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G U I D A N C E

GUIDANCE DOCUMENT ON APPLICATIONS FOR TECHNICAL EQUIVALENCE

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chorapi

Text Box

CA-July13-Doc.5.1.c


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LEGAL NOTICE 2

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This document contains guidance on Regulation (EU) No 528/2012 of the European 4

Parliament and of the Council of 22 May 2012 concerning the making available on the 5

market and use of biocidal products (Biocidal Products Regulation, BPR). This document 6

describes the BPR obligations and how to fulfil them. However, users are reminded that 7

the text of the BPR is the only authentic legal reference and that the information in this 8

document does not constitute legal advice. The European Chemicals Agency does not 9

accept any liability with regard to the contents of this document. 10

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Xxxxxxxxxxx: Xxxxxxxxxxx

Reference:

ISBN-13:

ISSN:

Publ.date:

Language:

© European Chemicals Agency, 2013

Cover page © European Chemicals Agency

Reproduction is authorised provided the source is fully acknowledged in the form

“Source: European Chemicals Agency, http://echa.europa.eu/”, and provided written

notification is given to the ECHA Communication Unit ([email protected]).

If you have questions or comments in relation to this document please send them (quote

the reference and issue date) using the information request form. The information

request form can be accessed via the Contact ECHA page at:

http://echa.europa.eu/about/contact_en.asp

European Chemicals Agency

Mailing address: P.O. Box 400, 00121 Helsinki, Finland

Visiting address: Annankatu 18, 00120 Helsinki, Finland

mailto:[email protected]

http://echa.europa.eu/about/contact_en.asp


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Table of contents 19

20

List of abbreviations............................................................................................................... 4 21

22

Introduction .......................................................................................................................... 6 23

24

PART I: Procedural Guidance................................................................................................... 7 25

1. Scope of Article 54 ............................................................................................................. 7 26

2. Definitions ........................................................................................................................ 9 27

3. Application for the assessment of technical equivalence ........................................................ 13 28

3.1. When and who should apply for technical equivalence assessment?............................... 13 29

3.2. How to apply for technical equivalence assessment? .................................................... 15 30

3.3. Information requirements for technical equivalence assessment ................................... 15 31

4. Assessment of the technical equivalence application............................................................. 17 32

4.1. Processing of the applications by the Agency .............................................................. 17 33

4.2. Outcome of the assessment of technical equivalence ................................................... 18 34

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PART II: Technical Guidance ................................................................................................. 19 36

5. Assessment of technical equivalence: Substance identity and analytical information 37

(Tier I) ......................................................................................................................... 19 38

6. Evaluation of technical equivalence: Tier II ......................................................................... 20 39

6.1. Toxicity .................................................................................................................. 20 40

6.1.1 Assessment of the toxicity of the impurity profile .............................................. 20 41

6.1.2 Decision making ............................................................................................ 21 42

6.2 Ecotoxicity .............................................................................................................. 22 43

6.2.1 Assessment of the ecotoxicity of the impurity profile .......................................... 22 44

6.2.2 Decision making ............................................................................................ 23 45

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References ......................................................................................................................... 25 47

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Annex I: template Technical equivalence report: Assessment for Tier II. .................................... 26 49

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List of abbreviations 53

54

Standard term / Abbreviation Explanation

ADI Acceptable daily intake

AOEL Acceptable operator exposure limit

ARfD Acute reference dose

BPD Directive 98/8/EC of the European Parliament and of the

Council on the placing on the market of biocidal products

BPD TNsG Technical guidance note under Biocidal Products Directive

BPR Regulation (EU) No 528/2012 of the European Parliament

and of the Council concerning the making available on the

market and use of biocidal products

CA Chemical abstract

CAS Chemical abstract (service or system)

CLP Regulation (EC) No 1272/2008 on Classification, Labelling

and Packaging

Dir Directive

EC European Communities or European Commission

ECHA European Chemicals Agency

g Gram(s)

GLP Good laboratory practice

IR Infrared spectroscopy

ISO International Standards Organisation

IUCLID International Uniform Chemical Information Database

IUPAC International Union for Pure and Applied Chemistry

kg Kilogram(s)

MS Member State

MSCA Member State competent authority

NMR Nuclear magnetic resonance spectroscopy

NOAEL No observed adverse effect level


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Standard term / Abbreviation Explanation

OECD Organisation for Economic Co-operation and Development

(Q)SAR (Quantitative) structure activity relationship

REACH Regulation (EC No 1907/2006) on Registration,

Evaluation, Authorisation and Restriction of Chemicals

R4BP Register for Biocidal Products

SDS Safety data sheet

TC Technical material

TE Technical equivalence

TK Technical concentrate

UV/VIS Ultraviolet-visible

UVCB Undefined or variable composition, complex reaction

products or biological material

v/v Volume per volume ratio

w/w Weight per weight ratio

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Introduction 57

The Biocidal Products Regulation (EU) No. 528/2012 (BPR) provides a centralised 58

procedure for the assessment of technical equivalence. The legal basis is Article 54 which 59

sets out the procedure for the assessment of technical equivalence applications, under 60

the responsibility of the Agency. 61

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Article 54(8) of the BPR prescribes that the Agency shall provide technical guidance on 63

the provisions on technical equivalence. This guidance document is intended to inform 64

potential applicants about their obligations resulting from the provisions of Article 54: 65

when they need to apply for an assessment of technical equivalence and on the 66

procedural steps in making that application. This is described in Part I: Procedural 67

Guidance. The guidance also informs potential applicants about the assessment 68

conducted by the Agency and the approach used for assessing the technical equivalence 69

of the alternative source of an active substance versus its reference source. This is 70

described in Part II: Scientific Guidance. 71

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Under the Biocidal Products Directive 98/8/EC (BPD), technical equivalence was assessed 73

by the Member State competent authority (MSCA). Guidance on technical equivalence 74

was available under the BPD in the form of a technical note for guidance (TNsG). The 75

assessment of technical equivalence described in this guidance is to a large extent based 76

on this TNsG. Where considered relevant, the guidance is harmonised with the 77

assessment of technical equivalence for plant protection products under Regulation (EC) 78

