Proposal for a Council Directive amending Annex VI to Directive 91/414/EEC as regards plant protection products containing micro-organisms
Date: 2003-12-22
Institutions: European Commission
Subjects: exchange of information, marketing standard, microorganism, plant health product

EN

EN

  EN

COMMISSION OF THE EUROPEAN COMMUNITIES

Brussels, 22.12.2003
COM(2003) 814 final

Proposal for a

COUNCIL DIRECTIVE

amending Annex VI to Directive 91/414/EEC as regards plant protection products
containing micro-organisms

(presented by the Commission)

EN

  EN

 
EXPLANATORY MEMORANDUM

Council  Directive  91/414/EEC  concerning  the  placing  of  plant  protection  products  on  the
market  requires  all  plant  protection  products  on  the  European  market  to  be  evaluated  in  a
uniform way for efficacy and risks to human health and the environment. For this end a dual
system is established. The active ingredients are evaluated at Community level, the products
containing these active ingredients at national level by the Member State authorizing the use.
To ensure that this is done in a consistent manner and to avoid wide discrepancies in national
evaluations  annex  VI  of  the  Directive  provides  uniform  principles  for  evaluation  and
authorisation  of  plant  protection  products.  So  far  these  principles  can  be  used  for  chemical
plant  protection  products  only  and  not  for  plant  protection  products  containing  micro-
organisms. The present proposal for a draft Council Directive is intended to fill this gap.

2

 
Proposal for a

COUNCIL DIRECTIVE

amending Annex VI to Directive 91/414/EEC as regards plant protection products
containing micro-organisms

(Text with EEA relevance)

THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty establishing the European Community,

Having  regard  to  Council  Directive  91/414/EC  of  15  July  1991  concerning  the  placing  of
plant protection products on the market1, and in particular Article 18 (1) thereof,

Having regard to the proposal from the Commission2,

Whereas:

(1)

(2)

(3)

(4)

(5)

(6)

1

2

3

In accordance with Council Directive 91/414/EEC Member States have to ensure that
plant protection products are not authorised unless they comply with the requirements
provided for in that Directive.

Directive 91/414/EEC provides for the establishment  of Uniform  Principles  pursuant
to  which  the  Member  States  have  to  carry  out  the  evaluation  of  plant  protection
products with a view to their authorisation.

Uniform  Principles  have  been  laid  down  for  Member  States  to  use  in  the  evaluation
and  authorisation  of  chemical  plant  protection  products  only.  However,  there  are  no
equivalent principles for Member States to apply in the evaluation and authorisation of
plant  protection  products  containing  micro-organisms.  It  is  appropriate  to  lay  down
additional Uniform Principles for this type of plant protection product. 

Requirements  for  the  dossiers  to  be  submitted  by  applicants  for  the  authorisation  of
plant  protection  products  containing  micro-organisms  having  been  included  in
Directive 91/414/EEC by Commission Directive 2001/36/EC3, it is now necessary to
lay down uniform principles for the evaluation of a dossier concerning plant protection
products containing micro-organisms based on such data requirements.

Directive 91/414/EEC should therefore be amended accordingly.

The Scientific Committee on Plants has provided an opinion on [an earlier version of]
this draft Council Directive, and this opinion has been taken into account,

OJ L 230, 19.8.1991, p 1. Directive as last amended by Commission Directive 2003/84/EC (OJ L 247,
30.9.2003, p 20).
OJ C , , p. .
OJ L 164, 20.6.2001, p. 1.

3

 
                                                
HAS ADOPTED THIS DIRECTIVE:

Article 1

Annex VI to Council Directive 91/414/EEC is amended in accordance with the Annex to this
Directive.

Article 2

1.

Member  States  shall  bring  into  force  the  laws,  regulations  and  administrative
provisions necessary to comply with this Directive by [insert date 6 months after the
entry into force] at the latest. They shall forthwith communicate to the Commission
the text of those provisions and a correlation table between those provisions and this
Directive.

When  Member  States  adopt  those  provisions,  they  shall  contain  a  reference  to  this
Directive  or  be  accompanied  by  such  a  reference  on  the  occasion  of  their  official
publication. Member States shall determine how such reference is to be made.

2.

Member States shall communicate to the Commission the text of the main provisions
of national law which they adopt in the field covered by this Directive.

This Directive shall enter into force on the [twentieth] day following that of its publication in
the Official Journal of the European Union.

Article 3

Article 4

This Directive is addressed to the Member States.

Done at Brussels,

For the Council
The President

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Annex VI is amended as follows:

ANNEX

(1)

The  title  “Uniform  Principles  for  evaluation  and  authorisation  of  plant  protection
products” is replaced by

“PART A 

Uniform Principles for evaluation and authorisation of chemical

plant protection products”

(2)

The following Part B is added:

“PART B

Uniform Principles for evaluation and authorisation of plant

protection products containing micro-organisms

CONTENTS

A.

B.

INTRODUCTION

EVALUATION

1.

2.

General principles

Specific principles

2.1.

Identity

2.1.1. Identity of the micro-organism in the product

2.1.2. Identity of the product

2.2. Biological, physical, chemical and technical properties 

2.2.1. Biological properties of the micro-organism in the product

2.2.2. Physical, chemical and technical properties of the product

2.3. Further information

2.4. Efficacy data

2.5.

Identification/detection and quantification methods

2.5.1. Analytical methods for the product 

2.5.2. Analytical methods for residues

2.6.

Impact on human and animal health

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2.6.1. arising from the product

2.6.2. arising from residues

2.7. Fate and behaviour in the environment

2.8. Effects on and exposure of non-target organisms

2.9. Conclusions and proposals

C.

DECISION-MAKING

1.

2.

General principles

Specific principles

2.1.

Identity

2.2. Biological and technical properties

2.3. Further information

2.4. Efficacy

2.5.

Identification/detection and quantification methods

2.6.

Impact on human and animal health

2.6.1. arising from the product

2.6.2. arising from residues

2.7. Fate and behaviour in the environment

2.8. Effects on non-target organisms

A.

INTRODUCTION

1.

The  principles  developed  in  this  Annex  aim  to  ensure  that  evaluations  and
decisions  with  regard  to  authorisation  of  plant  protection  products,  provided
they  are  microbial  plant  protection  products,  results  in  the  implementation  of
the  requirements  of  Article  4  (1)  (b),  (c),  (d)  and  (e)  of  this  Directive  by  all
Member States at a high level of protection of human and animal health and the
environment.

2.

In evaluating applications for granting authorisations Member States shall:

(a)

−

ensure  that  the  dossier  supplied  is  in  accordance  with  the
requirements of Annex IIIB, at the latest at the time of finalization
of  the  evaluation  for  the  purpose  of  decision-making,  without
prejudice, where relevant, to the provisions of Article 13 (1) (a), (4)
and (6) of this Directive,

6

 
– 

– 

ensure that the data submitted are  acceptable in  terms of quantity,
quality, consistency and reliability and sufficient to permit a proper
evaluation of the dossier,

evaluate,  where  relevant,  justifications  submitted  by  the  applicant
for not supplying certain data;

take  into  account  the  Annex  IIB  data  concerning  the  active  substance
consisting of micro-organisms (including viruses) in the plant protection
product,  submitted  for  the  purpose  of  inclusion  of  the  micro-organism
concerned  in  Annex  I,  and  the  results  of  the  evaluation  of  those  data,
without prejudice, where relevant, to the provisions of Article 13 (1) (b),
(2), (3) and (6) of this Directive;

take  into  consideration other  relevant  technical  or  scientific  information
they can reasonably possess with regard to the performance of the plant
protection  product  or  to  the  potentially  adverse  effects  of  the  plant
protection product, its components or its metabolites/toxins.

(b)

(c)

3. Where in the specific principles on evaluation reference is made to Annex IIB
data, this shall be understood as being the data referred to in point 2 (b).

4. Where the data and information provided are sufficient to permit completion of
the evaluation for one of the proposed uses, applications must be evaluated and
a decision made for the proposed use.

Taking  account  of  justifications  provided  and  with  the  benefit  of  any
subsequent clarifications, Member States shall reject applications for which the
data gaps are such that it is not possible to finalize the evaluation and to make a
reliable decision for at least one of the proposed uses.

During the process of evaluation and decision-making, the Member State shall
cooperate with the applicants in order to resolve  any  questions on  the dossier
quickly  or  to  identify  at  an  early  stage  any  additional  studies  necessary  for  a
proper evaluation of the dossier, or to amend any proposed conditions for the
use of the plant protection product or to modify its nature or its composition in
order  to  ensure  full  satisfaction  of  the  requirements  of  this  Annex  or  of  this
Directive.

Member States shall normally come to a reasoned decision within 12 months of
receiving a technically complete dossier. A technically complete dossier is one
that satisfies all the requirements of Annex IIIB.

The  judgements  made  by  the  competent  authorities  of  the  Member  States
during the evaluation and decision-making process must be based on scientific
principles,  preferably  recognized  at  international  level  and  be  made  with  the
benefit of expert advice.

A microbial plant protection product (in the following called product) contains
micro-organisms  (including  viruses)  and  formulation  substances.  It  may  also
contain relevant metabolites/toxins produced during growth, residues from the
growth  medium,  and  (microbial)  contaminants.  The  micro-organism,  relevant

5.

6.

7.

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metabolites/toxins  and  the  plant  protection  product  with  residual  growth
medium and (microbial) contaminants present must all be evaluated.

8. Member States must take into account those guidance documents taken note of

in the Standing Committee on the Food Chain and Animal Health (SCFCAH).

9.

For  genetically  modified  micro-organisms,  Directive  2001/18/EC  of  the
European Parliament and of the Council of 12 March 20014, must be taken into
account.  The  evaluation  in  the  framework  of  this  Directive  must  be  provided
and taken into account.

10. Definitions and explanation on microbiological terms

Antibiosis A relationship between two or more species in which one species is
actively harmed (as by the production of toxins by the harming species).

Antigenic Any substance that, as a result of coming in contact with appropriate
cells, induces a state of sensitivity and/or immune responsiveness after a latent
period (days to weeks) and which reacts in a demonstrable way with antibodies
and/or immune cells of the sensitized subject in vivo or in vitro.

Antimicrobial  Antimicrobial  agents  or  antimicrobial(s)  refer  to  naturally
occurring,  semi-synthetic  or  synthetic  substances  that  exhibit  antimicrobial
activity (kill or inhibit the growth of microorganisms.).

The term Antimicrobial(s) includes:

– 

– 

antibiotics,  which  refer  to  substances  produced  by  or  derived  from
microorganisms, and 

anticoccidials, which refer to substances that are active against coccidia,
single cell protozoan parasites.

CFU Colony-forming unit; an individual cell which is able to clone itself into
an entire colony of identical cells.

Colonisation  Proliferation  and  persistence  of  a  (micro)organism  in  an
environment,  such  as  on  external  (skin)  or  internal  (intestine,  lungs)  body
surfaces.  For  colonisation,  the  micro-organism  should  at  least  persist  for  a
longer  period  than  expected  in  a  specific  organ.  The  population  of  micro-
organisms may decline but at a slower rate than normal clearance, it may be a
steady  population  or  it  may  be  a  growing  population.  Colonisation  can  be
related  to  harmless  and  functional  micro-organisms  as  well  as  to  pathogenic
micro-organisms. The possible occurrence of effects is not indicated. 

