Legalize / European Union / Delegated Regulation

Commission Delegated Regulation (EU) 2021/805 of 8 March 2021 amending Annex II to Regulation (EU) 2019/6 of the European Parliament and of the Council (Text with EEA relevance)

Type Delegated Regulation

Publication 2021-05-21

State In force

Text As published

Department European Commission, SANTE

Source EUR-Lex

articles 2

This is the act as published. Later amendments are not folded into the text below: each one is a separate act in this repository and an entry in this law's history.

Reform history JSON API


21.5.2021	EN	Official Journal of the European Union	L 180/3

THE EUROPEAN COMMISSION,

Having regard to the Treaty on the Functioning of the European Union,

Having regard to Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary medicinal products and repealing Directive 2001/82/EC ¹, and in particular Article 146(2) thereof,

Whereas:

(1) It is appropriate to substantially update the requirements set out in Annex II to Regulation (EU) 2019/6, which took over the dossier requirements set out in Annex I to Directive 2001/82/EC of the European Parliament and of the Council ², as that Regulation did not update those dossier requirements at the time of repealing that Directive. The dossier requirements set out in Annex I to Directive 2001/82/EC had last been updated in 2009. Therefore, Annex II should be amended to take account of scientific progress and developments since 2009, including international guidance from the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), World Health Organisation (WHO) and the organisation of Economic cooperation and development (OECD) standards.

(2) It is also appropriate to set out requirements for biological veterinary medicinal products and novel therapy veterinary medicinal products introduced as new categories of veterinary medicinal products by Regulation (EU) 2019/6. For those products, specific technical requirements to be presented when applying for a marketing authorisation should be defined.

(3) Recognising that antimicrobial resistance to medicinal products is a growing health problem in the Union and worldwide, Regulation (EU) 2019/6 introduced specific legal provisions aimed at limiting the risk of development of antimicrobial resistance to medicinal products. It is therefore appropriate to introduce specific technical requirements for antimicrobial veterinary medicinal products.

(4) This Regulation should apply from 28 January 2022 in accordance with Article 153(3) of Regulation (EU) 2019/6.

(5) Regulation (EU) 2019/6 should therefore be amended accordingly,

HAS ADOPTED THIS REGULATION:

Article 1

Annex II to Regulation (EU) 2019/6 is replaced by the text in the Annex to this Regulation.

Article 2

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

It shall apply from 28 January 2022.

This Regulation shall be binding in its entirety and directly applicable in all Member States.

Done at Brussels, 8 March 2021.

For the Commission

The President

Ursula VON DER LEYEN

OJ L 4, 7.1.2019, p. 43.

Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products (OJ L 311, 28.11.2001, p. 1).

ANNEX

‘ANNEX II

REQUIREMENTS REFERRED TO IN ARTICLE 8(1), POINT (B)


SECTION I	GENERAL PRINCIPLES AND REQUIREMENTS	11

---	---	---
I.1.	General principles	11

---	---	---
I.2.	Dossier composition requirements	11

---	---	---
I.2.1.	Part 1: Summary of the dossier	11

---	---	---
I.2.2.	Part 2: Quality documentation (physicochemical, biological or microbiological information)	12

---	---	---
I.2.3.	Part 3: Safety documentation (safety and residues tests)	13

---	---	---
I.2.4.	Part 4: Efficacy documentation (pre-clinical studies and clinical trial(s))	13

---	---	---
I.2.5.	Detailed requirements for different types of veterinary medicinal products or marketing authorisation dossiers	14

---	---	---
SECTION II	REQUIREMENTS FOR VETERINARY MEDICINAL PRODUCTS OTHER THAN BIOLOGICAL VETERINARY MEDICINAL PRODUCTS	14

---	---	---
II.1.	Part 1: Summary of the dossier	14

---	---	---
II.2.	Part 2: Quality documentation (physicochemical, biological or microbiological information)	14

---	---	---
II.2A.	Product description	14

---	---	---
II.2A1.	Qualitative and quantitative composition	14

---	---	---
II.2A2.	Product development	16

---	---	---
II.2B.	Description of the manufacturing method	16

---	---	---
II.2C.	Production and control of starting material	16

---	---	---
II.2C1.	Active substance(s)	17

---	---	---
II.2C1.1.	Active substances listed in pharmacopoeias	18

---	---	---
II.2C1.2.	Active substances not listed in a pharmacopoeia	18

---	---	---
II.2C1.3.	Physicochemical characteristics liable to affect bioavailability	18

---	---	---
II.2C2.	Excipients	19

---	---	---
II.2C3.	Packaging (container-closure systems)	19

---	---	---
II.2C3.1.	Active substance	19

---	---	---
II.2C3.2.	Finished product	19

---	---	---
II.2C4.	Substances of biological origin	20

---	---	---
II.2D.	Control tests carried out on isolated intermediates during the manufacturing process	20

---	---	---
II.2E.	Control tests on the finished product	20

---	---	---
II.2E1.	General characteristics of the finished product	21

---	---	---
II.2E2.	Identification and assay of active substance(s)	21

---	---	---
II.2E3.	Identification and assay of excipient components	21

---	---	---
II.2E4.	Microbiological controls	21

---	---	---
II.2E5.	Batch-to-batch consistency	21

---	---	---
II.2E6.	Other controls	22

---	---	---
II.2F.	Stability test	22

---	---	---
II.2F1.	Active substance(s)	22

---	---	---
II.2F2.	Finished product	22

---	---	---
II.2G.	Other information	23

---	---	---
II.3	Part 3: Safety documentation (safety and residues tests)	23

---	---	---
II.3A.	Safety tests	23

---	---	---
II.3A1.	Precise identification of the product and of its active substance(s)	24

---	---	---
II.3A2.	Pharmacology	24

---	---	---
II.3A2.1.	Pharmacodynamics	24

---	---	---
II.3A2.2.	Pharmacokinetics	25

---	---	---
II.3A3.	Toxicology	25

---	---	---
II.3A4.	Other requirements	26

---	---	---
II.3A.4.1.	Special studies	26

---	---	---
II.3A.4.2.	Observations in humans	26

---	---	---
II.3A.4.3.	Development of resistance and related risk in humans	27

---	---	---
II.3A5.	User safety	27

---	---	---
II.3A6.	Environmental risk assessment	27

---	---	---
II.3B.	Residue tests	28

---	---	---
II.3B1.	Identification of the product	28

---	---	---
II.3B2.	Depletion of residues (metabolism and residue kinetics)	28

---	---	---
II.3B3.	Residue analytical method	29

---	---	---
II.4.	Part 4: Efficacy documentation (pre-clinical studies and clinical trial(s))	29