No. 1107/2009 as described in SANCO/10597/2003-rev.10.1 of 13 July 2012 (DG 79

SANCO, 2012). 80

81

The guideline does not address: 82

Active substances that are microorganisms; 83

Active substances that have poorly-defined chemical compositions, which might 84

be e.g. plant extracts, animal products and their derivates; 85

Active substances that are a nanomaterial. 86

87

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PART I: Procedural Guidance 89

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1. Scope of Article 54 91

Technical equivalence under Article 54 of the BPR entails the assessment of the 92

equivalence of an alternative source versus a reference source included in the Union list 93

of approved active substances. The general principle behind this assessment is that for 94

an active substance the level of hazard for human health and the environment must be 95

comparable for different sources of the active substance. Technical equivalence is defined 96

in the BPR in Article 3(1)(w): “technical equivalence means similarity, as regards the 97

chemical composition and hazard profile, of a substance produced either from a source 98

different to the reference source, or from the reference source but following a change to 99

the manufacturing process and/or manufacturing location, compared to the substance of 100

the reference source in respect of which the initial risk assessment was carried out” 101

(emphasis added). 102

103

The reference source is established based on the source(s) on which the risk assessment 104

was carried out and for which a decision has been taken by the Commission to approve 105

the active substance. This means that applications for technical equivalence are to be 106

submitted after the active substance is approved, when there is a change in source as 107

described in this definition1. The technical equivalence must be established before 108

applying for product authorisation. The applicant shall include the decision of the Agency 109

on the assessment of technical equivalence in the application for product authorisation. 110

111

At least two situations are foreseen when an applicant needs to apply for the assessment 112

of technical equivalence, where the biocidal product contains either: 113

an active substance from a different manufacturer than the one whose active 114

substance has been assessed for the inclusion in the Union list of approved active 115

substances, or 116

an active substance manufactured by the manufacturer whose substance has 117

been assessed for inclusion in the Union list of approved active substances, when 118

there is a change in the manufacturing process (e.g. change in starting materials) 119

or a different manufacturing location. 120

In the above mentioned situations, the active substance is considered as a substance 121

from a "source different from the reference source". In the present guidance document 122

the term "alternative source" is used to refer to these situations. In order to assess that 123

the active substance from the alternative source is technically equivalent to the one 124

already placed on the Union list of approved active substances, applicants for the 125

authorisation of biocidal products need to request the Agency to establish whether the 126

alternative source is technically equivalent with the reference source. 127

To do so, the applicant should submit a dossier containing information on the substance 128

identity, analytical data (including five batch analysis) and/or all available information on 129

the (eco)toxicological endpoints that can be relevant for the evaluation. Detailed 130

1 When it is necessary to establish the technical equivalence of different sources of an

active substance during the approval process (for example in case there are multiple

applicants or task forces consisting of members with different sources), the principles of

the technical equivalence assessment are the same, but in this case the MSCA (the

Evaluating CA under the BPR or the Rapporteur Member State under the BPD) is

responsible for establising technical equivalence.2 Source refers to the specific

manufacturing location of a substance. Hence, it does not refer to a specific applicant or

a manufacturer. It refers to a specific manufacturing plant for which the manufacturing

process has been outlined and the specifications of the starting materials are provided.


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information requirements are described in section 3.3. The prerequisite to technical 131

equivalence is that both the active substance from the alternative source and the one 132

from the reference source have the same identity. 133

Once this prerequisite is confirmed, a tiered approach is followed to assess the 134

equivalence of different sources of the active substance: Tier I consists of the evaluation 135

of analytical data. If equivalence can be ascertained from these data, the Tier II 136

assessment is not necessary. If equivalence cannot be established on the basis of the 137

Tier I data, further consideration is necessary whichrelates to the evaluation of 138

toxicological and ecotoxicological data under Tier II. 139

140

The process for the assessment of technical equivalence is depicted in Figure 2. Section 141

5 and 6 will explain the Tier I and II assessment in more detail. 142

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145 146

Figure 1: The assessment of technical equivalence. 147

148

Tier I

Tier II

Have the two substances the same identity?Question of Technical Equivalence

Is not relevant

Monoconstituent substancen=1, lower limit=80%

Multi-constitutent substance n>1, 10%<n<80%

Is the minimum degree of purity obtained with the new source lower?

For multi-constituent substances, are the tolerated variation in the quantitative

composition of the main constituents exceeded?

Are there new impurities

Are the limits of all non-relevant impurities exceeded by more than the acceptable

maximum increase?

Is there an unacceptable increase in the (eco)toxicity of the alternative source compared to the reference source?

Or

Or

Or

Substance Identification

Equivalence

Alternative source is Technically Equivalent

to reference source

Are the quantitative levels of impurities higher

Or

all NO

Alternative source is notTechnically Equivalent

to reference sourceYes

NO


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2. Definitions 149

Within the biocides framework under the BPR, the definition of ‘substance’, and the 150

convention for the identification and naming of substances from the REACH Regulation 151

(EC) No 1907/2006 are applied. Consequently, certain definitions relevant for the 152

assessment of technical equivalence are taken from REACH and the guidance document 153

“Guidance for identification and naming of substances under REACH and CLP” (ECHA, 154

2012). Below it is indicated if the definition originates from the BPR, REACH, FAO or this 155

guidance document. The definitions of significant and relevant impurity originate from 156

the BPR guidance document on information requirements (#Guidance document on 157

information requirements). 158

Technical equivalence (BPR) 159

Similarity, as regards the chemical composition and hazard profile, of a substance 160

produced either from a source different to the reference source2, or from the reference 161

source but following a change to the manufacturing process and/or manufacturing 162

location, compared to the substance of the reference source in respect of which the initial 163

risk assessment was carried out, as established in Article 54 of the BPR (Article 3(1)(w) 164

of the BPR). 165

Substance (REACH) 166

A chemical element and its compounds in the natural state or obtained by any 167

manufacturing process, including any additive necessary to preserve its stability and any 168

impurity deriving from the process used, but excluding any solvent which may be 169

separated without affecting the stability of the substance or changing its composition. 170