Ecological  niche Unique  environmental  position  occupied  by  a  particular
species,  perceived  in  terms  of  actual  physical  space  occupied  and  function
performed within the community or ecosystem.

4

Directive  2001/18/EC  of  the  European  Parliament  and  of  the  Council  of  12  March  2001  on  the
deliberate  release  into  the  environment  of  genetically  modified  organisms  and  repealing  Council
Directive 90/220/EEC (OJ L 106, 17.4.2001, p. 1).

8

 
                                                
Host  An  animal  (incl  humans)  or  plant  that  harbours  or  nourishes  another
organism (parasite). 

Host specificity The range of different host-species that can be colonised by a
microbial  species  or  strain.  A  host-specific  micro-organism  colonises  or  has
adverse effects on one or only a small number of different host-species. A non-
host-specific micro-organism might colonise or might have adverse effects on a
broad range of different host-species.

Infection  The  introduction  or  entry  of  a  pathogenic  micro-organism  into  a
susceptible  host,  whether  or  not  it  causes  pathological  effects  or  disease,  but
implies that the organism must enter the body of the host, usually the cells, and
be able to reproduce to form new infective units. Simply ingesting a pathogen
does not imply infection.

Infective Capable of transmitting an infection. 

Infectivity  The  characteristics  of  a  micro-organism  that  allows  it  to  infect  a
susceptible host.

Invasion  the  entry  of  a  micro-organism  into  the  host  body  (e.g.  actual
penetration of the integument, gut epithelial cells, etc.). "Primary invasiveness"
is a property of pathogenic micro-organisms.

Multiplication  Ability  of  a  micro-organism  to  reproduce  and  increase  in
numbers during an infection.

Mycotoxin A fungal toxin.

Non-viable  micro-organism  A  micro-organism  that  is  not  capable  of
replication or of transferring genetic material.

Non-viable  residue  A  residue  that  is  not  capable  of  replication  or  of
transferring genetic material. 

Pathogenicity The ability of a micro-organism to cause disease  and/or inflict
damage  on  the  host.  Many  pathogens  cause  disease  by  a  combination  of  (i)
toxigenicity  and  invasiveness  or  (ii)  toxigenicity  and  colonising  ability.
However, some invasive pathogens cause disease that results from an abnormal
reaction of the host’s defence system.

Symbiosis A type of interaction between organisms where one organism lives
in intimate association with another, which is favourable for both parts. 

Viable micro-organism A micro-organism that is capable of replication or of
transferring genetic material.

Viable  residue  A  residue  that  is  capable  of  replication  or  of  transferring
genetic material. 

Viroid Any 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

9

 
translated;  it  is  replicated  by  host  cell  enzymes.  Viroids  are  known  to  cause
several plant diseases.

Virulence Measurement of the degree of disease producing ability of a micro-
organism as indicated by the severity of the disease produced. Measure of the
dosage (inoculum size) required to cause a specific degree of pathogenicity. It
is  measured  experimentally  by  the  median  lethal  dose  (LD50)  or  median
infective dose (ID50).

B.

EVALUATION

The  objective  of  the  evaluation  is  to  identify  and  assess,  on  a  scientific  basis  and
until further experience is reached on a case by case basis, potential adverse effects
on  human  and  animal  health  and  the  environment  of  the  use  of  a  microbial  plant
protection  product.  The  evaluation  shall  also  be  carried  out  in  order  to  identify  the
need for risk management measures and recommend suitable measures.

Due to the ability of micro-organisms to replicate, there is a clear difference between
chemicals  and  micro-organisms  as  plant  protection  products.  Hazards  are  not
necessarily of the same nature as those presented by chemicals, especially in relation
to the capacity of micro-organisms to persist and multiply in different environments.
Moreover,  the  group  of  micro-organisms  consist  of  a  wide  range  of  different
organisms, all with their own unique characteristics. These differences between the
groups of micro-organism should be taken into account in the evaluation. 

The micro-organism in the plant protection product should ideally function as a cell
factory working directly on the spot where the target organism is harmful. Thus the
mode of action becomes a primary crucial step in the evaluation.

Micro-organisms may produce a range of different metabolites (e.g. bacterial toxins
or mycotoxins) many of which may have toxicological significance, and one or more
of which may be involved in the mode of action of the plant protection product. The
characterisation  and  identification  of  relevant  metabolites  should  be  warranted  and
the  toxicity  of  these  metabolites  should  be  addressed.  Information  on  production
and/or relevance of metabolites may be deduced from:

– 

– 

– 

– 

– 

the toxicity studies,

biological properties of the micro-organism,

the relationship to known plant, animal or human pathogens,

the mode of action,

analytical methods.

From  this  information,  metabolites  may  be  considered  as  possibly  relevant.
Therefore the exposure to these metabolites should be assessed, in order to decide on
their relevance.

1.

General principles

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1.

Having  regard  to  current  scientific  and  technical  knowledge,  Member
States shall evaluate the information in accordance with the requirements
of Annex IIB and IIIB and in particular:

2.

3.

(a)

(b)

identify  the  hazards  arising,  assess  their  significance  and  make  a
judgment  as  to  the  likely  risks  to  humans,  animals  or  the
environment; and

assess  the  performance  in  terms  of  efficacy  and  phytotoxicity/-
pathogenicity of the plant protection product for each use for which
authorisation is sought.

The  quality/methodology  of  tests,  where  there  are  no  standardised  test
methods,  must  be  evaluated  with  the  following  characteristics,  when
available, of the methods described:

relevance;  representativeness;  sensitivity;  specificity;  reproducibility;
interlaboratory validations; predictiveness.

In  interpreting  the  results  of  evaluations,  Member  States  shall  take  into
consideration  possible  elements  of  uncertainty  in  the  information
obtained  during  the  evaluation,  in  order  to  ensure  that  the  chances  of
failing  to  detect  adverse  effects  or  of  under-estimating  their  importance
are  reduced  to  a  minimum.  The  decision-making  process  shall  be
examined  to  identify  critical  decision  points  or  items  of  data  for  which
uncertainties could lead to a false classification of risk.

The  first  evaluation  made  shall  be  based  on  the  best  available  data  or
estimates reflecting the realistic conditions of use of the product.

This must be followed by a repeat evaluation, taking account of potential
uncertainties in the critical data and of a range of use conditions that are
likely  to  occur  and  resulting  in  a  realistic  worst-case  approach,  to
determine  whether  it  is  possible  that  the  initial  evaluation  could  have
been significantly different.

4. Member  States  shall  evaluate  the  resulting  microbial  product  that  is
applied  for  an  approval  in  that  Member  State.  This  means  that  the
information evaluated for the micro-organism can be taken into account.
Member States have to take into account that any added formulants might
have  an  impact  on  the  characteristics  of  the  product  compared  to  the
micro-organism.

5.

6.

In  evaluating  applications  and  granting  authorisations  Member  States
shall consider the proposed practical conditions of use and in particular to
the  purpose  of  use,  the  dose,  the  manner,  frequency  and  timing  of
applications,  and  the  nature  and  composition  of  the  product.  Whenever
possible  Member  States  shall  also  take  into  account  the  principles  of
integrated pest control.

In  the  evaluation  Member  States  shall  consider  the  agricultural,  plant
health  or  environmental  (including  climatic)  conditions  in  the  areas  of
use.

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7. Where specific principles of Section 2 provide for the use of calculation
models  in  the  evaluation  of  a  plant  protection  product,  those  models
shall:

– 

– 

– 

– 

– 

make a best possible estimation of  all relevant  processes involved
taking into account realistic parameters and assumptions,

be submitted to an analysis as referred to in B, point 1.3,

be  reliably  validated  with  measurements  carried  out  under
circumstances relevant for the use of the model,

be relevant to the conditions in the area of use.

be submitted with scientific details as to how the model calculates
an  estimate,  explaining  all  the  inputs  to  the  model  and  how  they
have been derived.

8.

The data requirements, Annex IIB and IIIB, contain guidance as to when
and how certain information must be submitted and procedures that must
be followed when preparing and evaluating a dossier. It must be ensured
that this guidance is respected. 

2.

Specific principles

Member States shall implement the following principles, for the evaluation of
the  data  and  information  submitted  in  support  of  applications,  and  without
prejudice to the general principles of Section 1: 

2.1.

Identity

2.1.1. Identity of the micro-organism in the product

Identity  of  the  micro-organism  should  be  clearly  established.  It
must  be ensured  that theappropriate  data  are  be  provided  to  allow
for checking the identity of the micro-organism at strain level in the
product.

The identity of the micro-organism shall be evaluated on the strain
level. Where the micro-organism is either a mutant or agenetically
modified  organism5,  the  specific  differences  from  other  strains
within  the  same  species  must  be  denoted.  Occurrence  of  resting
stages must be denoted.

The deposition of the strain at an internationally recognised culture
collection must be checked.

2.1.2.Identity of the product

Member  States  shall  evaluate  the  detailed  quantitative  and
qualitative  information  given  on  the  composition  of  the  product,

5

See for definition of ‘genetically modified’ Directive 2001/18/EEC.

12

 
                                                
as 

the  micro-organism 

such 
relevant
metabolites/toxins,  residual  growth  medium,  co-formulants  and
microbial contaminants present.

above), 

(see 

2.2 Biological, physical, chemical, and technical properties

2.2.1.Biological properties of the micro-organism in the product

2.2.1.1 The origin of the strain, the natural habitat including indications
on the normal background level, life cycle and the possibilities for
survival,  colonisation, 
reproduction  and  dispersal  must  be
evaluated. Proliferation of indigenous micro-organisms should after
a  short  growth  period  level  off  and  continue  along  the  line  of  the
background micro-organisms.

2.2.1.2. The  ability  of  micro-organisms  to  adapt  to  the  environment
must be evaluated. In particular, Member States are to take account
of the following principles:

(1) Depending  on  the  conditions  (e.g.  availability  of  substrates
for growth and metabolism) the micro-organisms can switch
on or off the expression of given phenotypic traits. 

(2) The  microbial  strains  most  adapted  to  the  environment  can
survive and multiply better than  the non-adapted. Therefore,
these strains will be in a selective advantage and can form the
majority within a population after a number of generations. 

(3) The  relatively  rapid  multiplication  of  micro-organisms  leads
to  a  higher  frequency  of  mutations.  If  the  mutation  is
beneficial for survival in the environment, this mutant strain
can become dominant. 

(4)

viruses,  in  particular,  can  change  rapidly  in  properties,
including virulence.

Therefore,  where  appropriate,  information  on  the  genetic  stability
of  the  micro-organism  under  the  environmental  conditions  of
proposed  use  must  be  evaluated,  as  well  as  information  on  the
micro-organism’s  capacity  to  transfer  genetic  material  to  other
organisms, and information on the stability of encoded traits.