---	---	---
II.4A.	Pre-clinical studies	29

---	---	---
II.4A1.	Pharmacology	29

---	---	---
II.4A.1.1.	Pharmacodynamics	29

---	---	---
II.4A.1.2.	Pharmacokinetics	29

---	---	---
II.4A2.	Development of resistance and related risk in animals	30

---	---	---
II.4A3.	Dose determination and confirmation	30

---	---	---
II.4A4.	Tolerance in the target animal species	30

---	---	---
II.4B.	Clinical trial(s)	31

---	---	---
II.4B1.	General principles	31

---	---	---
II.4B2.	Documentation	31

---	---	---
II.4B2.1.	Results of pre-clinical studies	31

---	---	---
II.4B2.2.	Results of clinical trials	32

---	---	---
SECTION III	REQUIREMENTS FOR BIOLOGICAL VETERINARY MEDICINAL PRODUCTS	32

---	---	---
SECTION IIIa	REQUIREMENTS FOR BIOLOGICAL VETERINARY MEDICINAL PRODUCTS OTHER THAN IMMUNOLOGICAL VETERINARY MEDICINAL PRODUCTS	33

---	---	---
IIIa.1.	Part 1: Summary of the dossier	33

---	---	---
IIIa.2.	Part 2: Quality documentation (physicochemical, biological or microbiological information)	33

---	---	---
IIIa.2A.	Product description	33

---	---	---
IIIa.2A1.	Qualitative and quantitative composition	33

---	---	---
IIIa.2A2.	Product development	34

---	---	---
IIIa.2A3.	Characterisation	34

---	---	---
IIIa.2A3.1.	Elucidation of structure and other characteristics	34

---	---	---
IIIa.2A3.2.	Impurities	35

---	---	---
IIIa.2B.	Description of the manufacturing method	35

---	---	---
IIIa.2C.	Production and control of starting materials	35

---	---	---
IIIa.2C1.	Starting materials listed in pharmacopoeias	36

---	---	---
IIIa.2C2.	Starting materials not listed in a pharmacopoeia	36

---	---	---
IIIa.2C2.1.	Starting materials of biological origin	36

---	---	---
IIIa.2C2.2.	Starting materials of non-biological origin	37

---	---	---
IIIa.2D.	Control tests during the manufacturing process	37

---	---	---
IIIa.2E.	Control tests on the finished product	38

---	---	---
IIIa.2E1	Finish product specification	38

---	---	---
IIIa.2E2	Method descriptions and validation of release tests	38

---	---	---
IIIa.2E3.	Reference standards or materials	39

---	---	---
IIIa.2F.	Batch-to-batch consistency	39

---	---	---
IIIa.2F1.	Active substance	39

---	---	---
IIIa.2F2.	Finished product	39

---	---	---
IIIa.2G.	Stability tests	39

---	---	---
IIIa.2H.	Other information	40

---	---	---
IIIa.3.	Part 3: Safety documentation (safety and residues tests)	40

---	---	---
IIIa.3A.	Safety tests	41

---	---	---
IIIa.3A1.	Precise identification of the product and of its active substance(s):	41

---	---	---
IIIa.3A2.	Pharmacology	41

---	---	---
IIIa.3A2.1.	Pharmacodynamics	42

---	---	---
IIIa.3A2.2.	Pharmacokinetics	42

---	---	---
IIIa.3A3.	Toxicology	42

---	---	---
IIIa.3A3.1.	Single-dose toxicity	42

---	---	---
IIIa.3A3.2.	Repeat-dose toxicity	42

---	---	---
IIIa.3A3.3.	Tolerance in the target species	43

---	---	---
IIIa.3A3.4.	Reproductive toxicity including developmental toxicity	43

---	---	---
IIIa.3A3.5.	Genotoxicity	43

---	---	---
IIIa.3A3.6.	Carcinogenicity	43

---	---	---
IIIa.3A3.7.	Exceptions	43

---	---	---
IIIa.3A4.	Other requirements	44

---	---	---
IIIa.3A4.1.	Special studies	44

---	---	---
IIIa.3A4.2.	Observations in humans	44

---	---	---
IIIa.3A4.3.	Development of resistance and related risk in humans	44

---	---	---
IIIa.3A5.	User safety	45

---	---	---
IIIa.3A6.	Environmental risk assessment	45

---	---	---
IIIa.3A6.1.	Environmental risk assessment of veterinary medicinal products not containing or consisting of genetically modified organisms	45

---	---	---
IIIa.3A6.2.	Environmental risk assessment for veterinary medicinal products containing or consisting of genetically modified organisms	45

---	---	---
IIIa.3B.	Residue tests	46

---	---	---
IIIa.3B1.	Identification of the product	46

---	---	---
IIIa.3B2.	Depletion of residues	46

---	---	---
IIIa.3B3.	Residue analytical method	46

---	---	---
IIIa.4.	Part 4: Efficacy documentation (pre-clinical studies and clinical trial(s))	47

---	---	---
IIIa.4A.	Pre-clinical studies	47

---	---	---
IIIa.4A1.	Pharmacology	47

---	---	---
IIIa.4A1.1.	Pharmacodynamics	47

---	---	---
IIIa.4A1.2.	Pharmacokinetics	47

---	---	---
IIIa.4A2.	Development of resistance and related risk in animals	48

---	---	---
IIIa.4A3.	Dose determination and confirmation	48

---	---	---
IIIa.4A4.	Tolerance in the target animal species	48

---	---	---
IIIa.4B.	Clinical trials	48

---	---	---
IIIa.4B1.	General principles	48

---	---	---
IIIa.4B2.	Documentation	49

---	---	---
IIIa.4B2.1.	Clinical trials	49

---	---	---
IIIa.4B2.2.	Clinical trials	49

---	---	---
SECTION IIIb	REQUIREMENTS FOR IMMUNOLOGICAL VETERINARY MEDICINAL PRODUCTS	50

---	---	---
IIIb.1.	Part 1: Summary of the dossier	50

---	---	---
IIIb.2.	Part 2: Quality documentation (physicochemical, biological and microbiological information)	50