171

Active substance (BPR) 172

A substance or microorganism that has an action on or against harmful organisms. 173

Technical material (TC) (FAO manual) 174

In accordance with the FAO manual (FAO, 2010), technical material is usually the final 175

product from preparation of the active substance prior to being formulated into an end-176

use product. This may contain a stabiliser and/or anti-caking or anti-static agents (if 177

required) but no other additives. 178

Technical material is usually ≥900 g/kg with solvent(s) removed during synthesis, with 179

only residual amounts remaining (usually ≤10%) and no solvent added subsequently. 180

Technical concentrate (TK) (FAO manual) 181

In accordance with the FAO manual (FAO, 2010), a technical concentrate may also be 182

the final product from preparation of the active substance but it may contain additives 183

(not formulants) in addition to a stabiliser, for example as safety agents. Technical 184

concentrates may also contain solvent(s) (including water), either deliberately added to 185

a technical material or not removed during preparation. 186

187

2 Source refers to the specific manufacturing location of a substance. Hence, it does not

refer to a specific applicant or a manufacturer. It refers to a specific manufacturing plant

for which the manufacturing process has been outlined and the specifications of the

starting materials are provided.


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Explanatory note on Technical material (TC) and Technical concentrate (TK) in

relation to the definition of substance.

As described above ‘substance’ is defined as a chemical element and its compounds in

the natural state or obtained by any manufacturing process, including any additive

necessary to preserve its stability and any impurity deriving from the process used, but

excluding any solvent which may be separated without affecting the stability of the

substance or changing its composition.

Hence there are two situations:

1. Solvent(s) cannot be removed /

separated from the substance

without affecting the stability or

changing its composition.

This situation refers to Technical

concentrate (TK).

2. Solvent(s) can be removed /

separated from the substance

without affecting the stability or

changing its composition.

This situation refers to Technical material

(TC).

For substance identity purposes additives other than stabilisers to the substance should

be removed / separated from the substance. Hence, processing agents, colorants,

denaturation agents etc. are not part of a substance.

188

Constituent (REACH guidance document) 189

Any single species present in a substance that can be characterised by its unique 190

chemical identity. 191

Main constituent (REACH guidance document) 192

A constituent, not being an additive or impurity, in a substance that makes a significant 193

part of that substance and is therefore used in substance naming and detailed substance 194

identification. 195

Mono-constituent substance (REACH guidance document) 196

As a general rule, a substance, defined by its composition, in which one main constituent 197

is present to at least 80% (w/w). 198

Multi-constituent substance (REACH guidance document) 199

As a general rule, a substance, defined by its composition, in which more than one main 200

constituent is present in a concentration >10% (w/w) and <80% (w/w). 201

UVCB substance (REACH guidance document) 202

Substances of unknown or variable composition, complex reaction products or biological 203

materials, also called UVCBs are substances that cannot be sufficiently identified by their 204

chemical composition, because: 205

• The number of constituents is relatively large and/or 206


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• The composition is, to a significant part, unknown and/or 207

• The variability of composition is relatively large or poorly predictable. 208

Polymer (REACH) 209

A substance consisting of molecules characterised by the sequence of one or more types 210

of monomer units. Such molecules must be distributed over a range of molecular weights 211

wherein differences in the molecular weight are primarily attributable to differences in 212

the number of monomer units. A polymer comprises the following: 213

a) a simple weight majority of molecules containing at least three monomer units 214

which are covalently bound to at least one other monomer unit or other reactant; 215

b) less than a simple weight majority of molecules of the same molecular weight. 216

217

In the context of this definition, a "monomer unit" means the reacted form of a monomer 218

substance in a polymer. 219

Impurity (REACH guidance document) 220

An unintended constituent present in a substance as manufactured. It may originate 221

from the starting materials or be the result of secondary or incomplete reactions during 222

the production process. While it is present in the final substance it was not intentionally 223

added. 224

Significant impurity (#Guidance document on Information Requirements) 225

An impurity is regarded as significant if it occurs or potentially occurs in a quantity ≥ 1 226

g/kg in the substance as manufactured. The limit of 1g/kg applies to the dry technical 227

material (TC) and therefore for technical concentrates (TK) the limit will apply to 228

theoretical dry material and hence impurities below this limit if they are ≥ 1 g/kg on a dry 229

weight basis, must also be determined. The impurity should be identified and quantified if 230

technically possible and included in the substance specification, with stated maximum 231

concentration. A significant impurity may be considered relevant or non-relevant 232

depending, in particular, on its known toxicological and eco-toxicological properties. 233

234

Relevant impurity/additive (#Guidance Document on Information 235

Requirements) 236

An impurity/additive considered being of toxicological and/or ecotoxicological relevance. 237

An impurity may be relevant even if it occurs in a quantity <1g/kg (e.g. very toxic 238

substances like dioxin). The relevant impurity should be identified and quantified if 239

technically possible and included in the substance specification, with stated maximum 240

concentration. 241

242

Relevant impurities may be defined as (#DG SANCO, 2012) substances including, but not 243

limited to, meeting the criteria to be classified as hazardous in accordance with CLP 244

Regulation (EC) No. 1272/2008, or the available information (e.g. from (Q)SARs) 245

indicates that the impurity has an (eco)toxicological hazard. Relevant impurities have the 246

inherent capacity to cause harmful/unacceptable effects within the meaning of Article 247

19(1)(b) of the BPR. Compared to the active substance, relevant impurities show 248

additional (comparable or more severe) toxic properties (in the sense of the definition 249

above). 250

Additive (REACH guidance document) 251

A substance that has been intentionally added to stabilise the substance, so other 252


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substances with other functions, e.g. pH-regulators or colouring agents are not 253

considered as additives. 254

255


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3. Application for the assessment of technical equivalence 256

