisms, and/or sterile filtrate/supernatant controls.  
(iv)  If pathogenicity/infectivity studies are requ ired for any of the non -target 
organisms groups indicated in point s 8.1 to 8.6, the choice of the appropriate 
species of that non -target organisms group shall be based on the biological 
properties of the micro -organism (including the specificity  of the host range , 
mode of action and ecology), the proposed use pattern(s) of the plant protection EN 36  EN product (e.g. treated crops, frequency, timings, use patterns such as spraying or 
brushing)  and consider  relevant guidelines, where available.  
Additional studies may  be conducted if tests referred to  in point s 8.1 to 8.6 
have shown adverse effects in one or more non -target organisms and may 
include studies on additional species.  
(v)  All known adverse effects on the environment shall be reported. Additional 
studies m ay be necessary to investigate the probable mechanisms involved and 
to assess the significance of these effects.  
(vi)  It may be necessary to conduct separate studies for metabolites of concern 
identified under  point  2.8, which constitute a relevant risk to non -target 
organisms. The study on non -target organisms shall be conducted in 
accordance with the relevant provision of Part  A.  
(vii)  In order to facilitate the assessment of the significance of test results obtained, 
the same species, recorded origin or, where possible, strain of each relevant 
non-target species shall be used in the various tests performed . 
8.1. Effects on terrestrial verteb rates  
A summary on potential infectivity and pathogenicity of the micro -organism to 
terrestrial vertebrates ( e.g. mammals, birds, reptiles, and amphibians)  shall be 
provided, based on the information already provided under Sections 1, 2, 3, 5 and 7 
and th at information  which may be retrieved from any other reliable source .  
Relevant pathogenicity/infectivity studies shall be performed  unless the applicant 
demonstrates, by following a weight of evidence approach, that 
pathogenicity/infectivity of the micro -organism to non -target terrestrial vertebrates 
can be assessed based on the summary provided . 
If these studies are required :  
– gross necropsy shall  be performed and 
– for micro -organisms with pathogenic mode of action or viruses (e.g. 
entomopathogens) that are expected to proliferate significantly in the 
environment following an application, the oral dose administered in the studies 
may be justified based on the informa tion submitted under point s 7.1 and 7.2.  
8.2. Effects on aquatic organisms  
8.2.1.  Effects on fish  
A summary on  potential  infectivity and pathogenicity of the micro -organism to fish 
shall be provided, based on the information already provided under Sections  1, 2, 3 
and 7 and th at information  which may be retrieved from any other reliable source .  
Relevant pathogenicity/infectivity studies shall be performed  unless the applicant 
demonstrates, by following a weight of evidence approach, that : 
– pathogenicity/infectivity of the micro -organism to fish can be assessed based 
on the summary provided ; or 
– exposure of fish to the micro -organism is expected to be none  based on 
information provided under  Section 7.  EN 37  EN Where adverse effects are observed in such studies , further relevant studies (e.g. 
under representative conditions in accordance with the proposed conditions of use ) 
shall be performed . 
8.2.2.  Effects on aquatic invertebrates  
A summary on potential infectivity and pathogenicity of the micro -organism to 
aquatic i nvertebrates shall be provided, based on the information already provided 
under Sections  1, 2, 3 and 7 and th at information  which may be retrieved from any 
other reliable source .  
Relevant pathogenicity/infectivity studies shall be performed  unless the app licant 
demonstrates, by following a weight of evidence approach, that : 
– pathogenicity/infectivity of the micro -organism to aquatic invertebrates can be 
assessed based on the summary provided , or 
– exposure of aquatic invertebrates to the micro -organism is expected to be none  
based on information provided under  Section  7. 
Where adverse effects are observed in such studies, further relevant studies  (e.g. 
under representative conditions in accordance with the proposed conditions of use) 
shall be performed . 
8.2.3.  Effects on algae  
A summary on  potential  infectivity and pathogenicity of the micro -organism to algae 
shall be provided, based on the information already provided under Sections  1, 2, 3 
and 7 and th at information  which may be retrieved from any other reliable source .  
Relevant  studies on pathogenic/infective effects on algae  growth and growth rate 
shall be performed  if the micro -organism is known to have an herbicidal mode of 
action or to be closely related to a plant pathogen, unless the applicant demonstrates, 
by following a weight of evidence approach, that : 
– pathogenicity/infectivity of the micro -organism  to algae  can be assessed based 
on the summary provided , or 
– exposure of algae to the micro -organism is expected to be none based on 
information provided under  Section  7. 
Where adverse effects are observed in such studies , further relevant  studies (e.g. 
under repres entative conditions in accordance with the proposed conditions of use) 
shall be performed . 
8.2.4.  Effects on aquatic macrophytes  
A summary on potential infectivity and pathogenicity of the micro -organism to 
aquatic  macrophytes  shall be provided, based on the inf ormation already provided 
under Sections 1, 2, 3 and 7 and th at information  which may be retrieved from any 
other reliable source .  
Relevant  studies on pathogenic/infective effects on aquatic  macrophytes  shall be 
performed if the micro -organism is known to have an herbicidal mode of action, or to 
be closely related to a plant pathogen, unless the applicant demonstrates, by 
following a weight of evidence approach, that : 
– pathogenicity/infectivity of the micr o-organism  to aquatic  macrophytes  can be 
assessed based on the summary provided , or EN 38  EN – exposure of aquatic macrophytes to the micro -organism is expected to be none  
based on information provided under  Section 7.  
Where adverse effects are observed in such stud ies, further relevant  studies (e.g. 
under representative conditions in accordance with the proposed conditions of use) 
shall be performed . 
