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 (Text with EEA relevance)
Modified by
- Commission Delegated Regulation (EU) 2021/805of 8 March 2021amending Annex II to Regulation (EU) 2019/6 of the European Parliament and of the Council(Text with EEA relevance), 32021R0805, May 21, 2021
- Commission Delegated Regulation (EU) 2023/183of 23 November 2022amending Regulation (EU) 2019/6 of the European Parliament and of the Council as regards the requirements on compliance with good laboratory practice for veterinary medicinal products set out in Annex II to that Regulation(Text with EEA relevance), 32023R0183, January 30, 2023
(a) substances that have anabolic, anti-infectious, antiparasitic, anti-inflammatory, hormonal, narcotic or psychotropic properties and that may be used in animals; (b) veterinary medicinal products prepared in a pharmacy or by a person permitted to do so under national law, in accordance with a veterinary prescription for an individual animal or a small group of animals ("magistral formula"); (c) veterinary medicinal products prepared in a pharmacy in accordance with the directions of a pharmacopoeia and intended to be supplied directly to the end-user ("officinal formula"). Such officinal formula shall be subject to a veterinary prescription when intended for food-producing animals.
(a) veterinary medicinal products containing autologous or allogeneic cells or tissues that have not been subjected to an industrial process; (b) veterinary medicinal products based on radio-active isotopes; (c) feed additives as defined in point (a) of Article 2(2) of Regulation (EC) No 1831/2003 of the European Parliament and of the Council Regulation (EC) No 1831/2003 of the European Parliament and of the Council of 22 September 2003 on additives for use in animal nutrition (OJ L 268, 18.10.2003, p. 29 ).(d) veterinary medicinal products intended for research and development; (e) medicated feed and intermediate products as defined in points (a) and (b) of Article 3(2) of Regulation (EU) 2019/4.
(1) "veterinary medicinal product" means any substance or combination of substances which fulfils at least one of the following conditions: (a) it is presented as having properties for treating or preventing disease in animals; (b) its purpose is to be used in, or administered to, animals with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action; (c) its purpose is to be used in animals with a view to making a medical diagnosis; (d) its purpose is to be used for euthanasia of animals;
(2) "substance" means any matter of the following origin: (a) human; (b) animal; (c) vegetable; (d) chemical;
(3) "active substance" means any substance or mixture of substances intended to be used in the manufacture of a veterinary medicinal product that, when used in its production, becomes an active ingredient of that product; (4) "excipient" means any constituent of a veterinary medicinal product other than an active substance or packaging material; (5) "immunological veterinary medicinal product" means a veterinary medicinal product intended to be administered to an animal in order to produce active or passive immunity or to diagnose its state of immunity; (6) "biological veterinary medicinal product" means a veterinary medicinal product where an active substance is a biological substance; (7) "biological substance" means a substance that is produced by or extracted from a biological source and that needs for its characterisation and the determination of its quality a combination of physico-chemical-biological testing, together with knowledge of the production process and its control; (8) "reference veterinary medicinal product" means a veterinary medicinal product authorised in accordance with Article 44, 47, 49, 52, 53 or 54 as referred to in Article 5(1) on the basis of an application submitted in accordance with Article 8; (9) "generic veterinary medicinal product" means a veterinary medicinal product which has the same qualitative and quantitative composition of active substances and the same pharmaceutical form as the reference veterinary medicinal product, and with regard to which bioequivalence with the reference veterinary medicinal product has been demonstrated; (10) "homeopathic veterinary medicinal product" means a veterinary medicinal product prepared from homeopathic stocks in accordance with a homeopathic manufacturing procedure described by the European Pharmacopoeia or, in the absence thereof, by the pharmacopoeias used officially in Member States;(11) "antimicrobial resistance" means the ability of micro-organisms to survive or to grow in the presence of a concentration of an antimicrobial agent which is usually sufficient to inhibit or kill micro-organisms of the same species; (12) "antimicrobial" means any substance with a direct action on micro-organisms used for treatment or prevention of infections or infectious diseases, including antibiotics, antivirals, antifungals and anti-protozoals; (13) "antiparasitic" means a substance that kills or interrupts the development of parasites, used for the purpose of treating or preventing an infection, infestation or disease caused or transmitted by parasites, including substances with a repelling activity; (14) "antibiotic" means any substance with a direct action on bacteria that is used for treatment or prevention of infections or infectious diseases; (15) "metaphylaxis" means the administration of a medicinal product to a group of animals after a diagnosis of clinical disease in part of the group has been established, with the aim of treating the clinically sick animals and controlling the spread of the disease to animals in close contact and at risk and which may already be subclinically infected; (16) "prophylaxis" means the administration of a medicinal product to an animal or group of animals before clinical signs of a disease, in order to prevent the occurrence of disease or infection; (17) "clinical trial" means a study which aims to examine under field conditions the safety or efficacy of a veterinary medicinal product under normal conditions of animal husbandry or as part of normal veterinary practice for the purpose of obtaining a marketing authorisation or a change thereof; (18) "pre-clinical study" means a study not covered by the definition of clinical trial which aims to investigate the safety or efficacy of a veterinary medicinal product for the purpose of obtaining a marketing authorisation or a change thereof; (19) "benefit-risk balance" means an evaluation of the positive effects of the veterinary medicinal product in relation to the following risks relating to the use of that product: (a) any risk relating to the quality, safety and efficacy of the veterinary medicinal products as regards animal or human health; (b) any risk of undesirable effects on the environment; (c) any risk relating to the development of resistance;
(20) "common name" means the international non-proprietary name recommended by the World Health Organization (WHO) for a substance or, if one does not exist, the name generally used; (21) "name of the veterinary medicinal product" means either an invented name not liable to confusion with the common name, or a common or scientific name accompanied by a trademark or the name of the marketing authorisation holder; (22) "strength" means the content of active substances in a veterinary medicinal product, expressed quantitatively per dosage unit, per unit of volume or per unit of weight according to the pharmaceutical form; (23) "competent authority" means an authority designated by a Member State in accordance with Article 137; (24) "labelling" means information on the immediate packaging or the outer packaging; (25) "immediate packaging" means the container or any other form of packaging that is in direct contact with the veterinary medicinal product; (26) "outer packaging" means packaging in which the immediate packaging is placed; (27) "package leaflet" means a documentation leaflet on a veterinary medicinal product which contains information to ensure its safe and efficacious use; (28) "letter of access" means an original document, signed by the data owner or its representative, which states that the data may be used for the benefit of the applicant in relation to the competent authorities, the European Medicines Agency established by Regulation (EC) No 726/2004 ("the Agency") or the Commission for the purposes of this Regulation; (29) "limited market" means a market for one of the following medicinal product types: (a) veterinary medicinal products for the treatment or prevention of diseases that occur infrequently or in limited geographical areas; (b) veterinary medicinal products for animal species other than cattle, sheep for meat production, pigs, chickens, dogs and cats;
(30) "pharmacovigilance" means the science and activities relating to the detection, assessment, understanding and prevention of suspected adverse events or any other problem related to a medicinal product; (31) "pharmacovigilance system master file" means a detailed description of the pharmacovigilance system used by the marketing authorisation holder with respect to one or more authorised veterinary medicinal products; (32) "control" means any task performed by a competent authority for the verification of compliance with this Regulation; (33) "veterinary prescription" means a document issued by a veterinarian for a veterinary medicinal product or a medicinal product for human use for its use in animals; (34) "withdrawal period" means the minimum period between the last administration of a veterinary medicinal product to an animal and the production of foodstuffs from that animal which under normal conditions of use is necessary to ensure that such foodstuffs do not contain residues in quantities harmful to public health; (35) "placing on the market" means the first making available of a veterinary medicinal product on the whole of the Union market or in one or more Member States, as applicable; (36) "wholesale distribution" means all activities consisting of procuring, holding, supplying or exporting veterinary medicinal products whether for profit or not, apart from retail supply of veterinary medicinal products to the public; (37) "aquatic species" mean species referred to in point (3) of Article 4 of Regulation (EU) 2016/429 of the European Parliament and of the Council Regulation (EU) 2016/429 of the European Parliament and of the Council of 9 March 2016 on transmissible animal diseases and amending and repealing certain acts in the area of animal health ("Animal Health Law") (OJ L 84, 31.3.2016, p. 1 ).(38) "food-producing animals" mean food-producing animals as defined in point (b) of Article 2 of Regulation (EC) No 470/2009; (39) "variation" means a change to the terms of the marketing authorisation for a veterinary medicinal product as referred to in Article 36; (40) "advertising of veterinary medicinal products" means the making of a representation in any form in connection with veterinary medicinal products in order to promote the supply, distribution, sale, prescription or use of veterinary medicinal products and comprising also the supply of samples and sponsorships; (41) "signal management process" means a process for performing active surveillance of pharmacovigilance data for veterinary medicinal products in order to assess the pharmacovigilance data and determine whether there is any change to the benefit-risk balance of those veterinary medicinal products, with a view to detecting risks to animal or public health or protection of the environment; (42) "potential serious risk to human or animal health or to the environment" means a situation where there is a significantly high probability that a serious hazard resulting from the use of a veterinary medicinal product will affect human or animal health or the environment; (43) "novel therapy veterinary medicinal product" means: (a) a veterinary medicinal product specifically designed for gene therapy, regenerative medicine, tissue engineering, blood product therapy, phage therapy; (b) a veterinary medicinal product issued from nanotechnologies; or (c) any other therapy which is considered as a nascent field in veterinary medicine;
(44) "epidemiological unit" means an epidemiological unit as defined in point (39) of Article 4 of Regulation (EU) 2016/429.
(a) the national procedure laid down in Articles 46 and 47; (b) the decentralised procedure laid down in Articles 48 and 49; (c) the mutual recognition procedure laid down in Articles 51 and 52; (d) the subsequent recognition procedure laid down in Article 53.
(a) the information set out in Annex I; (b) technical documentation necessary for demonstrating the quality, safety and efficacy of the veterinary medicinal product in accordance with the requirements set out in Annex II; (c) a summary of the pharmacovigilance system master file.
(a) documentation on the direct or indirect risks to public or animal health or to the environment of use of the antimicrobial veterinary medicinal product in animals; (b) information about risk mitigation measures to limit antimicrobial resistance development related to the use of the veterinary medicinal product.
(a) a copy of the written consent of the competent authorities to the deliberate release into the environment of the genetically modified organisms for research and development purposes, as provided for in Part B of Directive 2001/18/EC; (b) the complete technical file supplying the information required under Annexes III and IV to Directive 2001/18/EC; (c) the environmental risk assessment in accordance with the principles set out in Annex II to Directive 2001/18/EC; and (d) the results of any investigations performed for the purposes of research or development.
(a) the name of the veterinary medicinal product, followed by its strength and pharmaceutical form; (b) a statement of the active substances expressed qualitatively and quantitatively per unit or according to the form of administration for a particular volume or weight, using their common names; (c) the batch number, preceded by the word "Lot"; (d) the name or company name or logo name of the marketing authorisation holder; (e) the target species; (f) the expiry date, in the format: "mm/yyyy", preceded by the abbreviation "Exp."; (g) special storage precautions, if any; (h) route of administration; and (i) if applicable, the withdrawal period, even if such period is zero.