---	---	---
IIIb.2.A.	Product description	50

---	---	---
IIIb.2A1.	Qualitative and quantitative composition	50

---	---	---
IIIb.2A2.	Product development	51

---	---	---
IIIb.2B.	Description of the manufacturing method	52

---	---	---
IIIb.2C.	Production and control of starting materials	52

---	---	---
IIIb.2C1.	Starting materials listed in pharmacopoeias	53

---	---	---
IIIb.2C2.	Starting materials not listed in a pharmacopoeia	53

---	---	---
IIIb.2C2.1.	Starting materials of biological origin	53

---	---	---
IIIb.2C2.2.	Starting materials of non-biological origin	54

---	---	---
IIIb.2D.	Control tests during the manufacturing process	54

---	---	---
IIIb.2E.	Control tests on the finished product	55

---	---	---
IIIb.2F.	Batch-to-batch consistency	56

---	---	---
IIIb.2G.	Stability tests	56

---	---	---
IIIb.2H.	Other information	57

---	---	---
IIIb.3.	Part 3: Safety documentation (safety and residues tests)	57

---	---	---
IIIb.3A.	General requirements	57

---	---	---
IIIb.3B.	Pre-clinical studies	58

---	---	---
IIIb.3C.	Clinical trials	60

---	---	---
IIIb.3D.	Environmental risk assessment	60

---	---	---
IIIb.3E.	Assessment required for veterinary medicinal products containing or consisting of genetically modified organisms	61

---	---	---
IIIb.3F.	Residue tests to be included in the laboratory studies	61

---	---	---
IIIb.4.	Part 4: Efficacy documentation (pre-clinical studies and clinical trial(s))	61

---	---	---
IIIb.4A.	General requirements	61

---	---	---
IIIb.4B.	Pre-clinical studies	62

---	---	---
IIIb.4C.	Clinical trials	63

---	---	---
SECTION IV	REQUIREMENTS FOR SPECIFIC MARKETING AUTHORISATION APPLICATIONS	64

---	---	---
IV.1.	Applications for generic veterinary medicinal products	64

---	---	---
IV.2.	Applications for hybrid veterinary medicinal products	65

---	---	---
IV.3.	Applications for combination veterinary medicinal products	66

---	---	---
IV.4.	Applications based on informed consent	66

---	---	---
IV.5.	Applications based on bibliographic data	66

---	---	---
IV.6.	Applications for limited markets	68

---	---	---
IV.7.	Applications in exceptional circumstances	68

---	---	---
SECTION V	REQUIREMENTS FOR MARKETING AUTHORISATION APPLICATIONS FOR PARTICULAR VETERINARY MEDICINAL PRODUCTS	68

---	---	---
V.1.	Novel therapies veterinary medicinal products	68

---	---	---
V.1.1	General requirements	68

---	---	---
V.1.2.	Quality requirements	69

---	---	---
V.1.3.	Safety requirements	70

---	---	---
V.1.4.	Efficacy requirements	70

---	---	---
V.1.5.	Specific data requirements for particular types of novel therapy products	70

---	---	---
V.1.5.1.	Principles	70

---	---	---
V.1.5.2.	Gene therapy veterinary medicinal products	70

---	---	---
V.1.5.3.	Regenerative medicine, tissue engineering and cell therapy veterinary medicinal products	71

---	---	---
V.1.5.4.	Veterinary medicinal product specifically designed for phage therapy	72

---	---	---
V.1.5.5.	Veterinary medicinal product issued from nanotechnologies	72

---	---	---
V.1.5.6.	RNA antisense therapy and RNA interference therapy products	73

---	---	---
V.2.	Vaccine antigen master file	74

---	---	---
V.3.	Multi-strain dossier	75

---	---	---
V.4.	Vaccine platform technology	75

---	---	---
V.5.	Authorised homeopathic veterinary medicinal products	76

SECTION I

GENERAL PRINCIPLES AND REQUIREMENTS

I.1. General principles


	I.1.1.	The documentation accompanying an application for a marketing authorisation pursuant to Articles 8, and 18 to 25 shall be presented in accordance with the requirements set out in this Annex and shall take into account the guidance documents published by the Commission and the requirements for electronic format published by the Agency.

---	---	---
	I.1.2.	In assembling the dossier for application for a marketing authorisation, applicants shall also take into account the most up-to-date veterinary medicinal knowledge and the scientific guidelines relating to the quality, safety and efficacy of veterinary medicinal products published by the Agency.

---	---	---
	I.1.3.	For veterinary medicinal products, all relevant monographs of the European Pharmacopoeia, including general monographs and the general chapters, are applicable for the appropriate parts of the dossier.

---	---	---
	I.1.4.	The manufacturing processes for the active substance(s) and finished product shall comply with Good Manufacturing Practice (GMP).

---	---	---
	I.1.5.	All information which is relevant to the evaluation of the veterinary medicinal product concerned shall be included in the application, whether favourable or unfavourable to the product. In particular, all relevant details related to any incomplete or abandoned study or trial relating to the veterinary medicinal product shall be given.

---	---	---
	I.1.6.	Pharmacological, toxicological, residue and pre-clinical studies shall be carried out in conformity with the provisions related to Good Laboratory Practice (GLP) laid down in Directives 2004/10/EC ³ and 2004/9/EC of the European Parliament and of the Council ⁴.

---	---	---
	I.1.7.	All experiments on animals shall be conducted taking into account the principles laid down in Directive 2010/63/EU, notwithstanding the place of conduct of the experiments.

---	---	---
	I.1.8.	The environmental risk assessment connected with the release of veterinary medicinal products containing or consisting of Genetically Modified Organisms (GMOs) within the meaning of Article 2 of Directive 2001/18/EC shall be provided in the dossier as a separate document. The information shall be presented in accordance with the provisions of Directive 2001/18/EC, taking into account guidance published by the Commission.

---	---	---
	I.1.9.	The applicant shall confirm in Part 1 of the dossier for an application for marketing authorisation that all submitted data relevant to the quality, safety and efficacy of the veterinary medicinal product, including data publicly available, are not subject to protection of technical documentation.

I.2. Dossier composition requirements

Any dossier for an application for marketing authorisation for a veterinary medicinal product shall consist of the following parts:

I.2.1. Part 1: Summary of the dossier

Part 1 shall include administrative information as outlined in Annex I, as follows:

(a) Part 1A: points 1 to 4 and 6.1 to 6.4;

(b) Part 1B: point 5;

With regard to Part 1B, point 5.1, in connection to Article 35(1), point (l), an application proposing classification of a veterinary medicinal product as "not subject to veterinary prescription" shall include a critical review of the product characteristics in order to justify the suitability of such classification taking into consideration target and non-target animal safety, public health as well as environmental safety, as outlined in the criteria given in Article 34(3), points (a) to (g).

Each critical expert report shall be prepared with regard to the state of scientific knowledge at the time of submission of the application. It shall contain an evaluation of the various tests and trials which constitute the marketing authorisation dossier, and shall address all aspects relevant to the assessment of the quality, safety and efficacy of the veterinary medicinal product. It shall give detailed results of the tests and trials submitted and precise bibliographic references. Copies of the bibliographic references cited shall be provided.