2.2.1.3. The mode of action of the micro-organism should be evaluated
in  as  much  detail  as  possible.  The  possible 
role  of
metabolites/toxins for the mode of action should be evaluated and
when  identified,  minimal  effective  concentration  for  each  active
metabolite/toxin  should  be  established.  Information  on  mode  of
action  can  be  a  very  valuable  tool  to  identify  potential  risks.
Aspects to be considered in the evaluation, are:

– 

– 

Antibiosis

Induction of plant resistance

13

 
– 

– 

– 

– 

Interference  with  the  virulence  of  a  pathogenic  target
organism

Endophytic growth

Root colonisation

Competition of ecological niche (e.g. nutrients, habitats)

2.2.1.4.

In  order  to  estimate  the  effects  on  non-target  organisms,  the
information  on  the  micro-organism's  host  specificity  must  be
evaluated, taking into account the following.

The  ability  of  a  micro-organism  to  be  pathogenic  for  non-target
organisms (humans, animals, and other non-target organisms) must
be  assessed.  Any  relationship  to  known  plant,  animal  or  human
pathogens  that  are  species  of  the  genus  of  the  active  and/or
contaminating micro-organisms must be assessed. 

Pathogenicity as well as virulence are strongly related to the host-
species  (e.g.  determined  by  body  temperature,  physiological
environment)  and  to  the  host  conditions  (e.g.  health  condition,
immune  status).  For  example,  multiplication  in  humans  needs  the
ability  of  the  micro-organism  to  grow  at  the  body  temperature  of
the  host.  Some  micro-organisms  can  only  grow  and  be
metabolically  active  at  temperatures  (far)  below  or  above  human
body temperature, and therefore can not be pathogenic for humans.
However, it can also be related to the  route of  entry  of the micro-
organism into the host (oral, inhalation, skin/wound). For example,
a microbial species may cause  a  disease  via  skin  damage,  but  not
via the oral route. 

2.2.1.5. Resistance to antimicrobial agents of importance for human and
veterinary  medicine  must  be  assessed.  The  possibility  for  transfer
of genes coding for resistance
to  antimicrobial  agents  must  be
evaluated.

Many  micro-organisms  produce  antibiosis  substances  for  normal
interferences  in  the  microbial  community.  However,  interference
with  the  use  of  antimicrobial  agents  in  human  and  veterinary
medicine must be avoided.

2.2.2. Physical, chemical and technical properties of the product

2.2.2.1. Dependent  on  the  nature  of  the  micro-organism  and  the
formulation  type,  the  technical  properties  of  the  plant  protection
product must be evaluated.

2.2.2.2. Shelf-life  and  storage  stability  of  the  preparation  must  be
evaluated, taking into  account  the  possible  change  in  composition
such  as  growth  of  the  micro-organism  or  contaminating  micro-
organisms, production of metabolites/toxins, etc.

14

 
2.2.2.3. Member  States  shall  evaluate  the  physical  and  chemical
properties of the plant protection product and the retention of these
characteristics after storage and take into consideration:

– 

– 

where  a  suitable FAO6  specification  exists,  the  physical  and
chemical properties addressed in that specification,

where  no  suitable  FAO  specification  exists,  all  the  relevant
physical  and  chemical  properties  for  the  formulation  as
referred  to  in  the  "Manual  on  the  development  and  use  of
FAO specifications for plant protection products".

2.2.2.4. Where  the  proposed  label  claims  include  requirements  or
recommendations  for  use  of  the  preparation  with  other  plant
protection  products  or  adjuvants  as  a  tank  mix  and/or  where  the
proposed  label  includes  indications  on  the  compatibility  of  the
preparation  with  other  plant  protection  products  as  a  tank  mix,
those  products  or  adjuvants  must  be  physically  and  chemically
compatible in the tank  mix.  Biological  compatibility  must  also  be
demonstrated  for  tank-mixtures,  i.e.  it  must  be  shown  that  each
plant  protection  product  in  the  mixture  performs  as  expected  (no
antagonism occurs).

2.3. Further information

2.3.1. Quality  control  of  the  production  of  the  micro-organism  in  the

product

The quality assurance criteria for production of the micro-organism
must  be  evaluated.  In  the  evaluation  aspects  on  process  control,
good  manufacturing  practice,  operational  practices,  process  flows,
cleaning  practices,  microbial  monitoring  and  hygiene  conditions
should be taken into account to ensure a good quality of the micro-
organism. The quality, stability, purity etc., of the micro-organism
must be included in the quality control.

2.3.2. Quality control of the product

The  quality  assurance  criteria  must  be  evaluated.  If  the  product
contains  metabolites/toxins  produced  during  growth  and  residues
from the growth medium this should be evaluated. The occurrence
of contaminating micro-organisms must be evaluated.

2.4. Efficacy

2.4.1. Where  the  proposed  use  concerns  the  control  of  or  protection
against  an  organism,  Member  States  shall  evaluate  the  possibility
that  this  organism  could  be  harmful  under  the  agricultural,  plant
health and environmental (including climatic) conditions in the area
of the proposed use.

6

Food and Agriculture Organization of the United Nations

15

 
                                                
2.4.2. Member  States  shall  evaluate  whether  significant  damage,  loss  or
inconvenience could occur under the agricultural, plant health and
environmental  (including  climatic)  conditions  in  the  area  of
proposed use if the plant protection product were not used.

2.4.3. Member States shall evaluate the efficacy data (required in Annex
II) on the product in regard of the degree of control or the extent of
the  effect  desired  and  in  regard  of  the  relevant  experimental
conditions such as:

– 

– 

– 

– 

– 

– 

– 

– 

– 

the choice of the crop or cultivar,

the  agricultural  and  environmental  (including  climatic)
conditions (if it is necessary for reaching acceptable efficacy
such  data/information  should  also  be  given  for  the  time
before and after application),

the presence and density of the harmful organism,

the development stage of crop and organism,

the amount of the microbial plant protection product used,

if required on the label, the amount of adjuvant added,

the frequency and timing of the applications,

the type of application equipment,

the need for any special cleaning measures for the application
equipment.

2.4.4. Member  States shall  evaluate  the  performance  of  the  product  in  a
range  of  agricultural,  plant  health  and  environmental  (including
climatic) conditions likely to be encountered in practice in the area
of proposed use. The effect on integrated control must be included
in the evaluation. In particular consideration should be made to:

(i)

the  level,  consistency  and  duration  of  the  effect  sought  in
relation  to  the  dose  in  comparison  with  a  suitable  reference
product or products and an untreated control;

(ii) where relevant, effect on yield or reduction of loss in storage,
in  terms  of  quantity  and/or  quality,  in  comparison  with  a
suitable  reference  product  or  products  and  an  untreated
control.

Where  no  suitable  reference  product  exists,  Member  States  shall
evaluate the performance of the product to determine whether there
is  a  consistent  and  defined  benefit  under  the  agricultural,  plant
health and environmental (including climatic) conditions in the area
of proposed use.

16

 
2.4.5. Member  States shall  evaluate  the  degree of adverse effects on  the
treated  crop  after  use  of  the  product  according  to  the  proposed
conditions  of  use  in  comparison,  where  relevant,  with  a  suitable
reference product or products, where they exist, and/or an untreated
control. 

(a)

This  evaluation  will  take  into  consideration  the  following
information:

(i)

the efficacy data;

(ii)

other  relevant  information  on  the  product  such  as  nature  of
the product, dose, method of application, number and timing
of applications, incompatibility with other crop treatments;

(iii) all  relevant  information  on  the  micro-organism,  including
biological  properties  e.g.  mode  of  action,  survival,  host
specificity;

(b) This evaluation will include:

(i)

(ii)

(iii)

(iv)

(v)

the  nature,  frequency,  level  and  duration  of  observed
phytotoxic/phytopathogenic effects and the agricultural, plant
health and environmental (including climatic) conditions that
affect them;

the  differences  between  main  cultivars  with  regard  to  their
sensitivity to phytotoxic/phytopathogenic effects;

the  part  of  the  treated  crop  or  plant  products  where
phytotoxic/phytopathogenic effects are observed;

the  adverse  impact  on  the  yield  of  the  treated  crop  or  plant
products in terms of quantity and/or quality;

the  adverse  impact  on  treated  plants  or  plant  products  to  be
used  for  propagation,  in  terms  of  viability,  germination,
sprouting, rooting and establishment;

(vi) where micro-organisms  are  disseminated  the  adverse  impact

on adjacent crops.

2.4.6. Where the product label includes requirements for use of the plant
protection product with other plant protection products and/or with
adjuvants as a tank mix, Member States shall make the evaluations
above  in  relation  to  the  information  supplied  for  the  tank  mix.
Where  the  product  label  includes  recommendations  for  use  of  the
plant protection product with other plant protection products and/or
with  adjuvants  as  a  tank  mix,  Member  States  shall  evaluate  the
appropriateness of the mix and of its conditions of use.

2.4.7. Where  the  available  data  indicate  that  the  micro-organism  or
significant  relevant  metabolites/toxins,  degradation  and  reaction

17

 
products from the formulants  persist  in  soils and/or  in  or  on  plant
substances in significant quantities after use of the plant protection
product  according  to  the  proposed  conditions  of  use,  Member
States  shall  evaluate  the  degree  of  adverse  effects  on  subsequent
crops.

2.4.8. Where  the  proposed  use  of  the  plant  protection  product  aims  to
have  an  effect  on  vertebrates,  Member  States  shall  evaluate  the
mechanism  by  which  this  effect  is  obtained  and  the  observed
effects on the behaviour and health of the target animals; when the
intended  effect  is  to  kill  the  target  animal  they  shall  evaluate  the
time necessary to obtain the death of the animal and the conditions
under which death occurs.

This  evaluation  will 
information:

take 

into  consideration 

the  following

(i)

(ii)

all relevant information as provided for in Annex IIB and the
results  of  the  evaluation  thereof,  including  the  toxicological
studies;

all  relevant  information  on  the  plant  protection  product  as
provided  for  in  Annex  IIIB,  including  toxicological  studies
and efficacy data.

2.5.

Identification/detection and quantification methods

Member States shall evaluate the analytical  methods  proposed  for  post-
registration control and monitoring purposes of the viable and non-viable
components both in the formulation and as residues in/on treated  crops.
Sufficient validation is required for pre-authorisation methods and post-
authorisation  monitoring  methods.  Methods  that  are  considered  suitable
for post-authorisation monitoring must be clearly identified. 

2.5.1. Analytical methods for the product 

2.5.1.1. Non-viable components 

Member  States  shall  evaluate  the  analytical  methods  proposed  to
identify  and  quantify  the  toxicologically,  ecotoxicologically  or
environmentally  significant  non-viable  components  resulting  from
the  micro-organism  and/or  present  as  impurity  or  co-formulants
(including eventually resulting breakdown and/or reaction products
thereof).

This  evaluation  will  take  into  consideration  the  information  on
analytical methods as provided  for in Annex  IIB  and  IIIB and the
results  of  the  evaluation  thereof.  In  particular,  the  following
information must be taken into account:

– 

– 

the specificity and linearity of the proposed methods,

the precision (repeatability) of the proposed methods,

18

 
– 

– 

the importance of interferences,

the  accuracy  of 
concentrations,

the  proposed  methods  at  appropriate

– 

the limit of quantification of the proposed methods.