(a) the information referred to in Article 10(1); (b) the contents by weight, volume or number of immediate packaging units of the veterinary medicinal product; (c) a warning that the veterinary medicinal product must be kept out of the sight and reach of children; (d) a warning that the veterinary medicinal product is "for animal treatment only"; (e) without prejudice to Article 14(4), a recommendation to read the package leaflet; (f) in the case of homeopathic veterinary medicinal products, the statement "homeopathic veterinary medicinal product"; (g) in the case of veterinary medicinal products not subject to a veterinary prescription, the indication or indications; (h) the marketing authorisation number.
(a) the name of veterinary medicinal product; (b) the quantitative particulars of the active substances; (c) the batch number, preceded by the word "Lot"; (d) the expiry date, in the format: "mm/yyyy", preceded by the abbreviation "Exp.".
(a) the name or company name and permanent address or registered place of business of the marketing authorisation holder and of the manufacturer and, where applicable, of the representative of the marketing authorisation holder; (b) the name of the veterinary medicinal product, followed by its strength and pharmaceutical form; (c) qualitative and quantitative composition of the active substance or substances; (d) the target species, the dosage for each species, the method and route of administration and, if necessary, advice on correct administration; (e) the indications for use; (f) the contra-indications and adverse events; (g) if applicable, the withdrawal period, even if such period is zero; (h) special storage precautions, if any; (i) information essential for safety or health protection, including any special precautions relating to use and any other warnings; (j) information on the collection systems referred to in Article 117 applicable to the veterinary medicinal product concerned; (k) the marketing authorisation number; (l) contact details of the marketing authorisation holder or its representative, as appropriate, for the reporting of suspected adverse events; (m) classification of the veterinary medicinal product as referred to in Article 34.
(a) the scientific name of the stock or stocks followed by the degree of dilution, using the symbols of the European Pharmacopoeia or, in the absence thereof, of the pharmacopoeias used officially in Member States;(b) name or company name and permanent address or registered place of business of the registration holder and, where appropriate, of the manufacturer; (c) method of administration and, if necessary, route of administration; (d) pharmaceutical form; (e) special storage precautions, if any; (f) the target species and, where appropriate, dosage for each such species; (g) a special warning, if necessary, for the homeopathic veterinary medicinal product; (h) registration number; (i) withdrawal period, if applicable; (j) the statement "homeopathic veterinary medicinal product".
(a) bioavailability studies have demonstrated bioequivalence of a generic veterinary medicinal product with the reference veterinary medicinal product or a justification is provided as to why such studies were not performed; (b) the application satisfies the requirements set out in Annex II; (c) the applicant demonstrates that the application concerns a generic veterinary medicinal product of a reference veterinary medicinal product for which the period of protection of the technical documentation laid down in Articles 39 and 40 has elapsed or is due to elapse in less than two years.
(a) there are changes in the active substance or substances, indications for use, strength, pharmaceutical form or route of administration of the generic veterinary medicinal product compared to the reference veterinary medicinal product; (b) bioavailability studies cannot be used to demonstrate bioequivalence with the reference veterinary medicinal product; or (c) there are differences relating to raw materials or in manufacturing processes of the biological veterinary medicinal product and the reference biological veterinary medicinal product.
(a) the benefit of the availability on the market of the veterinary medicinal product to the animal or public health outweighs the risk inherent in the fact that certain documentation has not been provided; (b) the applicant provides the evidence that the veterinary medicinal product is intended for a limited market.
(a) a requirement to introduce conditions or restrictions, in particular concerning the safety of the veterinary medicinal product; (b) a requirement to notify to the competent authorities or the Agency, as applicable, of any adverse event relating to the use of the veterinary medicinal product; (c) a requirement to conduct post-authorisation studies.
(a) verify that the data submitted complies with the requirements laid down in Article 8; (b) assess the veterinary medicinal product regarding the quality, safety and efficacy documentation provided; (c) draw up a conclusion on the benefit-risk balance for the veterinary medicinal product.
(a) test the veterinary medicinal product, its starting materials and, if necessary, intermediate products or other constituent materials in order to ensure that the control methods employed by the manufacturer and described in the application documents are satisfactory; (b) verify that, in the case of veterinary medicinal products intended for food-producing animals, the analytical detection method proposed by the applicant for the purposes of residue depletion tests is satisfactory and suitable for use to reveal the presence of residue levels, particularly those exceeding the maximum residue level of the pharmacologically active substance established by the Commission in accordance with Regulation (EC) No 470/2009, and for the purpose of official controls of animals and products of animal origin in accordance with Regulation (EU) 2017/625.
(a) a summary of the product characteristics containing the information laid down in Article 35; (b) details of any conditions or restrictions to be imposed as regards the supply or safe and effective use of the veterinary medicinal product concerned, including the classification of a veterinary medicinal product in accordance with Article 34; (c) the text of the labelling and package leaflet referred to in Articles 10 to 14.
(a) veterinary medicinal products which contain narcotic drugs or psychotropic substances, or substances frequently used in the illicit manufacture of those drugs or substances, including those covered by the United Nations Single Convention on Narcotic Drugs of 1961 as amended by the 1972 Protocol, the United Nations Convention on Psychotropic Substances of 1971, the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances of 1988 or by Union legislation on drug precursors; (b) veterinary medicinal products for food-producing animals; (c) antimicrobial veterinary medicinal products; (d) veterinary medicinal products intended for treatments of pathological processes which require a precise prior diagnosis or the use of which may have effects which impede or interfere with subsequent diagnostic or therapeutic measures; (e) veterinary medicinal products used for euthanasia of animals; (f) veterinary medicinal products containing an active substance that has been authorised for less than five years in the Union; (g) immunological veterinary medicinal products; (h) without prejudice to Council Directive 96/22/EC Council Directive 96/22/EC of 29 April 1996 concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of ß-agonists, and repealing Directives 81/602/EEC, 88/146/EEC and 88/299/EEC (OJ L 125, 23.5.1996, p. 3 ).
(a) the administration of the veterinary medicinal product is restricted to pharmaceutical forms requiring no particular knowledge or skill in using the products; (b) the veterinary medicinal product does not present a direct or indirect risk, even if administered incorrectly, to the animal or animals treated or to other animals, to the person administering it or to the environment; (c) the summary of the product characteristics of the veterinary medicinal product does not contain any warnings of potential serious adverse events deriving from its correct use; (d) neither the veterinary medicinal product nor any other product containing the same active substance has previously been the subject of frequent adverse event reporting; (e) the summary of the product characteristics does not refer to contra-indications related to the use of the product concerned in combination with other veterinary medicinal products commonly used without prescription; (f) there is no risk for public health as regards residues in food obtained from treated animals even where the veterinary medicinal product is used incorrectly; (g) there is no risk to public or animal health as regards the development of resistance to substances even where the veterinary medicinal product containing those substances is used incorrectly.
(a) name of the veterinary medicinal product followed by its strength and pharmaceutical form and, where applicable, a list of the names of the veterinary medicinal product, as authorised in different Member States; (b) qualitative and quantitative composition of the active substance or substances and qualitative composition of excipients and other constituents stating their common name or their chemical description and their quantitative composition, if that information is essential for proper administration of the veterinary medicinal product; (c) clinical information: (i) target species; (ii) indications for use for each target species; (iii) contra-indications; (iv) special warnings; (v) special precautions for use, including in particular special precautions for safe use in the target species, special precautions to be taken by the person administering the veterinary medicinal product to the animals and special precautions for the protection of the environment; (vi) frequency and seriousness of adverse events; (vii) use during pregnancy, lactation or lay; (viii) interaction with other medicinal products and other forms of interaction; (ix) administration route and dosage; (x) symptoms of overdose and, where applicable, emergency procedures and antidotes in the event of overdose; (xi) special restrictions for use; (xii) special conditions for use, including restrictions on the use of antimicrobial and antiparasitic veterinary medicinal products in order to limit the risk of development of resistance; (xiii) if applicable, withdrawal periods, even if such periods are zero;
(d) pharmacological information: (i) Anatomical Therapeutic Chemical Veterinary Code ("ATCvet Code"); (ii) pharmacodynamics; (iii) pharmacokinetics.
In case of an immunological veterinary medicinal product, instead of points (i), (ii) and (iii), immunological information; (e) pharmaceutical particulars: (i) major incompatibilities; (ii) shelf life, where applicable after reconstitution of the medicinal product or after the immediate packaging has been opened for the first time; (iii) special precautions for storage; (iv) nature and composition of immediate packaging; (v) requirement to use take-back schemes for veterinary medicinal products for the disposal of unused veterinary medicinal products or waste materials derived from the use of such products and, if appropriate, additional precautions regarding hazardous waste disposal of unused veterinary medicinal products or waste materials derived from the use of such products;
(f) name of the marketing authorisation holder; (g) marketing authorisation number or numbers; (h) date of the first marketing authorisation; (i) date of the last revision of the summary of the product characteristics; (j) if applicable, for veterinary medicinal products referred to in Article 23 or 25, the statement: (i) "marketing authorisation granted for a limited market and therefore assessment based on customised requirements for documentation"; or (ii) "marketing authorisation in exceptional circumstances and therefore assessment based on customised requirements for documentation";
(k) information on the collection systems referred to in Article 117 applicable to the veterinary medicinal product concerned; (l) classification of the veterinary medicinal product as referred to in Article 34 for each Member State in which it is authorised.
(a) the application does not comply with this Chapter; (b) the benefit-risk balance of the veterinary medicinal product is negative; (c) the applicant has not provided sufficient information on the quality, safety or efficacy of the veterinary medicinal product; (d) the veterinary medicinal product is an antimicrobial veterinary medicinal product presented for use as performance enhancer in order to promote the growth of treated animals or to increase yields from treated animals; (e) the proposed withdrawal period is not long enough to ensure food safety or is insufficiently substantiated; (f) the risk for public health in case of development of antimicrobial resistance or antiparasitic resistance outweighs the benefits of the veterinary medicinal product to animal health; (g) the applicant has not provided sufficient proof of efficacy as regards the target species; (h) the qualitative or quantitative composition of the veterinary medicinal product is not as stated in the application; (i) risks to public or animal health or to the environment are not sufficiently addressed; or (j) the active substance within the veterinary medicinal product meets the criteria for being considered persistent, bioaccumulative and toxic or very persistent and very bioaccumulative, and the veterinary medicinal product is intended to be used in food-producing animals, unless it is demonstrated that the active substance is essential to prevent or control a serious risk to animal health.
(a) the period of the protection of technical documentation as set out in Articles 39 and 40 of this Regulation has elapsed, or is due to elapse in less than two years; (b) the applicants have obtained written agreement in the form of a letter of access with regard to that documentation.
(a) 10 years for veterinary medicinal products for cattle, sheep for meat production, pigs, chickens, dogs and cats; (b) 14 years for antimicrobial veterinary medicinal products for cattle, sheep for meat production, pigs, chickens, dogs and cats containing an antimicrobial active substance which has not been an active substance in a veterinary medicinal product authorised within the Union on the date of the submission of the application; (c) 18 years for veterinary medicinal products for bees; (d) 14 years for veterinary medicinal products for animal species other than those referred to in points (a) and (c).