3.1. When and who should apply for technical equivalence assessment? 257

As stated, technical equivalence shall be assessed where relevant, after the approval of 258

an active substance (i.e. when the reference source has been established and the active 259

substance has been included in the Union list of approved substances). Since an 260

applicant for product authorisation must provide evidence that the active substance to be 261

used in the biocidal product has either been approved or is technically equivalent to an 262

active substance included on the Union list of approved substances, applications for 263

technical equivalence shall be submitted to the Agency before product authorisation 264

(both national or Union). Examples of situations and scenarios where the assessment of 265

technical equivalence is required are listed in Table 1 and are described in detail below. 266

In the first scenario, the applicant can be: 267

the participant in the Review Programme who supported the active substance, or 268

the applicant who submitted the application for the active substance under Article 269

11 of Directive 98/8/EC (BPD) (new active substance), or 270

the applicant who submitted the application for the active substance under Article 271

7 of the BPR. 272

The applicant changes location of the manufacturing plant without changing the 273

manufacturing process or the starting materials. In this case, the applicant has detailed 274

knowledge on the composition of the reference source and submits a Tier I application for 275

technical equivalence. The information requirements for Tier I are described in section 276

3.3. In some cases a Tier II application may be necessary, for example when a change to 277

new equipment leads to a change in the impurity profile. Assuming the decision of the 278

Agency is that technical equivalence has been demonstrated, this decision can then be 279

used by the applicant (if they are also a holder of an authorisation or will apply for 280

product authorisation) or their downstream users (being formulators holding an 281

authorisation or applying for product authorisation) in the authorisation applications. This 282

can either be a first authorisation or a change to an already existing authorisation 283

through an application for an administrative change under Implementing Regulation (EU) 284

No 354/2013 (see item 5 of Section 1 of Title 1 of the Annex). 285

The second scenario is similar to the first one, except that here the manufacturing 286

process (e.g. process or quality of starting materials) is changed. In this case, the 287

applicant has detailed knowledge on the composition of the reference source. However, 288

he needs to decide whether to submit a Tier I or a Tier II application for technical 289

equivalence. Not all changes in the manufacturing process may trigger an application for 290

technical equivalence, for example minor changes in the operational conditions. A special 291

case is when the specifications of the starting materials are different, where for minor 292

changes no establishment of technical equivalence according to Article 54 may be 293

necessary. An example is a change in the specifications of a solvent if there is a change 294

of supplier. It may not be necessary in such cases to assess the technical equivalence, 295

for example if the purity of the solvent is not lowered. Relevant is the assessment of the 296

possible effect on the end product, being the active substance. This has to be assessed 297

by the applicant before sending in an application, where the applicant may consult with 298

the Agency before submitting an application. 299

The third scenario entails the introduction of a new source where the substance 300

manufacturer is different from the manufacturer whose substance was evaluated for the 301

purpose of substance approval (so the applicant is a manufacturer of the ‘alternative’ 302

active substance). Hence, the applicant has no detailed knowledge on the composition of 303

the reference source apart from the minimum purity and the relevant impurities (if 304


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present). In such cases, it is recommended to submit a Tier I application first and if the 305

Agency cannot conclude on that basis that the alternative source is technically 306

equivalent, submit a Tier II application. 307

In the fourth scenario the applicant is a formulator of a biocidal product who wants to 308

change supplier of the active substance(s) in the biocidal product he places on the 309

market, or his supplier changes the manufacturing process (including a change of the 310

starting materials) or location. In this case, the formulator will need to apply for an 311

administrative change under Implementing Regulation (EU) No 354/2013 to his 312

authorisation and that application shall contain the decision of the Agency on technical 313

equivalence. The process for obtaining this decision is described in the scenarios above. 314

The last and fifth scenario for which an application is required is the change from pilot-315

scale to large-scale production. 316

It can occur that more than one reference source (with different levels of purity of the 317

active substance and/or different identities and concentration ranges of relevant 318

impurities) are included in the Union list of approved active substances. This is for 319

example the case when there are several applicants for the same active substance or 320

when the applicant is (representing) a consortium or task force in the approval process. 321

In such a case the alternative source will be compared by the Agency to all reference 322

sources and needs to be technically equivalent to at least one of them. 323

324

NUMBER OF SCENARIO

APPLICANT / SITUATION FOR TECHNICAL EQUIVALENCE ASSESSMENT

SCENARIO DETAIL OF SCENARIO

INFORMATION REQUIREMENTS FOR TECHNICAL EQUIVALENCE ASSESSMENT

1 Reference source included in the submission which led to approval

Change or addition of a new manufacturing location

Same manufacturing process, same starting materials

Provide information as required according to the tiered approach of

the technical equivalence assessment

2 A reference source included in the submission which led to approval

Change of manufacturing process or addition of alternative manufacturing process

New/modified process, or new starting material(s) introduced or changes in specifications of starting materials*

3 New source not included in the submission which led to approval of the active substance

Introduction of new manufacturing location and/or process

Manufacturing location and process different from reference source

4 Formulator or its supplier Existing formulated product with new source different from the reference source included in the submission which lead to approval

Formulator wishes to change source

5 Reference source included in the submission which led to approval

Change from pilot-scale to large-scale production

Information must be resubmitted once the industrial scale production plant enters into operation and production has stabilised.