The critical expert reports shall be signed and dated by the author of those reports, and information about the author’s educational background, training and occupational experience shall be attached. The professional relationship of the author with the applicant shall be declared.

The critical expert reports and the appendices shall contain precise and clear cross-references to the information contained in the technical documentation.

Where Part 2 is presented using the format of the Common Technical Document (CTD), the quality overall summary (QOS) shall be used for the critical expert report on quality.

For Parts 3 and 4 the critical expert report shall also include a tabulated summary of all technical documentation and relevant data submitted.

I.2.2. Part 2: Quality documentation (physicochemical, biological or microbiological information)


	(1)	The pharmaceutical quality (physicochemical, biological or microbiological) data shall include for the active substance(s) and for the finished veterinary medicinal product information on the manufacturing process, the characterisation and properties, the quality control procedures and requirements, the stability as well as a description of the composition, the development and presentation of the veterinary medicinal product.

---	---	---
	(2)	All monographs, including specific monographs, general monographs and general chapters of the European Pharmacopoeia are applicable. For immunological veterinary medicinal products, all monographs, including specific monographs, general monographs and general chapters of the European Pharmacopoeia are applicable, unless otherwise justified. In the absence of a European Pharmacopoeia monograph, the monograph of a Member State pharmacopoeia may be applied. In cases where a substance is described neither in the European Pharmacopoeia nor in the pharmacopoeia of a Member State, compliance with the monograph of a third country pharmacopoeia may be accepted if its suitability is demonstrated; in such cases, the applicant shall submit a copy of the monograph accompanied by a translation where appropriate. Data to demonstrate the ability of the monograph to adequately control the quality of the substance shall be presented.

---	---	---
	(3)	If tests other than those mentioned in the pharmacopoeia are used, the use of such tests shall be justified by providing proof that the materials, if tested in accordance with the pharmacopoeia, would meet the quality requirements of the relevant pharmacopoeial monograph.

---	---	---
	(4)	All test procedures for analysis and quality control shall take account of established guidance and requirements. The results of the validation studies shall be provided. All the test procedure(s) shall be described in sufficient detail so as to be reproducible in control tests, carried out at the request of the competent authority and in order to be properly assessed by the competent authority. Any special apparatus and equipment, which may be used shall be described in adequate manner, accompanied by a diagram, if relevant. The formulae of the laboratory reagents shall be supplemented, if necessary, by the method of preparation. In the case of test procedures included in the European Pharmacopoeia or the pharmacopoeia of a Member State, this description may be replaced by a detailed reference to the pharmacopoeia in question.

---	---	---
	(5)	Where available, chemical and biological reference material of the European Pharmacopoeia shall be used. If other reference preparations and standards are used, they shall be identified and described in detail.

---	---	---
	(6)	The pharmaceutical quality (physicochemical, biological or microbiological) data for the active substance and/or the finished product may be included in the dossier in Common Technical Document (CTD) format.

---	---	---
	(7)	For biological veterinary medicinal products, including immunologicals, information on solvents needed for making the final product preparation shall be included in the dossier. A biological veterinary medicinal product is regarded as one product even when more than one solvent is required so that different preparations of the final product can be prepared, which may be for administration by different routes or methods of administration. Solvents supplied with biological veterinary medicinal products may be packed together with the active substance vials or separately.

---	---	---
	(8)	In accordance with Directive 2010/63/EU and the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, tests shall be carried out in such a way as to use the minimum number of animals and to cause the least pain, suffering, distress or lasting harm. If available, an alternative in vitro test shall be used when this leads to replacement or reduction of animal use or reduction of suffering.

I.2.3. Part 3: Safety documentation (safety and residues tests)


	(1)	The dossier on the safety studies shall include the following: (a) synthesis of the tests which have been carried out in compliance with this Part, with detailed references to the published literature containing an objective discussion of all the results obtained. Omission of any tests or trials listed and inclusion of an alternative type of study shall be indicated and discussed; (b) a statement of compliance with good laboratory practice for pre-clinical studies, where applicable, together with a discussion of the contribution that any non-GLP study may make to the overall risk assessment, and justification of non-GLP status.

---	---	---
	(2)	The dossier shall include the following: (a) an index of all studies and trials included in the dossier; (b) a justification for the omission of any type of study and trial; (c) an explanation of the inclusion of an alternative type of study or trial; (d) a discussion of the contribution that any non-GLP study or trial may make to the overall risk assessment and justification of non-GLP status.

I.2.4. Part 4: Efficacy documentation (pre-clinical studies and clinical trial(s))


	(1)	The dossier on efficacy shall include all pre-clinical and clinical documentation, whether favourable or unfavourable to the veterinary medicinal products, in order to enable an objective overall assessment of the benefit/risk balance of the product.

---	---	---
	(2)	The dossier on the efficacy studies shall include the following: (a) synthesis of the tests which have been carried out in compliance with this Part, with detailed references to the published literature containing an objective discussion of all the results obtained. Omission of any tests or trials listed and inclusion of an alternative type of study shall be indicated and discussed; (b) a statement of compliance with good laboratory practice for pre-clinical studies, where applicable, together with a discussion of the contribution that any non-GLP study may make to the overall risk assessment, and justification of non-GLP status.

---	---	---
	(3)	The dossier shall include the following: (a) an index of all studies included in the dossier; (b) a justification for the omission of any type of study; (c) an explanation of the inclusion of an alternative type of study.

---	---	---
	(4)	The purpose of the trials described in this Part is to demonstrate the efficacy of the veterinary medicinal product. All claims made by the applicant with regard to the properties, effects and use of the product shall be fully supported by results of specific trials contained in the application for marketing authorisation.

---	---	---
	(5)	All efficacy trials shall be conducted in accordance with a fully considered detailed protocol, which shall be recorded in writing prior to commencement of the trial. The welfare of the trial animals shall be subject to veterinary supervision and shall be taken fully into consideration during the elaboration of any trial protocol and throughout the conduct of the trial.

---	---	---
	(6)	Clinical trials (field trials) shall be conducted in accordance with established principles of good clinical practice, unless otherwise justified.

---	---	---
	(7)	Before the commencement of any field trial, the informed consent of the owner of the animals to be used in the trial shall be obtained and documented. In particular, the animal owner shall be informed in writing of the consequences of participation in the trial for the subsequent disposal of treated animals or for the taking of foodstuffs from treated animals.