(a) a reduction in the antimicrobial or antiparasitic resistance; or (b) an improvement of the benefit-risk balance of the veterinary medicinal product,
(a) veterinary medicinal products developed by means of one of the following biotechnological processes: (i) recombinant DNA technology; (ii) controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes including transformed mammalian cells; (iii) hybridoma and monoclonal antibody methods;
(b) veterinary medicinal products intended primarily for use as performance enhancers in order to promote the growth of treated animals or to increase yields from treated animals; (c) veterinary medicinal products containing an active substance which has not been authorised as a veterinary medicinal product within the Union at the date of the submission of the application; (d) biological veterinary medicinal products which contain or consist of engineered allogeneic tissues or cells; (e) novel therapy veterinary medicinal products.
(a) a list of all decisions granting, suspending or revoking marketing authorisations which concern the veterinary medicinal product; (b) information on the variations introduced since the grant of the marketing authorisation by decentralised procedure laid down in Article 49(7) or by mutual recognition procedure laid down in Article 52(8); (c) a summary report on pharmacovigilance data.
(a) for veterinary medicinal products authorised within the Union by the Commission and by the competent authorities: (i) name of the veterinary medicinal product; (ii) active substance or substances, and the strength of the veterinary medicinal product; (iii) summary of product characteristics; (iv) package leaflet; (v) the assessment report; (vi) list of sites where the veterinary medicinal product is manufactured; and (vii) the dates of the placing of the veterinary medicinal product on the market in a Member State;
(b) for homeopathic veterinary medicinal products registered in accordance with Chapter V within the Union by the competent authorities: (i) name of the registered homeopathic veterinary medicinal product; (ii) package leaflet; and (iii) lists of sites where the registered homeopathic veterinary medicinal product is manufactured;
(c) veterinary medicinal products allowed to be used in a Member State in accordance with Article 5(6); (d) the annual volume of sales and information on the availability for each veterinary medicinal product.
(a) the technical specifications of the product database including the electronic data exchange mechanism for exchanging with the existing national systems and the format for electronic submission; (b) the practical arrangements for the functioning of the product database, in particular to ensure protection of commercially confidential information and security of exchange of information; (c) detailed specifications of the information to be included, updated and shared in the product database and by whom; (d) contingency arrangements to be applied in case of unavailability of any of the functionalities of the product database; (e) where appropriate, data to be included in the product database in addition to the information referred to in paragraph 2 of this Article.
(a) the types of antimicrobial medicinal products used in animals for which data shall be collected; (b) the quality assurance that Member States and the Agency shall put in place to ensure quality and comparability of data; and (c) the rules on the methods of gathering data on the use of the antimicrobial medicinal products used in animals and on the method of transfer of those data to the Agency.
(a) within two years from 28 January 2022 , data shall be collected at least for the species and categories included in Commission Implementing Decision 2013/652/EUCommission Implementing Decision 2013/652/EU of 12 November 2013 on the monitoring and reporting of antimicrobial resistance in zoonotic and commensal bacteria (OJ L 303, 14.11.2013, p. 26 ).11 December 2018 ;(b) within five years from 28 January 2022 , data shall be collected for all food-producing animal species;(c) within eight years from 28 January 2022 , data shall be collected for other animals which are bred or kept.
(a) the need for a scientific assessment of changes in order to determine the risk to public or animal health or to the environment; (b) whether changes have an impact on the quality, safety or efficacy of the veterinary medicinal product; (c) whether changes imply no more than a minor alteration to the summary of product characteristics; (d) whether changes are of an administrative nature.
(a) a description of the variation; (b) data referred to in Article 8 relevant to the variation; (c) details of the marketing authorisations affected by the application; (d) where the variation leads to consequential variations to the terms of the same marketing authorisation, a description of those consequential variations; (e) where the variation concerns marketing authorisations granted under the mutual recognition or decentralised procedures, a list of Member States which granted those marketing authorisations.
(a) reference veterinary medicinal products which have the same qualitative and quantitative composition of their active substances and the same pharmaceutical form and for which marketing authorisations have been granted in accordance with Article 47 in different Member States for the same marketing authorisation holder; (b) generic and hybrid veterinary medicinal products.
(a) target species; (b) clinical information referred to in point (c) of Article 35(1); (c) the withdrawal period.
(a) any unfavourable and unintended reaction in any animal to a veterinary medicinal product; (b) any observation of a lack of efficacy of a veterinary medicinal product following its administration to an animal, whether or not in accordance with the summary of product characteristics; (c) any environmental incidents observed following the administration of a veterinary medicinal product to an animal; (d) any noxious reaction in humans exposed to a veterinary medicinal product; (e) any finding of a pharmacologically active substance or marker residue in a product of animal origin exceeding the maximum levels of residues established in accordance with Regulation (EC) No 470/2009 after the set withdrawal period has been respected; (f) any suspected transmission of an infectious agent via a veterinary medicinal product; (g) any unfavourable and unintended reaction in an animal to a medicinal product for human use.
(a) the number and at the latest within two years from 28 January 2022 the incidence of suspected adverse events reported each year, broken down by veterinary medicinal product, animal species and type of suspected adverse event;(b) the results and outcomes referred to in Article 81(1) that arise from the signal management process performed by the marketing authorisation holder for veterinary medicinal products or groups of veterinary medicinal products.
(a) elaborating and maintaining the pharmacovigilance system master file; (b) allocating reference numbers to the pharmacovigilance system master file and communicating that reference number to the pharmacovigilance database for each product; (c) notifying the competent authorities and the Agency, as applicable, of the place of operation; (d) establishing and maintaining a system which ensures that all suspected adverse events which are brought to the attention of the marketing authorisation holder are collected and recorded in order to be accessible at least at one site in the Union; (e) compiling the suspected adverse event reports referred to in Article 76(2), evaluating them, where necessary, and recording them in the pharmacovigilance database; (f) ensuring that any request from the competent authorities or the Agency for the provision of additional information necessary for the evaluation of the benefit-risk balance of a veterinary medicinal product is answered fully and promptly; (g) providing competent authorities or the Agency, as applicable, with any other information relevant to detecting a change to the benefit-risk balance of a veterinary medicinal product, including appropriate information on post-marketing surveillance studies; (h) applying the signal management process referred to in Article 81 and ensuring that any arrangements for the fulfilment of responsibilities referred to in Article 77(4) are in place; (i) monitoring the pharmacovigilance system and ensuring that if needed, an appropriate preventive or corrective action plan is prepared, implemented and, where necessary, ensuring changes to the pharmacovigilance system master file; (j) ensuring that all personnel of the marketing authorisation holder involved in the performance of pharmacovigilance activities receives continued training; (k) communicating any regulatory measure that is taken in a third country and is related to pharmacovigilance data to the competent authorities and to the Agency within 21 days of receipt of such information.
(a) it is administered by a route described in the European Pharmacopoeia or, in the absence thereof, by the pharmacopoeias used officially in Member States;(b) it has a sufficient degree of dilution to guarantee its safety, and shall not contain more than one part per 10000 of the mother tincture;(c) it has no therapeutic indication appearing on its labelling or in any information relating thereto.
(a) scientific name or other name given in a pharmacopoeia of the homeopathic stock or stocks, together with a statement of the route of administration, pharmaceutical form and degree of dilution to be registered; (b) a dossier describing how the homeopathic stock or stocks are obtained and controlled, and justifying their homeopathic use, on the basis of an adequate bibliography; in the case of homeopathic veterinary medicinal products containing biological substances, a description of the measures taken to ensure the absence of pathogens; (c) the manufacturing and control file for each pharmaceutical form and a description of the method of dilution and potentisation; (d) the manufacturing authorisation for the homeopathic veterinary medicinal products concerned; (e) copies of any registrations obtained for the same homeopathic veterinary medicinal products in other Member States; (f) the text to appear on the package leaflet, outer packaging and immediate packaging of the homeopathic veterinary medicinal products to be registered; (g) data concerning the stability of the homeopathic veterinary medicinal product; (h) in the case of homeopathic veterinary medicinal products intended for food-producing animal species, the active substances shall be those pharmacologically active substances allowed in accordance with Regulation (EC) No 470/2009 and any acts adopted on the basis thereof.
(a) to manufacture veterinary medicinal products even if intended only for export; (b) to engage in any part of the process of manufacturing a veterinary medicinal product or of bringing a veterinary medicinal product to its final state, including engagement in the processing, assembling, packaging and repackaging, labelling and relabelling, storing, sterilising, testing or releasing it for supply as part of that process; or (c) to import veterinary medicinal products.
(a) veterinary medicinal products which are to be manufactured or imported; (b) name or company name and permanent address or registered place of business of the applicant; (c) pharmaceutical forms which are to be manufactured or imported; (d) details about the manufacturing site where the veterinary medicinal products are to be manufactured or imported; (e) a statement to the effect that the applicant fulfils the requirements laid down in Articles 93 and 97.
(a) have at its disposal suitable and sufficient premises, technical equipment and testing facilities, for the activities stated in its manufacturing authorisation; (b) have at its disposal the services of at least one qualified person referred to in Article 97 and ensure that the qualified person operates in compliance with that Article; (c) enable the qualified person referred to in Article 97 to carry out his or her duties, particularly by providing access to all the necessary documents and premises, and by placing at his or her disposal all the necessary technical equipment and testing facilities; (d) give at least a 30 days prior notice to the competent authority before the replacement of the qualified person referred to in Article 97 or, if prior notice is not possible because the replacement is unexpected, inform the competent authority immediately; (e) have at its disposal the services of staff complying with the legal requirements existing in the relevant Member State as regards both manufacture and controls; (f) allow the representatives of the competent authority access to the premises at any time; (g) keep detailed records of all veterinary medicinal products which the holder of a manufacturing authorisation supplies in accordance with Article 96, and keep samples of each batch; (h) only supply veterinary medicinal products to wholesale distributors of veterinary medicinal products; (i) inform the competent authority and the marketing authorisation holder immediately if the holder of a manufacturing authorisation obtains information that veterinary medicinal products which fall within the scope of its manufacturing authorisation are, or are suspected of being, falsified irrespective of whether those veterinary medicinal products were distributed within the legal supply chain or by illegal means, including illegal sale by means of information society services; (j) comply with good manufacturing practice for veterinary medicinal products and use as starting materials only active substances which have been manufactured in accordance with good manufacturing practice for active substances and distributed in accordance with good distribution practice for active substances; (k) verify that each manufacturer, distributor and importer within the Union from whom the holder of a manufacturing authorisation obtains active substances is registered with the competent authority of the Member State in which the manufacturer, distributor and importer are established, in accordance with Article 95; (l) perform audits based on a risk assessment on the manufacturers, distributors and importers from whom the holder of a manufacturing authorisation obtains active substances.
(a) name or company name and permanent address or registered place of business; (b) the active substances which are to be imported, manufactured or distributed; (c) particulars regarding the premises and the technical equipment.
(a) date of the transaction; (b) name of the veterinary medicinal product, and marketing authorisation number if applicable, as well as pharmaceutical form and strength, as appropriate; (c) quantity supplied; (d) name or company name and permanent address or registered place of business of the recipient; (e) batch number; (f) date of expiry.