325

Table 1: List of possible scenarios when a technical equivalence needs to be assessed 326

(*It has to be decided on a case-by-case which changes trigger the need for new data 327

and technical equivalence assessment). 328

329

330


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3.2. How to apply for technical equivalence assessment? 331

The applicant shall use IUCLID to prepare a technical equivalence dossier. The template 332

for active substance should be used. A dossier must contain: 333

information on the substance identity; 334

study summaries for the required endpoints (analytical, toxicological and 335

ecotoxicological data) depending on whether the application is submitted for Tier I 336

or Tier II; 337

the original test reports underlying the study summaries (to be submitted as 338

attachments in the IUCLID file); 339

a summary providing a self-assessment of technical equivalence for Tier II: a 340

template for this summary is presented in Annex I of this guidance document. The 341

summary should be included as an attachment in the IUCLID file. 342

Once the dossier is generated, the applicant should submit it to the Agency using the 343

Register for Biocidal Products (R4BP). More detailed information on the compilation of the 344

technical dossier in IUCLID as well as information on the R4BP can be found in a separate 345

manual that will be available on the Agency website. 346

347

3.3. Information requirements for technical equivalence assessment 348

The information requirements of Tier I and Tier II are described below. An applicant 349

applying for a Tier II assessment (without applying first for a Tier I assessment), is 350

required to also include the information required for a Tier I assessment in the 351

application. 352

Information requirements – Tier I 353

354

To assess technical equivalence, the following information is required to be submitted for 355

the alternative source of the active substance: 356

Applicant (name, address and contact person) (chapter II sections 1.1 and 357

1.23); 358

Manufacturer of the active substance (name, address, head office and 359

location of manufacturing plant(s)), if different from the applicant; 360

Common name proposed or accepted by ISO and synonyms (usual name, 361

trade name, abbreviation) (chapter II section 2.1); 362

Chemical name (IUPAC and CA nomenclature or other international chemical 363

name(s)) (chapter II section 2.2); 364

CAS number, EC, INDEX and CIPAC numbers (if allocated) (chapter II 365

section 2.4); 366

Molecular and structural formula (including SMILES notation, if available and 367

appropriate) (chapter II section 2.5); 368

Information on optical activity and full details of any isomeric composition (if 369

applicable and appropriate) (chapter II section 2.6); 370

Molar mass (chapter II section 2.7); 371

Method of manufacture (synthesis pathway) of the active substance 372

3 In brackets the relevant chapter and section of the Guidance on Information

Requirements.


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including information on starting materials and solvents including the 373

specifications (chapter II section 2.8); 374

Specification of active substance purity as manufactured in g/kg, g/l or 375

%w/w (%v/v) as appropriate, including the upper and lower limit (chapter II 376

section 2.9); 377

The identity of any impurities and additives including by-products of 378

synthesis, optical isomers, unreacted and end-groups of polymers and 379

unreacted starting materials of UVCB substances (chapter II section 2.10); 380

Analytical profile of at least five representative batches (g/kg active 381

substance) including information on content of the impurities; 382

Analytical method used in the five batch analysis. The analytical method 383

needs to be a validated method (chapter II, section 5.1). Quality control 384

data can be submitted (for example, to modify the minimum purity or the 385

maximum limit of some impurities from what is shown in the five batch 386

analysis data) also, however it shall be noted that such data cannot replace 387

the five batch analysis. Where the active substance is manufactured as 388

technical concentrate (TK) then as well as a specification for the active 389

substance as manufactured, a dry weight specification must be provided. 390

The dry weight specification can be determined by calculation (chapter II 391

section 2.11); 392

Absorption spectra data (UV/VIS, IR, NMR) and a mass spectrum, molar 393

extinction coefficient at relevant wavelengths, where relevant for the purified 394

active substance of stated specification (chapter II, section 3.6). 395

Full description of each endpoint can be found in the Guidance document on Information 396

Requirements (chapter II dossier requirements active substance), available on the 397

Agency website. 398

399

Information requirements - Tier II 400

Additional information requirements for a Tier II application depend on the individual 401

case and applicants are invited to consider the Guidance document on information 402

requirements. The information submitted should cover human health and environmental 403

hazards, including the potential for bioaccumulation and persistence. The applicant 404

should submit all available information. Concerning animal testing, the applicant can 405

consult chapter I, section 1.2 (8) in the Guidance document on Information 406

Requirements. The assessment of eco-toxicity or environmental fate properties like 407

octanol-water partition coefficient, hydrolysis and biodegradation should be based on any 408

available information, including previously conducted studies or at least valid (Q)SAR 409

information. 410

411


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4. Assessment of the technical equivalence application 412

4.1. Processing of the applications by the Agency 413

Figure 2 depicts the processing of an application for technical equivalence by the Agency. 414

415

416

417 418

Figure 2. Processing of the application for the assessment of technical equivalence. 419

420

421

The procedure is as follows: 422

1. Once the application has been submitted, the Agency will check that it fulfils the 423

technical requirements for processing. 424

2. The Agency validates the application, checks the type of the application (defined 425

by the applicant) and sends out the relevant invoice. The Implementing 426

Regulation (EU) No 564/2013 foresees in Annex III three possible application 427

types with different fees as follows: 428

a. Fee, when difference between the active substance sources is limited to a 429

change in manufacturing location, and application is based solely on 430

analytical data (Tier I): EUR 5 000; 431

b. Fee, when difference between the active substance sources goes beyond a 432

change in manufacturing location, and application is based solely on 433

analytical data (Tier I): EUR 20 000. 434

c. Fee when previous conditions are not met (Tier II): EUR 40 000.. 435

3. When the applicant has paid the fee, the scientific assessment of the application 436

starts and the applicant is informed of this via R4BP. If the applicant does not pay 437

the fee within 30 days, the Agency will not process the application and inform the 438

applicant. 439

4. The Agency has 90 days to take a decision on technical equivalence. During the 440

assessment, the Agency can ask for additional information from the applicant and 441

may ask the applicant to submit the additional information within a specified time 442

limit. This time limit may not exceed 180 days except where justified by the 443

nature of the data requested or in exceptional circumstances. If the applicant does 444

not submit the additional information within the time limit specified by the 445

Agency, the Agency will reject the application on the grounds that there is 446

ApplicationTIER I

Fee for Tier I ECHA’s Draft decision

ECHA’s decision: Is alternative

source Technically Equivalent?

Possibility to apply for

TIER II

Application TIER II

Fee for Tier IIPossible

additonal information

request

Possible additional

information request

ECHA’s draft decision

ECHA’s decision: Is alternative

source Technically Equivalent?