I.2.5. Detailed requirements for different types of veterinary medicinal products or marketing authorisation dossiers


	(1)	Detailed requirements for different types of veterinary medicinal products or specific types of marketing authorisation dossiers are outlined in the following Sections of this Annex: (a) Section II describes the standardised requirements for applications for veterinary medicinal products other than biological veterinary medicinal products; (b) Section III describes the standardised requirements for applications for biological veterinary medicinal products: (i) Section IIIa describes the standardised requirements for applications for biological veterinary medicinal products other than immunological veterinary medicinal products; (ii) Section IIIb describes the standardised requirements for applications for immunological veterinary medicinal products; (c) Section IV describes the dossier requirements for specific types of marketing authorisation dossiers; (d) Section V describes the dossier requirements for particular types of veterinary medicinal products.

SECTION II

REQUIREMENTS FOR VETERINARY MEDICINAL PRODUCTS OTHER THAN BIOLOGICAL VETERINARY MEDICINAL PRODUCTS

The following detailed requirements shall apply to veterinary medicinal products other than biological veterinary medicinal products, except where otherwise set out in Section IV.

II.1. Part 1: Summary of the dossier

Please refer to Section I.

II.2. Part 2: Quality documentation (physicochemical, biological or microbiological information)

II.2A. Product description

II.2A1. Qualitative and quantitative composition


	(1)	Qualitative composition of all the constituents of the medicinal product shall mean the designation or description of: (a) active substance(s); (b) excipients, the constituents of the excipients, whatever their nature or the quantity used, including colouring matter, preservatives, adjuvants, stabilisers, thickeners, emulsifiers, flavouring and aromatic substances; (c) other constituents, intended to be ingested or otherwise administered to animals, of the outer covering of the veterinary medicinal products, such as capsules, gelatine capsules, intraruminal devices; (d) any relevant data concerning the immediate packaging and if relevant the outer packaging and, where appropriate, its manner of closure, together with details of devices with which the veterinary medicinal product will be used or administered and which will be supplied with the medicinal product.

---	---	---
	(2)	The usual terminology to be used in describing the constituents of veterinary medicinal products means, notwithstanding the application of the other provisions of Article 8: (a) in respect of substances which appear in the European Pharmacopoeia or, failing this, in the national pharmacopoeia of one of the Member States, the main title at the head of the monograph in question, with reference to the pharmacopoeia concerned; (b) in respect of other substances, the international non-proprietary name (INN) recommended by the World Health Organisation (WHO), which may be accompanied by another non-proprietary name, or, failing these, the exact scientific designation; (c) constituents not having an international non-proprietary name or an exact scientific designation shall be described by a statement of how and from what they were prepared, supplemented, where appropriate, by any other relevant details; (d) in respect of colouring matter, designation by the “E” code assigned to them by Directive 2009/35/EC of the European Parliament and Council.

---	---	---
	(3)	In order to give the quantitative composition of all the active substances and excipients of the veterinary medicinal products, it is necessary, depending on the pharmaceutical form concerned, to specify the mass, or the number of units of biological activity, either per dosage-unit or per unit of mass or volume, of each active substance and excipient.

---	---	---
	(4)	Units of biological activity shall be used for substances which cannot be defined chemically. Where an international unit of biological activity has been defined, this shall be used. Where no international unit has been defined, the units of biological activity shall be expressed in such a way as to provide unambiguous information on the activity of the substances by using where applicable the European Pharmacopoeia Units.

---	---	---
	(5)	Quantitative composition shall be supplemented: (a) in respect of single-dose preparations: by the mass or units of biological activity of each active substance in the unit container, taking into account the usable volume of the product, after reconstitution, where appropriate; (b) in respect of veterinary medicinal products to be administered by drops: by the mass or units of biological activity of each active substance contained per drop or contained in the number of drops corresponding to 1 ml or 1 g of the preparation; (c) in respect of pharmaceutical forms to be administered in measured quantities: by the mass or units of biological activity of each active substance per measured quantity.

---	---	---
	(6)	Active substances present in the form of compounds or derivatives shall be described quantitatively by their total mass, and if necessary or relevant, by the mass of the active entity or entities of the molecule.

---	---	---
	(7)	For veterinary medicinal products containing an active substance which is the subject of an application for marketing authorisation in the Union for the first time, the quantitative statement of an active substance which is a salt or hydrate shall be systematically expressed in terms of the mass of the active entity or entities in the molecule. All subsequently authorised veterinary medicinal products in the Member States shall have their quantitative composition stated in the same way for the same active substance.

II.2A2. Product development


	(1)	An explanation shall be provided with regard to the choice of composition, constituents, packaging, the intended function of the excipients in the finished product and the method of manufacture including justification of the selection of the method and details of the sterilisation processes and/or aseptic procedures used of the finished product. This explanation shall be supported by scientific data on development pharmaceutics. Any overage, with justification thereof, shall be stated. The microbiological characteristics (microbiological purity and antimicrobial activity) and usage instructions shall be proven to be appropriate for the intended use of the veterinary medicinal product as specified in the marketing authorisation application dossier.

---	---	---
	(2)	A study of the interaction between finished product and the primary packaging shall be submitted wherever the risk of such interaction is regarded as possible, especially where injectable preparations are concerned.

---	---	---
	(3)	The proposed pack sizes shall be justified in relation to the proposed route of administration, the posology and the target species in particular for antimicrobial (active) substances.

---	---	---
	(4)	When a dosing device is provided with the finished product, the accuracy of the doses(s) shall be demonstrated.

---	---	---
	(5)	When an accompanying test is recommended to be used with the finished product (e.g. a diagnostic test), relevant information about the test shall be provided.

---	---	---
	(6)	For veterinary medicinal products intended for incorporation into feed, information shall be provided on inclusion rates, instructions for incorporation, homogeneity in-feed and compatibility/suitable feed.

II.2B. Description of the manufacturing method


	(1)	The description of the manufacturing method accompanying the application for marketing authorisation pursuant to Article 8 shall be drafted in such a way as to give an adequate synopsis of the nature of the operations employed.

---	---	---
	(2)	For that purpose, it shall include at least: (a) the actual manufacturing formula for the proposed commercial batch size(s), with the quantitative particulars of all the substances used. Any substances that may disappear in the course of manufacture shall be stated; any overage shall be indicated; (b) description of the various stages of manufacture with information on process operating conditions, in a narrative way accompanied by a process flow chart; (c) in the case of continuous manufacture, full details of precautions taken to ensure the homogeneity of the finished product. Information as to how a batch is defined shall be provided (for example, expressed in terms of a period of time or a quantity of product, and may be expressed as ranges); (d) a list of in-process controls including the stage of manufacture at which they are conducted and the acceptance criteria; (e) experimental studies validating the manufacturing process and, where appropriate, a process validation scheme for production scale batches; (f) for sterile products, where non-pharmacopoeial sterilisation conditions are used, details of the sterilisation processes and/or aseptic procedures used.

