Cabinet of Ministers Regulations No. 1061 in Riga 2009 (September 15. No 57 24) amendments to the Cabinet of Ministers of 18 July 2006, regulations No. 600 "registration procedures for veterinary medicinal products" Issued in accordance with article 5 of the law on Pharmacy 3 and 6 points to make the Cabinet on 18 July 2006, regulations No. 600 "registration procedures for veterinary medicinal products" (Latvian journal, 2006, 127 no; 2007, 161 no) the following amendments: 1. Express 2.6. subparagraph by the following: "2.6 2.6.1. veterinary medicinal product: any substance or compound animal substances for treating or preventing disease;
2.6.2. any substance or compound of substances that can be used to enter animals or to restore, correct or modify physiological functions in it, causing the pharmacological, immunological or metabolic action, or to determine veterinary diagnosis; ".
2. Express 2.9. subparagraph by the following: "2.9. name of the medicinal product: 2.9.1. name of manufacturer, which differs from the General name (the World Health Organization recommended international non-proprietary name (INN) or, if such is not recommended, the commonly used name);
2.9.2. the General or scientific name accompanied by a trade mark or holder of the registration certificate (owner) name. "
3. Express 5.6. subparagraph by the following: ' 5.6. medicinal products manufactured in a drugstore. "
4. Delete paragraph 5.7.
5. Express 8.1 paragraph by the following: "8.1 registration of veterinary medicinal products, the State Agency of medicines shall determine the membership of non-prescription or prescription of veterinary medicinal product group."
6. Supplement with 8.4 and 8.5 of chapter I paragraph by the following: "Only practicing veterinarian 8.4 allowed to perform transactions with the following medicines: 8.4 1. immunological medicinal product;
2. General anesthesia 8.4;
8.4. the Narcotic Painkillers 3;
8.4 4. psychotropic features;
8.4 5. specific farmakoterapeitisk group of medications if their use is subject to the special precautions or they may possibly have harmful effects on human or animal health.
8.5 If the product is distributed in Latvia or the owner of the certificate of registration has been submitted to the national agency of the medicinal product, notification of the actual distribution of medicines (trade) launch date in Latvia or the notification of the last of the medicinal products to be placed on the market in Latvia (temporarily or permanently), the State Agency of medicines in accordance with the laws and regulations of the State Agency of medicines to the public provided by the paid service price list down the benefits of a veterinary medicinal product post-marketing surveillance annual fee If the following conditions are met: 1.8.5 the previous calendar year in the veterinary medicinal product concerned was distributed in Latvia and their annual turnover does not exceed 1500 lats;
8.5 2. veterinary medicinal product, the holder of the registration certificate (the owner) has been submitted to the national agency of the medicinal product, notification of the actual distribution of veterinary medicinal products (trade) launch date in Latvia or for veterinary medicinal products that are placed on the market in Latvia last (temporarily or permanently). "
7. Replace paragraph 10, the words "in number and volume VI" veterinary drug "with the words" and the number "document item volume VI, part B" notice to the applicant, the application of the veterinary medicinal product, the contents and presentation of the dossier ".
8. Express 13.2. subparagraph by the following: "13.2. name of the veterinary medicinal product;".
9. Replace paragraph 28, the words "European economic area countries have applied to register the composition of the veterinary medicinal product" with the words "is well established in the European Community veterinary practice".
10. Express 31 and 32 as follows: "31. In the case of veterinary medicinal products containing active substances used in veterinary medicinal products registered in composition (combined veterinary medicinal products), but so far not used the same composition of the veterinary medicinal product for therapeutic purposes, for the following active substances of medicines submitted to clinical and clinical research results and, if necessary, safety and residues testing results.
32. with regard to the rules referred to in paragraph 31 of the veterinary medicinal product does not provide scientific references relating to each individual active substance (informed consent for the application). "
11. the express 37 as follows: "37. Applicant shall prepare the documentation to be added to the application for registration according to the following requirements: 37.1. When designing a registration application, the documentation to be added to comply with this provision, in chapter II 2., 3., 3.1 and 3.2 requirements set out in the annex and pharmaceutical law referred to in article 28.1, the European Commission (hereinafter referred to as the guidelines) published in medicinal products of the European Community legal framework document item volume VI, part B" applicant that veterinary medicinal product, the contents and presentation of the dossier ";
37.2. take into account the latest scientific knowledge of veterinary medicinal products and the European Commission guidelines on the quality, safety and efficacy of the veterinary medicinal product, which is published by the European Commission European Community pharmaceutical legislative framework vocabulary document;
37.3. veterinary medicinal products other than immunological veterinary medicinal products, in terms of quality (physico-chemical, biological, and microbiological tests), and the imunoloģiskaj veterinary medicinal products as regards quality, safety and efficacy of the documentation concerned apply also to European Pharmacopoeia Monographs General monographs and General chapters;
23.2. the documentation described in veterinary medicinal products, the production process comply with the principles of good manufacturing practice for medicinal products of the European Community, the legal framework of the document specified in the item's volume IV guidelines, as well as the manufacture of veterinary medicinal products regulations regulatory requirements;
37.5. the documentation includes information about the assessment of the veterinary medicinal product to be registered. The applicant in the State Agency of medicines shall submit information concerning the veterinary medicinal products to be registered to the tests carried out or studies which are incomplete or have not been completed;
23.4. the documentation describes the pharmacological, toxicological, and safety of residue checks carried out in accordance with good laboratory practice regulations regulatory requirements;
37.7. animal testing is carried out in accordance with the laws and regulations on the procedures to be carried out with izmēģinājumdzīvniek, and a procedure for the provision of welfare izmēģinājumdzīvniek;

23.5. the documentation indicates the environmental risk assessment of a veterinary medicinal product containing or consisting of genetically modified organisms. The information submitted in accordance with the laws and regulations on the procedures for genetically modified organisms released into the environment or the market, and of the European Parliament and of the Council of 31 March 2004, Regulation (EC) No 726/2004 laying down the procedures for the authorisation and supervision of medicinal products for human and veterinary use Community procedures and establishing a European Medicines Agency, taking into account the guidelines of the European Commission. "
12. To complement the chapter II with 37.1, 37.2 and 37.3 points as follows: "the State Agency of medicines of 37.1 may determine exceptions to the registration of veterinary medicinal products, in the case of veterinary medicinal products intended for certain species of animals and small market share (one species, rare, rare veterinary diagnosis manipulation). Exceptions, the State Agency of medicines shall take into account relevant scientific guidelines or scientific advice.
23.1 all information that is not included in the initial application shall be accompanied by the documentation, as well as the use of the medicinal product safety oversight (the vigilan farmak ces) information the applicant shall submit to the State Agency of medicines to counter a push the risk-benefit ratio.
37.3 of the veterinary medicinal product registration certificate holder (holder) information on changes in the content of the registration dossiers submitted in accordance with Commission of 3 June 2003, Regulation (EC) no 1084/2003 on cue they look changes the marketing authorization (registration certificate) membership conditions which the national competent authority issued relating to medicinal products for human use and veterinary medicinal products, ruled (hereinafter Regulation No 1084/2003), or the Commission of 3 June 2003, Regulation (EC) No 1085/2003 concerning the examination of variations of a marketing authorisation for medicinal products for human use and veterinary medicinal products (registration certificate) conditions covered by Council Regulation (EEC) No 2309/93 (hereinafter Regulation No 1085/2003) if the veterinary medicinal product concerned on its registration certificate holder (holder) has received the corresponding regulations 1084/2003 or article 1 of regulation 1085/2003 article 1. "
13. Replace paragraph 44 number and the words "and 37" with numbers and words "37, 37.1 and 37.2 points".
14. Replace the 60.1 in number and the words "and 37" with numbers and words "37, 37.2 and 37.3 points".
15. Express, 68 and 69 67. paragraph by the following: "67. Registration certificate is considered invalid if any pharmaceutical form or the marketing of packaging: 67.1. within a period of three years following the adoption of the decision on the registration of veterinary medicinal products are not placed on the market;
67.2. After placing it on the market for three consecutive years are not admitted.
68. the national agency of medicinal products, taking into account the exceptional circumstances and human or animal health shall have the right to make exceptions to this rule in paragraph 67 of the said conditions, if you received the registration certificate of the veterinary medicinal product (holder) of the owner of the application for the certificate of registration of veterinary medicinal products in action.
69. The veterinary medicinal product, the registration certificate holder (holder) that rule 68 of the applications referred to in paragraph shall submit to the State Agency of medicines no later than three months before this rule 67.1. or 67.2. condition referred to, stating the reasons for the certificate of registration of veterinary medicinal products activities. "
16. To supplement the provisions of the following paragraph 69.1:69.1 the State Agency of medicines ": 69.1 1. This provision referred to in paragraph 68 of the receipt of the application to the administrative procedure law reviewing: 69.1 1.1. grounds referred to in the application;
69.1 1.2. the veterinary medicinal products concerned on the importance of human and animal health (even if the medicinal product is in need of rare animal diseases, rare medical manipulation, rare, exotic or minor species animal disease treatment or prevention), in consultation with the food and veterinary service and the Latvian Association of veterinary surgeons;
69.1 2. Decides on the registration certificate of the veterinary medicinal product actions saving or termination of the registration certificate;
3. determine the application in 69.1 of the veterinary medicinal product concerned activities registration certificate extension for a period of not more than three years;
69.1 4. inform the owner of the registration certificate of the decision taken. "
17. Add to the informative reference to European Union directive to point 4 as follows: "4) Commission 10 February 2009. directive 2009/9/EC of the European Parliament and the Council amending Directive 2001/82/EC on the Community code for veterinary medicinal products."
18. Make annex 2 as follows: "2. the annex to Cabinet of Ministers of 18 July 2006, regulations no 600 requirements for veterinary medicinal products other than immunological veterinary medicinal products 1. the summary dossier 1. application for the registration of veterinary medicinal products: 1. the veterinary medicinal product is identified by name and name of the active substance together with the strength and pharmaceutical form, the method and route of Administration (in accordance with the provisions of 13.6.) and the appearance of the finished product description , including packaging, labelling and instructions for use (according to this provision, section 13.13 and 13.14.17);
1.2. indicate the applicant's name and address, the manufacturer of the veterinary medicinal product, together with the name and address of the sites involved in the production, testing and release phases, the manufacturer of the finished product and the manufacturer of the active substance, the name and address of the importer (if applicable);
1.3. precise identification of the number and names of the documents, submitted together with the application, as well as information about the submitted samples of the veterinary medicinal product;
1.4. Add a document showing that the manufacturer has received special permission (license) manufacture of the veterinary medicinal product concerned in accordance with the veterinary pharmaceutical regulatory laws and requirements.
1.5. the information with a list of countries that have been granted a special permit (license) manufacture of the veterinary medicinal product concerned;
1.6. Description of the veterinary medicinal product copies in accordance with the provisions of paragraph 35 of the above requirements. A copy of the description is confirmed by the participating States, the competent authorities concerned;
1.7. add information with a list of the countries that submitted or refused the application for registration.