2.5.1.2. Viable components 

Member States shall evaluate the methods proposed to quantify and
identify the current strain and especially methods that discriminate
the current strain from closely related strains. 

This  evaluation  will  take  into  consideration  the  information  on
analytical methods as provided  for in Annex  IIB  and  IIIB and the
results  of  the  evaluation  thereof.  In  particular,  the  following
information must be taken into account:

– 

– 

– 

– 

the specificity of the proposed methods,

the precision (repeatability) of the proposed methods,

the importance of interferences,

the quantifiability of the proposed methods. 

2.5.2. Analytical methods for the determination of residues

2.5.2.1. Non-viable residues

Member  States  shall  evaluate  the  analytical  methods  proposed  to
identify  and  quantify  the  toxicologically,  ecotoxicologically  or
environmentally  significant  non-viable  residues  resulting  from  the
micro-organism  and/or  present  as  impurity  or  co-formulants
(including eventually resulting breakdown and/or reaction products
thereof).

This  evaluation  will  take  into  consideration  the  information  on
analytical methods as provided  for in Annex  IIB  and  IIIB and the
results  of  the  evaluation  thereof.  In  particular,  the  following
information must be taken into account:

– 

– 

– 

– 

– 

the specificity and linearity of the proposed methods,

the precision (repeatability) of the proposed methods,

the reproducibility (independent laboratory validation) of the
proposed methods,

the importance of interferences,

the  accuracy  of 
concentrations,

the  proposed  methods  at  appropriate

19

 
– 

the limit of quantification of the proposed methods.

2.5.2.2. Viable residues

Member States shall evaluate the methods proposed to identify the
current strain  and especially  methods that discriminate the current
strain from closely related strains. 

This  evaluation  will  take  into  consideration  the  information  on
analytical methods as provided  for in Annex  IIB  and  IIIB and the
results  of  the  evaluation  thereof.  In  particular,  the  following
information must be taken into account:

– 

– 

– 

– 

the specificity of the proposed methods,

the precision (repeatability) of the proposed methods,

the importance of interferences,

the quantifiability of the proposed methods. 

2.6.

Impact on human or animal health

The impact on human or animal health must be evaluated. In particular,
Member States are to take account of the following principles:

(1) Due to the ability  of micro-organisms to replicate, there is  a clear
difference  between  chemicals  and  micro-organisms  as  plant
protection products. Hazards are not necessarily of the same nature
as  those  presented  by  chemicals,  especially  in  relation  to  the
capacity  of  micro-organisms  to  persist  and  multiply  in  different
environments. 

(2) The  pathogenicity  of  the  micro-organism  to  humans  and  (non-
target) animals, infectiveness of the micro-organism, ability of the
micro-organism  to  colonise,  toxicity  of  metabolites/toxins  as  well
as  toxicity  of  residual  growth  medium,  contaminants  and  co-
formulants, are important endpoints in assessing the adverse effects
arising from the product. 

(3) Colonisation, infectiveness and toxicity comprise a complex set of
interactions between micro-organism and host and these endpoints
may not be resolved easily as independent endpoints. 

(4) Combining  these  endpoints,  the  most  important  aspects  of  the

micro-organism that must be assessed are:

– 

– 

the  ability  to  persist  and  multiply  in  a  host  (indicative  of
colonisation or infectivity)

the  ability  to  produce  (non-adverse  or  adverse)  effects  in  a
host (indicative of infectivity, pathogenicity, and/or toxicity). 

20

 
Moreover, the complexity of the biological issues should be taken
into  account  in  evaluating  the  hazards  and  risks  of  these  products
for  human  and  animals.  An  assessment  of  pathogenicity  and
infectiveness  is  necessary  even  if  the  potential  of  exposure  is
deemed low.

For  risk  assessment  purposes  the  acute  toxicity  studies  must
include  at  least  two  doses  (e.g.  one  very  high  dose  and  one
corresponding to the expected exposure under practical conditions). 

2.6.1. Effects on human or animal health arising from the product 

2.6.1.1. Member  States  shall  evaluate  operator  exposure  to  the  micro-
organism,  and/or  to  toxicologically  relevant  compounds  in  the
product  (e.g.  their  metabolites/toxins,  residual  growth  medium,
contaminants  and  co-formulants),  likely  to  occur  under  the
proposed  conditions  of  use  (including 
in  particular  dose,
application  method  and  climatic  conditions).  Realistic  data  are  to
be used on exposure and, if such data are not available, a suitable,
validated  calculation  model,  when  available  a  European
harmonised  generic  exposure  database  for  plant  protection
products.

(a)

(i)

This  evaluation  will  take  into  consideration  the  following
information:

toxicity, 

infectivity  and
the 
the  medical  data  and 
pathogenicity  studies  as  provided  for  in  Annex  IIB,  and  the
results  of  the  evaluation  thereof.  Tier  1  tests  should  provide
an  evaluation of  a micro-organism with respect to its ability
to  persist  or  grow  in  the  host  and  the  ability  to  cause
effects/reactions  in  the  host.  Parameters  that  indicate  the
absence of the ability to persist and multiply in the host, and
the  ability  to  produce  (non-adverse  or  adverse)  effects  in  a
host,  are  a  fast  and  complete  clearance  from  the  body,  no
activation  of  the  immune  system,  no  histopathological
changes,  and  replication  far  below  or  far  above  mammalian
body  temperatures.  These  parameters  can  in  some  cases  be
deduced  from  acute  studies  and  existing  human  data,  and
sometimes only from repeated dose studies. 

The evaluation based on the relevant parameters of the Tier 1
tests  should  lead  to  an  assessment  of  the  possible  effects  at
occupational  exposure,  taking  into  account  the  intensity  and
duration  including  exposure  due  to  repeated  use  during
practical use.

The  toxicity  of  certain  metabolites/toxins  can  only  be
assessed,  if  it  has  been  warranted  that  the  test  animals  are
actually exposed to these metabolites/toxins. 

21

 
(ii)

other  relevant  information  on  the  micro-organism,  the
metabolites/toxins,  residual  growth  medium,  contaminants
and co-formulants in the product, such as biological, physical
and chemical properties (e.g. survival of the micro-organism
at  the  body  temperature  of  humans  and  animals;  ecological
and/or
niche; 
metabolites/toxins during application)

the  micro-organism 

behaviour 

of 

(iii)

the toxicological studies provided for in Annex IIIB,

(iv) other relevant information as provided for in Annex IIIB such

as:

composition of the preparation,

nature of the preparation,

size, design and type of packaging,

field of use and nature of crop or target,

method  of  application  including  handling,  loading  and
mixing of product,

exposure reduction measures recommended,

protective clothing recommendations,

maximum application rate,

minimum spray application volume stated on the label,

number and timing of applications

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

(b) Considering the information mentioned above (2.6.1.1. point
a) the following overall end-points need to be evaluated with
respect to single or repeated operator exposure at the intended
use: 

– 

– 

– 

persistence or growth of the micro-organism in the host

(adverse) effects observed

observed  or  expected  effects  of  contaminants  (including
contaminating micro-organisms)

– 

observed or expected effects of relevant metabolites/toxins

If  there  are  indications  for  colonisation  in  the  host  and/or  if
any  adverse  effects,  indicative  of  toxicity/infectivity  are
observed,  taking  into  account  the  exposure  scenario  (i.e.
acute or repeated exposure), further testing is indicated.

22

 
(c)

This  evaluation  shall  be  made  for  each  type  of  application
method  and  application  equipment  proposed  for  use  of  the
product  as  well  as  for  the  different  types  and  sizes  of
containers  to  be  used,  taking  into  account  mixing,  loading
operations,  application  of  the  product  and  cleaning  and
routine  maintenance  of  application  equipment.  Where
relevant,  other  authorized  uses  of  the  product  in  the  area  of
envisaged use containing the same active substance or which
give rise to the same residues may also be taken into account.
It  should  be  taken  into  account  that  if  replication  of  the
micro-organism  is  expected,  exposure  assessment  could  be
highly speculative. 

(d) The  absence  or  presence  of  the  potential  for  colonisation  or
effects in operators at the tested dose levels as provided for in
Annex  IIB  and  IIIB  should  be  discussed  with  regard  to  the
measured or estimated human exposure. This risk assessment,
preferably quantitative, should be made also considering e.g.
the  mode  of  action,  biological,  physical  and  chemical
properties of the micro-organism and other substances in the
formulation. 

2.6.1.2. Member States shall examine information relating to the nature
and  characteristics  of  the  packaging  proposed  with  particular
reference to the following aspects:

– 

– 

– 

– 

– 

the type of packaging,

its dimensions and capacity,

the size of the opening,

the type of closure,

its strength, leakproofness and resistance to normal transport
and handling,

– 

its resistance to and compatibility with the contents.

2.6.1.3. Member  States  shall  examine  the  nature  and  characteristics  of
the  protective  clothing  and  equipment  proposed  with  particular
reference to the following aspects:

– 

– 

– 

obtainability and suitability,

effectiveness,

ease  of  wearing  taking  into  account  physical  stress  and
climatic conditions,

– 

its resistance to and compatibility with the product

23

 
2.6.1.4. Member  States  shall  evaluate  the  possibility  of  exposure  of
other humans (workers exposed after the application of the product
(re-entry)  or  bystanders)  or  animals  to  the  micro-organism  and/or
to  other  toxicologically  relevant  compounds  in  the  product  under
the  proposed  conditions  of  use.  This  evaluation  will  take  into
consideration the following information:

(i)

(ii)

toxicity, 

the  medical  data  and 
infectivity  and
the 
pathogenicity  studies  as  provided  for  in  Annex  IIB,  and  the
results  of  the  evaluation  thereof.  Tier  1  tests  should  provide
an  evaluation of  a micro-organism with respect to its ability
to  persist  or  grow  in  the  host  and  the  ability  to  cause
effects/reactions  in  the  host.  Parameters  that  indicate  the
absence of the ability to persist and multiply in the host, and
the  ability  to  produce  (non-adverse  or  adverse)  effects  in  a
host,  are  a  fast  and  complete  clearance  from  the  body,  no
activation  of  the  immune  system,  no  histopathological
changes,  and  replication  far  below  or  far  above  mammalian
body  temperatures.  These  parameters  can  in  some  cases  be
deduced  from  acute  studies  and  existing  human  data,  and
sometimes only from repeated dose studies. 

The evaluation based on the relevant parameters of the Tier 1
tests  should  lead  to  an  assessment  of  the  possible  effects  at
occupational  exposure,  taking  into  account  the  intensity  and
duration  including  exposure  due  to  repeated  use  during
practical use.

The  toxicity  of  certain  metabolites/toxins  can  only  be
assessed,  if  it  has  been  warranted  that  the  test  animals  are
actually exposed to these metabolites/toxins. 