II.2C. Production and control of starting material


	(1)	For the purposes of this point, “starting materials” shall mean active substances, excipients and packaging (immediate packaging with its closure system and, if applicable, outer packaging and any dosing device supplied with the veterinary medicinal product).

---	---	---
	(2)	The dossier shall include the specifications and information on the tests to be conducted for quality control of all batches of starting materials.

---	---	---
	(3)	The routine tests carried out on starting materials shall be carried out in the same manner as stated in the dossier.

---	---	---
	(4)	Where a certificate of suitability has been issued by the European Directorate for the Quality of Medicines and HealthCare for a starting material, active substance or excipient, that certificate constitutes the reference to the relevant monograph of the European Pharmacopoeia.

---	---	---
	(5)	Where a certificate of suitability is referred to, the manufacturer shall give an assurance in writing to the applicant that the manufacturing process has not been modified since the granting of the certificate of suitability by the European Directorate for the Quality of Medicines and HealthCare. In case the field “box of access” in the certificate is completed and signed, that requirement shall be deemed to be fulfilled without the need for additional assurance.

---	---	---
	(6)	Certificates of analysis shall be presented for the starting materials in order to demonstrate compliance with the defined specification.

II.2C1. Active substance(s)


	(1)	The required data shall be submitted in one of the three ways as detailed in points (2) to (4).

---	---	---
	(2)	The following details shall be submitted: (a) information on the identity, structure and a list of physicochemical and other relevant properties of the active substance shall be provided, in particular physicochemical properties that potentially affect the safety and efficacy of the active substance. Where relevant, evidence of molecular structure shall include the schematic amino acid sequence and relative molecular mass; (b) information on the manufacturing process shall include a description of the active substance manufacturing process that represents the applicant’s commitment for the manufacture of the active substance. All materials needed in order to manufacture the active substance(s) shall be listed, identifying where each material is used in the process. Information on the quality and control of those materials shall be provided. Information demonstrating that materials meet standards which are appropriate for their intended use shall be provided; (c) information on quality control shall contain tests (including acceptance criteria) carried out at every critical step, information on the quality and control of intermediates and process validation and/or evaluation studies as appropriate. It shall also contain validation data for the analytical methods applied to the active substance, where appropriate; (d) information on impurities shall indicate predictable impurities together with the levels and nature of observed impurities. It shall also contain information on the safety of those impurities where relevant.

---	---	---
	(3)	Active Substance Master File For a non-biological active substance, the applicant may arrange for the information on active substance in point (2) to be supplied directly to the competent authorities by the manufacturer of the active substance as an Active Substance Master File. In this case, the manufacturer of the active substance shall provide the applicant with all the data (applicant’s part of the Active Substance Master File) which may be necessary for the latter to take responsibility for the veterinary medicinal product. A copy of the data provided by the active substance manufacturer to the applicant shall be included in the medicinal product dossier. The manufacturer of the active substance shall confirm in writing to the applicant that he shall ensure batch-to-batch consistency and not modify the manufacturing process or specifications without informing the applicant.

---	---	---
	(4)	Certificate of suitability issued by the European Directorate for the Quality of Medicines and HealthCare The certificate of suitability and any additional data relevant to the dosage form not covered by the certificate of suitability shall be provided.

II.2C1.1. Active substances listed in pharmacopoeias


	(1)	Active substances fulfilling the requirements of the European Pharmacopoeia or, in the absence of a European Pharmacopoeia monograph, the pharmacopoeia of one of the Member States shall be deemed to comply sufficiently with Article 8. In this case the description of the analytical methods and procedures shall be replaced in each relevant section by an appropriate reference to the pharmacopoeia in question.

---	---	---
	(2)	In cases where a specification contained in a monograph of the European Pharmacopoeia or in the national pharmacopoeia of a Member State is insufficient to ensure the quality of the substance, the competent authorities may request more appropriate specifications from the applicant, including acceptance criteria for specific impurities with validated test procedures.

---	---	---
	(3)	The competent authorities shall inform the authorities responsible for the pharmacopoeia in question. The marketing authorisation holder shall provide the authorities of that pharmacopoeia with the details of the alleged insufficiency and the additional specifications applied.

II.2C1.2. Active substances not listed in a pharmacopoeia


	(1)	Active substances which are not listed in any pharmacopoeia shall be described in the form of a monograph under the following headings: (a) the name of the constituent, meeting the requirements of Part II.2A1, point (2) shall be supplemented by any trade or scientific synonyms; (b) the definition of the substance, set down in a form similar to that used in the European Pharmacopoeia, shall be accompanied by any necessary explanatory evidence, in particular concerning the molecular structure. Where substances may only be described by their manufacturing method, the description shall be sufficiently detailed to characterise a substance which is constant both on its composition and in its effects; (c) methods of identification may be described in the form of complete techniques as used for production of the substance, and in the form of tests which ought to be carried out as a routine matter; (d) purity tests shall be described in relation to each individual predictable impurity, especially those which may have a harmful effect, and, if necessary, those which, having regard to the combination of substances to which the application refers, might adversely affect the stability of the medicinal product or distort analytical results; (e) tests and acceptance criteria to control parameters relevant to the finished product, such as sterility shall be described and methods shall be validated where relevant; (f) with regard to complex substances of plant or animal origin, a distinction shall be made between the case where multiple pharmacological effects render chemical, physical or biological control of the principal components necessary, and the case of substances containing one or more groups of principles having similar activity, in respect of which an overall method of assay may be accepted.

---	---	---
	(2)	Those data shall demonstrate that the proposed set of test procedures is sufficient to control the quality of the active substance from the defined source.

II.2C1.3. Physicochemical characteristics liable to affect bioavailability

The following data concerning active substances shall be provided as part of the general description of the active substances if the bioavailability of the veterinary medicinal product depends on them:

(a) crystalline form and solubility;

(b) particle size;

(d) oil/water coefficient of partition;

(e) pK/pH values.

Points (a) to (c) are not applicable to substances used solely in solution.

II.2C2. Excipients


	(1)	Excipients fulfilling the requirements of the European Pharmacopoeia or, in the absence of a European Pharmacopoeia monograph, the pharmacopoeia of one of the Member States shall be deemed to comply sufficiently with Article 8. In that case, the description of the analytical methods and procedures shall be replaced in each relevant section by an appropriate reference to the pharmacopoeia in question. Where appropriate, additional tests to control parameters such as particle size, sterility, and/or residual solvents, shall supplement the requirements of the monograph.

---	---	---
	(2)	In the absence of a pharmacopoeial monograph a specification shall be proposed and justified. The requirements for specifications as set out in Part II.2C1.2(1) points (a) to (e) for the active substance shall be followed. The proposed methods and their supporting validation data shall be presented.