2. The applicant shall provide a description of a veterinary medicinal product prepared in accordance with the provisions of paragraph 35 of these requirements, and the primary and secondary packaging labelling of the packaging mock-up with instructions for use, if necessary, prepared in accordance with the legislation on the labelling of the veterinary medicinal product, distribution, and control arrangements. The applicant shall specify one or more veterinary medicinal products the final trade samples or models which contain information in at least one of the official languages of the European Union. Mock-ups can be submitted in printed form or electronically, if the State Agency of medicines has previously given consent.
3. a detailed summary (summary) presented under this rule 13, 15 and 17 of the said requirements. Summary points: 3.1 pharmaceutical (physico-chemical, biological or microbiological), safety and residue detection research and testing results;
3.2 pre-clinical and clinical studies;
3.3. the veterinary medicinal product, the possible environmental risk assessment test results.
4. the summary is prepared, subject to the following requirements: 4.1 the application taken into account during the available scientific data;
4.2. summary points and appraise the various inspections, tests and studies which justify the added documentation of the registration certificate;
4.3. the summary shall include and describe the issues relating to veterinary medicinal products, quality, safety and efficacy assessment;
4.4. the detailed inspection, submitted and results of the tests and precise bibliographical references;
4.5. the relevant summary data compiled in the annex tables, if possible, or in graphical form;
4.6 Summary and its annexes shall contain precise cross references to the registration documentation attached to the application.
5. Summary information on the expert's education, training and work experience, as well as experts and reflect the applicant's professional commitments. A summary of the data and the signature of the expert.
6. If the veterinary medicinal product to be included in the composition of the active substance is also included in the people medicinal products registered under the Cabinet of Ministers may 9 2006, regulations No 376 "registration procedure of medicines" (hereinafter Regulation No 376), the summary referred to in paragraph 3 can be replaced with the active substances concerned overall quality summary provided under Regulation No 376 3. module 2 14.
7. If the State Agency of medicines shall be publicly announced that the finished product chemical, pharmaceutical and biological or microbiological information can be included in the documentation of the common technical document only (CDT), a summary of the results of the tests shall provide pharmaceutical overall quality summary form.
8. Overall quality summary without previous consent of the State Agency of medicines can be used for application for a veterinary medicinal product for a specific species or of indications concerning a small market share (one species, rare, rare veterinary diagnosis manipulation).
2. Pharmaceutical (physico-chemical, biological or microbiological) information (quality) 2.1 General information 9. Information and documents accompanying the application for the registration of veterinary medicinal products licence according to section 13.10. these provisions are the following: 9.1. information concerning the pharmaceutical (physico-chemical, biological or microbiological) data as well as information about ready for the veterinary medicinal product, the description of the manufacturing process and properties, the quality control procedures and requirements , stability, as well as a description of the composition of the veterinary medicinal product, development and presentation;
9.2. test procedure developed, corresponding to the raw materials and the finished product quality analysis and control, taking into account the relevant processes of the specific guidelines and requirements. Displays the approval (validation) of research results;
9.3. a detailed and accurate description of the test procedure, so that it can be repeated in control tests, carried out at the request of the State Agency of medicines. Detailed special hardware and equipment descriptions, which can be used for the tests (if possible, adding the chart);
9.4. information on laboratory reagent formulas which supplemented by preparation method (if necessary);
9.5. Description of the procedure is replaced by a detailed reference to the pharmacopoeia concerned, if test procedures are included in the European Pharmacopoeia or national pharmacopoeias official. The tests are mainly used in the European Pharmacopoeia chemical and biological reference materials. If you use other reference preparations and standards, they identified and described;
9.6. the chemical, pharmaceutical, biological or microbiological information provided in accordance with regulations No. 376 3. module 3 (19, 20, 21, 22 and 23). You can replace this information with the relevant documents relating to veterinary medicinal products to be registered, if the veterinary medicinal products to be registered include active substance also used human medicinal products registered in accordance with Regulation No 376 these requirements.
9.7. the documentation concerning the veterinary medicinal product or prepared chemical, pharmaceutical and biological or microbiological information that shall be included in the common technical document, if medicine Government Agency publicly announced that it is allowed. Common technical document without the State Agency of medicines of the prior consent of the application may be used for veterinary medicinal products specific species or indications, which affects a small part of the market (one species, rare, rare veterinary diagnosis manipulation).
10. in paragraph 9 of this annex, the information and documents taken into account in the development of European Pharmacopoeia Monographs and General chapters or, if this is not possible, the Member States officially applied to the pharmacopoeia monographs.
2.2. the quality of the components and controls 11. Veterinary medicinal products (components) of the qualitative information includes the following information: 11.1. for active substances;
11.2. on the constituents of the excipients, whatever their nature or the quantity used, including colouring matter, preservatives, excipients, stabilisers, thickeners, emulsifiers, flavour and aromatic substances;
11.3. data on the outer covering of the medicinal product (capsules, gelatine capsules) components, intended for ingestion or otherwise enter animals;

11.4. the data on the primary packaging of the medicinal product and, if necessary, for secondary packaging. Data on packaging (closing), as well as on the use of the medicinal product and the devices that are supplied with the product.
12. The generally accepted terminology is terminology used in describing the constituents of the veterinary medicinal product notwithstanding the provisions referred to in point 13.3. conditions: 12.1. ingredients which appear in the European Pharmacopoeia or, failing this, of Member States ' official pharmacopoeias Pharmacopoeia monograph used used in the main title, giving reference to the pharmacopoeia concerned;
12.2. ingredients which do not appear in the European Pharmacopoeia or national pharmacopoeias, the official noted the international non-proprietary name recommended by the World Health Organization, which allowed to add other non-proprietary name, or, failing these, the exact scientific designation. Ingredients not granted the international non-proprietary name or the scientific name, description, outlining how and from what components they are prepared, supplemented, where appropriate, by any other relevant details;
12.3. colours denoted by E number, assigned to them under this provision the requirements of annex 4.
13. to provide information on the composition of veterinary medicinal products, active substances included in the quantitative composition, pharmaceutical form for each active substance mass or units of biological activity, unit of mass or volume.
14. the units of biological activity shall be used for substances that cannot be detected chemically. If the World Health Organization an international unit of biological activity has been defined by using this unit.
15. The absence of an international unit of biological activity, the units of biological activity shall be expressed in such a way as to provide unambiguous information on the activity of the substance, as the case with the European Pharmacopoeia units.
16. If possible, indicate the biological activity per unit of mass or volume, and the following information: 16.1. single dose of veterinary medicinal products, active substances, by the mass or units of biological activity in a single dose packaging (containers), if necessary, in the light of the extent of use of the product after preparation for use;
16.2. veterinary medicinal products to be administered by drops, by the active mass or units of biological activity, one drops, or of the number of drops corresponding to 1 ml or 1 g of the preparation;
16.3. syrups, emulsions, granular preparations and other pharmaceutical forms to be measured quantities of active substances – mass or units of biological activity in a certain quantity of medicines.
17. Active substances present in the form of compounds or derivatives shall be described quantitatively by their total mass, and if necessary or appropriate,-the mass of the active entity or entities of the molecule.
18. In the case of veterinary medicinal products containing the active substance, to which all the Member States for the first time subject to the application of the registration certificate, these active substances (salt or hydrate) quantitative statement systematically expressed molecules of the active element of the mass. All veterinary medicinal products to be registered later, Member States shall have their quantitative composition in respect of one and the same active substance indicate the same way.
19. The pharmaceutical form design: 19.1 provides clarification on the composition of the veterinary medicinal product selection, primary packaging components, possible future packaging, secondary packaging, if any, as well as the intended function of the excipients in the finished product and method of production of the finished products. Explanations based on scientific data on the pharmaceutical form;
19.2. determine the dose increase, justified;
19.3. prove that the microbiological characteristics of the veterinary medicinal product (mikrobiol logical purity and antimicrobial activity) and comply with the instructions for use of a veterinary medicinal product intended use as described in the documentation attached to the registration certificate.
2.3. Description of the method of production for 20 points each for the manufacturer and each production site or production and testing involved in the company name, address, and responsibility.
21. the application of the registration certificate shall be accompanied by the description of the manufacturing method, which according to this provision, the bottom paragraph 13.4. be prepared to give an appropriate summary of the manufacturing process. The description of the manufacturing method shall include the following: 21.1. list of the production phase to be able to assess whether the medicine used in the preparation of the form of action leads to negative changes in the constituents of the medicinal product;
21.2. full details concerning precautions taken to ensure the homogeneity of the finished product, if the production process is continuous;
21.3. the actual manufacturing formula, stating: 21.3.1. substances used in the production of quantitative information. Many of the excipients of the mu permitted about as far as it is necessary for the description of the pharmaceutical form;
21.3.2. substances which may disappear in the course of manufacture;
21.3.3. the reasons for the increase of the dose;
21.4. the overview of the stages of manufacture at which sampling control during production, and the applicable limits (quantities), where other data in the documents supporting the application show such tests are necessary for the quality control of the finished product;
21.5. the pilot study description to validate the production process and, if necessary, process validation scheme for the production of the volume of the series;
21.6. the description of the method of sterilization or aseptic techniques should be maintained sterile procedures used for the sterilization of the products used in the pharmacopoeia standard sterilization method.
2.4. control of raw materials inputs are 22 veterinary medicinal products and, where appropriate, the veterinary pharmaceutical primary packaging (containers), including the (closing), as mentioned in paragraph 11 of this annex.
23. the documentation for the control of raw materials include specifications and information on all series of the raw material quality control tests.
24. submission of the registration certificate showing the regular tests, the raw material for each series. When the raw material is used for the series of tests, which are not mentioned in the Pharmacopoeia, test applications, providing evidence that the raw material complies with the quality requirements of pharmacopoeia.
25. If the European Directorate for the quality of medicines provided by raw materials, active substances or excipients, certificate of conformity certificate is a reference to the relevant monograph of the European Pharmacopoeia.