The  toxicity  of  certain  metabolites/toxins  can  only  be
assessed,  if  it  has  been  warranted  that  the  test  animals  are
actually exposed to these metabolites/toxins. 

other  relevant  information  on  the  micro-organism,  the
metabolites/toxins,  residual  growth  medium,  contaminants
and co-formulants in the product, such as biological, physical
and chemical properties (e.g. survival of the micro-organism
at  the  body  temperature  of  humans  and  animals;  ecological
niche; 
and/or
metabolites/toxins during application)

the  micro-organism 

behaviour 

of 

(iii)

the toxicological studies provided for in Annex IIIB; 

(iv) other relevant information on  the  product  as  provided  for  in

Annex IIIB such as:

– 

re-entry  periods,  necessary  waiting  periods  or  other
precautions to protect humans and animals,

– 

method of application, in particular spraying,

24

 
– 

– 

– 

– 

maximum application rate,

maximum spray application volume,

composition of the preparation,

into  account 

excess remaining on plants and plant products after treatment,
taking 
influence  of  factors  such  as
temperature,  UV  light,  pH  and  the  presence  of  certain
substances,

the 

– 

further activities whereby workers are exposed.

2.6.2. Effects on human or animal health arising from residues

In the evaluation, non-viable and viable residues must be addressed
separately.  Viruses  and  viroids  should  be  considered  as  viable
residues  since  they  are  capable  of  transferring  genetic  material
(although strictly speaking they are not living). 

2.6.2.1. Non-viable residues

(a) Member  States  shall  evalate  the  possibility  of  exposure  of
humans  or  animals  to  the  non-viable  residues  and  their
degradation  products  via  the  food  chain  due  to  the  possible
occurrence  in/on  edible  parts  of  treated  crops.  In  particular,
the following information should be taken into account: 

– 

– 

– 

– 

– 

the stage of development of the micro-organism at which the
non-viable residues are produced,

the  development  stages/life  cycle  of  the  micro-organism
under  the  typical  environmental  conditions;  in  particular,
attention  shall  be  paid  to  estimate  the  likelihood  of  survival
and multiplication of the micro-organism in or on crops, food
or feed,  and,  as  a  consequence,  the  likelihood  of  production
of non-viable residues,

the  stability  of  relevant  non-viable  residues  (including  the
effects of factors  such  as temperature,  UV  light,  pH  and  the
presence of certain substances),

any experimental study showing whether or not relevant non-
viable residues are translocated in plants,

data  on  the  proposed  good  agricultural  practice  (including
number and timing of applications, maximum application rate
and  minimum  spray  application  volume).  Furthermore,
proposed  pre-harvest 
intervals  for  envisaged  uses,  or
withholding  periods  or  storage  periods,  in  the  case  of  post-
harvest  uses  and  additional  data  on  application  as  provided
for in Annex IIIB,

25

 
– 

where  relevant,  other  authorised  uses  of  plant  protection
products in the area of envisaged use, i.e. containing the same
residues.

(b) Member  States  shall  evaluate  the  toxicity  of  the  non-viable
residues and their degradation products with special attention
to  the  specific  information  as  provided  in  Annex  IIB  and
IIIB.

(c) Where  non-viable  residues  or  their  degradation  products  are
considered 
toxicologically  relevant  for  humans  and/or
animals and when exposure is not considered negligible,  the
actual levels in/on the edible parts of treated crops should be
determined by taking into consideration:

– 

– 

– 

analytical methods for the non-viable residues,

the  growth  curves  of  the  micro-organism  under  optimal
conditions,

the  production/formation  of  non-viable  residues  at  relevant
moments (e.g. at the anticipated harvest time).

2.6.2.2. Viable residues

(a) Member  States  shall  evaluate  the  possibility  of  exposure  of
humans or  animals  to  the  viable  residues  via  the  food  chain
due to the possible occurrence in/on (edible parts of) treated
crops.  In  particular,  the  following  information  should  be
taken into account:

– 

– 

– 

– 

– 

the  likelihood  of  survival,  persistence  and  multiplication  of
the micro-organism in or on crops, food or feed. The various
development stages/life cycles of the micro-organism should
be addressed,

information concerning the ecological niche,

information on fate and distribution in the various parts of the
environment,

natural  occurrence  of  the  micro-organism  (and/or  a  related
micro-organism),

data  on  the  proposed  good  agricultural  practice  (including
number and timing of applications, maximum application rate
and  minimum  spray  application  volume).  Furthermore,
proposed  pre-harvest 
intervals  for  envisaged  uses,  or
withholding  periods  or  storage  periods,  in  the  case  of  post-
harvest  uses  and  additional  data  on  application  as  provided
for in Annex IIIB,

26

 
– 

where  relevant,  other  authorised  uses  of  plant  protection
products in the area of envisaged use, i.e. containing the same
micro-organism or which results in the same residues.

(b) Member States shall evaluate the specific information on the
ability of viable residues to persist or grow in the host and the
ability to cause effects/reactions in the host. In particular, the
following information should be taken into account:

– 

– 

– 

– 

(c)

– 

– 

– 

infectivity  and
the 
the  medical  data  and 
pathogenicity  studies  as  provided  for  in  Annex  IIB,  and  the
results of the evaluation thereof,

toxicity, 

development  stages/life  cycle  of  the  micro-organism  under
the  typical  environmental  conditions  (e.g.  in/on  the  treated
crop),

mode of action of the micro-organism,

biological  properties  of 
the  micro-organism  (e.g.  host
specificity). The various development stages/life cycles of the
micro-organism should be addressed.

In the case that viable residues are considered toxicologically
relevant for humans and/or animals and when exposure is not
considered negligible, the actual levels in/on the edible parts
of  treated  crops  should  be  determined  by  taking  into
consideration:

analytical methods for the viable residues,

the  growth  curves  of  the  micro-organism  under  optimal
conditions,

the  possibilities  of  extrapolating  data  from  one  crop  to
another.

2.7. Fate and behaviour in the environment

The  biocomplexity  of  the  ecosystems  and  interactions  in  the  microbial
communities must be taken into account. 

Information  on  the  origin  and  properties  (e.g.  specificity)  of  the  micro-
organism/its  residual  metabolites/toxins  and  its  intended  use  forms  the
basis for an assessment of environmental fate and behaviour. The mode
of action should be taken into consideration.

An  assessment  shall  be  made  of  the  fate  and  behaviour  of  any  known
relevant  metabolite  that  is  produced  by  the  micro-organism.  The
assessment  shall  be  made  for  each  environmental  compartment,  and  is
triggered by the criteria in section 7 (iv) of AnnexIIB to this Directive.

27

 
In  the  evaluation  of  the  fate  and  distribution  of  the  plant  protection
product  in  the  environment,  Member  States  shall  have  regard  to  all
aspects of the environment, including biota. The potential for persistence
and  multiplication  of  the  micro-organism  has  to  be  assessed  in  all
environmental  compartments  unless  it  can  be  justified  that  the  micro-
organism  will  not  reach  a  specific  compartment.  The  mobility  of  the
micro-organism and its residual metabolites/toxins has to be considered.

2.7.1. Member  States  shall  evaluate  the  possibility  of  exposure  of
organisms  in  the  aquatic  compartment,  both  groundwater  and
surface water, of the product under the proposed conditions of use;
if this possibility exists they shall evaluate the risk for the aquatic
compartment.  The  micro-organism  may  give  rise  to  risks  from  its
potential  ability 
the  environment  by
multiplication  and  can  therefore  have  a  long-lasting  or  permanent
impact on the microbial community or their predators. 

to  establish 

itself 

in 

This  evaluation  will 
information:

take 

into  consideration 

the  following

– 

– 

– 

– 

– 

– 

biological properties

survival of the micro-organism in the environment 

ecological niche 

background  level  of  exposure  of  an  indigenous  micro-
organism

information on fate and distribution in the various parts of the
environment 

where  relevant,  other  authorised  uses  of  plant  protection
products  in  the  area  of  envisaged  use,  e.g.  containing  the
same  active  substance  or  which  gives  rise  to  the  same
residues.

2.7.2. Member  States  shall  evaluate  the  possibility  of  exposure  of
organisms  in  the  atmosphere  of  the  product  under  the  proposed
conditions  of  use;  if  this  possibility  exists  they  shall  evaluate  the
risk for the atmosphere. The transport, short-range and long-range,
of  the  micro-organism  in  the  atmosphere  should  be  taken  into
account.

2.7.3. Member  States  shall  evaluate  the  possibility  of  exposure  of
organisms  in  the  terrestrial  compartment  of  the  product  under  the
proposed  conditions  of  use;  if  this  possibility  exists  they  shall
evaluate  the  risk  for  the  terrestrial  compartment.  The  micro-
organism  may  give  rise  to  risks  from  its  potential  ability  to
establish  itself  in  the  environment  by  multiplication  and  can
therefore have a long-lasting or permanent impact on the microbial
community or their predators.

28

 
This  evaluation  will 
information:

take 

into  consideration 

the  following

– 

– 

– 

– 

– 

– 

biological properties

survival of the micro-organism in the environment

ecological niche

background  level  of  exposure  of  an  indigenous  micro-
organism

information on fate and distribution in the various parts of the
environment

where  relevant,  other  authorised  uses  of  plant  protection
products  in  the  area  of  envisaged  use,  e.g.  containing  the
same  active  substance  or  which  gives  rise  to  the  same
residues.

2.8. Effects on and exposure of non-target organisms

Information  on  the  ecology  of  the  micro-organism  and  effects  on  the
environment should be assessed as well as possible exposure levels  and
effects of its relevant metabolites/toxins. A concluding assessment of the
environmental  risks  the  product  may  cause,  is  necessary  taking  into
account the normal exposure to micro-organisms both in the environment
as well as in the body of organisms.

Member  States  shall  evaluate  the  possibility  of  exposure  of  non-target
organisms  under  the  proposed  conditions  of  use  and  if  this  possibility
exists they shall evaluate the risk for these organisms.

To  assess  the  possibility  of  exposure  the  following  information  should
also be taken into consideration:

– 

– 

– 

– 

– 

survival of the micro-organism in the respective compartment

ecological niche

background level of exposure of an indigenous micro-organism

information  on  fate  and  distribution  in  the  various  parts  of  the
environment

where  relevant,  other  authorized  uses  of  product  in  the  area  of
envisaged use  containing the same active substance or which  give
rise to the same residues.

2.8.1. Member  States  shall  evaluate  the  possibility  of  exposure  of  and
effects  on  terrestrial  wildlife  (non-domestic  birds,  mammals  and
other terrestrial vertebrates).

29

 
2.8.1.1. The  micro-organism  may  give  rise  to  risks  from  its  potential
ability to infect and multiply in avian and mammalian host systems.
Whether  the  identified  risks  could  be  changed  due  to  the
formulation  of  the  product  shall  be  assessed,  taking  into  account
the following information on the micro-organism:

– 

– 

– 

– 

mode of action

other biological properties

studies on mammalian toxicity, pathogenicity and infectivity 

studies on avian toxicity, pathogenicity and infectivity.

An assessment of infectivity and pathogenicity is necessary even if
the potential of exposure is deemed low.