(a) the manufacturer holds a manufacturing authorisation; (b) the manufacturer possesses a certificate of good manufacturing practice as referred to in Article 94; or (c) the veterinary medicinal product concerned has been granted a marketing authorisation in that Member State or, in the case of a request to the Agency, that it has been granted a centralised marketing authorisation.
(a) the applicant has at its disposal technically competent staff and in particular at least one person designated as responsible person, meeting the conditions provided for in national law; (b) the applicant has suitable and sufficient premises complying with the requirements laid down by the relevant Member State as regards the storage and handling of veterinary medicinal products; (c) the applicant has a plan guaranteeing effective implementation of any withdrawal or recall from the market ordered by the competent authorities or the Commission or undertaken in cooperation with the manufacturer or marketing authorisation holder of the veterinary medicinal product concerned; (d) the applicant has an appropriate record-keeping system ensuring compliance with the requirements referred to in Article 101; (e) the applicant has a statement to the effect that it fulfils the requirements referred to in Article 101.
(a) inform the applicant of the outcome of the evaluation; (b) grant, refuse or change the wholesale distribution authorisation; and (c) upload the relevant information of the authorisation in the manufacturing and wholesale distribution database referred to in Article 91.
(a) date of the transaction; (b) name of the veterinary medicinal product including, as appropriate, pharmaceutical form and strength; (c) batch number; (d) expiry date of the veterinary medicinal product; (e) quantity received or supplied, stating pack size and number of packs; (f) name or company name and permanent address or registered place of business of the supplier in the event of purchase or of the recipient in the event of sale.
(a) they have the same qualitative and quantitative composition in terms of active substances and excipients; (b) they have the same pharmaceutical form; (c) they have the same clinical information and, if applicable, withdrawal period; and (d) they have been manufactured by the same manufacturer or by a manufacturer working under licence according to the same formulation.
(a) submit a declaration to the competent authority in the destination Member State and take appropriate measures to ensure that the wholesale distributor in the source Member State will keep it informed of any pharmacovigilance issues; (b) notify the marketing authorisation holder in the destination Member State about the veterinary medicinal product to be obtained from the source Member State and intended to be placed on the market in the destination Member State at least one month prior to submitting to the competent authority the application for parallel trade in that veterinary medicinal product; (c) submit a written declaration to the competent authority of the destination Member State that the marketing authorisation holder in the destination Member State was notified in accordance with point (b) together with a copy of that notification; (d) not trade a veterinary medicinal product which has been recalled from the market of the source Member State or destination Member State for quality, safety or efficacy reasons; (e) collect suspected adverse events and report them to the marketing authorisation holder of the parallel-traded veterinary medicinal product.
(a) name of the veterinary medicinal products; (b) active substances; (c) pharmaceutical forms; (d) classification of the veterinary medicinal products in the destination Member State; (e) marketing authorisation number of the veterinary medicinal products in the source Member State; (f) marketing authorisation number of the veterinary medicinal products in the destination Member State; (g) name or company name and permanent address or registered place of business of the wholesale distributor in the source Member State and of the wholesale distributor in the destination Member State.
(a) date of the transaction; (b) name of the veterinary medicinal product including, as appropriate, pharmaceutical form and strength; (c) batch number; (d) quantity received or supplied; (e) name or company name and permanent address or registered place of business of the supplier in the event of purchase, or of the recipient in the event of sale; (f) name and contact details of the prescribing veterinarian and, where appropriate, a copy of the veterinary prescription; (g) marketing authorisation number.
(a) the contact details of the competent authority of the Member State in which the retailer offering the veterinary medicinal products is established; (b) a hyperlink to the website of the Member State of establishment set up in accordance with paragraph 8 of this Article; (c) the common logo established in accordance with paragraph 6 of this Article is clearly displayed on every page of the website that relates to the offer for sale at a distance of veterinary medicinal products and contains a hyperlink to the entry of the retailer in the list of permitted retailers referred to in point (c) of paragraph 8 of this Article.
(a) information on its national law applicable to the offering of veterinary medicinal products for sale at a distance by means of information society services, in accordance with paragraphs 1 and 2, including information on the fact that there may be differences between Member States regarding the classification of the supply of the veterinary medicinal products; (b) information on the common logo; (c) a list of retailers established in the Member State permitted to offer veterinary medicinal products for sale at a distance by means of information society services in accordance with paragraphs 1 and 2 as well as the website addresses of those retailers.
(a) identification of the animal or groups of animals to be treated; (b) full name and contact details of the animal owner or keeper; (c) issue date; (d) full name and contact details of the veterinarian including, if available, the professional number; (e) signature or an equivalent electronic form of identification of the veterinarian; (f) name of the prescribed medicinal product, including its active substances; (g) pharmaceutical form and strength; (h) quantity prescribed, or the number of packs, including pack size; (i) dosage regimen; (j) for food-producing animal species, withdrawal period even if such period is zero; (k) any warnings necessary to ensure the proper use including, where relevant, to ensure prudent use of antimicrobials; (l) if a medicinal product is prescribed in accordance with Articles 112, 113 and 114, a statement to that effect; (m) if a medicinal product is prescribed in accordance with Article 107(3) and (4), a statement to that effect.
(a) shall not be used in accordance with Articles 112, 113 and 114; or (b) shall only be used in accordance with Articles 112, 113 and 114 subject to certain conditions.
(a) risks to animal or public health if the antimicrobial is used in accordance with Articles 112, 113 and 114; (b) risk for animal or public health in case of development of antimicrobial resistance; (c) availability of other treatments for animals; (d) availability of other antimicrobial treatments for humans; (e) impact on aquaculture and farming if the animal affected by the condition receives no treatment.
(a) date of the first administration of the medicinal product to the animals; (b) name of the medicinal product; (c) quantity of the medicinal product administered; (d) name or company name and permanent address or registered place of business of the supplier; (e) evidence of acquisition of the medicinal products they use; (f) identification of the animal or group of animals treated; (g) name and contact details of the prescribing veterinarian, if applicable; (h) withdrawal period even if such period is zero; (i) duration of treatment.
(a) the administration of the product to animals may interfere with the implementation of a national programme for the diagnosis, control or eradication of animal disease; (b) the administration of the product to animals may cause difficulties in certifying the absence of disease in live animals or contamination of foodstuffs or other products obtained from treated animals; (c) the strains of disease agents to which the product is intended to confer immunity is largely absent in terms of geographic spread from the territory concerned.
(a) a marketing authorisation for the veterinary medicinal product to be administered to the animals has been granted by the competent authorities of the Member State in which the veterinarian is established or by the Commission; (b) the veterinary medicinal products concerned are transported by the veterinarian in their original packaging; (c) the veterinarian follows the good veterinary practice applied in the host Member State; (d) the veterinarian sets the withdrawal period specified on the labelling or package leaflet of the veterinary medicinal product used; (e) the veterinarian does not retail any veterinary medicinal product to an owner or keeper of animals treated in the host Member State unless this is permissible under the rules of the host Member State.
(a) a veterinary medicinal product authorised under this Regulation in the relevant Member State or in another Member State for use in the same species or another animal species for the same indication or for another indication; (b) if there is no veterinary medicinal product as referred to in point (a) of this paragraph, a medicinal product for human use authorised in accordance with Directive 2001/83/EC or Regulation (EC) No 726/2004; (c) if there is no medicinal product as referred to in point (a) or (b) of this paragraph, a veterinary medicinal product prepared extemporaneously in accordance with the terms of a veterinary prescription.
(a) a veterinary medicinal product authorised under this Regulation in the relevant Member State or in another Member State for use in the same or in another food-producing terrestrial animal species for the same indication, or for another indication; (b) if there is no veterinary medicinal product as referred to in point (a) of this paragraph, a veterinary medicinal product authorised under this Regulation in the relevant Member State for use in a non-food-producing animal species for the same indication; (c) if there is no veterinary medicinal product as referred to in point (a) or (b) of this paragraph, a medicinal product for human use authorised in accordance with Directive 2001/83/EC or Regulation (EC) No 726/2004; or (d) if there is no medicinal product as referred to in point (a), (b) or (c) of this paragraph, a veterinary medicinal product prepared extemporaneously in accordance with the terms of a veterinary prescription.
(a) a veterinary medicinal product authorised under this Regulation in the relevant Member State or in another Member State for use in the same or in another food-producing aquatic species and for the same indication or for another indication; (b) if there is no veterinary medicinal product as referred to in point (a) of this paragraph, a veterinary medicinal product authorised under this Regulation in the relevant Member State or in another Member State for use with a food-producing terrestrial species containing a substance present in the list established in accordance with paragraph 3; (c) if there is no veterinary medicinal product as referred to in point (a) or (b) of this paragraph, a medicinal product for human use authorised in accordance with Directive 2001/83/EC or Regulation (EC) No 726/2004 and containing substances present in the list established in accordance with paragraph 3 of this Article; or (d) if there is no medicinal product as referred to in point (a), (b) or (c) of this paragraph, a veterinary medicinal product prepared extemporaneously in accordance with the terms of a veterinary prescription.
(a) a veterinary medicinal product authorised under this Regulation in the relevant Member State or in another Member State for use with a food-producing terrestrial animal species; (b) if there is no veterinary medicinal product as referred to in point (a) of this paragraph, a medicinal product for human use authorised in accordance with Directive 2001/83/EC or Regulation (EC) No 726/2004.
(a) risks to the environment if the food-producing aquatic species are treated with those substances; (b) impact on animal and public health if the food-producing aquatic species affected cannot receive an antimicrobial listed in accordance with Article 107(6); (c) availability or lack of availability of other medicinal products, treatments or measures for prevention or treatment of diseases or certain indications in food-producing aquatic species.
(a) for meat and offal from food-producing mammals and poultry and farmed game birds the withdrawal period shall not be less than: (i) the longest withdrawal period provided in its summary of the product characteristics for meat and offal multiplied by factor 1,5; (ii) 28 days if the medicinal product is not authorised for food-producing animals; (iii) one day, if the medicinal product has a zero withdrawal period and is used in a different taxonomic family than the target species authorised;
(b) for milk from animals producing milk for human consumption the withdrawal period shall not be less than: (i) the longest withdrawal period for milk provided in the summary of the product characteristics for any animal species multiplied by factor 1,5; (ii) seven days, if the medicinal product is not authorised for animals producing milk for human consumption; (iii) one day, if the medicinal product has a zero withdrawal period;
(c) for eggs from animals producing eggs for human consumption the withdrawal period shall not be less than: (i) the longest withdrawal period for eggs provided in the summary of the product characteristics for any animal species multiplied by factor 1,5; (ii) 10 days, if the product is not authorised for animals producing eggs for human consumption;
(d) for aquatic species producing meat for human consumption the withdrawal period shall not be less than: (i) the longest withdrawal period for any of the aquatic species indicated in the summary of the product characteristics multiplied by factor of 1,5 and expressed as degree-days; (ii) if the medicinal product is authorised for food-producing terrestrial animal species, the longest withdrawal period for any of the food-producing animal species indicated in the summary of product characteristics multiplied by a factor of 50 and expressed as degree-days, but not exceeding 500 degree-days; (iii) 500 degree-days, if the medicinal product is not authorised for food-producing animal species; (iv) 25 degree-days if the highest withdrawal period for any animal species is zero.