26. Where reference is made to this annex referred to in paragraph 25 of the certificate of conformity, the manufacturer of the veterinary medicinal product, the applicant must provide written assurance that the manufacturing process of the medicinal product concerned has not been changed since the European Directorate for the quality of medicines of the issue of the certificate of conformity.
27. To demonstrate compliance with the specification, submit a certificate of analysis of raw materials.
28. control of the active substance during each manufacturer and each proposed production site or production and testing participating organization (object) name, address, and responsibility.
29. The active substance manufacturer or the applicant may agree that the well-publicized active substances information shall be submitted by the manufacturer of the active substance of the medicinal product by the national agency directly in a separate document as the active substance master file, which shall include the following information: 29.1. detailed description of the manufacturing process;
29.2. the production process quality control;
3. a description of process validation.
30. If the active substance master file development, manufacturer: 30.1. the applicant provided all the data required, taking responsibility for veterinary medicinal products;
30.2. the applicant declares in writing that the manufacturer provides the entire series consistency and without the applicant not modify the manufacturing process or specifications;
30.3. the documents and information proving the 30.2. changes referred to in paragraph below, the State Agency of medicines shall be submitted, as well as the applicant, in so far as the applicant's share of the active substance master file.
31. If the active substance is not available in the certificate of conformity, the manufacturer or the applicant provides information on the method of production, quality control and impurities, as well as the testimony of the molecular structure of the substance, taking into account the following conditions: 19.3. information on the production process of the active substance shall be included in the description of the manufacturing process, which reflect the applicant's involvement in the manufacture of the active substance. Lists all active substances required for production materials, identifying where each material is used in the production process. Provides information on the quality and control of these materials, as well as information establishing that the material complies with the intended use;
31.2. the content of the quality control included in each of the critical production stages the performance of the tests (including the validation criteria), information on the quality and control of intermediates, and information on the process validation and evaluation studies (or). If necessary, the information also contains validation data for the active substance used in the analysis;
31.3. the content of impurities (indic) indicate the expected impurities, the level of impurities and also features, as well as, where appropriate, information concerning the safety of these impurities;
19.5. the biotechnology of the veterinary medicinal product shall include evidence from molecular structure schematic amino acids sequence and relative molecular mass.
32. the pharmacopoeia of active substances shall be carried out and described in accordance with the following conditions: 32.1. the general European Pharmacopoeia Monographs and special active substances referred to in the European Pharmacopoeia;
32.2. components that meet the requirements of the European Pharmacopoeia or in the pharmacopoeia of a Member State used the requirements considered appropriate if they comply with the provisions referred to in point 1.4. requirements. In this case, the analysis methods and procedures in each section, the description shall be replaced by the corresponding reference to the pharmacopoeia concerned;
32.3. If the specification of the European Pharmacopoeia or national pharmacopoeias official is not sufficient to ensure the quality of the active substance, the State Agency of medicines the applicant requires appropriate specifications and detailed specific impurity limits (limits) with validated testing procedures. The State Agency of medicines shall inform the authorities responsible for the pharmacopoeia in question. The holder of the registration certificate (the owner) shall provide the authorities of that Pharmacopoeia with the details of the alleged insufficiency and the additional specifications applied;
32.4. If the European Pharmacopoeia Monographs are missing for the active substance, but this is an active substance described in the used officially in the Member States, the Member States allowed to use the official pharmacopoeia monographs used;
32.5. If the active substance not described in the European Pharmacopoeia Monographs and Pharmacopoeia Member States officially used in monographs, allowed to use third country pharmacopoeia monograph, these monographs are certified. The applicant shall provide a copy of the monograph in question and the translation, if required, as well as data that confirms the test procedure included in the monograph compliance with quality control of the active substance.
33. active substances not listed in the Pharmacopoeia, description, specifying such information (components that are not included in any pharmacopoeia monographs description format): 33.1. the component name that corresponds to paragraph 12 of this annex to the requirements of and supplemented with commercial or scientific synonyms;
33.2. the definition of the substance according to the European Pharmacopoeia. Accompanied by the necessary explanations, especially those that affect the molecular structure. Where substances can only be described by their method of manufacture, giving an accurate description, to characterize a substance which is constant (constant) and composition, both in terms of exposure;
33.3. identification methods, which can be described as full of substance production methods and tests to be carried out as a routine matter;
20.8. Description of purity test in relation to the total quantity. Total quantity represents projected impurities, especially those which may cause adverse effects and, if necessary, impurities, which can negatively affect the stability of the veterinary medicinal product or change the results of the analysis, having regard to the combination of substances to which the application for registration;
33.5. Description of tests and restrictions. The tests are carried out to monitor the product parameters such as particle size, sterility, and, if necessary, make methods validation;
20.9. complex plants or substances of animal origin indicate the difference, if diverse pharmacological effects due to the need of the main components of the physico-chemical or biological control, or if the active substance is from one or more of the main groups of substances with similar effect, which may be the subject of a general assessment method.

34. in paragraph 33 of this annex, the testing procedures are sufficient to control the quality of the active substances derived from defined source.
35. In the case of active substances which affect the bio-availability of veterinary medicinal products, a more general description of these substances, regardless of whether the substance is mentioned in the Pharmacopoeia or not, provide the following information (indicate the active substance of physico-chemical characteristics liable to affect bio-availability): 21.8. substances crystalline form and solubility coefficients;
35.2. particle size (where appropriate, after pulverization);
35.3. the degree of hidrācij;
35.4. oil/water partition coefficient;
22.1. the pK/pH values.
36. In this annex, 35.2 and 35.3 21.8... "the bottom paragraph shall not apply to substances used only solutions.
37. control of excipients description carried out and in accordance with the following conditions: 37.1. all substances listed in the European Pharmacopoeia, European Pharmacopoeia Monographs, General and specific;
37.2. control of excipients, compliance with the requirements set out in the relevant monograph of the European Pharmacopoeia. If this is not the European Pharmacopoeia Monographs, can be used officially in the Member States used in the pharmacopoeia. If the Member State has not used officially in the appropriate monograph may use third country pharmacopoeia. If a third country pharmacopoeia monograph, confirms the conformity of the monograph. Specify additional tests of the control parameters (such as particle size, sterility, solvent residues), in addition to the requirements of the monograph. If there is no relevant Pharmacopoeial monograph, propose and justify a specification. For specifications comply with the requirements referred to in paragraph 32. Specifies the validation of the proposed method and the data;
37.3. the control of veterinary medicinal products include colorants compliance with the requirements of laws and regulations on the colouring matters which may be added to medicinal products, with the exception of veterinary medicinal products intended for topical use (e.g. impregnated with insecticides of the collar and tag, which is based on the use of colouring agents);
23.2. the control of veterinary medicinal products included on the purity criteria for the colours of the compliance with the criteria laid down in the laws and regulations on safety requirements for food additives and food, that use of the food additive;
37.5. new adjuvant (adjuvant that veterinary medicinal products used for the first time, or route of administration of the medicinal product is new) description shall specify details of production, characteristics of excipients and control provide cross-references to the safety data obtained both in clinical and pre-clinical studies.
38. the system of sealing and describe the controls are carried out in accordance with the following conditions: 38.1. provides information concerning the sealing system. The level of information to be determined according to the active substance, physical position (for example, liquid, solid);
38.2. provides information about the final sealing systems. The level of information required for appropriate veterinary medicinal products, route of administration and dosage form of physical status (for example, liquid, solid);
23.8. to control the final product packaging materials meet the requirements of the relevant monograph of the European Pharmacopoeia. If not, the following monographs are authorised for use in the Member States used in the pharmacopoeia. If Member States do not have official pharmacopoeias of the monograph in question, allowed to use third country certifying its compliance with the pharmacopoeia. If you do not want the pharmacopoeia monographs, proposes and the packaging material specifications;
23.9. indicate the scientific data on the final product packaging material choices and compliance;
38.5. provides information about a new contact in a delivered finished product packaging material composition, production and safety;
24.0 points specifications and performance data on dosing or injection device, which includes the complete with veterinary medicinal products.
39. substances of biological origin and description of the controls carried out in accordance with the following conditions: 39.1. If in the manufacture of veterinary medicinal products used in micro-organisms, tissues of either plant or animal origin, cells or fluids (including blood) of human or animal origin or biotechnological cell constructs the description and document the origin and history of the raw materials;
24.4. Description of raw materials including information about the manufacturing strategy, purification or inactivation procedures and their validation, all the manufacturing processes of internal control procedures to ensure product quality, safety and homogeneity of the series;
39.3. when cell banks are used, the cell characteristics shall not reflect changes in the gum before and after the passage of the production;
24.5. conduct tests to determine whether the cultural materials, cell banks, serum funds and, if possible, the raw materials from which they are derived, is not a foreign agent;
24.5. If using animal or human origin, describes the measures taken to prevent potentially pathogenic agents in these materials. If it is not possible to avoid the presence of potentially pathogenic adventitious agents, raw materials may be used only in case of further processing raw materials ensure the Elimination of pathogenic agents or inactivation and this procedure has been validated;
24.6. the applicant provides documentary evidence that the culture of materials, plating cells, serum series and other animal material relating to transmissible spongiform encephalopathy (TSE), comply with the instructions of the European Commission animal spongiform encephalopathy agent to reduce the risk of dissemination products for human use and veterinary medicinal products, as well as the relevant monograph of the European Pharmacopoeia. European Directorate for the quality of medicines issued certificates of conformity with reference to the relevant monograph of the European Pharmacopoeia can be used for proof of compliance.
2.5. production control tests carried out at intermediate stages in the production of 40 intermediate control tests. The documentation contains details of control tests that can be carried out at an intermediate stage of the manufacturing process to ensure production technical parameters and production continuity.
41. the control tests are essential for checking the conformity of the veterinary medicinal product formula, if:

41.1. the applicant an exceptional finished product testing offers a method of analysis that does not include assessment of all active substances or excipients, all components subject to the same requirements as the active substances;
41.2. quality control of the finished product depends on in-process control, especially where the substance in question is significantly affected by its method of production.
42. If intermediate prior to further processing or stored in the original Assembly, intermediate storage time shall be based on stability studies findings.
2.6. The final control of the finished product is 43. series all units of a pharmaceutical form which are made from the same initial quantity of material and undergoing the same production and (or) the sterilization operation on the string, or-in a continuous process of production in the case of any specified period dosage forms manufactured units.
44. The finished product controls are carried out in the final series.
45. the registration application to the accompanying documentation specifies the tests which are carried out routinely on each of the final series, as well as the frequency of the tests, which are not carried out regularly. Specifies the output limits for veterinary medicinal products (output).
46. the registration application, the documentation attached to include data on the final product control tests carried out, skipping the veterinary medicinal product. Documentation shall be submitted in accordance with the following conditions: 46.1. use relevant European Pharmacopoeia Monographs and General chapters or, failing that, a member of the official pharmacopoeia monographs used rules that apply to all the products defined in the monograph;
28.7. If using other test procedures and limit values than those recorded in the relevant monograph of the European Pharmacopoeia and the General section or used officially in the Member States, show that, when testing of finished products in accordance with those monographs, specific pharmaceutical form test results conform to relevant Pharmacopoeial quality control requirements.
47. the General characteristics of the finished product inspection include certain tests of the General characteristics of the product. These tests relate to the average weight of the final product and the maximum deflection control, mechanics, physical or microbiological characteristics, organoleptic characteristics, physical characteristics (such as density, pH, refractive index).
48. The test referred to in paragraph 47 of the principal applicant for each of the properties in each case sets standards and tolerance limits.
49. The applicant: 30.5. detailed and accurate description of the finished product to the General properties of the test conditions, appropriate equipment used, hardware and standards, if they are not specified in the European Pharmacopoeia or national pharmacopoeias or official pharmacopoeia methods provided are not applicable;
30.6. the solid dosage forms for oral (per os) input, perform test for in vitro specific active substances or substance release and dissolution rate, unless there is a reasonable requirement to act otherwise. The State Agency of medicines may be required to conduct such tests, even if solid dosage forms route of Administration is another.
50. active substance identification and verification shall be carried out, taking a representative sample of the production series or more dosage units analysed individually.
51. The active substance content of the finished product the maximum permitted deviation during production may not exceed ± 5%, if there is no justification for increased permissible deviation.
52. on the basis of the stability tests, the manufacturer will propose and justify maximum permissible deviation bounds ready for veterinary medicinal products the active substance content up to the proposed expiry date.
53. If the active substance contained in the mixture are numerous or active substance quantities are so small that the test would require complex and difficult test for each series of veterinary medicinal products, of one or more of the active substance may be omitted provided that appropriate tests carried out at intermediate stages of the manufacturing process. This derogation shall not be subject to the requirements of the substances concerned. Simplified technique shall be supplemented by a quantitative evaluation method, which allows the State Agency of medicines to check conformity with the veterinary medicinal product specifications after the placing on the market of medicinal products.
54. If the physical-chemical methods cannot provide adequate information on the quality of veterinary medicinal products used in vivo or in vitro biological tests. If possible, test that includes reference materials and statistical analysis allowing calculation of the confidence limits. If you can not make the finished testing of veterinary medicinal products, the test shall be carried out as later production in the interim.
55. If the production process is observed in the degradation product, maximum levels for individual and total degradation products indicated immediately after the end of the production period.
56. If in accordance with this annex, paragraph 20 and 21 conditions data provided show that the veterinary medicinal product, the production process considerably increases the dose of the active substance, or if the stability data indicates that the activity of the active substance during storage will reduce, ready for the veterinary medicinal product control tests that substance shall be included in the description of chemical research and, where appropriate, toxicological, pharmacological research as well as the characteristics of the products or the degradation test.
57. The excipient components identification test: 57.1. identification, upper and lower limit test shall be carried out each individual the preservatives and adjuvants for antimikrobioloģisk that can affect the bioavailability of the active substance, unless bio-availability does not guarantee other appropriate tests;
57.2. identification and an upper limit test is performed for each antioxidant and excipient that can negatively affect the body's physiological functions, including lower limit test for antioxidants it released.
58. In addition to pharmacological toxicological tests that are included in the registration application, the documentation accompanying the analysis data shall include information on safety inspections, such as sterility, bacterial endotoxin, if such tests must be carried out regularly to ensure the quality of veterinary medicinal products.
59. the stability of the active substance tested and described in accordance with the following conditions:

59.1. points of the active substance testing time and storage conditions, except in the case of an active substance is included in the European Pharmacopoeia and the manufacturer of the final product fully immediately take active substance testing before its use in the manufacture of the final product;
59.2. the stability data provided to justify the repeated tests of time and storage conditions. Description of the stability tests, the test protocol used, validation of analytical procedures, the type and details of the test results. Submit to the stability of the active substance requirements (obligations) the summary of the test protocol;
59.3. where active substances originating from the source that is specified in the application documentation, is available on the certificate of conformity of the active substance that contains repeated testing time and storage conditions, allowed not to provide stability of the active substance data.
60. The final product stability test shall be carried out and described in accordance with the following conditions: 60.1. submit a description of the research, which is defined in the applicant's proposed product, recommended storage conditions and the specifications at the end of the period of validity;
60.2. Description of the stability test, the test protocol used, validation of analytical procedures, the type and details of the test results;
60.3. where before the intended entry of finished veterinary medicinal product prepared for human or dilute, detailing information regarding the renewed or diluted medicine recommended expiration date and specifications, accompanied by the relevant data on stability;
60.4. If there is a package, provide daudzdev stability data to justify the validity of the final product after the package is opened for the first time, and defines the specification of use;
60.5. If ready veterinary medicinal products may occur, the degradation products the applicant shall indicate the methods of identification and testing procedures;
60.6. the opinion shall include the results of analyses, justifying the proposed validity period and usage period of validity of the recommended storage conditions and the specifications of the finished medicinal products for veterinary use of the storage and the end of the term of validity of the recommended storage conditions;
60.7. indicates the maximum individual and total degradation products, the level of the veterinary medicinal product by the end of the period of validity;
60.8. submit a study on the packaging of the veterinary medicinal product and interaction, if this interaction is considered possible, especially injectable preparations;
60.9. provide ready veterinary medicinal product stability requirements (obligations) the summary of the test protocol.
61. the documentation permitted include other not listed in this annex with the quality of the veterinary medicinal product related information.
62. The healing of premixtures shall contain the following information: 62.1. feed premixtures or you gave;
62.2. guidance on the inclusion of feed premixtures;
38.7. medicated feed (feed, which added therapeutic premix) homogeneity;
38.8. compatibility with feed premixtures;
62.5. stability of feed premixtures;
38.9. medicated feed.
63. Notes specification healing feed used in the production of the Medicated pre-mixes in accordance with the recommended instructions for use.
3. Safety tests and residue tests 3.1. Safety Inspection 64. Documentation safety indicates the following: 64.1. veterinary medicinal products possible toxicity and use dangerous or undesirable effects which may occur in animals recommended conditions of use of the product. Side effects be assessed according to the severity of the pathological condition concerned;
64.2. potential adverse effects in humans, which can lead to residues of the veterinary medicinal product or substance in foodstuffs obtained from animals that were treated with the medicinal product. Indicate which of the problems these residues may create in the industrial processing of foodstuffs;
64.3. risks to the human exposure to a veterinary medicine, for example, medicinal products for animals;
64.4. the risk environment possible, which can lead to the use of veterinary medicinal products.
65. paragraph 64 of this annex, the information referred to in points with reliable and valid data. Experimental techniques in the development and evaluation of the results of the use of mathematics and statistical methods. Provides information on veterinary medicinal products, the latest therapeutic potential and on the risks associated with this medicine.
66. Allowed to test the output connection of the metabolites, if they constitute relevant residues.
67. If the pharmaceutical use of excipients used for the first time, proceed as with the active substance.
68. the product and its active substances are the exact identification indicates the following: 68.1. international non-proprietary name (INN);
68.2. the international theoretical and practical chemistry (IUPAC) nomenclature of Association;
68.3. analytical overview of the index of Chemistry (Chemical Abstract Service-CAS) number;
68.4. therapeutic, pharmacological and chemical classification;
68.5. synonyms and abbreviations;
68.6. structural formula;
68.7. molecular formula;
68.8. molecular weight;
42.8. the level of impurities;
impurities 68.10. qualitative and quantitative composition;
68.11. physical characteristics;
No 68.12. melting point;
68.13. boiling point;
No 68.14. vapour pressure;
68.15. solubility in water and organic solvents expressed in g/l, with indication of temperature;
68.16. density;
68.17. refractive, rotational spectrum;
68.18. pharmaceutical form.
69. Pharmacological studies are conducted and described in accordance with the following conditions: 69.1. include information on pharmacological studies conducted with the pilot (laboratory) animals and target species in accordance with Chapter 4 of this annex;
EB 69.2. If the veterinary medicinal product has pharmacological action, at the same time not becoming toxic reaction, or the effects of the veterinary medicinal product is at such low doses, which can cause toxic reactions, the pharmacological effects are taken into account in assessing the safety of veterinary medicinal products. Pharmacological studies can help to understand the phenomena of toxicity;
69.3. documentation for the safety of the veterinary medicinal product includes detailed information about the pharmacological tests conducted with the pilot (laboratory) animals, and relevant information on clinical research with the target animal species.
70. Pharmacological studies are assessed:

70.1. pharmacodynamic. Provides information about the effects of the active substance and information on primary and secondary pharmacodynamic effects, to understand and describe the side effects observed in studies with animals;
70.2. pharmacokinetics. Description of the active substance and its metabolites of toxicological tests used in animal species, including information on the absorption of the veterinary medicinal product, distribution, metabolism and excretion (ADM). With veterinary medicinal products evaluated by the intake or exposure related data in pharmacological and toxicological studies to determine appropriate veterinary medicinal product efficacy and duration of the exposure. Documentation drawn up in accordance with Chapter 4 of this annex, provides a comparison with the data obtained in pharmacokinetic studies in the target species to determine the toxicological tests for the significance of the results obtained in relation to the toxicity of the veterinary medicinal product to the target species;
70.3. toxicology. A toxicological dossier drawn up in accordance with the instructions of the European Medicines Agency on the general approach to checks and instructions for specific studies. Documentation shall include information on: 70.3.1. reference tests carried out the new design for food-producing animals of veterinary medicinal products, in order to assess the food of animal origin existing safety levels;
70.3.2. additional tests that can be performed, taking into account the specific toxicological considerations, for example, in relation to the structure of the active substance, the class and type of activity;
70.3.3. the tests which can clear the Basic or additional interpretation of the data obtained in the tests.
71. The final product take one dose toxicity test. Tests on single-dose toxicity the acute substance found toxic effects as well as effects and extinction of this accession. The tests to be selected, to provide information about the safety of a man who entered the veterinary medicinal product to the animals, for example, where a prolonged or significant effects of the veterinary medicinal product inhalation or skin contact, check the use concerned. Tests on one-dose toxicity shall be carried out to determine: 71.1. likely effect of the target species, if there has been an acute overdose;
71.2. the possible consequences to people, if the active substance is to pass to enter the man;
71.3. dose that can be useful to use repeated dose toxicity tests.
72. Repeated dose toxicity tests shall be carried out in accordance with the following conditions: 72.1. repeated dose toxicity tests are intended to reveal any physiological or pathological changes caused by the investigational product the active substance or combination of active substances reuse, and to determine the appropriate dosage for this change in dosage;
72.2. pharmacologically active substances or medicinal products intended for use only in animals of the non food, allowed to make repeated dose toxicity study with experiments and scientific purposes of species of animals used. This study you can do research in the target animal. The type and frequency of use, as well as the duration of the study, pursuant to the choice of the intended clinical use. The person responsible for the research or tests (researcher), basic research in the description, duration and the amount of the dose;
72.3. If pharmacologically active substances or veterinary medicinal products intended for use in food-producing animals, take the repeated dose toxicity studies of rodent species and animal species other than rodents to determine the target organs and target characteristics, as well as the appropriate species and dose the amount of use of chronic toxicity studies, if any, to be taken. Repeated dose toxicity study duration is not less than 90 days;
72.4. researcher based choice of species, in view of scientific breakthroughs on product metabolism in animals and humans. The substance is administered orally (per os). Researchers should clearly define and use in argument and frequencies, as well as the duration of the study;
72.5. maximum level selected so as to bring harmful effects of the veterinary medicinal product. The lowest dose level not showing signs of toxicity;
72.6 at. toxic effects assessment based on observations on animal behaviour, growth, haematology and physiological tests, especially relating to excretory as well as autopsy reports and accompanying histological data. Each test group choice and range depends on the animal species and from the knowledge of the period;
72.7. If that study in accordance with the requirements of this regulation, joining the new combinations, the researcher can modify repeated dose toxicity tests, indicating the modifications, if the toxicity tests do not show any potentiation or novel toxic effects.
73. Tolerance in the target species. Provides a summary of the intolerance of the veterinary medicinal product (intoleranc) signs observed by research with animals of the target species in accordance with this annex 108. the requirements referred to in point (usually the end product of the study). Indicate the relevant study, doses were found to be using intolerance as well as the respective animal species and varieties. A detailed description of the unexpected physiological changes. The full report of the study included documentation in accordance with Chapter 4 of this annex.
74. Reproductive toxicity tests, including a developmental (the body's individual development), and describes the toxicity in accordance with the following conditions: 74.1. the study of the effects on reproduction shall be carried out to determine the potential of male or female reproductive function deterioration or harmful effects on progeny resulting from veterinary medicinal products or investigational use;
74.2. If pharmacologically active substances or veterinary medicinal products intended for use in food-producing animals, studies of the effects on reproduction shall be carried out as a multi-generation reproduction study is designed to determine the effects on mammalian reproduction. The study describes the effects on male or female fertility, mating, aizmešano and strengthening of the fruit, the female's ability to maintain the pregnancy by the established deadline, the perinatal period, lactation, offspring survival, growth and development from birth to weaning, calves as a grown animal sexually and successive reproduction. Use at least three different doses. The maximum dose is selected so as to bring harmful effects. The lowest dose level show no signs of toxicity.