8.3. Effects on bees  
A summary on potential infectivity and pathogenicity of the micro -organism to bees 
shall be provided,  based on the information already provided under Sections  1, 2, 3 
and 7 and th at information  which may be retrieved from any other reliable source .  
Relevant pathogenicity/infectivity studies, including adult and larval stages,  shall be 
performed , unless the applicant demonstrates, by following a weight of evidence 
approach, that : 
– the micro -organism is not pathogenic/infective to bees based on the summary 
provided , or 
– exposure of bees to the micro -organism is expected to be none  based on 
information provid ed under  Section 7.  
Where  adverse effects are observed in such studies , further relevant  studies (e.g. field 
studies under representative conditions in accordance with the proposed conditions 
of use for use) shall be performed .  
8.4. Effects on  non-target  arthr opods other than bees  
A summary on potential infectivity and pathogenicity of the micro -organism to non-
target arthropods other than bees shall be provided, based on the information already 
provided under Sections 1, 2, 3 and 7 and th at information  which may be retrieved 
from any other reliable source .  
Relevant pathogenicity/infectivity studies shall be performed  unless the applicant 
demonstrates, by following a weight of evidence approach, that : 
– pathogenicity/infectivity of the micro -organism to n on-target arthropods other 
than bees can be assessed based on the summary provided , or 
– exposure of non -target arthropods to the micro -organism is expected to be none  
based on information provided under  Section 7.  
If studies are required, they shall be performed on two  arthropod species other than 
bees playing a role in biological control  and comprising different taxonomic groups 
(orders) , where possible , for which agreed testing protocols are available , and t he 
applicant shall provide a justification fo r number and  taxonomy of the tested species. 
Moreover,  these tests may require conditions affecting growth or viability of the 
micro -organism (e.g. high osmotic potential of the test matrices).  
Where adverse effects are observed in such studies , further relevant  studies ( e.g. 
extended laboratory tests or field studies  under representative conditions in 
accordance with the proposed conditions of use) shall be performed . 
8.5. Effects on non-target meso - and macro -organisms in soil   
A summary on potential infecti vity and pathogenicity of the micro -organism to non-
target soil meso - and macro -organisms  shall be provided, based on the information 
already provided under Sections 1, 2, 3 and 7 and th at information  which may be 
retrieved from any other reliable source .  EN 39  EN Relevant  pathogenicity/infectivity studies shall be performed  unless:  
– pathogenicity/infectivity of the micro -organism to non -target soil meso - and 
macro -organisms can be assessed based on the summary provided , or 
– exposure of meso - and macro soil organisms to the micro -organism is expected 
to be none  based on information provided under  Section 7.  
If studies are required, they shall be performed on two non-target meso - and macro -
organisms species chosen based on the biological properties of the micro -organism 
under evaluation , where possible, for which agreed testing protocols are available .  
Where adverse effects are observed in such studies , further relevant  studies (e.g. 
under representative conditions in accordanc e with the proposed conditions of use) 
shall be performed . 
8.6. Effects on non-target terrestrial plants  
A summary on potential infectivity and pathogenicity of the micro -organism to non-
target terrestrial plants shall be provided, based on the information alr eady provided 
under Sections 1, 2, 3 and 7 and th at information  which may be retrieved from any 
other reliable source .  
Relevant  studies on pathogenic/infective effects on non -target terrestrial plants shall 
be performed  if the micro -organism is known to have an herbicidal mode of action or 
to be closely related to a plant pathogen, unless the applicant demonstrates, by 
following a weight of evidence approach, that : 
– pathogenicity/infectivity of the micro -organism to non -target terrestrial plants 
can be assessed based on the summary provided , or 
– exposure of non -target plants to the micro -organism is expected to be none  
based on information provided under  Section 7.  
Where adverse effects are observed in such studies , furthe r relevant studies (e.g. 
under representative conditions in accordance with the proposed conditions of use) 
shall be performed . 
8.7. Additional studies on the micro -organism  
Further data may need to be submitted on potential pathogenicity/infectivity of the 
micro-organism on non -target species different from those assessed to fulfil the 
requirements set out in point s 8.1 to 8.6.   
The data may also consist of a summary including the information already provided 
under Sections 2, 3, 5 and 7 and those which may be retrieved from any other source, 
or from  additional infectivity and pathogenicity studies.  
8.8. Information and toxicity studies on metabolites  
8.8.1.  Information on metabolites  
All the available information (e.g. scientific literature, studies results) on the 
toxicological characterization of the metabolites and the related identified hazards 
relevant to non-target organisms,  collected or generated to identify the metabolites of 
concern listed under point 2.8 and relevant to non-target organisms , shall be 
submitted.  This information shall concern metabolites for which a hazard to non-
target organisms  is identified and, where relevant, other metabolites which are 
considered of no c oncern and which therefore do not requir e further risk 
characterization . EN 40  EN For those metabolites  for which a hazard to non -target organisms  is identified,  an 
estimation of exposure of the relevant non-target organisms  shall be provided under 
point 7.4.1.  
8.8.2.  Additional toxicity studies on metabolites of concern  
For metabolite(s) of concer n, identified based on information provided on hazard to 
(see point 8.8.1) and exposure of (see points 7.4.1 and 7.4.2) non -target organisms  
and listed under  point  2.8, further relevant information on the ir toxicity to the non-
target organisms , which are relevant (e.g. based on exposure, and indication of 
toxicity)  among those described in point s 8.1 to 8.6 , shall be provided . In case it is 
necessary to generate experime ntal data, relevant studies on ecotoxicology as 
provided for in Section  8 of Part A shall be submitted .’