---	---	---
	(3)	A declaration shall be submitted to confirm that colouring matters for inclusion in veterinary medicinal products satisfy the requirements of Directive 2009/35/EC of the European Parliament and of the Council ⁵ except where the application for a marketing authorisation concerns certain veterinary medicinal products for topical use, such as medicated collars and ear tags.

---	---	---
	(4)	A declaration shall be submitted to confirm that colouring matters used meet the purity criteria laid down in Commission Regulation (EU) No 231/2012 ⁶.

---	---	---
	(5)	For novel excipients, that is to say excipient(s) used for the first time in the Union in a veterinary medicinal product or by a new route of administration, details of manufacture, characterisation, and controls, with cross references to support both clinical and non-clinical safety data shall be provided. For colouring matters, the declarations of compliance in points (3) and (4) shall be considered sufficient.

II.2C3. Packaging (containers and closure systems)

II. 2C3.1. Active substance


	(1)	Information on the container and its closure system for the active substance including the identity of each immediate packaging material and their specifications shall be given. The level of information required shall be determined by the physical state (liquid, solid) of the active substance.

---	---	---
	(2)	Where a certificate of suitability for the active substance from the proposed source is submitted and specifies a container and its closure system, the detailed information on these for the active substance from that source may be replaced by a reference to the valid certificate of suitability.

---	---	---
	(3)	Where an Active Substance Master File from the proposed source is submitted and specifies a container and its closure system, the detailed information on these for the active substance from that source may be replaced by a reference to the Active Substance Master File.

II. 2C3.2. Finished product


	(1)	Information on the container and its closure system and any device for the finished product including the identity of each immediate packaging material and their specifications shall be given. The level of information required shall be determined by the route of administration of the veterinary medicinal product and the physical state (liquid, solid) of the dosage form.

---	---	---
	(2)	In the absence of a pharmacopoeial monograph, a specification shall be proposed and justified for the packaging material.

---	---	---
	(3)	For packaging materials that are used for the first time in the Union and that are in contact with the product, information on their composition, manufacture and safety shall be presented.

II.2C4. Substances of biological origin


	(1)	Information on the source, processing, characterisation and control of all materials of biological origin (human, animal, herbal or from microorganisms) used in the manufacture of the veterinary medicinal products shall be provided, including viral safety data, in accordance with relevant guidelines.

---	---	---
	(2)	Documentation shall be supplied to demonstrate that materials originating from animal species relevant for the transmission of transmissible spongiform encephalopathies (TSE) comply with the Note for Guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products, as well as with the corresponding monograph of the European Pharmacopoeia. Certificates of Suitability issued by the European Directorate for the Quality of Medicines and HealthCare, with reference to the relevant monograph of the European Pharmacopoeia, may be used to demonstrate compliance.

II.2D. Control tests carried out on isolated intermediates during the manufacturing process


	(1)	For the purposes of this section, “isolated intermediate” shall mean partly processed material that may be stored for a defined amount of time and that shall undergo further processing step(s) before it becomes finished product.

---	---	---
	(2)	A specification shall be set for each intermediate and the analytical methods shall be described and validated, if applicable.

---	---	---
	(3)	Information on the primary packaging of the intermediate product shall be provided if different from that for the finished product.

---	---	---
	(4)	A shelf life and storage conditions for the intermediate product shall be defined on the basis of the data resulting from stability studies.

II.2E. Control tests on the finished product


	(1)	For the control of the finished product, a batch of a finished product comprises all the units of a pharmaceutical form which are made from the same initial quantity of material and have undergone the same series of manufacturing and/or sterilisation operations. In case of continuous manufacture, the batch size may be expressed in terms of a period of time or a quantity of product, and may be expressed as ranges.

---	---	---
	(2)	The tests, which are carried out on the finished product shall be listed. A justification for the proposed specification shall be provided. The frequency of the tests which are not carried out routinely shall be stated and justified. Acceptance criteria for release shall be indicated.

---	---	---
	(3)	The dossier shall include particulars relating to control tests on the finished product at release and their validation. They shall be submitted in accordance with the following requirements.

---	---	---
	(4)	If test procedures and acceptance criteria other than those mentioned in the relevant monographs and general chapters of the European Pharmacopoeia, or failing this, in the pharmacopoeia of a Member State are used, those procedures and criteria shall be justified by providing proof that the finished product would, if tested in accordance with those monographs, meet the quality requirements of that pharmacopoeia for the pharmaceutical form concerned.

II.2E1. General characteristics of the finished product


	(1)	Certain tests of the general characteristics of a product shall always be included among the tests on the finished product. Those tests shall, wherever applicable, relate to the control of average masses/volumes and maximum deviations, to mechanical, physical tests, visual appearance, physical characteristics such as, pH or particle size. For each of those characteristics, standards and acceptance criteria shall be specified by the applicant.

---	---	---
	(2)	The conditions of the tests, where appropriate, the equipment/apparatus employed and the standards shall be described in sufficient detail whenever they are not given in the European Pharmacopoeia or the pharmacopoeia of a Member State; the same shall apply in cases where the methods prescribed by such pharmacopoeias are not applicable.

II.2E2. Identification and assay of active substance(s)


	(1)	Identification and assay of the active substance(s) shall be carried out either in a representative sample from the production batch or in a number of dosage units analysed individually.

---	---	---
	(2)	Unless there is appropriate justification, the maximum acceptable deviation in the active substance content of the finished product shall not exceed ± 5 % at the time of manufacture.

---	---	---
	(3)	In certain cases of particularly complex mixtures, where assay of active substances which are very numerous or present in very low amounts would necessitate an intricate investigation difficult to carry out in respect of each production batch, the assay of one or more active substances in the finished product may be omitted, on the express condition that such assays are made at intermediate stages in the production process. That simplified technique may not be extended to the characterisation of the substances concerned. It shall be supplemented by a method of quantitative evaluation, enabling the competent authority to have the conformity of the medicinal product with its specification verified after it has been placed on the market.

---	---	---
	(4)	An in vivo or in vitro biological assay shall be obligatory when physicochemical methods cannot provide adequate information on the quality of the product. Such an assay shall, whenever possible, include reference materials and statistical analysis allowing calculation of confidence limits. Where those tests cannot be carried out on the finished product, they may be performed at an intermediate stage, as late as possible in the manufacturing process.

---	---	---
	(5)	The maximum acceptable levels of individual and total degradation products immediately following manufacture shall be indicated. The rationale for the inclusion or exclusion of degradation products in the specification shall be presented.