2.8.1.2. The product may give  rise to toxic effects due to toxins or co-
formulants.  For  such  an  assessment  the  following  information
should be taken into consideration:

– 

– 

– 

studies on mammalian toxicity

studies on avian toxicity 

information on fate and distribution in the various parts of the
environment

If  mortality  or  signs  of  intoxication  are  observed  in  the  tests  then
this evaluation will include a calculation of toxicity/exposure ratios
based on the quotient of LD50 and the estimated exposure expressed
in mg/kg body weight.

2.8.2. Member  States  shall  evaluate  the  possibility  of  exposure  of  and

effects on aquatic organisms.

2.8.2.1. The  micro-organism  may  give  rise  to  risks  from  its  potential
ability  to  infect  and  multiply  in  aquatic  organisms.  Whether  the
identified  risks  could  be  changed  due  to  the  formulation  of  the
product  shall  be  assessed,  taking  into  account  the  following
information on the micro-organism:

– 

– 

– 

mode of action

other biological properties

studies on toxicity, pathogenicity and infectivity

An assessment of infectivity and pathogenicity is necessary even if
the potential of exposure is deemed low.

2.8.2.2. The product may give  rise to toxic effects due to toxins or co-
formulants.  For  such  an  assessment  the  following  information
should be taken into consideration:

30

 
– 

– 

studies on toxicity to aquatic organisms

information on fate and distribution in the various parts of the
environment.

If  mortality  or  signs  of  intoxication  are  observed  in  the  tests  then
this evaluation will include a calculation of toxicity/exposure ratios
based  on  the  quotient  of  EC50/NOEC  and  the  estimated  exposure
expressed in ml/litre.

2.8.3. Member  States  shall  evaluate  the  possibility  of  exposure  of  and

effects on bees.

2.8.3.1. The  micro-organism  may  give  rise  to  risks  from  its  potential
ability  to infect and multiply in  bees.  Whether  the  identified  risks
could  be  changed  due  to  the  formulation  of  the  product  shall  be
assessed,  taking  into  account  the  following  information  on  the
micro-organism:

– 

– 

– 

mode of action

other biological properties

studies on toxicity, pathogenicity and infectivity

An assessment of infectivity and pathogenicity is necessary even if
the potential of exposure is deemed low.

2.8.3.2. The product may give  rise to toxic effects due to toxins or co-
formulants.  For  such  an  assessment  the  following  information
should be taken into consideration:

– 

– 

studies on toxicity to bees 

information on fate and distribution in the various parts of the
environment.

If  mortality  or  signs  of  intoxication  are  observed  in  the  tests  then
this  evaluation  will  include  a  calculation  of  the  hazard  quotient,
based on the quotient of the dose in g/ha and the LD50 in (cid:1)g/bee.

2.8.4. Member  States  shall  evaluate  the  possibility  of  exposure  of  and

effects on other arthropods than bees.

2.8.4.1.

If the micro-organism is indigenous to the environment only the
highest intended application rate of the microbial product has to be
taken  into  account.  To  assess  the  possibility  of  exposure  the
following information should be taken into consideration:

– 

survival of the micro-organism in the respective compartment
valid for non-target arthropods (atmosphere and/or terrestrial
compartment)

– 

ecological niche

31

 
– 

– 

– 

background  level  of  exposure  of  an  indigenous  micro-
organism

information on fate and distribution in the various parts of the
environment

where relevant, other authorized uses of products in the area
of envisaged use, e.g. containing the same active substance or
which give rise to the same residues.

2.8.4.2. The  micro-organism  may  give  rise  to  risks  from  its  potential
ability  to  infect  and  multiply  in  other  arthropods  than  bees.
Whether  the  identified  risks  could  be  changed  due  to  the
formulation  of  the  product  shall  be  assessed,  taking  into  account
the following information on the micro-organism:

– 

– 

– 

mode of action

other biological properties

studies  on 
honeybees and other arthropods 

toxicity,  pathogenicity  and 

infectivity 

to

An assessment of infectivity and pathogenicity is necessary even if
the potential of exposure is deemed low.

2.8.4.3. The product may give  rise to toxic effects due to toxins or co-
formulants.  For  such  an  assessment  the  following  information
should be taken into consideration:

– 

– 

studies on toxicity to arthropods

information on fate and distribution in the various parts of the
environment

– 

available data from biological primary screening

If  mortality  or  signs  of  intoxication  are  observed  in  the  tests  then
this evaluation will include a calculation of toxicity/exposure ratios
based  on  the  quotient  of  ER50  (effective  rate)  and  the  estimated
exposure expressed in mg/ha.

2.8.5. Member  States  shall  evaluate  the  possibility  of  exposure  of  and

effects on earthworms.

2.8.5.1.

If the micro-organism is indigenous to the environment only the
highest  intended  application  rate  of  the  microbial  plant  protection
product  has  to  be  taken  into  account.  To  assess  the  possibility  of
exposure 
into
consideration:

information  should  be 

the  following 

taken 

– 

– 

survival of the micro-organism in the terrestrial compartment

ecological niche

32

 
– 

– 

– 

background  level  of  exposure  of  an  indigenous  micro-
organism

information on fate and distribution in the various parts of the
environment

where  relevant,  other  authorized  uses  of  preparations  in  the
area  of  envisaged  use,  e.g.  containing  the  same  active
substance or which give rise to the same residues.

2.8.5.2. The  micro-organism  may  give  rise  to  risks  from  its  potential
ability to infect and multiply in earthworms. Whether the identified
risks could be changed due to the formulation of the product shall
be  assessed,  taking  into  account  the  following  information  on  the
micro-organism:

– 

– 

– 

mode of action

other biological properties

studies on earthworm toxicity, pathogenicity and infectivity

An assessment of infectivity and pathogenicity is necessary even if
the potential of exposure is deemed low.

2.8.5.3. The product may give  rise to toxic effects due to toxins or co-
formulants.  For  such  an  assessment  the  following  information
should be taken into consideration:

– 

– 

studies on earthworm toxicity

information on fate and distribution in the various parts of the
environment

If  mortality  or  signs  of  intoxication  are  observed  in  the  tests  then
this evaluation will include a calculation of toxicity/exposure ratios
based on the quotient of LC50 and the estimated exposure expressed
in mg/kg dry weight soil.

2.8.6. Member  States  shall  evaluate  the  possibility  of  exposure  of  and

effects on soil micro-organisms.

2.8.6.1.

If the micro-organism is indigenous to the environment only the
highest  intended  application  rate  of  the  microbial  plant  protection
product  has  to  be  taken  into  account.  To  assess  the  possibility  of
exposure 
into
consideration:

information  should  be 

the  following 

taken 

– 

– 

– 

survival of the micro-organism in the terrestrial compartment

ecological niche

background  level  of  exposure  of  an  indigenous  micro-
organism

33

 
– 

– 

information on fate and distribution in the various parts of the
environment

where  relevant,  other  authorized  uses  of  preparations  in  the
area  of  envisaged  use,  e.g.  containing  the  same  active
substance or which give rise to the same residues.

2.8.6.2. The  micro-organism  may  give  rise  to  risks  from  its  potential
ability  to  interfere  with  the  biogeochemical  nutrient  cycles  in  the
environment. Whether the identified risks could be changed due to
the  formulation  of  the  product  shall  be  assessed,  taking  into
account the following information on the micro-organism:

– 

– 

mode of action

other biological properties

2.8.6.3. Member  States  shall  evaluate  the  impact  of  exotic/non-
indigenous micro-organisms on non-target micro-organisms and on
their  predators  after  use  of  the  product  according  to  the  proposed
conditions of use. Experimental data are not normally required, i.e.
where  it  can  be  justified  that  a  proper  risk  assessment  can  be
performed with the available information.

2.8.6.4. The product may give  rise to toxic effects due to toxins or co-
formulants.  For  such  an  assessment  the  following  information
should be taken into consideration:

– 

information on fate and distribution in the various parts of the
environment

– 

all available information from biological primary screening.

2.8.7. Member  States  shall  evaluate  the  possibility  of  exposure  of  and

effects on other species.

2.8.7.1. To assess the possibility of exposure the following information

should be taken into consideration:

– 

– 

– 

– 

survival of the micro-organism in the respective compartment
valid for other species (atmosphere, aquatic and/or terrestrial
compartment)

ecological niche

background  level  of  exposure  of  an  indigenous  micro-
organism

where relevant, other authorized uses of product in the area of
envisaged use containing the same active substance or which
give rise to the same residues.

34

 
2.8.7.2. The  micro-organism  may  give  rise  to  risks  from  its  potential
ability  to  infect  and  multiply  in  other  species.  Whether  the
identified  risks  could  be  changed  due  to  the  formulation  of  the
product  shall  be  assessed,  taking  into  account  the  following
information on the micro-organism:

– 

– 

mode of action

studies on mammalian toxicity, pathogenicity and infectivity

An assessment of infectivity and pathogenicity is necessary even if
the potential of exposure is deemed low.

2.8.7.3. The product may give  rise to toxic effects due to toxins or co-
formulants.  For  such  an  assessment  the  following  information
should be taken into consideration:

– 

– 

studies on toxicity to other species

information on fate and distribution in the various parts of the
environment.

If  mortality  or  signs  of  intoxication  are  observed  in  the  tests  then
this evaluation will include a comparison of exposure and effect.

2.8.8. Member States shall evaluate the environmental impact.

2.8.8.1.

If there is a possibility for exposure of organisms to the product
under the proposed conditions of use and if the micro-organism has
a potential to infect and multiply in organisms and the product may
give  rise  to  toxic  effects  due  to  toxins  or  co-formulants  Member
States  shall  evaluate  the  risk  for  the  specific  environmental
compartment.

2.8.8.2.

If the product interferes with the biogeochemical nutrient cycles
in the environment this should be assessed when assessing the risk
for the specific environmental compartment.

The following aspects should be considered:

– 

– 

– 

impact of the micro-organism (if non-indigenous) on the total
microbial population dynamics and activity

interferences with biogeochemical nutrient cycles

impact  of  the  micro-organism  on  predators  of  non-target
micro-organisms

The  impact  on  the  number  and  activity  of  target  micro-organisms
for  which  control is claimed shall be excluded. Experimental data
are not normally required, i.e. where it can be justified that a proper
risk assessment can be performed with the available information.

In the atmosphere possible climatic effects have to be considered.

35

 
Interference  with  nutrient  uptake  in  mycorrhiza  has  to  be
considered.

2.9. Conclusions and proposals

Member  States  shall  make  conclusions  on  the  need  for  further
information and/or testing and the need for limiting the risks.

Member  States  shall  justify  the  proposals  for  the  classification  and
labelling of the micro-organism and the product.

C.

DECISION-MAKING

1.

General principles

1. Where appropriate, Member States shall impose conditions or restrictions
with  the  authorisations  they  grant.  The  nature  and  severity  of  these
measures  must  be  selected  on  the  basis  of,  and  be  appropriate  to,  the
nature and extent of the expected advantages and the risks likely to arise.

2. Member States shall ensure that decisions on authorisations, take account
of  the  agricultural,  plant  health  or  environmental  (including  climatic)
conditions in the areas of envisaged use. Such considerations may result
in specific conditions and restrictions of use, and, in authorisation being
granted for some but not other areas within the Member State in question.