(a) veterinarians; (b) persons permitted to supply veterinary medicinal products in accordance with national law.
(a) the advertising is limited to immunological veterinary medicinal products; (b) the advertising includes an express invitation to the professional keepers of animal to consult the veterinarian about the immunological veterinary medicinal product.
(a) manufacturers and importers of veterinary medicinal products and active substances; (b) distributors of active substances; (c) marketing authorisation holders; (d) holders of a wholesale distribution authorisation; (e) retailers; (f) owners and keepers of food-producing animals; (g) veterinarians; (h) holders of a registration for homeopathic veterinary medicinal products; (i) holders of veterinary medicinal products referred to in Article 5(6); and (j) any other persons having obligations under this Regulation.
(a) the intrinsic risks associated with the activities of the persons referred to in paragraph 1 and the location of their activities; (b) the past record of the persons referred to paragraph 1 as regards the results of controls performed on them and their previous compliance; (c) any information that might indicate non-compliance; (d) the potential impact of non-compliance on public health, animal health, animal welfare and the environment.
(a) inspect the premises, equipment, means of transport, records, documents and systems, related to the objective of the inspection; (b) inspect and take samples with a view to submitting them for an independent analysis by an Official Medicines Control Laboratory or by a laboratory designated for that purpose by a Member State; (c) document any evidence deemed necessary by the representatives; (d) carry out the same controls on any parties performing the tasks required under this Regulation with, for or on behalf of the persons referred to in paragraph 1.
(a) restriction of supply of the veterinary medicinal product at the request of the competent authority and, in the case of centrally authorised veterinary medicinal products, also at the request of the Commission to the competent authority; (b) restriction of the use of the veterinary medicinal product at the request of the competent authority and, in the case of centrally authorised veterinary medicinal products, also at the request of the Commission to the competent authority; (c) suspension of a marketing authorisation by the competent authority having granted that marketing authorisation and, in the case of centrally authorised veterinary medicinal products, by the Commission.
(a) the marketing authorisation holder does not comply with the requirements set out in Article 58; (b) the marketing authorisation holder does not comply with the requirements set out in Article 127; (c) the pharmacovigilance system established in accordance with Article 77(1) is inadequate; (d) the marketing authorisation holder does not fulfil its obligations laid down in Article 77; (e) the qualified person responsible for pharmacovigilance does not fulfil his or her tasks as laid down in Article 78.
(a) suspend the wholesale distribution authorisation; (b) suspend the wholesale distribution authorisation for one or more categories of veterinary medicinal products; (c) revoke the wholesale distribution authorisation for one or more categories of veterinary medicinal products.
(a) suspend the manufacture of veterinary medicinal products; (b) suspend imports of veterinary medicinal products from third countries; (c) suspend or revoke the manufacturing authorisation for one or more pharmaceutical forms; (d) suspend or revoke the manufacturing authorisation for one or more activities in one or more manufacturing sites.
(a) the benefit-risk balance of the veterinary medicinal product is no longer positive; (b) the qualitative or quantitative composition of the veterinary medicinal product is not as stated in the summary of the product characteristics referred to in Article 35; (c) the recommended withdrawal period is insufficient to ensure food safety; (d) the control tests referred to in Article 127(1) have not been carried out; or (e) the incorrect labelling might lead to a serious risk to animal or public health.
(a) exerted a decisive influence over the marketing authorisation holder; or (b) were involved in, or could have addressed, such failure to comply with the obligation by the marketing authorisation holder.
(a) any infringement procedure initiated by a Member State against the same marketing authorisation holder on the basis of the same legal grounds and the same facts; and (b) any sanctions, including penalties, already imposed on the same marketing authorisation holder on the basis of the same legal grounds and the same facts.
(a) procedures to be applied by the Commission when imposing fines or periodic penalty payments, including rules on the initiation of the procedure, measures of inquiry, rights of defence, access to file, legal representation and confidentiality; (b) further detailed rules on the imposition by the Commission of financial penalties on legal entities other than the marketing authorisation holder; (c) rules on duration of procedure and limitation periods; (d) elements to be taken into account by the Commission when setting the level of, and imposing, fines and periodic penalty payments, as well as the conditions and methods for their collection.
(a) procedures for appointing and replacing the Chair; (b) the appointment of members of any working parties or scientific advisory groups on the basis of the lists of accredited experts referred to in the second subparagraph of Article 62(2) of Regulation (EC) No 726/2004 and procedures for consultation of working parties and scientific advisory groups; (c) a procedure for urgent adoption of opinions, particularly in relation to the provisions of this Regulation on market surveillance and pharmacovigilance.
(a) carry out the tasks conferred on it under this Regulation and Regulation (EC) No 726/2004; (b) prepare scientific opinions of the Agency on questions relating to the evaluation and use of veterinary medicinal products; (c) prepare opinions on scientific matters concerning the evaluation and use of veterinary medicinal products on the request of the Executive Director of the Agency or the Commission; (d) prepare opinions of the Agency on questions concerning the admissibility of applications submitted in accordance with the centralised procedure, and on granting, varying, suspending or revoking marketing authorisations for centrally authorised veterinary medicinal products; (e) take due account of any request made by Member States for scientific opinions; (f) provide guidance on important questions and issues of general scientific nature; (g) give a scientific opinion, in the context of cooperation with the World Organisation for Animal Health, concerning the evaluation of certain veterinary medicinal products intended exclusively for markets outside the Union; (h) advise on the maximum limits for residues of veterinary medicinal products and biocidal products used in animal husbandry which may be accepted in foodstuffs of animal origin in accordance with Regulation (EC) No 470/2009; (i) provide scientific advice on the use of antimicrobials and antiparasitics in animals in order to minimise the occurrence of resistance in the Union, and update that advice when needed; (j) provide objective scientific opinions to the Member States on the questions which are referred to the Committee.
(a) examine questions concerning mutual recognition and decentralised procedures; (b) examine advice from the pharmacovigilance working party of the Committee concerning risk management measures in pharmacovigilance related to veterinary medicinal products authorised in Member States and issue recommendations to the Member States and to the marketing authorisation holders, as necessary; (c) examine questions concerning variations to the terms of marketing authorisations granted by Member States; (d) provide recommendations to Member States whether a specific veterinary medicinal product or a group of veterinary medicinal products is to be considered a veterinary medicinal product within the scope of this Regulation; (e) coordinate the selection of the lead authority responsible for the assessment of the results of the signal management process referred to in Article 81(4); (f) draw up and publish an annual list of reference veterinary medicinal products which shall be subject to harmonisation of the summaries of product characteristics in accordance with Article 70(3).
(a) Part 1A: points 1 to 4 and 6.1 to 6.4; (b) Part 1B: point 5; (c) Part 1C: point 6.5.
(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) statement of compliance with GLP for pre-clinical safety 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.
(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.
(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 GLP for pre-clinical safety 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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(a) crystalline form and solubility; (b) particle size; (c) state of hydration; (d) oil/water coefficient of partition; (e) pK/pH values.
(a) a copy of the study plan (protocol); (b) a statement of compliance with good laboratory practice, where applicable; (c) a description of the methods, apparatus and materials used; (d) a description and justification of the test system; (e) a description of the results obtained, in sufficient detail, to allow the results to be critically evaluated independently of their interpretation by the author; (f) a statistical analysis of the results where appropriate; (g) a discussion of the results, with comment on observed and no-observed-effect levels, and on any unusual findings; (h) the name of the laboratory; (i) the name of the study director; (j) signature and date; (k) place and period of time during which the study was undertaken; (l) key for abbreviations and codes, irrespective of whether they are internationally accepted or not; (m) description of mathematical and statistical procedures.
(a) the potential toxicity of the veterinary medicinal product and any dangerous or undesirable effects in target species which may occur under the proposed conditions of use; (b) the potential risks which may result from the exposure of human beings to the veterinary medicinal product, for example, during its administration to the animal; (c) the potential risks to the environment resulting from the use of the veterinary medicinal product.
(a) International Non-proprietary Name (INN); (b) International Union of Pure and Applied Chemistry Name (IUPAC); (c) Chemical Abstract Service (CAS) number; (d) therapeutic, pharmacological and chemical classification; (e) synonyms and abbreviations; (f) structural formula; (g) molecular formula, (h) molecular weight; (i) degree of purity; (j) qualitative and quantitative composition of impurities; (k) description of physical properties: (i) melting point, (ii) boiling point, (iii) vapour pressure, (iv) solubility in water and organic solvents expressed in g/l, with indication of temperature, (v) density, (vi) refraction of light, optical rotation, etc.;
(l) formulation of the product.
(a) the possible effects of acute overdose in the target species; (b) the possible effects of accidental administration to humans; (c) the doses which may usefully be employed in the repeat dose studies.
(a) under the intended conditions of use, oral ingestion of the veterinary medicinal product by the animal is to be expected, or (b) under the intended conditions of use, oral exposure of the user of the veterinary medicinal product is to be expected.
(a) the identification of resistant bacteria or resistance determinants that could be associated with human illness (zoonotic and/or commensal bacteria) and are selected by the use of the antimicrobial veterinary medicinal product in target animals (hazard identification); (b) the probability of release of the identified hazard(s) from the target animal species as a result of the use of the veterinary medicinal product under consideration; (c) the probability of subsequent human exposure to the identified hazard(s) via the foodborne route or through direct contact, and the resulting consequences (adverse health effects) to human health. Guidance is available in VICH GL27 and EU GLs.
(a) the identification of resistant bacteria or resistance determinants that could be associated with human illness and are selected by the use of the antimicrobial veterinary medicinal product in target animals; (b) an estimate of exposure of zoonotic and commensal bacteria in the target animal species based on the conditions of use of the veterinary medicinal product under consideration; (c) consideration of subsequent human exposure to antimicrobial resistance (AMR), and the resulting consequences to human health.
(a) the target animal species, and the proposed pattern of use; (b) the method of administration, in particular the likely extent to which the product will enter directly into environmental systems; (c) the possible excretion of the product, its active substances or relevant metabolites into the environment by treated animals; persistence in such excreta; (d) the disposal of unused veterinary medicinal product or other waste product.
(a) to what extent, and for how long residues of the veterinary medicinal product or its metabolites persist in the edible tissues of the treated animal or in milk, eggs and/or honey (wax, if appropriate) obtained therefrom; (b) that in order to prevent any risk to the health of the consumer of foodstuffs from treated animals, it is possible to establish realistic withdrawal periods which may be observed under practical farming conditions; (c) that the analytical method(s) used in the residues depletion study are sufficiently validated to provide the necessary reassurance that the residues data submitted are suitable as the basis for a withdrawal period.
(a) composition; (b) the physical and chemical (potency and purity) test results for the relevant batch(es); (c) batch identification.
(a) to describe the basic pharmacokinetic characteristics (namely absorption, distribution, metabolism and excretion) of the active substance in the formulation; (b) use of this basic pharmacokinetic characteristics to investigate the relationships between dosage regimen, plasma and tissue concentration over time and pharmacological, therapeutic or toxic effects; (c) where appropriate, to compare pharmacokinetic parameters between different target species and to explore possible species differences having an impact on target animal safety and efficacy of the veterinary medicinal product; (d) where appropriate, to compare bioavailability to support bridging of safety and efficacy information between different products, pharmaceutical forms, strengths or routes of administration, or to compare the impact of changes in manufacturing or composition.