II.2E3. Identification and assay of excipient components

An identification test and an upper and lower limit test shall be obligatory for each individual antimicrobial preservative and for any excipient that is liable to affect the bioavailability of the active substance, unless the bioavailability is guaranteed by other appropriate tests. An identification test and an upper limit test shall be obligatory for any antioxidant and for any excipient liable to adversely affect physiological functions, with a lower limit test also included for antioxidants at time of release.

II.2E4. Microbiological controls

Particulars of microbiological tests, such as sterility and bacterial endotoxins, shall be included in the analytical particulars wherever such tests shall be undertaken as a matter of routine in order to verify the quality of the product.

II.2E5. Batch-to-batch consistency

In order to ensure the quality of the product is consistent from batch to batch and to demonstrate conformity with the specification, batch data shall be provided giving the results for all tests performed in general on [3] batches manufactured at the proposed manufacturing site(s) according to the described production process.

II.2E6. Other controls

Any other test considered necessary to confirm the quality of the medicinal product shall be controlled.

II.2F. Stability test

II.2F1. Active substance(s)


	(1)	A retest period and storage conditions for the active substance shall be specified except when the manufacturer of the finished product fully retests the active substance immediately before its use in the manufacture of the finished product.

---	---	---
	(2)	Stability data shall be presented to provide evidence on how the quality of an active substance varies with time under the influence of a variety of environmental factors and to support the defined retest period and storage conditions, if applicable. The type of stability studies conducted, protocols used, the analytical procedures used and their validation together with the detailed results shall be presented.

---	---	---
	(3)	Where a certificate of suitability for the active substance from the proposed source is available and specifies a retest period and storage conditions, stability data for the active substance from that source may be replaced by a reference to the valid certificate of suitability.

---	---	---
	(4)	Where an Active Substance Master File from the proposed source is submitted and specifies stability data, the detailed information on the stability for the active substance from that source may be replaced by a reference to the Active Substance Master File.

II.2F2. Finished product


	(1)	A description shall be given of the investigations by which the shelf life, the recommended storage conditions and the specifications at the end of the shelf life proposed by the applicant have been determined.

---	---	---
	(2)	The type of stability studies conducted, protocols used, the analytical procedures used and their validation together with the detailed results shall be presented.

---	---	---
	(3)	Where a finished product requires reconstitution or dilution prior to administration, details of the proposed shelf life and specification for the reconstituted/diluted product are required, supported by relevant stability data.

---	---	---
	(4)	In the case of multi-dose containers, where relevant, stability data shall be presented to justify a shelf life for the product after it has been broached or opened for the first time and an in-use specification shall be defined.

---	---	---
	(5)	Where a finished product is liable to give rise to degradation products, the applicant shall declare those products and indicate the identification methods and test procedures used.

---	---	---
	(6)	Where the stability data show that the assay of the active substance declines on storage, the description of the control tests on the finished product shall include, where appropriate, the chemical and, if necessary, the toxico-pharmacological investigation of the changes that this substance has undergone, and possibly the characterisation and/or assay of the degradation products.

---	---	---
	(7)	The maximum acceptable level of individual and total degradation products at the end of shelf life shall be indicated and justified.

---	---	---
	(8)	On the basis of the stability test results, the tests and their acceptance criteria, that are carried out on the finished product over the course of the shelf life shall be listed and justified.

---	---	---
	(9)	The conclusions shall contain the results of analyses, justifying the proposed shelf life and if appropriate, the in-use shelf life, under the recommended storage conditions.

---	---	---
	(10)	Additionally, for veterinary medicinal products intended for incorporation into feed, information shall be provided on the stability and the proposed shelf life after incorporation into feed. A specification for the medicated feed manufactured using those veterinary medicinal products in accordance with the recommended instructions for use shall also be provided.

II.2G. Other information

Information relating to the quality of the veterinary medicinal product not covered elsewhere in this Part may be included in the dossier under this point.

II.3 Part 3: Safety documentation (safety and residues tests)

Reading this document does not replace reading the official text published in the Official Journal of the European Union. We assume no responsibility for any inaccuracies arising from the conversion of the original to this format.

This text is published under EUR-Lex's own terms of reuse, not a Legalize or public-domain licence. EUR-Lex
Creative Commons Attribution 4.0 International (CC BY 4.0)
© European Union, https://eur-lex.europa.eu — Source: EUR-Lex (Publications Office of the European Union). Reused under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence. Only EU legislation published in the printed Official Journal of the European Union is deemed authentic; consolidated texts are reproduced here for documentation purposes and have been reformatted to Markdown.

Commission Delegated Regulation (EU) 2021/805 of 8 March 2021 amending Annex II to Regulation (EU) 2019/6 of the European Parliament and of the Council (Text with EEA relevance)

Article 1

Article 2

ANNEX

REQUIREMENTS REFERRED TO IN ARTICLE 8(1), POINT (B)

Table of Contents

SECTION I

GENERAL PRINCIPLES AND REQUIREMENTS

I.1. General principles

I.2. Dossier composition requirements

I.2.1. Part 1: Summary of the dossier

I.2.2. Part 2: Quality documentation (physicochemical, biological or microbiological information)

I.2.3. Part 3: Safety documentation (safety and residues tests)

I.2.4. Part 4: Efficacy documentation (pre-clinical studies and clinical trial(s))

I.2.5. Detailed requirements for different types of veterinary medicinal products or marketing authorisation dossiers

SECTION II

REQUIREMENTS FOR VETERINARY MEDICINAL PRODUCTS OTHER THAN BIOLOGICAL VETERINARY MEDICINAL PRODUCTS

II.1. Part 1: Summary of the dossier

II.2. Part 2: Quality documentation (physicochemical, biological or microbiological information)

II.2A. Product description

II.2A1. Qualitative and quantitative composition

II.2A2. Product development

II.2B. Description of the manufacturing method

II.2C. Production and control of starting material

II.2C1. Active substance(s)

II.2C1.1. Active substances listed in pharmacopoeias

II.2C1.2. Active substances not listed in a pharmacopoeia

II.2C1.3. Physicochemical characteristics liable to affect bioavailability

II.2C2. Excipients

II.2C3. Packaging (containers and closure systems)

II. 2C3.1. Active substance

II. 2C3.2. Finished product

II.2C4. Substances of biological origin

II.2D. Control tests carried out on isolated intermediates during the manufacturing process

II.2E. Control tests on the finished product

II.2E1. General characteristics of the finished product

II.2E2. Identification and assay of active substance(s)

II.2E3. Identification and assay of excipient components

II.2E4. Microbiological controls

II.2E5. Batch-to-batch consistency

II.2E6. Other controls

II.2F. Stability test

II.2F1. Active substance(s)

II.2F2. Finished product

II.2G. Other information

II.3 Part 3: Safety documentation (safety and residues tests)