3. Member States shall ensure that the authorised amounts, in terms of rates
and  number  of  applications,  are  the  minimum  necessary  to  achieve  the
desired  effect  even  where  higher  amounts  would  not  result 
in
unacceptable risks to human or animal health or to the environment. The
authorized  amounts  must  be  differentiated  according  to,  and  be
appropriate to, the agricultural, plant health or environmental (including
climatic)  conditions  in  the  various  areas  for  which  an  authorisation  is
granted. However, the rates and the number of applications may not give
rise to undesirable effects such as the development of resistance.

4. Member  States  shall  ensure  that  decisions  respect  the  principles  of
integrated  pest  control  if  the  product  is  intended  for  use  in  conditions
where these principles are relied on.

5.

6.

Since the evaluation is to be based on data concerning a limited number
of  representative  species,  Member  States  shall  ensure  that  use  of  plant
protection  products  does  not  have  any  long-term  repercussions  for  the
abundance and diversity of non-target species.

Before issuing an authorisation, Member States shall ensure that the label
of the product:

– 

– 

fulfils the requirements of Article 16 of this Directive,

also  contains  the  information  on  protection  of  users  required  by
Community legislation on worker protection,

36

 
– 

– 

specifies in particular the conditions or restrictions under which the
plant protection product may  or may not be used as  referred to in
points 1, 2, 3, 4 and 5 above.

The authorisation shall mention the particulars indicated in Article
16 (1) (g) and (h) of this Directive.

7.

Before issuing authorisations, Member States shall:

(a)

ensure  that  the  proposed  packaging  is  in  accordance  with  the
provisions of Directive 1999/45/EC;

(b)

ensure that:

– 

– 

– 

the procedures for destruction of the plant protection product,

the procedures for neutralization of any adverse effects of the
product if it is accidentally dispersed, and

the procedures for the decontamination and destruction of the
packaging, 

– 

are in accordance with the relevant regulatory provisions.

8.

No authorisation shall be  granted unless all the requirements referred to
in section  2  ‘Specific  principles’  of  this  chapter  are  satisfied.  However,
when one or more of the specific decision-making requirements referred
to in Part C, points 2.3 or 2.4 are not fully satisfied, authorisations shall
be  granted only where the advantages of the use of  the plant  protection
product  under  the  proposed  conditions  of  use  outweigh  the  possible
adverse effects of its use. Any restrictions on use of the product relating
to  non-compliance  with  some  of  the  aforementioned  requirements  must
be mentioned on the label. These advantages can be in terms of:

– 

– 

– 

– 

advantages  for and  compatibility with  integrated  control  measures
or organic farming,

facilitating  strategies  to  minimize  the  risk  of  development  of
resistance,

reduced risk for operators and consumers

reduced  contamination  of  the  environment  and  reduced  impact  on
non-target species;

9. Where  an  authorisation  has  been  granted  according  to  the  requirements
provided  for  in  this  Annex,  Member  States  may,  by  virtue  of  Article  4
(6):

(a)

define,  where  possible,  preferably  in  close  co-operation  with  the
applicant,  measures  to  improve  the  performance  of  the  plant
protection product, and/or

37

 
(b)

define,  where  possible,  in  close  co-operation  with  the  applicant,
measures  to  reduce  further  the  exposure  that  could  occur  during
and after use of the plant protection product.

Member States shall inform applicants of any measures identified under
(a)  or  (b)  and  shall  invite  applicants  to  provide  any  supplementary  data
and information necessary to demonstrate performance or potential risks
arising under the changed conditions.

10. Member  states  shall  ensure,  as  far  as  is  practically  possible,  that  for  all
micro-organisms  that  are  considered  for  an  authorisation,  the  applicant
has taken into account all available relevant knowledge and information
in literature at the time of submission.

11. Where the micro-organism has been  genetically modified,  as  defined  in
Directive  2001/18/EC,  no  authorisation  shall  be  given  unless  the
evaluation according to the Directive 2001/18/EC has been submitted, as
stated  in  Article  1  (3)  of  this  Directive.  The  relevant  decision  taken  by
the competent authorities of Directive 2001/18/EC has to be provided. 

12.

In  accordance  with  Article  1(3),  no  authorisation  shall  be  granted  for  a
genetically  modified organism  unless authorisation  is  granted  according
to  the  provisions  in  Directive  2001/18/EC  part  C,  under  which  that
organism can be released into the environment. 

13. No  authorisation  shall  be  granted  if  relevant  metabolites/toxins  (i.e.  if
expected  to  be  of  concern  to  human  health  and/or  the  environment)
known  to  be  formed  by  the  micro-organism,  and/or  by  microbial
contaminants are present in the product, unless it can be shown that the
amount is at an acceptable level before and after its proposed use.

14. Member  States  shall  ensure  that  adequate  quality  control  measures  are
applied to ensure the identity of the micro-organism and contents of the
product. Such quality control measures must be taken along the lines of
existing  systems,  such  as  Hazard  Analysis  Critical  Control  Point
(HACCP).

2.

Specific principles

The  specific principles shall apply  without prejudice  to the  general  principles
referred to in Section 1.

2.1.

Identity

For  an  authorisation  the  Member  State  shall  ensure  that  the  micro-
organism is deposited at an internationally recognised  culture  collection
and has an accession number. The micro-organism must be identified and
named  at  the  species  level  and  characterised  at  the  strain  level.  There
must also be information on whether the micro-organism is a wild type or
a spontaneous or induced mutant, or a genetically modified organism.

2.2. Biological and technical properties 

38

 
2.2.1. There  must  be  sufficient  information  on  the  minimum  and
maximum  content  of  the  micro-organism  in  the  material  used  for
the  manufacturing  of  products,  as  well  as  in  the  product.  The
content  of  other  components  and  formulants  in  the  product  and
contaminating  micro-organisms  derived  from 
the  production
process  must  be  sufficiently  defined.  Member  States  shall  ensure
that  the  level  of  contaminating  organisms  is  controlled  to  an
acceptable  level.  The  contents  should  be  expressed  in  terms  as
provided for in Article 6(2) of Directive 1999/45/EC for chemicals
and  in  appropriate  terms  for  micro-organisms  (number  of  active
units per volume or weight or any other manner that is relevant to
the  micro-organism).  In  addition:  the  physical  nature  and  state  of
the  product  must  be  provided,  preferably  according  to  the
"Catalogue of pesticide formulation types and international coding
system (GIFAP Technical Monograph n° 2. 1989)".

2.2.2. No authorisation shall be granted if there may be interference with
the use of antimicrobial agents in human or veterinary medicine at
any  stage  of  the  development  of  the  microbial  plant  protection
product.

2.3. Further information

2.3.1. There  must  be  no  relevant  phytotoxic  effects  on  treated  plants  or
indicates

the  proposed 

label 

plant  products  except  where 
appropriate limitations of use.

2.3.2. There  must  be  no  reduction  of  yield  at  harvest  due  to  phytotoxic
effects below that which could  be obtained without the use  of the
plant  protection  product,  unless  this  reduction  is  compensated  for
by  other  advantages  such  as  an  enhancement  of  the  quality  of  the
treated plants or plant products.

2.3.3. There  must  be  no  unacceptable  adverse  effects  on  the  quality  of
treated  plants  or  plant  products,  except  in  the  case  of  adverse
effects on processing where proposed label claims specify that the
preparation should not be applied to crops to be used for processing
purposes.

2.3.4. There must be no unacceptable adverse effects on treated plants or
plant products used for propagation or reproduction, such as effects
on  viability,  germination,  sprouting,  rooting  and  establishment,
except  where  proposed  label  claims  specify  that  the  preparation
should  not  be  applied  to  plants  or  plant  products  to  be  used  for
propagation or reproduction.

2.3.5. There must be no unacceptable impact on succeeding crops, except
where  proposed  label  claims  specify  that  particular  crops,  which
would be affected, should not be grown following the treated crop.

2.3.6. There  must  be  no  unacceptable  impact  on  adjacent  crops,  except
where proposed label claims specify that the preparation should not
be applied when particular sensitive adjacent crops are present.

39

 
2.3.7. Where  proposed  label  claims  include  requirements  for  use  of  the
preparation with other plant protection products or adjuvants, as  a
tank mix, the mixture must  comply  with  the  principles  referred to
in points 2.4.1 to 2.4.4.

2.3.8. The  proposed  instructions  for  cleaning  the  application  equipment
must  be  both  practical  and  effective  so  that  they  can  be  applied
with ease so as to ensure the removal of residual traces of the plant
protection product which could subsequently cause damage.

2.3.9. No authorisation shall be granted unless there is full information on
continuous  quality  control  of  the  production  method,  production
process  and  product.  In  particular,  the  occurrence  of  spontaneous
changing of major characteristics of the micro-organism and of the
absence/presence of  contaminating  organisms  shall  be  considered.
The quality assurance criteria for the production and the techniques
used to ensure a uniform product must be sufficiently described and
specified.

2.3.10.

If there is evidence of a development of resistance of pathogens
towards the product, the Member State shall decide if the submitted
resistance  management  strategy  addresses  this  adequately  and
sufficiently.

2.4. Efficacy data

2.4.1. Where the proposed uses include recommendations for the control
of  or protection  against organisms which are  not  considered  to  be
harmful on the basis of experience  acquired or  scientific  evidence
under  normal  agricultural,  plant  health  and  environmental
(including  climatic)  conditions  in  the  areas  of  proposed  use  or
where the other intended effects are not considered to be beneficial
under those conditions, no authorisation shall be granted for those
uses.

2.4.2. The level, consistency and duration of control or protection or other
intended effects must be similar to those resulting from the use of
suitable reference products. If no suitable reference product exists,
the  plant  protection  product  must  be  shown  to  give  a  defined
benefit in terms of the level, consistency and duration of control or
protection  or  other  intended  effects  under  the  agricultural,  plant
health and environmental (including climatic) conditions in the area
of proposed use.

2.4.3. Where  relevant,  yield  response  when  the  product  is  used  and
reduction  of  loss  in  storage  must  be  quantitatively  and/or
qualitatively  similar  to  those  resulting  from  the  use  of  suitable
reference products. If no suitable reference product exists, the plant
protection product must be shown to give a consistent and defined
quantitative  and/or  qualitative  benefit  in  terms  of  yield  response
and reduction of loss in storage under the agricultural, plant health

40

 
and  environmental  (including  climatic)  conditions  in  the  area  of
proposed use.

2.4.4. Conclusions as to the performance of the preparation must be valid
for  all  areas  of  the  Member  State  in  which  it  is  to  be  authorized,
and  must  hold  for  all  conditions  under  which  its  use  is  proposed,
except  where  the  proposed  label  specifies  that  the  preparation  is
intended  for  use  in  certain  specified  circumstances  (e.g.  light
infestations, particular soil types or particular growing conditions).

2.4.5. Where  proposed  label  claims  include  requirements  for  use  of  the
preparation  with  other  specified  plant  protection  products  or
adjuvants as a tank mix, the mixture must achieve the desired effect
and comply with the principles referred to in points 2.4.1 to 2.4.4.
Where  proposed  label  claims  include  recommendations  for  use  of
the  preparation  with  specified  plant  protection  products  or
adjuvants  as  a  tank  mix,  Member  States  shall  not  accept  the
recommendations unless they are justified.