(a) tests demonstrating pharmacological activity, including tests demonstrating the pharmacodynamic mechanisms underlying the therapeutic effect and tests demonstrating the main pharmacokinetic profile; (b) tests and investigations on resistance, if applicable; (c) tests demonstrating target animal safety; (d) tests to determine and confirm the dose (including dose interval, duration of treatment and any re-treatment interval).
(a) a summary; (b) a study protocol; (c) a detailed description of the objectives, design and conduct to include methods, apparatus and materials used, details such as species, age, weight, sex, number, breed or strain of animals, identification of animals, dose, route and schedule of administration; (d) a statistical analysis of the results, if applicable; (e) an objective discussion of the results obtained, leading to conclusions on the efficacy and target animal safety of the veterinary medicinal product.
(a) the number of control and test animals treated either individually or collectively, with a breakdown according to species, breed or strain, age and sex; (b) the number of animals withdrawn prematurely from the trials and the reasons for such withdrawal; (c) in the case of control animals, whether they have: (i) received no treatment, (ii) received a placebo, or (iii) received another veterinary medicinal product authorised in the Union that has demonstrated an acceptable level of efficacy and been approved for the proposed indication(s) for use in the same target animal species, or (iv) received the same active substance under investigation in a different formulation or by a different route;
(d) the frequency of observed adverse reactions; (e) observations as to the effect on animal performance, if appropriate; (f) details concerning test animals which may be at increased risk owing to their age, their mode of rearing or feeding, or the purpose for which they are intended, or animals the physiological or pathological condition of which requires special consideration; (g) a statistical evaluation of the results.
(a) the active substance(s); (b) the constituent(s) of the excipients, whatever their nature or the quantity used, including adjuvants, preservatives, stabilisers, thickeners, emulsifiers, colouring matter, flavouring and aromatic substances, markers, etc.; (c) the composition, that is to say, list of all components of the dosage form and their amount on a per-unit basis (including overages, if any), the function of the components, and a reference to their quality standards (for example, compendial monographs or manufacturer’s specifications); (d) accompanying reconstitution solvent(s); (e) the type of container and its closure used for the dosage form and for any accompanying reconstitution solvents and devices, if applicable. If the device is not delivered together with the biological veterinary medicinal product, relevant information about the device shall be provided.
(a) in respect of substances which appear in the European Pharmacopoeia or, failing this, in the pharmacopoeia of one of the Member States, the main title of the monograph in question, which will be obligatory for all such substances, with reference to the pharmacopoeia concerned; (b) in respect of other substances, the INN recommended by the WHO, which may be accompanied by another non-proprietary name or, failing these, the exact scientific designation; substances 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; (c) in respect of colouring matter, designation by the "E" code assigned to them in Directive 2009/35/EC.
(a) the choice of composition and the choice of the constituents, in particular relative to their intended functions and their respective concentrations; (b) the inclusion of a preservative in the composition shall be justified; (c) the immediate packaging and the suitability of the container and its closure system used for the storage and use of the finished product. A study of the interaction between the 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; (d) the microbiological characteristics (microbiological purity and antimicrobial activity) and usage instructions; (e) the possible further packaging, outer packaging, if relevant; (f) the proposed pack sizes related to the proposed route of administration, the posology and the target species; (g) any overage(s) in the formulation to guarantee minimum potency at end of shelf life with justification; (h) the selection of the manufacturing process of the active substance and the finished product; (i) differences between the manufacturing process(es) used to produce batches used in clinical trials and the process described in the application for marketing authorisation shall be discussed; (j) when a dosing device is provided with the finished product, the accuracy of the doses(s) shall be demonstrated; (k) 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. (l) This explanation shall be supported by scientific data on product development.
(a) the various stages of manufacture, including production of the active substance and description of the purification steps; (b) a process flow chart of all successive steps shall be given so that an assessment can be made of the reproducibility of the manufacturing procedure and of the risks of adverse effects on the finished products, such as microbiological contamination; (c) in the case of continuous manufacture, full details concerning precautions taken to ensure the homogeneity and consistency of each batch of the finished product. Information on how a batch is defined and on the proposed commercial batch size(s) shall be provided; (d) listing of all the substances at the appropriate steps where they are used, including those which cannot be recovered in the course of manufacturing; (e) the details of the blending, with the quantitative particulars of all the substances used, including an example for a representative production batch; (f) list of in-process controls including the stage of manufacture at which they are conducted and acceptance criteria; (g) for sterile products, where non-pharmacopoeial sterilisation conditions are used, details of the sterilisation processes and/or aseptic procedures used.
(a) the name of the starting material meeting the requirements of point IIIa.2A1(4) shall be supplemented by any trade or scientific synonyms; (b) the description of the starting material, set down in a form similar to that used in a descriptive item in the European Pharmacopoeia; (c) the function of the starting material; (d) methods of identification; (e) any special precautions which may be necessary during storage of the starting material and, if necessary, its storage life shall be given.
(a) a copy of the study plan (protocol); (b) a statement of compliance with good laboratory practice, where applicable; (c) a description of the methods, apparatus and materials used; (d) a description and justification of the test system; (e) a description of the results obtained, in sufficient detail to allow the results to be critically evaluated independently of their interpretation by the author; (f) a statistical analysis of the results where appropriate; (g) a discussion of the results, with comment on observed and no-observed-effect levels, and on any unusual findings; (h) the name of the laboratory; (i) the name of the study director; (j) signature and date; (k) place and period of time during which the study was undertaken; (l) key for abbreviations and codes, irrespective of whether they are internationally accepted or not; (m) description of mathematical and statistical procedures.
(a) the potential toxicity of the veterinary medicinal product and any dangerous or undesirable effects in target species which may occur under the proposed conditions of use; (b) the potential risks which may result from the exposure of human beings to the veterinary medicinal product, for example, during its administration to the animal; (c) the potential risks to the environment resulting from the use of the veterinary medicinal product.
(a) international non-proprietary name (INN); (b) International Union of Pure and Applied Chemistry Name (IUPAC); (c) Chemical Abstract Service (CAS) number; (d) therapeutic, pharmacological and chemical classification; (e) synonyms and abbreviations; (f) structural formula; (g) molecular formula; (h) molecular weight; (i) degree of impurity; (j) qualitative and quantitative composition of impurities; (k) description of physical properties; (l) solubility in water and organic solvents expressed in g/l, with indication of temperature; (m) refraction of light, optical rotation, etc.; (n) formulation of the product.
(a) the possible effects of acute overdose in the target species; (b) the possible effects of accidental administration to humans; (c) the doses which may usefully be employed in the repeat dose studies.
(a) under the intended conditions of use, oral ingestion of the veterinary medicinal product by the animal is to be expected, or (b) under the intended conditions of use, oral exposure of the user of the veterinary medicinal product is to be expected.
(a) the identification of resistant bacteria or resistance determinants that could be associated with human illness (zoonotic and/or commensal bacteria) and are selected by the use of the antimicrobial veterinary medicinal product in target animals (hazard identification); (b) the probability of release of the identified hazard(s) from the target animal species as a result of the use of the veterinary medicinal product under consideration; (c) the probability of subsequent human exposure to the identified hazard(s) via the foodborne route or through direct contact, and the resulting consequences (adverse health effects) to human health. Guidance is available in VICH GL27 and EU GLs.
(a) the identification of resistant bacteria or resistance determinants that could be associated with human illness and are selected by the use of the antimicrobial veterinary medicinal product in target animals; (b) an estimate of exposure of zoonotic and commensal bacteria in the target animal species based on the conditions of use of the veterinary medicinal product under consideration; (c) consideration of subsequent human exposure to AMR, and the resulting consequences to human health.
(a) the target animal species, and the proposed pattern of use; (b) the method of administration, in particular the likely extent to which the product will enter directly into environmental systems; (c) the possible excretion of the product, its active substances or relevant metabolites into the environment by treated animals; persistence in such excreta; (d) the disposal of unused veterinary medicinal product or other waste product.
(a) to what extent, and for how long, residues of the veterinary medicinal product or its metabolites persist in the edible tissues of the treated animal or in milk, eggs and/or honey (wax if appropriate) obtained therefrom; (b) that in order to prevent any risk to the health of the consumer of foodstuffs from treated animals, it is possible to establish realistic withdrawal periods which may be observed under practical farming conditions; (c) that the analytical method(s) used in the residue depletion study are sufficiently validated to provide the necessary reassurance that the residues data submitted are suitable as the basis for a withdrawal period.
(a) composition; (b) the physical and chemical (potency and purity) test results for the relevant batch(es); (c) batch identification.
(a) to describe the basic pharmacokinetic characteristics (namely absorption, distribution, metabolism and excretion) of the active substance in the formulation; (b) to investigate the relationships between dosage regimen, plasma and tissue concentration over time and pharmacological, therapeutic or toxic effects; (c) where appropriate, to compare pharmacokinetic parameters between different target species and to explore possible species differences having an impact on target animal safety and efficacy of the veterinary medicinal product; (d) where appropriate, to compare bioavailability to support bridging of safety and efficacy information between different products, pharmaceutical forms, strengths or routes of administration, or to compare the impact of changes in manufacturing or composition, including pilot and final formulations.
(a) tests demonstrating pharmacological activity; (b) tests demonstrating the pharmacodynamic mechanisms underlying the therapeutic effect; (c) tests demonstrating the main pharmacokinetic profile; (d) tests demonstrating target animal safety; (e) tests to determine and confirm the dose (including dose interval, duration of treatment and any re-treatment interval); (f) tests and investigations on resistance, if applicable.
(a) a summary; (b) a study protocol; (c) a detailed description of the objectives, design and conduct to include methods, apparatus and materials used, details such as species, age, weight, sex, number, breed or strain of animals, identification of animals, dose, route and schedule of administration; (d) a statistical analysis of the results; (e) an objective discussion of the results obtained, leading to conclusions on the efficacy and target animal safety of the veterinary medicinal product.
(a) the number of control and test animals treated either individually or collectively, with a breakdown according to species, breed or strain, age and sex; (b) the number of animals withdrawn prematurely from the trials and the reasons for such withdrawal; (c) in the case of control animals, whether they have: (i) received no treatment; (ii) received a placebo; (iii) received another veterinary medicinal product authorised in the Union that has demonstrated an acceptable level of efficacy and been approved for the proposed indication(s) for use in the same target animal species; or (iv) received the same active substance under investigation in a different formulation or by a different route;
(d) the frequency of observed adverse reactions; (e) observations as to the effect on animal performance, if appropriate; (f) details concerning test animals which may be at increased risk owing to their age, their mode of rearing or feeding, or the purpose for which they are intended, or animals the physiological or pathological condition of which requires special consideration; (g) a statistical evaluation of the results.
(a) the active substance(s); (b) the constituents of the adjuvants; (c) the constituent(s) of other excipients, whatever their nature or the quantity used, including preservatives, stabilisers, colouring matter, flavouring and aromatic substances, markers, etc. (d) accompanying reconstitution solvents.