75. A developmental toxicity test is carried out and described in accordance with the following conditions: 75.1. If pharmacologically active substances or veterinary medicinal products intended for use in food-producing animals, take a developmental toxicity test. This test is performed to determine drug or substance-induced side effects females and embryos and foetal development when exposed the female substance or drug effects throughout the gestation period of implantation of Ovum until the day before farrowing. The following side effects: the potential enhanced toxicity compared with non pregnant females observed toxicity, embryo or fetal death, fetal growth and structural changes in the fruit;
75.2. developmental toxicity test is carried out on rats. In assessing the results, it may be necessary to perform the tests with other species of animals in accordance with the established guidelines;
75.3. If pharmacologically active substances or veterinary medicinal products intended for use in animals from which non-food products, a developmental toxicity test is carried out in at least one species, which may be the target species, if the medicinal product is intended for use in breeding females. However, if the use of the veterinary medicinal product to trigger significant human exposure to exposure of the medicinal product concerned, who enters the Hall, must be made to the standard animal developmental toxicity tests.
76. Genotoxicity tests and a description in accordance with the following conditions: 76.1. genotoxicity tests are carried out, the potential to detect any changes to the substance being studied can lead to genetic material of the cell. Substance for the first time to include veterinary medicinal products, assess the genotoxic properties;
76.2. the standard in vitro and in vivo genotoxicity test series in accordance with the instructions laid down take on an active substance. In some cases, you might want to check one or more of the metabolites that occur as residues of medicinal products in foodstuffs of animal origin.
77. Carcinogenicity tests performed and described in accordance with the following conditions: 77.1. to decide on the need to conduct carcinogenicity tests pharmacologically active substances or veterinary medicinal product, the results of genotoxicity tests, structure-activity relationships and findings in systemic toxicity tests, which can be significantly longer generation research construct period studies;
77.2. take into account the specific mechanisms of toxicity known species, as well as differences in studies of species used in the target species of animal and human metabolism;
77.3. If test carcinogenesis, take at least two years of study with rats and 18 months of research with mice. Carcinogenicity test can be performed with one rodent species, preferably the rat if there is sufficient scientific basis.
78. In the case of veterinary medicinal products intended for use locally, the test is carried out on the systemic absorption of the target species. If it is shown that systemic absorption is negligible, not make the repeated dose toxicity test, reproductive toxicity tests and carcinogenicity tests, except if: 78.1. According to the proposed conditions of use, it is possible that the animal will pick up a veterinary drug oral (per os);
78.2. According to the proposed conditions of use, it is possible that the people who put the drugs, jeopardize the animals of veterinary medicinal products, which is not in contact with the skin (e.g. inhalation, contact with mucous membranes);
78.3. active substance or metabolites can penetrate with the drugs processed animal origin foodstuffs (for example, injectable preparations in the udder).
79. special studies: 79.1. the groups of substances or, if the animals in the repeated dose toxicity tests, the observed effects include changes that indicate, for example, on imūntoksicitāt, neurotoxicity or endocrine dysfunction. Carry out further research, such as sensitization studies or delayed neurotoxicity studies;
79.2. allowed to take, considering the nature of the product, to evaluate the toxic effects or possible irritation of the underlying mechanism. These studies are usually carried out with a finished product;
79.3. making and evaluation of the results of the study, take into account the level of development of science in the period when the registration application is prepared to accompanying documentation.
80. microbiological properties of residues: 80.1. Description of potential effects on the human gut microbial. The potential risks of robioloģisk by Mike the human gut microbial causes for connection with antimicrobial properties, in accordance with the guidelines laid down;
80.2. Description of potential effects on the industrial processing of food organisms used. In some cases, you can perform tests to determine whether microbiological active residues affect technological processes in the industrial processing of foodstuffs.
81. the observations concerning the human body to provide information, or veterinary medicinal products pharmacologically active substances are used as medicinal products in human medicine. If there is such a fact, gives an overview of the effects observed (including adverse effects) in humans and on observed impacts and take the safety evaluation of veterinary medicinal products, taking into account the results of research published (bibliography). If the components of the veterinary medicinal product is not used or are no longer used as medicinal products in human therapy, the reasons.
82. the development of resistance: 82.1. submit data on resistant bacteria (associated with human health), caused by the use of the veterinary medicinal product to animals. Description of the following development of resistance mechanism. If necessary, propose to take measures to curb the use of the veterinary medicinal product concerned the development of resistance;
82.2. in accordance with Chapter 4 of annex focuses on resistance, associated with the clinical use of the product. In the case of mutual reference to Chapter 4 of this annex sets out data.
83. the safety of users. Describe the effects on people found that enter or put the veterinary medicinal product to animals, indicating that the action of the medicinal product, the significance and duration. Develop appropriate warnings to users and other risk management measures.

84. the environmental risk assessment shall be carried out on genetically modified organisms-veterinary medicinal products, in order to assess the potential of the use of veterinary medicines adverse effects on the environment and determine the impact of this risk. The evaluation also describes the necessary precautionary measures to reduce environmental risk. The environmental risk assessment shall be carried out in accordance with the following requirements: 84.1. always carry out the environmental risk assessment is the first stage. More detailed information about the assessment provided in accordance with the guidelines laid down. The assessment of the veterinary medicinal product, the description of the potential environmental impact and the level of risk associated with these effects, taking into account in particular the following issues: 84.1.1. the target species and the proposed pattern of use;
84.1.2. usage, especially the extent to which the veterinary medicinal product will enter directly into environmental systems;
84.1.3. the veterinary medicinal product, its active substances or relevant metabolites into the possible release of animals into the environment and sustainability in such excretions;
84.1.4. unused veterinary medicinal products or other waste disposal;
52.3. environmental risk assessment carried out in the second phase, further specific studies on the operation of the product and the impact on specific ecosystems, in accordance with the guidelines laid down. Take into account the impact of veterinary medicinal products on the environment and the amount of available information on the substance of the physical/chemical, pharmacological and/or toxicological characteristics, including the metabolites identified risk in the case, obtained more tests and trials as defined by these regulations;
84.3. in the case of veterinary medicinal products containing genetically modified organisms carry out the environmental risk assessment of genetically modified organisms-veterinary medicinal products, and the application shall be accompanied by documents required in accordance with the laws and regulations governing the movement of genetically modified organisms.
3.2. the news and documents on safety inspections, safety inspection documentation 85. include the following information: 85.1. all documentation of the studies included in the indicators;
85.2. report, which shows that included both favourable and unfavourable data that the applicant is aware of the time of submission;
85.3. grounds for the non-inclusion of any research;
85.4. explanation for the inclusion of other types of research;
85.5. the discussion of the possible contribution of the study by the General risk assessment made before the laws of good laboratory practice.
86. in any research report is: 53.5, a copy of the plan of study (Protocol);
86.2. compliance report to good laboratory practice, where applicable;
86.3. the methods used in the study, around the ratūr and material;
86.4. test system description and justification;
86.5. sufficiently detailed description of the results obtained to be critical to assess independently of the author's interpretations;
86.6. According to case, the statistical analysis of the results;
discussion of the results and 86.7. comments regarding sighted (not on the Rota Nova) impact levels and unusual findings;
86.8. detailed description and detailed discussion of the results of the study relating to the safety of the active substance profiles and their relation to the potential risks caused by residues to humans.
3.3. testing for residues of the 87. tests shall be carried out to determine: 87.1. the release of food residues from tissue or eggs, milk, and honey from animals which use drugs;
87.2. under which conditions and to what extent residues persist in foodstuffs of animal origin;
101.8. withdrawal period.
88. in the case of medicinal products intended for food-producing animals for residues in the documentation indicates: 88.1. to what extent and how long the veterinary drug residues or metabolites thereof in animal tissues in nature or derived from it in milk, eggs or honey;
88.2. information that is possible to set the executable the withdrawal period for veterinary medicinal products, which can observe the practical farming conditions, in order to prevent a risk to health of the consumer, or difficulties in the industrial processing of foodstuffs;
88.3. information that tests of residue analytical methods used are appropriate to the validated to ensure the required repeated assurances that the residue data are provided justification for the withdrawal period for veterinary medicinal products.
89. Pharmacokinetics (absorption, distribution, metabolism and excretion) description in accordance with the following conditions: 89.1. a summary of pharmacokinetic data provided when creating cross-references to the pharmacokinetic studies in target species, filed under Chapter 4 of this annex (no need to submit a complete report of the study);
89.2. residues of veterinary medicinal products farmakokinētisko studies carried out to assess the drug absorption, distribution, metabolism target species, as well as the release of it;
89.3. Specifies the information that the veterinary medicinal product or the finished product characteristics that are comparable in terms of bioavailability with the relevant veterinary medicinal product prepared characteristics, is used in the target species, the maximum recommended dose;
89.4. fully describe the extent of absorption of the veterinary medicinal product, taking into account the input method. If use locally systemic absorption of the veterinary medicinal product is not important, you can not perform further tests of residue;
89.5. describes the spread of veterinary medicinal products, target species, taking into account the ability of the drug to bind plasma proteins or passage into milk or eggs, or the accumulation of lipophilic compounds;
55.7. description the health withdrawal routes of the target species of the organism. Identifies and describes the major metabolites.
90. the release levels down, finding any residues are being depleted and the speed at which residues of target species dwindle after the last use of the veterinary medicinal product.
91. the withdrawal period for veterinary medicinal products of the animals body, determine the current levels of the test animals in a given period of time, choosing a sufficient number of times to perform the test at different periods of time after the last dose of veterinary medicinal products administered the test animal. Use appropriate validated analytical methods. Specifies the use of the technical procedures and methods used for reliability and sensitivity.
92. the withdrawal of residue tests, detailed description of the analytical method used and its validation.
93. the following description of the analytical methods characteristics: 93.1. specificity;
93.2. accuracy;
93.3. precision;
93.4. detection limit;
93.5. quantitative limits;