Technical Equivalence could not be stablished

TE Decision numberFor Product

authorisation

No

No

Technical Equivalence could not be stablished

Yes

Yes

Applicant’s comments

Applicant’scomments

15 days

15 days

90 days

90 days


18

insufficient information available to assess technical equivalence. The applicant 447

will receive the request for additional information via R4BP and the additional 448

information will need to be submitted by updating the application (the IUCLID 449

dossier). 450

5. If necessary, the Agency can consult the competent authority that prepared the 451

evaluation of the active substance. This is foreseen in cases where the Agency 452

needs additional information on the reference source established. 453

6. The Agency prepares a draft decision and submits this to the applicant via R4BP 454

for comments. The comments need to be provided to the Agency via R4BP within 455

a deadline specified by the Agency. 456

7. When preparing the final decision, the Agency takes into account comments made 457

by the applicant (if any) and communicates the final decision to the applicant and 458

the MSCAs via R4BP. 459

8. The applicant has the right to submit an appeal to the ECHA Board of Appeal 460

according to Article 77 of the BPR. 461

462

4.2. Outcome of the assessment of technical equivalence 463

The decision by the Agency on technical equivalence can be positive (the alternative 464

source is considered to be technically equivalent to the reference source) or negative 465

(when the sources are not technically equivalent or when there is insufficient information 466

available to assess the technical equivalence) (see Figure 2). 467

468

A positive decision on technical equivalence is necessary for product authorisation and 469

should be included in the product authorisation dossier or the dossier for an 470

administrative change to be submitted under Implementing Regulation (EU) No 471

354/2013. In the case of a negative decision in Tier II, the applicant may adjust for 472

example, the manufacturing process and submit a new application (either Tier I or Tier 473

II) to the Agency. 474

475

The best placed to apply for technical equivalence assessment is the manufacturer of the 476

substance produced from the alternative source because of his knowledge of the process 477

and substance. However, a biocidal product authorisation holder or a formulator can also 478

apply, provided that they have the required information available. 479

If the assessment of technical equivalence is necessary the applicant should inform, 480

when relevant, the downstream actors in the supply chain (e.g. biocidal product 481

authorisation holders, formulators) of the need to apply subsequently on the basis of the 482

technical equivalence assessment for an administrative change under Implementing 483

Regulation (EU) No 354/2013. 484

485


19

PART II: Technical Guidance 486

487

5. Assessment of technical equivalence: Substance identity and 488

analytical information (Tier I) 489

The decision tree for assessing technical equivalence was depicted in Figure 2. 490

To address similarity of substances with regard to chemical composition and hazard 491

profile, first the identity of the substance is assessed. This assessment is based on the 492

“Guidance for identification and naming of substances under REACH and CLP” (ECHA, 493

2012). 494

For the evaluation of technical equivalence of the alternative source versus the reference 495

source, the following criteria will be used in Tier I. If all of the following conditions are 496

met, the alternative source is considered to be technically equivalent to the reference 497

source: 498

• The minimum degree of purity obtained with the alternative source is equal to or 499

higher than the one obtained with the reference source, and 500

• For a multi-constituent substance, each main constituent remains in the 10-80% 501

range and the concentration of each main constituent does not deviate by more 502

than 5% absolute or 10% relative, whichever is larger, and 503

• No new impurity or additive is present, and 504

• The limit of each relevant impurity or additive is not exceeded, and 505

• The limits of all significant but not relevant impurities as certified on the basis of a 506

five batch analysis for the reference source are not exceeded by more than the 507

following levels. 508

509

Limits of significant but not relevant impurities

in the technical specifications of the reference

source

Acceptable maximum increase in the

alternative source4

≤6g/kg 3g/kg

>6g/kg 50% of the certified limit

510

Table 2: Levels of significant but not relevant impurities 511

512

513

If one of these conditions is not met, the Tier I assessment cannot conclude that the two 514

sources are technically equivalent. In such a case the applicant may submit an 515

application for Tier II assessment. 516

517

4 These quantitative criteria are based on the FAO manual (2010)


20

6. Evaluation of technical equivalence: Tier II 518

6.1. Toxicity 519

The objective of the evaluation is to identify whether there is an unacceptable change in 520

toxicity profile for the alternative source as compared to the reference source as a result 521

of: 522

• The presence of any new impurities or additives in the alternative source 523

compared to the reference source and/or 524

• Increased levels of relevant impurities or additives that are present in both the 525

alternative and reference sources, and/or 526

• Increased levels of non-relevant impurities, present in both the alternative and 527

the reference sources, which exceed the limits mentioned in Table 2. 528

If new relevant impurities or changes in the levels of relevant impurities occur, the 529

applicant must provide a reasoned case to show that the alternative source is not 530

significantly more toxic than the reference source and if necessary data supporting the 531

reasoned case. 532

If there is evidence that such changes will not have a significant adverse effect on the 533

toxicity of the alternative source (as compared with the reference source), the 534

alternative source is technically equivalent to the reference source. However, if there is 535

evidence that such changes will have a significant adverse effect on the toxicity of the 536

alternative source as compared with the reference source, the alternative source is not 537

considered to be technically equivalent to the reference source. 538

The upper limits specified for relevant impurities of toxicological concern in the 539

alternative source should not exceed the limits as established for the reference source. If 540

it is proposed that the limits for the reference source should be amended, then the 541

applicant will need to provide a justification to support such a proposal. 542

543

6.1.1 Assessment of the toxicity of the impurity profile 544

First of all it should be considered if there is any available data for the impurity (as a 545

pure substance or present as an impurity) and whether the impurity is of toxicological 546

concern. Impurities of interest (because they are new or present at increased levels) can 547

be initially divided into the following categories: 548

Impurities of no toxicological concern: compounds for which the toxicity is known 549

to be low (certain non-critical inert materials, mineral salts, water, etc.). An 550

additional toxicological evaluation would generally not be required, but the 551

applicant would have to submit a justification. 552

Impurities of known toxicological concern: if one or several such impurities are 553

present in the alternative source but not in the reference source, evidence would 554

be needed to show that they will not result in a significantly increased toxicity 555

compared to the reference source. If sufficient evidence cannot be provided, the 556

alternative source will be regarded as not equivalent to the reference source. If an 557

impurity of toxicological concern has been identified as a relevant impurity in the 558