(a) in respect of substances which appear in the European Pharmacopoeia or, failing this, in the pharmacopoeia of one of the Member States, the main title of the monograph in question, which will be obligatory for all such substances, with reference to the pharmacopoeia concerned; (b) in respect of other substances, the INN recommended by the WHO, which may be accompanied by another non-proprietary name or, failing these, the exact scientific designation; substances 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; (c) in respect of colouring matter designation by the "E" code assigned to them in Directive 2009/35/EC.
(a) the choice of composition and the choice of the constituents, in particular relative to their intended functions and their respective concentrations; (b) the inclusion of a preservative in the composition shall be justified; (c) the immediate packaging and the suitability of the container and its closure system used for the storage and use of the finished product. 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; (d) the possible further packaging, outer packaging if relevant; (e) the proposed pack sizes related to the proposed route of administration, the posology and the target species; (f) any overage(s) in the formulation to guarantee minimum potency/antigen content at end of shelf life with justification; (g) the selection of the manufacturing process of the active substance and the finished product; (h) differences between the manufacturing process(es) used to produce batches used in clinical trials and the process described in the application for marketing authorisation shall be discussed; (i) when an accompanying test is recommended to be used with the finished product (e.g. diagnostic test), relevant information about the test shall be provided.
(a) the various stages of manufacture (including production of the antigen and purification procedures) accompanied by a process flow chart so that an assessment may be made of the reproducibility of the manufacturing procedure and of the risks of adverse effects on the finished products, such as microbiological contamination; (b) in the case of continuous manufacture, full details concerning precautions taken to ensure the homogeneity and consistency of each batch of the finished product. Information on how a batch is defined and on the proposed commercial batch size(s) shall be provided; (c) listing of all the substances at the appropriate steps where they are used, including those which cannot be recovered in the course of manufacturing; (d) the details of the blending, with the quantitative particulars of all the substances used, including an example for a representative production batch; (e) list of in-process controls including the stage of manufacture at which they are conducted; (f) for sterile products, where non-pharmacopoeial sterilisation conditions are used, details of the sterilisation processes and/or aseptic procedures used.
(a) details of the source of the materials; (b) details of any processing, purification and inactivation applied, with data on the validation of those processes and controls during production; (c) details of any tests for contamination carried out on each batch of the substance.
(a) the name of the starting material meeting the requirements of point (3) of Part IIIb.2A1. shall be supplemented by any trade or scientific synonyms; (b) the description of the starting material, set down in a form similar to that used in a descriptive item in the European Pharmacopoeia; (c) the function of the starting material; (d) methods of identification; (e) any special precautions which may be necessary during storage of the starting material and, if necessary, its storage life shall be given.
(a) the safety of the immunological veterinary medicinal product when administered to the target species and any undesirable effects which may occur under the proposed conditions of use; those undesirable effects shall be evaluated in relation to potential benefits of the product; (b) the potential harmful effects to man of residues of the veterinary medicinal product or substance in foodstuffs obtained from treated animals; (c) the potential risks which may result from the exposure of human beings to the veterinary medicinal product, for example, during its administration to the animal; (d) the potential risks to the environment resulting from the use of the veterinary medicinal product.
(a) the target animal species and the proposed pattern of use; (b) the route and method of administration, in particular the likely extent to which the product will enter directly into the environmental system; (c) the possible excretion or secretion of the product, its active substances into the environment by treated animals, persistence in such excreta or secreta; (d) the disposal of unused or waste product.
(a) the efficacy studies shall be in line with the general European Pharmacopeia requirements; Deviations shall be justified. (b) the primary parameter on which determination of efficacy is based needs to be defined by the investigator at the time of study design and shall not be changed after the study is completed; (c) the planned statistical analysis shall be described in detail in the study protocols; (d) the choice of antigens or vaccine strains shall be justified on the basis of epizoological data; (e) efficacy trials carried out in the laboratory shall be controlled trials, including untreated control animals unless this is not justified for animal welfare reasons and efficacy can be otherwise demonstrated.
(a) The efficacy of an immunological veterinary medicinal product shall be demonstrated for each category of target animal species in which its use is recommended, by each recommended route and method of administration and using the proposed schedule of administration. Unless otherwise justified, the onset and duration of immunity shall be established and supported by data from trials. (b) The influence of passively acquired maternally derived antibodies on the efficacy of vaccines when administered to animals at an age at which maternally acquired immunity is still present shall be adequately evaluated, if appropriate. (c) The efficacy of each of the components of multivalent and combined immunological veterinary medicinal products shall be demonstrated. If the product is recommended for administration in combination with or at the same time as another veterinary medicinal product, to the efficacy of the association shall be demonstrated by appropriate studies. Any known interactions with any other veterinary medicinal products shall be described. (d) Whenever a product forms part of a vaccination scheme recommended by the applicant, the priming or booster effect or the contribution of the veterinary immunological product to the efficacy of the scheme as a whole shall be demonstrated. (e) The dose to be used shall be the quantity of the product to be recommended for use and the batch used for efficacy testing shall be taken from a batch or batches produced according to the manufacturing process described in Part 2 of the application. (f) For diagnostic immunological veterinary medicinal products administered to animals, the applicant shall indicate how reactions to the product are to be interpreted. (g) For vaccines intended to allow a distinction between vaccinated and infected animals (marker vaccines), where the efficacy claim is reliant on in vitro diagnostic tests, sufficient data on the diagnostic tests shall be provided to allow adequate assessment of the claims related to the marker properties.
(a) a summary; (b) a statement of compliance with good laboratory practice for pre-clinical studies, where applicable; (c) the name of the body having carried out the studies; (d) a detailed experimental protocol giving a description of the methods, apparatus and materials used, details such as species or breed of animals, categories of animals, where they were obtained, their identification and number, the conditions under which they were housed and fed (stating, inter alia, whether they were free from any specified pathogens and/or specified antibodies, the nature and quantity of any additives contained in the feed), dose, route, schedule and dates of administration, a description and a justification of the statistical methods used; (e) in the case of control animals, whether they received a placebo or no treatment; (f) in the case of treated animals and, where appropriate, whether they received the test product or another product authorised in the Union; (g) all general and individual observations and results obtained (with averages and standard deviations), whether favourable or unfavourable. The data shall be described in sufficient detail to allow the results to be critically evaluated independently of their interpretation by the author. The individual data shall be presented in tabular form. By way of explanation and illustration, the results may be accompanied by reproductions of recordings, photomicrographs, etc.; (h) the nature, frequency and duration of observed adverse reactions; (i) the number of animals withdrawn prematurely from the studies and reasons for such withdrawal; (j) a statistical analysis of the results, where such is called for by the test programme, and variance within the data; (k) occurrence and course of any intercurrent disease; (l) all details concerning veterinary medicinal products (other than the product under study), the administration of which was necessary during the course of the study; (m) any other observations and deviations from the protocol and possible impact on the results; (n) an objective discussion of the results obtained, leading to conclusions on the safety and efficacy of the product.
(a) a summary; (b) a statement of compliance with good clinical practice; (c) name, address, function and qualifications of the investigator in charge; (d) place and date of administration, identity code that may be linked to the name and address of the owner of the animal(s); (e) details of the trial protocol, giving a description of the methods, apparatus and materials used, details such as the route and method of administration, the schedule of administration, the dose, the categories of animals, the duration of observation, the serological response and other investigations carried out on the animals after administration; (f) in the case of control animals, whether they received a placebo, a competitor product or no treatment; (g) identification of the treated and control animals (collective or individual, as appropriate), such as species, breeds or strains, age, weight, sex, physiological status; (h) a brief description of the method of rearing and feeding, stating the nature and quantity of any additives contained in the feed; (i) all the particulars on observations, performances and results (with averages and standard deviation); individual data shall be indicated when tests and measurements on individuals have been carried out; (j) a statistical analysis of the results, where such is called for by the test programme, and variance within the data; (k) all observations and results of the trials, whether favourable or unfavourable, with a full statement of the observations and the results of the objective tests of activity required to evaluate the product; the techniques used shall be specified and the significance of any variations in the results explained; (l) effects on the animals’ performance; (m) the number of animals withdrawn prematurely from the trials and reasons for such withdrawal; (n) the nature, frequency and duration of observed adverse reactions; (o) occurrence and course of any intercurrent disease; (p) all details concerning veterinary medicinal products (other than the product under study) which have been administered either prior to or concurrently with the test product or during the observation period; details of any interactions observed; (q) any other observations and deviations for the protocol and possible impact on the results; (r) an objective discussion of the results obtained, leading to conclusions on the safety and efficacy of the product.
(a) the grounds for claiming bioequivalence; (b) a summary of impurities present in batches of the active substance(s) as well as those of the finished medicinal product (and where relevant decomposition products arising during storage) together with an evaluation of those impurities; (c) an evaluation of the bioequivalence studies or other information that may provide support for claiming bioequivalence in accordance with relevant guidance published by the Agency; (d) any additional data in order to demonstrate the equivalence of safety and efficacy properties of different salts, esters or derivatives of an authorised active substance; (e) a review of the user safety risk assessment focusing on differences between the generic and reference veterinary medicinal products (for example, composition in excipients); (f) a review of environmental risk assessment, where relevant.
(a) evidence to demonstrate equivalent or differing depletion of residues from the administration site, which may be substantiated by appropriate residue depletion studies; (b) evidence to demonstrate target animal tolerance at the administration site, which may be substantiated by appropriate target animal tolerance studies.
(a) all the data referred to in Parts 1 and 2 of Sections II or III, as appropriate, of this Annex; (b) for Parts 3 and 4 of the dossier, hybrid applications may rely in part on the results of the appropriate safety, residue, pre-clinical studies and clinical trials for an already authorised reference veterinary medicinal product, and in part on new data. New data shall include a user safety risk assessment and an environmental risk assessment in accordance with Article 18(7), if applicable. In addition, for relevant products (for example, antimicrobials, antiparasitics) the risk of development of resistance shall be addressed, if applicable.
(a) the time over which an active substance has been regularly used in the target species using the proposed route of administration and dosage regimen; (b) quantitative aspects of the use of the active substance(s), taking into account the extent to which the substance(s) has or have been used in practice, and the extent of use on a geographical basis; (c) the degree of scientific interest in the use of the active substance(s) (reflected in the published scientific literature); (d) the coherence of scientific assessments.
(a) veterinary medicinal products other than biological veterinary medicinal products; (b) biological veterinary medicinal products other than immunological veterinary medicinal products; (c) immunological veterinary medicinal products.