93.6. practicality and usability in normal laboratory conditions;
93.7. sensitivity to disturbance;
58.3. the resulting levels of stability.
94. the suitability of the proposed analytical methods shall be assessed according to the level of scientific progress at the time of registration application.
95. The analytical method described the internationally approved format.
3.4. Messages and documents for residue tests tests used 96. veterinary medicinal products shall identify and test documentation on the identification of the medicinal product concerned shall contain the following information: 96.1. the composition of the veterinary medicinal product;
96.2. the series of physical and chemical test (activity and purity);
96.3. serial identification;
59.9. relationship to the final product;
96.5. highlighted the specific activity of substances and radiological purity;
96.6. position of labelled atoms in the molecule.
97. the determination of residue documentation shall include: 60.3. all documentation of the studies included in the list;
97.2. a statement that the applicant documentation includes all data, both favourable and unfavourable, that the applicant is aware of the time of submission;
60.5. justification of any kind of test or test not for inclusion;
60.5. the justification for the inclusion of alternative types of tests, if any;
97.5. the assessment of the potential contribution of research to the General risk assessment made before the law on good laboratory practice comes into force;
97.6. proposal for the withdrawal period for veterinary medicinal products of the animal's body.
98. in each research report (in the report) shall contain the following information: a copy of the study plan 98.1. (Protocol);
98.2. report on the applicant's compliance with the study of good laboratory practice, if it is to be applied;
98.3. a description of the methods, apparatus and materials used;
98.4. detailed description of the results obtained, in order to be able to critically evaluate the results independently of the author's interpretations;
98.5. the results of the statistical analysis, if necessary;
the result of the discussion; 98.6.
61.3. an objective discussion of the results obtained and the proposals for the withdrawal period for veterinary medicinal products, in order to ensure that the resulting from animals treated foods is not the amount of residue that can pose risks to consumer health and life.
4. (non-clinical) preclinical and clinical studies 4.1. Preclinical studies pre-clinical studies 99. to determine the veterinary pharmacological activity and tolerance.
100. Veterinary medicinal products the active substance included pharmacodynamic effect of the description in accordance with the following conditions: 100.1. the exact description of the mechanism of action and pharmacological effects, with the use of the recommended practices. The results shall be expressed in quantitative indicators (such as the use of dose-effect curves, time-effect curves) and, if possible, compare with the substance, which is well known. If the applicant wishes to identify active substances of higher efficiency than the substance, which is well known, indicate the difference, as well as its statistical significance;
100.2. the active substance shall provide a general pharmacological assessment, in particular the possible secondary pharmacological effects. Overall, research on the main body function;
100.3. the description of finished product other characteristics (such as routes, pharmaceutical form) exposure to pharmacological activity of the active substance;
100.4. provide detailed information on the active substance, if the recommended dose is equal to or slightly less than the dose that can cause side effects;
100.5. detailed description of the research methods used, which is not the standard method to this method can reproduce. The researchers validated the methods, outlines the results of the studies and specific case studies indicate the statistical significance;
If there is not sufficient justification for 100.6. otherwise, specify information about the modifications with regard to the quantitative reaction resulting from reuse of the substance;
100.7. specify information about the combinations of substances, stating its pharmacologically or with clinical indications. Pharmacodynamic or pharmacokinetic studies shows the interactions that may lead to the combination of substances according to clinical use. If the combination of scientifically based clinical trials, indicate whether the substance of the impact of the combination can be demonstrated in animals, and check the significance of adverse effects. If the combination includes a novel active substance, prior in-depth study.
101. A study on the development of resistance in the description: 101.1. list of data about the potential clinical significance of emergence of resistant organisms, which can lead to the use of veterinary medicinal products. Description of the following development of resistance mechanism. The applicant proposes that measures to limit the development of resistance, which can lead to the use of the veterinary medicinal product under the proposed conditions of use;
101.2. mutual reference to Chapter 3 of this annex at the selected data description, if necessary.
102. Pharmacokinetic studies: 102.1. the description of the active substance basic farmakokinētisko data relating to veterinary medicines clinical safety and efficacy assessment;
102.2. outline the objectives of pharmacokinetic studies conducted with the target animal species.
103. In the target animal pharmacokinetic studies taken are broken down into the following areas: 103.1. descriptive pharmacokinetics leading to determine basic parameters;
103.2. Basic use parameters to explore the relationships between dosage regimen, plasma and tissue concentrations over time and pharmacologic, therapeutic or toxic effects;
103.3. comparative kinetics, to explore possible differences in the various target species which may affect the safety of the target animals and the efficacy of the veterinary medicinal product.
104. Pharmacokinetic study of the target species are required in addition to pharmacodynamic studies to determine effective dose mode (route of administration, dose, and the place of the dosing interval, enter the number of times). According to certain variables population size (for example, age, disease), if possible, an additional farmakokinētisko studies to determine dosage regime.
105. the pharmacokinetic studies indicate cross-referenced if submitted pursuant to Chapter 3 of this annex.
106. If the new combination of active substances used, which investigated in accordance with the requirements of this regulation, and if it can be justified that this set of substances in combination does not change their pharmacokinetic properties, does not need to be conducted in specific combinations of pharmacological studies.

107. Pharmacokinetic studies shall take appropriate bioavailability studies to establish bioequivalence in the following cases: 107.1. the newly formulated veterinary medicinal products compared to existing medicinal products;
107.2. road or entering new technique compared with the existing one.
108. Tolerance in the target species of animals as veterinary medicines investigated local and systemic effects. The objective of these studies is to characterize intoleranc (intolerance) signs and determine the appropriate safety margin, using the recommended route of administration. Safety margin can be determined by increasing the therapeutic dose or duration of treatment. Report of the studies included data on possible pharmacological effects and side effects.
4.2.109. Clinical trials clinical research aims to discover or to substantiate the efficacy of the veterinary medicinal product, using the recommended dose mode and using the recommended route of administration, as well as provide the medicine indications and contra-indications according to species, age, breed and gender, usage instructions and possible side effects.
110. the pilot data during clinical trials based on data obtained in normal practice (field).
111. If there is no approval, clinical studies carried out with control animals (controlled clinical studies). Efficacy results obtained are compared with the results of efficacy in the target species of animals which have been treated with the European Union authorized veterinary medicinal products having the same indications and target species as the investigational medicinal product, or with placebo (medicine without the active ingredient).
112. Report on all clinical trial results regardless of whether the results are favourable or unfavourable. Research protocol development, clinical trials analysis and assessment using statistical principles.
113. In the case of veterinary medicinal products intended for use on the animal's overall performance enhancer, particular attention: 113.1. animal productivity (yield);
animal product quality 113.2. (organoleptic, nutritional, hygienic and technological qualities of the cough);
113.3. target species of animal feed consumption efficiency and growth;
113.4. target species the animal's overall health.
114. Veterinary Medicine clinical studies carried out in accordance with a detailed research protocol.
115. the clinical field studies are conducted in accordance with the principles of good clinical practice, unless otherwise specified.
116. Before undertaking field studies, agreed with studies of animals used owner (holder) and documented his consent to the use of animals in research in the field. The owner of the animal shall be informed in writing of the study animals used in the conditions and restrictions of food of animal origin products from animals used in research. The animal's owner signed and dated copy of the certificate included in the study documentation.
117. Field studies of veterinary medicinal products to be used for marking apply the form requirements of the labelling of the veterinary medicinal product regulatory law, if not carried out field research by "blind" method. In any case, in clear and indelible markings indicate the phrase "for use only in veterinary field studies".
4.3. Information and documents in the documentation of the efficacy of 118. veterinary medicinal products shall be inserted before the clinical documentation and clinical research and (or) results, whether favourable or unfavourable to ensure unbiased product overall risk-benefit assessment of the relationship.
119. a detailed description of the pre-clinical study results: 119.1. tests demonstrating the pharmacological effects;
119.2. tests demonstrating the therapeutic efficacy of the existing farmakodinamisko mechanisms;
119.3. tests demonstrating the main farmakokinētisko profiles;
119.4. tests demonstrating the target animal safety;
119.5. where tests investigating the resistance.
120. If, during testing, the unexpected results, a detailed description of them.
121. Pre-clinical studies also provide the following information in detail: 121.1. study summary;
121.2. a detailed experimental protocol, which specifies the methods, apparatus and materials used, animal species, age, weight, sex, number, breed or line identification, enter the dose, route and schedule;
121.3. the results of the statistical analysis;
objective discussion of the results of 121.4., making conclusions about the safety and efficacy of the product.
122. If the pre-clinical study completely or partially in the description does not include any data that justifies it.
123. Information about clinical studies, each researcher submitted to the individual pages of the Protocol if the investigational medicinal products for animal use, individual and collective of the Protocol pages if the investigational medicinal products for animal use (collectively).
124. The news on clinical studies indicate the following information: 124.1. responsible investigator's last name, address, title and qualifications;
124.2. the place and date when the investigational medicinal products used in animals;
124.3. animal owner's name and address;
124.4. research protocol specifying the study methods, including random and "blind" method, information on the investigational medicinal product administration, use of graphics, the dose, identification of animals used in studies, species, breed or strain, age, weight, sex, number, physiological status;
124.5. studies of animals used the method of rearing and feeding, stating the composition and type of feed, as well as the additives contained in the feed type and quantity;
124.6. research in animal disease history (as full as possible), describing the illness and disease course also studies the intervals;
124.7. diagnosis and means of diagnosis;
124.8. clinical signs (description in accordance with generally accepted criteria);
124.9. accurate clinical trials of veterinary medicinal products used in the final identification of the form and the series of chemical and physical tests;
124.10. veterinary medicinal products, route of administration, the dose, the method and frequency, as well as the precautions during use of the product (e.g. injection), if any;
124.11. medicine and subsequent duration of the period of observation;
124.12. information about other veterinary medicinal products used in the study of the investigational medicinal product prior to or simultaneously with them. If the medicinal product is used simultaneously with the investigational medicinal product, details information about the observed interaction;