2.4.6. The  intended  effect  on  vertebrates  to  be  controlled  shall  be
obtained  without  unnecessary  suffering  and  unnecessary  pain  for
these animals.

2.5.

Identification/detection and quantification methods

The methods proposed must reflect the state of the art.

2.5.1. No  authorisation  shall  be  granted  unless  there  is  an  adequate
method  of  sufficient  quality  to  identify  and  determine  the  micro-
organism  and  the  non-viable  components  (e.g.  toxins,  impurities
and  co-formulants)  in  the  product.  In  the  case  of  a  product
containing  more  than  one  micro-organism,  the  recommended
methods  should  be  sufficiently  capable  of 
identifying  and
determining the content of each one. 

2.5.2. No  authorisation  shall  be  granted  unless  there  is  an  adequate
method  of 
identify  and  determine
toxicologically,  ecotoxicologically  or  environmentally  relevant
viable and/or non-viable residues in/on treated crops.

sufficient  quality 

to 

2.6.

Impact on human and animal health 

2.6.1. Effects arising from the product

2.6.1.1. No  authorisation  shall  be  granted  if  the  information  in  the
dossier indicates that the micro-organism is pathogenic to  humans
or non-target animals under the proposed uses. 

2.6.1.2. No authorisation shall be  granted if the micro-organism and/or
the  product  containing  the  micro-organism  might,  under  the
recommended  use,  including  a  realistic  worst  case  scenario,
colonise or cause adverse effects in humans or animals.

41

 
When  making  a  decision  on  the  authorisation  of  the  microbial
product,  Member  States  shall  consider  possible  effects  on  all
human  populations,  namely  professional  users,  non-professional
users  and  humans  exposed  directly  or  indirectly  though  the
environment and at work, and animals.

2.6.1.3. All micro-organisms should be regarded as potential sensitisers,
unless it is proven by relevant information that there is no risk for
sensitisation,  also  taking  into  account  immuno-compromised  and
other  sensitive  individuals.  Therefore,  protective  clothing  and
suitable  gloves  should  be  worn  and  the  product  containing  the
micro-organism  should  not  be  inhaled.  Moreover,  the  proposed
conditions of use may require use of additional items of protective
clothing and equipment.

Where  the  proposed  conditions  of  use  require  use  of  items  of
protective  clothing,  no  authorisation  shall  be  granted  unless  those
items are effective and in accordance with the relevant Community
provisions,  and  are  readily  obtainable  by  the  user  and  unless  it  is
feasible  to  use  them  under  the  circumstances  of  use  of  the  plant
protection  product,  taking  into  account  climatic  conditions  in
particular. 

2.6.1.4. No authorisation shall be granted if it is known that transfer of
genetic material from the micro-organism to other organisms, may
lead  to  adverse  effects  on  human  and  animal  health,  including
resistance to known therapeutics.

2.6.1.5. Plant protection products which because of particular properties
or  if  mishandled  or  misused  could  lead  to  a  high  degree  of  risk
must be subject to particular restrictions such as restrictions on the
size of packaging, formulation type, distribution, use or manner of
use.  Moreover,  plant  protection  products  which  are  classified  as
very toxic may not be authorized for use by non-professional users.

2.6.1.6. Waiting  and  re-entry  safety  periods  or  other  precautions  must
be  such  that  no  colonisation  or  adverse  effects  are  expected  to
bystanders  or  workers  exposed  after  the  application  of  the  plant
protection product 

2.6.1.7. Waiting  and  re-entry  safety  periods  or  other  precautions  must
be established in such a way that no colonisation or adverse effects
are expected to animals.

2.6.1.8. Waiting and re-entry periods or other precautions to ensure that
no colonisation or adverse effects are expected must be realistic; if
necessary special precautionary measures must be prescribed.

2.6.1.9. The conditions of the authorisation shall be in compliance with
Council  Directive  98/24/EC  on  Chemical  Agents,  and  Council
Directive  2000/54/EC  on  Biological  Agents 
.The  provided
experimental data and information relevant to the recognition of the
symptoms of infection or pathogenicity and on the effectiveness of

42

 
first  aid  and  therapeutic  measures  shall  be  considered.  The
conditions of the authorisation shall also be in compliance with the
Council  Directive  1999/38/EC  on  the  protection  of  workers  from
the risks related to exposure to carcinogens at work and extending
it to mutagens.
The conditions of the authorisation shall also be
in  compliance  with  the  Council  Directive  1989/656/EEC  on  the
minimum health and safety requirements for the use by workers of
personal protective equipment at the workplace.

2.6.2. Effects on human and animal health arising from residues

2.6.2.1. No  authorisation  shall  be  granted  unless  there  is  sufficient
information for products containing the micro-organism, to decide
that  there  is  no  unacceptable  health  risk  for  man  and/or  animals
arising from exposure to the micro-organism, its residual traces and
metabolites/toxins remaining in or on plants or plant products.

2.6.2.2. No authorisation shall be  granted unless viable  residues  and/or
non-viable residues occurring reflect the minimum quantities of the
plant  protection  product  necessary  to  achieve  adequate  control
corresponding  to  good  agricultural  practice,  applied  in  such  a
manner  (including  pre-harvest  intervals  or  withholding  periods  or
storage  periods)  that  the  viable  residues  and/or  toxins  at  harvest,
slaughter or after storage are reduced to a minimum.

2.7. Fate and behaviour in the environment

2.7.1. No  authorisation  shall  be  granted  if  the  available  information
indicates  that  there  may  be  unacceptable  adverse  environmental
effects  due  to  the  fate  and  behaviour  of  the  product.  This
information  shall  be  provided  according  to  Annex  IIIB  of  this
directive,  and  be  based  on  the  origin,  the  properties,  and  the
survival  of  the  micro-organism  and  its  residual  metabolites/toxins
as  well  as  on  its  intended  use,  taken  together  with  other  relevant
information.

2.7.2. No  authorisation  shall  be  granted  if  it  is  known  that  transfer  of
genetic material from the micro-organism to other organisms, may
lead to adverse effects to the environment.

2.7.3. No  authorisation  shall  be  granted  unless  there  is  sufficient
information on possible persistence / competitiveness of the micro-
organism  and  relevant  secondary  metabolites/toxins  in  or  on  the
crop under the environmental conditions prevailing at and after the
intended use.

2.7.4. No  authorisation  shall  be  granted  if  it  can  be  expected  that  the
micro-organism  and  /  or  its  possible  relevant  metabolites/toxins
will  persist  in  the  environment  in  concentrations  considerably
higher than the natural background conditions, taking into account
the  years,  unless  a  robust  risk
repeated  applications  over 
assessment 
from  accumulated  plateau
risk 
the 
concentrations is acceptable.

indicates 

43

 
2.8. Effects on non-target organisms

Member States shall ensure that the available information is sufficient to
permit  a  decision  to  be  taken  as  to  whether  there  may  be  unacceptable
effects  on  non-target  species  (flora  and  fauna),  due  to  exposure  to  the
product  containing  the  micro-organism  and  from  its  intended  use.  This
information shall be provided according to Annex IIIB of this directive,
and be based on identity and biological properties as well as on fate and
behaviour,  taken  together  with  that  for  one  or  more  preparations
containing the micro-organism.

Member  States  shall  pay  special  attention  to  beneficial  organisms  used
for  biological  control  and  organisms  playing  an  important  role  in
integrated control.

2.8.1. Where there is a possibility of birds, mammals and other non-target
terrestrial  vertebrates  being  exposed,  no  authorisation  shall  be
granted if:

– 

– 

the  micro-organism  is  pathogenic  to  birds,  mammals  and
other non-target terrestrial vertebrates,

in  case  of  toxic  effects  due  to  components  in  the  product,
such  as  relevant  metabolites/toxins,  the  toxicity/exposure
ratio  is  less  than  10  on  the  basis  of  acute  LD50  or  the  long-
term toxicity/exposure ratio is less than 5, unless it is clearly
established through an appropriate risk assessment that under
field  conditions  no  unacceptable  effects  occur  -  directly  or
indirectly - after use of the plant protection product according
to the proposed conditions of use.

2.8.2. Where there is a possibility of aquatic organisms being exposed, no

authorisation shall be granted if:

– 

– 

the micro-organism is pathogenic to aquatic organisms ,

in case of toxic effects due to components in the product such
as  relevant  metabolites/toxins,  the  toxicity/exposure  ratio  is
less than 100 in case of acute toxicity (EC50) to daphnia and
fish  and  10  for  long-term/chronic  toxicity  to  algae  (EC50),
daphnia  (NOEC)  and  fish  (NOEC),  unless  it  is  clearly
established through an appropriate risk assessment that under
field  conditions  no  unacceptable  impact  on  the  viability  of
exposed  species  occurs  -  directly  or  indirectly  -  after  use  of
the  plant  protection  product  according  to  the  proposed
conditions of use.

2.8.3. Where  there  is  a  possibility  of  honeybees  being  exposed,  no

authorisation shall be granted: 

– 

if the micro-organism is pathogenic to honeybees,

44

 
– 

in case of toxic effects due to components in the product such
as relevant metabolites/toxins, unless it is clearly established
through  an  appropriate  risk  assessment  that  under  field
conditions  there  are  no  unacceptable  effects  on  honeybee
larvae,  honeybee  behaviour,  or  colony  survival  and
development  after  use  of  the  plant  protection  product
according to the proposed conditions of use.

2.8.4. Where  there  is  a  possibility  of  arthropods  other  than  honeybees

being exposed, no authorisation shall be granted if:

– 

– 

the  micro-organism  is  pathogenic  to  arthropods  other  than
honeybees,

in case of toxic effects due to components in the product such
as relevant metabolites/toxins, unless it is clearly established
through  an  appropriate  risk  assessment  that  under  field
conditions 
those
is  no  unacceptable 
organisms after use of the plant protection product according
to the proposed conditions of use. Any claims for selectivity
and proposals for use in integrated pest management systems
shall be substantiated by appropriate data.

impact  on 

there 

2.8.5. Where  there  is  a  possibility  of  earthworms  being  exposed,  no

authorisation shall be granted if:

– 

– 

the micro-organism is pathogenic to earthworms

in case of toxic effects due to components in the product such
as  relevant  metabolites/toxins,  the  toxicity/exposure  ratio  is
less  than  10,  or  the  long-term  toxicity/exposure  ratio  is  less
than 5, unless it is clearly established through an appropriate
risk  assessment  that  under  field  conditions  earthworm
populations  are  not  at  risk  after  use  of  the  plant  protection
product according to the proposed conditions of use.

2.8.6. Where  there  is  a  possibility  of  non-target  soil  micro-organisms
being exposed, no authorisation shall be granted, unless it is clearly
established through an appropriate risk assessment that under field
conditions  there  is  no  unacceptable  impact  on  the  microbial
community  after  use  of  the  plant  protection  product  according  to
the  proposed  conditions  of  use,  taking  account  of  the  ability  of
micro-organisms to multiply.

45