21

reference source, it has to be demonstrated that the levels in the alternative 559

source are acceptable. 560

New impurities of unknown toxicological concern (>1 g/kg) or increased levels of 561

significant but non-relevant impurities: these impurities would elicit a further 562

evaluation. The applicant should demonstrate that the hazard of the alternative 563

source is not significantly increased as compared to the reference source5. 564

If an impurity of toxicological concern in the alternative source does not exceed an 565

acceptable limit concentration for the relevant impurity as established for the reference 566

source, the applicant may indicate that there is no increased hazard for the alternative 567

source when compared to the reference source., A higher concentration of an impurity of 568

toxicological concern in the alternative source with respect to the reference source may 569

be acceptable if the alternative source has similar or lower toxicity in critical toxicity 570

studies than the reference source. 571

572

6.1.2 Decision making 573

When making a decision the following outcomes are possible: 574

• The alternative source does not present a greater hazard; and hence the 575

alternative source can be considered as technically equivalent to the reference source. 576

It is concluded or it cannot be excluded on the basis of the information available 577

that the alternative source presents a greater hazard than the reference source; 578

hence the alternative source cannot be considered as technically equivalent to the 579

reference source. 580

For deciding if the toxicological profile will be considered equivalent to that of the 581

reference source, a difference of factor 2 between the toxicological data provided on the 582

active substance (based on acute oral, dermal and inhalation toxicity, skin and eye 583

irritation, skin sensitisation) for the alternative source compared to the reference source 584

(or by a factor greater than that of the appropriate dosage increments, if more than 2; 585

this might apply where an acute NOAEL is determined) will be used as an indicative value 586

where the data for the alternative source do not lead to a more severe hazard 587

classification. In addition, there should be no change in the assessment in those studies 588

which produce either positive or negative results unless the alternative source is less 589

hazardous, for example mutagenicity or corrosivity6. 590

Where necessary, additional toxicological data from repeated administration (sub-acute 591

to chronic) and studies such as reproductive and developmental toxicity, genotoxicity, 592

and carcinogenicity will be assessed by these criteria provided that, where appropriate, 593

the organs affected are the same. The "no observable effect levels" (NOELs) or "no 594

observable adverse effect levels" (NOAELs) should not differ by more than the difference 595

5 It can be imagined that the hazard of the alternative source is significantly increased by the sum of

all new or increased impurities rather than by one impurity alone. In this case, which is expected to occur only very seldomly, the alternative source will be considered not technically equivalent to the reference source.

6 So for example, the alternative source can only be less corrosive.


22

in the dose levels used. 596

In cases where the effect determining a critical NOAEL differs (different effects on the 597

same organs and/or different mechanisms of action) between the two sources, technical 598

equivalence cannot be demonstrated without additional scientific argumentation. ECHA 599

will assess on a case-by-case basis whether effects are truly toxicologically different. A 600

critical NOAEL is one that could have implications for setting reference doses (ADI, ARfD 601

or AOEL). 602

Irrespective of the above three paragraphs, if a more severe hazard classification is 603

necessary for the alternative source compared to the reference source, the two sources 604

cannot be considered technically equivalent. 605

606

6.2 Ecotoxicity 607

Ecotoxicity covers environmental hazards, including the potential for bio-accumulation 608

and persistence into the environment. The objective is, similar to toxicity, to identify 609

whether there is an unacceptable increase in the environmental hazard profile of the 610

alternative source relative to the reference source as a result of: 611

• The presence of any new impurities or additives in the alternative source 612

compared to the reference source and /or 613

• Increased levels of relevant impurities or additives that are present in both the 614

alternative and reference sources and / or 615

• Increased levels of non-relevant impurities, present in both the alternative and 616

the reference sources, which exceed the limits mentioned in Table 2. 617

If new relevant impurities or changes in the levels of relevant impurities occur, the 618

applicant must provide a reasoned case to show that the alternative source has not a 619

more hazardous ecotoxicity profile (including a significantly higher bio-accumulation and 620

persistence) than the reference source and if necessary provide data supporting the 621

reasoned case. 622

If the assessment concludes that such changes will not make the alternative source more 623

hazardous to the environment than the reference source, the alternative source will be 624

considered technically equivalent to the reference source. If it is not the case, the 625

alternative source will not be considered to be technically equivalent to the reference 626

source. 627

If relevant, the upper limits specified for relevant impurities of ecotoxicological concern 628

established and accepted in the reference source should be taken into account in the 629

hazard assessment. If the applicant proposes that established limits for the reference 630

source are amended, the applicant should provide a justification to support such a 631

proposal. 632

633

6.2.1 Assessment of the ecotoxicity of the impurity profile 634

First of all it should be considered if there is any available data for the impurity (as a 635


23

pure substance or present as an impurity) and whether the impurity is of ecotoxicological 636

concern. Impurities of interest (because they are new or present at increased levels) can 637

be initially divided into the following categories: 638

639

Impurities of no ecotoxicological concern: compounds for which the ecotoxicity is 640

known to be low (certain non-critical inert materials, mineral salts, water, etc.). 641