(a) information shall be provided on all the starting materials used for the manufacture of the active substance, including the products necessary for the genetic modification of cells, as applicable, subsequent culture and preservation of the genetically modified cells, taking into consideration the possible absence of purification steps; (b) for products containing a microorganism or a virus, data on the genetic modification, sequence analysis, attenuation of virulence, tropism for specific tissues and cell types, cell cycle dependence of the microorganism or virus, pathogenicity and characteristics of the parental strain shall be provided; (c) process-related impurities and product-related impurities shall be described in the relevant sections of the dossier and in particular replication competent virus contaminants if the vector is designed to be replication incompetent; (d) for plasmids, quantification of the different plasmid forms shall be undertaken throughout the shelf life of the product; (e) for genetically modified cells, the characteristics of the cells before and after the genetic modification, as well as before and after any subsequent freezing/storage procedures, shall be tested. For genetically modified cells, in addition to the specific requirements for gene therapy medicinal products, the quality requirements for cell therapy medicinal products and tissue engineered products shall apply; (f) off-target insertions (leading, for example, to tumours/cancer, metabolic dysfunctions) and insertional mutagenesis and genotoxicity (insertion of genetic elements and the expression of DNA-modifying proteins as mediators of genotoxic side effects) in target species need to be considered; (g) germline transmission studies shall be provided, unless otherwise justified.
(a) summary information shall be provided on procurement and testing of the animal tissue and cells used as starting materials. If non-healthy cells or tissues are used as starting materials, their use shall be justified; (b) the potential variability introduced through the animal tissues and cells shall be addressed as part of the validation of the manufacturing process, characterisation of the active substance and the finished product, development of assays, setting of specifications and stability; (c) for the genetic modification of the cells, the technical requirements specified for gene therapy products shall apply; (d) relevant information shall be provided on the characterisation of the cell population or cell mixture in terms of identity, purity (for example, extraneous agents and cellular contaminants), viability, potency, karyology, tumourigenicity and suitability for the intended medicinal use. The genetic stability of the cells shall be demonstrated; (e) the impact and interactions of any components likely to interact (directly or as a result of degradation or metabolism) with the active substance shall be investigated; (f) where a three-dimensional structure is part of the intended function, the differentiation state, structural and functional organisation of the cells and, where applicable, the extracellular matrix generated shall be part of the characterisation for those cell-based products.
(a) size distribution of particles shall be determined; (b) a suitable in vitro test for their function and possible delivery capacity (if used as drug delivery system) shall be used.
(a) The nanoparticles for drug delivery could influence the toxicity of the medicinal product. The toxicity of the active substance is pivotal to the product but the toxicity of the nanoparticle for drug delivery shall also be considered, as they may introduce specific risks (agglomerates, cytotoxicity), may convey impurities by adsorption, may generate toxic materials by degradation or solubilisation, or may be transferred through physiological barrier (haemato-encephalic, foeto-placental, cell and nuclear membranes, etc.). In this context: (i) when physiological barriers are crossed, the impact of nanoparticles for drug delivery shall be investigated on the corresponding organ(s); (ii) the impact of agglomerates shall be investigated in the different targeted organs, focusing in particular on the risk of embolism in the smaller blood vessels; (iii) safety issues of the nanoparticles for drug delivery may be linked to a cumulative effect, a degradation profile or persistence in the body with negative effects on the functions of the targeted organs; (iv) safety issues might also be perceived at the cell level. Cells might not always be able to eliminate the nanoparticles conveyed through the cell membrane, leading to cytotoxicity especially via the induction of an oxidative stress. The toxicological assays to be implemented shall be able to assess this cytotoxicity and the related aspects, such as the generation of toxic free radicals and biopersistence.
(b) The toxicology profile of the active substances contained in nanoparticles for drug delivery may differ as they may be distributed differently into various internal organs (different solubility in biological matrices), or as they may unexpectedly cross various biological barriers within the body, such as the brain barrier. (c) The side effects linked to the active substances may be exacerbated when they are delivered by nanoparticles. (d) Immunosafety issues such as immunotoxicity (direct damage to immune cells), immunostimulation, immunosuppression and immunomodulation (such as complement activation, inflammation, activation of the innate or adaptive immunity), were already identified for nanomedicines. (e) The capacity of nanoparticles to create inflammatory or allergic reactions shall be considered. The capacity to penetrate into the blood stream and to induce inflammatory reactions may lead to disseminated intravascular coagulation or fibrinolysis with further consequences such as thrombosis. The haemocompatibility of the nanoparticles shall therefore be checked.
(a) the minimum amount of RNA segments per volume needs to be established as part of control tests of the finished product, as well as the confirmation that the RNA segments present the correct sequence; (b) for certain antisense therapy products falling under Section II of this Annex a potency bioassay may be needed for their release testing; (c) stability studies shall include a test to monitor the degradation rate of the RNA segments over time; (d) for RNA antisense therapy products, the possible harmful effects due to on- or off-target binding shall be addressed as well as possible non-antisense harmful effects due to, for example, accumulation, pro-inflammatory responses and aptamer binding; (e) for RNAi therapy products, the possible harmful effects of off-target interference (due to the positive RNAi strand) shall be addressed, as well as the possibility of crossing the blood-brain barrier and causing central nervous system disorders; (f) for RNA antisense therapy and RNA interference therapy products intended for gene therapy the requirements for gene therapy veterinary medicinal product shall be considered.
(1) the obligation, as an applicant, to provide accurate information and documentation as referred to in Article 6(4); (2) the obligation to provide, in an application submitted in accordance with Article 62, the data referred to in point (b) of paragraph 2 of that Article; (3) the obligation to comply with the conditions referred to in Articles 23 and 25; (4) the obligation to comply with conditions included in the marketing authorisation of the veterinary medicinal product, as referred to in Article 36(1); (5) the obligation to introduce any necessary variation to the terms of the marketing authorisation to take account of technical and scientific progress and enable the veterinary medicinal products to be manufactured and checked by means of generally accepted scientific methods, as provided for in Article 58(3); (6) the obligation to keep up to date the summary of product characteristics, package leaflet and labelling with current scientific knowledge, as provided for in Article 58(4); (7) the obligation to record in the product database the dates when its authorised veterinary medicinal products are placed on the market and information on the availability for each veterinary medicinal product in each relevant Member State and, as applicable, the dates of any suspension or revocation of the marketing authorisations concerned, as well as data relating to the volume of sales of the medicinal product, as provided in Article 58(6) and (11) respectively; (8) the obligation to provide within the time limit set at the request of a competent authority or the Agency any data demonstrating that the benefit-risk balance remains positive, as provided for in Article 58(9); (9) the obligation to supply any new information which may entail a variation to the terms of the marketing authorisation, to notify any prohibition or restriction imposed by the competent authorities of any country in which the veterinary medicinal product is marketed, or to supply any information that may influence the evaluation of the risks and benefits of the medicinal product, as provided for in Article 58(10); (10) the obligation to place the veterinary medicinal product on the market in accordance with the content of the summary of the product characteristics and the labelling and package leaflet as contained in the marketing authorisation; (11) the obligation to record and report suspected adverse events for their veterinary medicinal products, in accordance with Article 76(2); (12) the obligation to collect specific pharmacovigilance data additional to the data listed in Article 73(2) and to carry out post-marketing surveillance studies in accordance with Article 76(3); (13) the obligation to ensure that public announcements relating to information on pharmacovigilance concerns are presented objectively and are not misleading and to notify them to the Agency, as provided for in Article 77(11); (14) the obligation to operate a pharmacovigilance system for the fulfilment of pharmacovigilance tasks, including maintenance of a pharmacovigilance system master file in accordance with Article 77; (15) the obligation to submit, at the request of the Agency, a copy of its pharmacovigilance system master file(s), as provided for in Article 79(6); (16) the obligation to carry out signal management process and to record the results and outcomes of that process in accordance with Article 81(1) and (2); (17) the obligation to provide to the Agency all available information relating to the Union interest referral, as referred to in Article 82(3).
| Directive 2001/82/EC | This Regulation |
|---|---|
| Article 1 | Article 4 |
| Article 2(1) | Article 2(1) |
| Article 2(2) | Article 3 |
| Article 2(3) | Article 2(2),(3) and (4) |
| Article 3 | Article 2(4) |
| Article 4(2) | Article 5(6) |
| Article 5 | Article 5 |
| Article 5(1) second sentence | Article 38(3) |
| Article 5(2) | Article 58(1) |
| Article 6(1), (2) | Article 8(3) |
| Article 6(3) | Article 8(4) |
| Article 7 | Article 116 |
| Article 8 | Article 116 |
| Article 8 third sentence | |
| Article 9 | Article 9 |
| Article 10 | Article 112 |
| Article 11 | Articles 113, 114 and 115 |
| Article 12 | Article 8 |
| Article 13(1) | Article 18 |
| Article 13(2) | Article 4(8) and (9) |
| Article 13(3),(4) | Article 19 |
| Article 13(5) | Articles 38, 39 and 40 |
| Article 13(6) | Article 41 |
| Article 13a | Article 22 |
| Article 13b | Article 20 |
| Article 13c | Article 21 |
| Article 14 | Article 35 |
| Article 16 | Article 85 |
| Article 17 | Article 86 |
| Article 18 | Article 87 |
| Article 19 | Article 85 |
| Article 20 | Article 85 |
| Article 21(1) | Article 47 |
| Article 21(2) | Article 46 |
| Article 22 | Article 48 |
| Article 23 | Articles 28 and 29 |
| Article 24 | Article 30 |
| Article 25 | Article 33 |
| Article 26(3) | Articles 25 and 26 |
| Article 27 | Article 58 |
| Article 27a | Article 58(6) |
| Article 27b | Article 60 |
| Article 28 | Article 5(2) |
| Article 30 | Article 37 |
| Article 31 | Articles 142 and 143 |
| Article 32 | Articles 49 and 52 |
| Article 33 | Article 54 |
| Article 35 | Article 82 |
| Article 36 | Article 83 |
| Article 37 | Article 84 |
| Article 38 | Article 84 |
| Article 39 | Article 60 |
| Article 40 | Article 129 |
| Article 44 | Article 88 |
| Article 45 | Article 89 |
| Article 46 | Article 90 |
| Article 47 | Article 90 |
| Article 48 | Article 92 |
| Article 49 | Article 90 |
| Article 50 | Articles 93 and 96 |
| Article 50a | Article 95 |
| Article 51 | Article 89 |
| Article 52 | Article 97 |
| Article 53 | Article 97 |
| Article 55 | Article 97 |
| Article 56 | Article 97 |
| Article 58 | Articles 10 and 11 |
| Article 59 | Article 12 |
| Article 60 | Article 11(4) |
| Article 61 | Article 14 |
| Article 64 | Article 16 |
| Article 65 | Articles 99 and 100 |
| Article 66 | Article 103 |
| Article 67 | Article 34 |
| Article 68 | Article 103 |
| Article 69 | Article 108 |
| Article 70 | Article 111 |
| Article 71 | Article 110 |
| Article 72 | Article 73 |
| Article 73 | Articles 73 and 74 |
| Article 74 | Article 78 |
| Article 75 | Article 77 |
| Article 76 | Article 79 |
| Article 78(2) | Article 130 |
| Article 80 | Article 123 |
| Article 81 | Article 127 |
| Article 82 | Article 128 |
| Article 83 | Articles 129 and 130 |
| Article 84 | Article 134 |
| Article 85(1),(2) | Article 133 |
| Article 85(3) | Articles 119 and 120 |
| Article 87 | Article 79(2) |
| Article 88 | Article 146 |
| Article 89 | Article 145 |
| Article 90 | Article 137 |
| Article 93 | Article 98 |
| Article 95 | Article 9(2) |
| Article 95a | Article 117 |