An additional ecotoxicological evaluation would generally not be required, but the 642

applicant would have to submit a justification. 643

Impurities of known ecotoxicological concern: if one or several of such impurities 644

are present in the alternative source but not in the reference source, evidence 645

would be needed to show that they will not result in a significantly increased 646

ecotoxicity compared to the reference source. If sufficient evidence cannot be 647

provided, the alternative source will be regarded as not equivalent to the 648

reference source. If an impurity of ecotoxicological concern has been identified as 649

a relevant impurity in the reference source, it has to be demonstrated that the 650

levels in the alternative source are acceptable. 651

New impurities of unknown ecotoxicological concern or levels of significant but 652

non-relevant impurities increased above the relevant acceptable threshold: these 653

impurities would elicit a further evaluation. The applicant should demonstrate that 654

the hazard to the environment of the alternative source is not significantly 655

increased as compared to the reference source7. 656

If an impurity of ecotoxicological concern in the alternative source does not exceed an 657

acceptable limit concentration for the relevant impurity as established for the reference 658

source, the applicant may indicate that there is no increased hazard for the alternative 659

source when compared to the reference source. A concentration of an impurity of 660

ecotoxicological concern in the alternative source than in the reference source may be 661

acceptable if the alternative source has similar or lower ecotoxicity in critical ecotoxicity 662

studies than the reference source. 663

664

6.2.2 Decision making 665

When making a decision the following outcomes are possible: 666

The alternative source does not present a greater hazard to the environment; 667

hence the alternative source can be considered as technically equivalent to the reference 668

source. 669

It is concluded or it cannot be excluded on the basis of the information available 670

that the alternative source presents a greater hazard to the environment than the 671

reference source; hence the alternative source cannot be considered as technically 672

equivalent to the reference source. 673

7 It can be imagined that the hazard of the alternative source is significantly increased by the sum of all new or increased impurities rather than by one impurity alone. In this case which is expected to occur only very seldomly, the alternative source will be considered not technically equivalent to the reference source.


24

For deciding if the ecotoxicological hazard profile will be considered equivalent to that of 674

the reference source, a difference of a factor 5 between the endpoint of ecotoxicological 675

data provided on the active substance (based on acute toxicity to the same aquatic and 676

terrestrial species) for the alternative source compared to the reference source (or by a 677

factor greater than that of the appropriate dosage increments, if greater than 2) will be 678

used as an indicative value where the data for the alternative source do not lead to a 679

more severe hazard classification for the environment. In addition, there should be no 680

change in the assessment in those studies which produce either positive or negative 681

results unless the alternative source is less hazardous, for example tests for ready 682

biodegradability. 683

Where necessary, additional ecotoxicological data from long term studies on aquatic or 684

terrestrial organisms tested for the reference substance, bioaccumulation and 685

biodegradation studies in relevant environmental compartment will be assessed by these 686

criteria provided that, where appropriate, the tested species and environmental 687

compartments are the same. 688

Irrespective of the above three paragraphs, if a more severe hazard classification for the 689

environment is necessary for the alternative source compared to the reference source 690

(e.g. due to differences in biodegradation or bioaccumulation potential), the two sources 691

cannot be considered technically equivalent. 692

693


25

References 694

DG ENV (2008): Technical Notes for Guidance on the assessment of technical 695

equivalence of substances regulated under Directive 98/8/EC. 696

DG SANCO (2012): Guidance document on the assessment of the equivalence of 697

technical materials of substances regulated under Regulation (EC) No 1107/2009. 698

ECHA (2008): Guidance document on information requirements and chemical 699

assessment. Chapter R.6: QSARs and grouping of chemicals. 700

ECHA (2012): Guidance for identification and naming of substances under REACH and 701

CLP. 702

FAO/WHO Joint Meeting on Pesticide Specifications (JMPS) (2010): Manual on 703

Development and Use of FAO and WHO specifications for Pesticides (second revision of 704

the First Edition, Rome). 705

706


26

Annex I: template Technical equivalence report: Assessment for Tier II. 707

708


27

709

Technical equivalence report 710

711

Assessment for Tier II 712

713

Based on Regulation (EC) No 528/2012 714

(BPR Regulation), 715

Article 54 716

717

Substance Name: 718

719

720

721

722

723

724

725

726

727

728

729

730

731

Date: 732

733


28

STATEMENT OF SUBJECT MATTER AND PURPOSE FOR WHICH THE REPORT 734

WAS PREPARED 735

736

737

This report was prepared in accordance with the guidance document “Guidance 738

document on applications for technical equivalence” under Regulation (EC) No 528/2012. 739

740

The applicant must indicate in the table below which case has been examined for 741

TIER I: 742

743

744

Technical material from a new/different manufacturer

Change in the manufacturing process, and/or manufacturing location.

Data from industrial scale production vs pilot scale production 745

746

747

748

1. APPLICANT 749

750

Applicant 751

752

753

Manufacturer of the active substance, if different from the applicant 754

755

756

Common name proposed or accepted by ISO and synonyms 757

758

759

Chemical name (IUPAC and CA nomenclature or other international chemical 760

name(s)) 761

762

763

CAS number, EC, INDEX and CIPAC numbers (if allocated) 764

765

766

767

768

769

2. EVALUATION OF THE SOURCES OF THE SUBSTANCE (TIER II) 770

771

772

TOXICOLOGY 773

774

2.1.1. ASSESSMENT OF EQUIVALENCE 775

776


29

777

Endpoint

Result8

Alternative source Reference source9

Toxicokinetics

Acute toxicity - oral

Acute toxicity - dermal

Acute toxicity - inhalation

Skin corrosion / irritation

Serious eye damage / eye

irritation

Respiratory sensitisation

Skin sensitisation

Repeated dose toxicity

Germ cell mutagenicity

Carcinogenicity

Toxicity to reproduction -

fertility

Toxicity to reproduction -

development

Toxicity of metabolites and

degradation products

Neurotoxicity

Inmunotoxicity

778

779

780

2.1.2. CONCLUSIONS 781

782

783

784

785

8 Fill in the results for those endpoints for which data are available. 9 Data for the reference source can be taken from the published Assessment Report for

the active substance included on the Union list of approved substances.


30

786

ECOTOXICOLOGY 787

788

2.1.3. ASSESSMENT OF EQUIVALENCE 789

790

Endpoint

Result1

Alternative source Reference source2

Environmental fate and behaviour

Abiotic degradation -

hydrolisis

Abiotic degradation - photo

Biodegradation

Ecotoxicological studies

Short term toxicity test - fish

Short term toxicity test –

aquatic invertebrates

Growth inhibition on algae

Further toxicity studies on

aquatic organisms

Bioconcentration

Terrestrial toxicity (for

example earthworm and

plants)

791

792

793

2.1.4. CONCLUSIONS 794

795

796

797

3. OVERALL CONCLUSION FOR TIER II 798

799

800

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