124.13. clinical research results based on the criteria of efficacy and galauzstādījum (end point) (disease, symptom or sign of a clinical trial, to be achieved, one of the study's objectives, outcomes) that set out the clinical study protocol, including the results of statistical analysis;
124.14. unexpected impact, whether it is negative or positive, and the unexpected effects of measures taken. The exploration of possible cause-and-effect relationship;
124.15. the effect on value (productivity) (e.g. egg-laying, milk production, reproductive function), if any;
124.16. impact of veterinary medicinal products processed foods of animal origin, quality, especially the impact of veterinary medicinal products intended for Administration to increase the total value of the animal;
124.17. conclusions on the investigational medicinal product safety and efficacy of each case or collect information regarding the frequency or other relevant variables, as it relates to the use of the investigational medicinal product to animals;
If not a justification, 124.18. apply any of the above conditions.
125. The holder of the registration certificate (the owner) original documents which constitute the basis of the data submitted, stored or ensure the storage of not less than five years after the veterinary medicinal product is no longer registered.
126. Clinical research results summarizes the research and the results summary (synopsis), indicating: the number of checks, 126.1. studies the number of animals used, which applied to investigational medicinal products individually or in a group, in preparing the documentation on the species, breed or strain, age and sex;
126.2. number of animals before the time of end of studies, and the reasons for such termination;
126.3. control animals and the information about it, or they will not be treated, or received a placebo, other European Union veterinary medicinal product authorised in the same indications for use the same target species, as well as whether received the active substance being studied in other formations or another route of administration;
the observed adverse reactions frequency 126.4.;
126.5. observations on the effect on value (productivity);
information about the study of 126.6. animals, which may have increased risk, taking into account their age, breeding or feeding or the purpose for which they are intended, or information about the animals that a physiological or pathological State to decide in particular;
statistical evaluation of results 126.7..
127. Finally, the investigator shall make general conclusions about the veterinary drug safety and efficacy under the proposed conditions of use, in particular the evaluation of information relating to indications and contra-indications, dosage and average duration of use of the product, the observed interactions with other veterinary medicinal products or feed additives for special precautions to be observed during the use of the medicinal product, and clinical symptoms of overdose, if such is observed.
128. as regards veterinary medicinal products the researchers combined makes conclusions on the safety and efficacy of medicinal products compared to each of the active substances included in the separate use. "
19. Annex 3 to express the following: "3. the Cabinet of Ministers of 18 July 2006, regulations no 600 requirements imunoloģiskaj veterinary medicinal products 1. the summary dossier 1. application for the registration of veterinary medicinal products: 1.1. immunological veterinary medicinal products identifies by name and the name of the active substance, information on the possible biological activity (potential) exposure or credit, pharmaceutical form, method and route of administration, as well as the final presentation, including packaging , marking, instructions for use, and description of the veterinary medicinal product. The solvent is allowed to pack together with ampoules of vaccine (bottle) or separately. The documentation includes information about solvents that are necessary to prepare the vaccine preparations ready for use. Immunological veterinary medicinal products shall be considered as one product, even if you need more than one solvent to the finished product could be produced from a variety of preparations intended for use in animals with different types or methods of administration;
1.2. indicate the applicant's name and address, the name and address of the manufacturer and the sites involved in the different stages of the production and monitoring, the manufacturer of the finished product and the manufacturer of the active substance and, where appropriate, the name and address of the importer;
1.3. list of documents (number and name) submitted with the application;
1.4. provide information on samples submitted;
1.5. a copy of the document certifying that the manufacturer has the right to produce immunological veterinary medicinal products, in accordance with governing the manufacture of veterinary medicinal products regulations;
1.6. add it to a list of organisms that do the production site;
1.7. add it to the list of countries which have been granted the certificate of registration of veterinary medicinal products, as well as a list of countries in which the application is filed or rejected;
1.8. Notes bibliographical references and add them.
2. the applicant shall submit the application: 2.1 description of the veterinary medicinal product prepared in accordance with the provisions of paragraph 35 of these requirements.
2.2. the primary and secondary packaging labelling of the packaging mock-up with instructions for use, if required. These documents have been drawn up in accordance with the legislation on the labelling of the veterinary medicinal product, distribution, and control arrangements;
2.3. one or more veterinary medicinal products the final trade samples or models which contain information in at least one of the official languages of the Member States. Mock-ups can be submitted in printed form on paper or electronically, if the State Agency of medicines has previously given consent.
3. a detailed summary (summary) prepared in accordance with the provisions of article 15, taking into account the following requirements: 3.1 summary includes the application time of the available scientific data;
3.2. the summary shall include an assessment of the tests and trials that form the documentation of the registration certificate, and the immunological veterinary medicinal product quality, safety and efficacy assessments;
3.3. Summary give a test and research results and precise bibliographical references;
3.4. the relevant summary data compiled in the annexes, if possible, tables or graphical way;

3.5. Summary and its annexes shall contain precise cross references to the registration documentation attached to the application.
4. Summary information on the expert's education, training and work experience, as well as experts and reflect the applicant's professional relationship. A summary of the data and the signature of the expert.
2. chemical, pharmaceutical and biological or microbiological information General information 2.1 5. Information and documents accompanying the application for the registration of veterinary medicinal products licence according to section 13.10. these provisions are as follows: 5.1 develop test procedures, which comply with the quality of the raw materials and finished product analysis and control requirements, indicating the approval (validation) of research results;
5.2. details of special hardware and equipment descriptions, which can be used for the tests (if possible, adding the chart);
5.3. information on laboratory reagent formulas (if necessary, indicate the method for preparation of reagents);
5.4. If the test procedures are included in the European Pharmacopoeia or national pharmacopoeias, the official description of the procedure is replaced by a detailed reference to the pharmacopoeia in question. The tests are mainly used in the European Pharmacopoeia chemical and biological reference materials. If you use other reference preparations and standards, it identifies and describes in detail.
6. in paragraph 5 of this annex, the information and documents are taken into account in the drafting of European Pharmacopoeia Monographs and General chapters or, if this is not possible, the Member States officially applied to the pharmacopoeia monographs.
 2.2. qualitative and quantitative components of figures 7. Information on the immunological veterinary medicinal product component (component) quality include: 7.1 the information on the active substance;
7.2. information on the constituents of the excipients, whatever their nature or the quantity used, including colouring matter, preservatives, excipients, stabilisers, thickeners, emulsifiers, flavour and aromatic substances;
7.3. information about animals-use form;
7.4. data on the primary packaging (containers), and its conclusion, as well as data on the use of immunological veterinary medicinal products and devices used for the Administration, which will be delivered with the medicinal product. If the device is not supplied with the imunoloģiskaj veterinary medicinal products, providing information about the device, if required, the assessment of the medicinal product.
8. The generally accepted terminology is terminology used in describing the constituents of immunological veterinary medicinal products, regardless of the rules referred to in point 13.3. conditions: 8. substances which appear in the European Pharmacopoeia or national pharmacopoeias, the official use of the main name used in monographs, giving reference to the pharmacopoeia concerned;
8.2. other substances indicates the international non-proprietary name recommended by the World Health Organization, which may be accompanied by another non-proprietary name or, failing these, the exact scientific name. Substances which are not assigned to the international non-proprietary name or the scientific name, description, outlining the manner in which the substances are manufactured, supplemented, where appropriate, by any other relevant details;
8.3. colours denoted by E number, allocated to them according to the rules referred to in annex 4.
9. to provide information on quantitative immunological veterinary medicinal products, medicinal form indicates the number of organisms, the specific protein content, the mass, the international unit (IU) or units of biological activity of dosage unit or volume. Adjuvant and excipient components indicate the mass and capacity, taking into account paragraph 13 of this annex.
10. the use of units of biological activity, if it is set.
11. the units of biological activity, for which no published data exist shall be expressed in such a way as to provide unambiguous information on the activity of components, such as determining the immunological effects justifying the method of determining the dose.
12. in the course of the development of the medicinal product: 12.1 provides an explanation of the immunological veterinary medicinal product composition, ingredients and packaging. Explanations based on scientific data on the development of the medicinal product;
12.2. a dose increase, justified.
2.3. Description of the method of production 13. Registration application under this rule 13.4. section added the description of the manufacturing method shall be prepared so as to provide a sufficient overview of the production process. The description of the manufacturing method shall include the following: 13.1 a list of manufacture (including purification Antigen design and procedures) to be able to assess the repeatability of production procedures and the risk of side effects;
13.2. the most important stage of the production process and the whole production process validation, outlining the results of three successive product series produced using the described method;
13.3. full details concerning precautions taken to ensure the homogeneity of all finished product series and uniformity, where there is continuous production;
13.4. a list of all substances used in the relevant stages of production, including the substances which it is not possible to restore the course of manufacture;
13.5. detailed information on the mixing of quantitative data on the substances used;
13.6. the production phases, which take control samples.
2.4. the production and control of raw materials 14. Inputs are all ingredients used in particular in the manufacture of immunological veterinary medicinal products.
15. One is a raw material used in the manufacture of the active substance in the cultivation medium that has several components. Of culture medium qualitative and quantitative composition of the description in accordance with the State Agency of medicines of the prescribed information on the quality of the finished product and possible risks. If the preparation of culture medium used materials of animal origin, include information on the species of animal used and the tissues.
16. the submission of the registration certificate showing the regular tests carried out on each issue of substance series.
17. The monographs of the European Pharmacopoeia are applicable to all the active substances referred to in the European Pharmacopoeia.
18. In respect of other substances, the National Medicines Agency may request a member of the European Pharmacopoeia or in the pharmacopoeia of the officially used in the Republic of Latvia in respect of products produced.
19. If the components comply with the requirements of the European Pharmacopoeia or in the pharmacopoeia of a Member State to use the official requirements and the rules referred to in point 1.4. requirements analysis methods and procedures in each section of the description is replaced by appropriate reference to the pharmacopoeia in question.

20. colours meet the requirements of the regulatory legislation on the colouring matters which may be added to medicinal products.
21. in the application of the registration certificate showing the regular tests carried out on each series of raw materials, as well as in cases where the tests have been used that are not listed in the pharmacopoeias, shall provide evidence that raw materials meet the relevant Pharmacopoeial quality requirements.
22. a national medicines agency may require from the applicant of the registration certificate of the appropriate specifications, if the specification or other terms specified in the European Pharmacopoeia or national pharmacopoeias, the official is not enough to ensure the quality of the substance. About a possible loophole is informed by the authority responsible for the pharmacopoeia in question.
23. Third country pharmacopoeia monographs is used when the raw material is described neither in the European Pharmacopoeia nor used officially in the Member States. In this case, submit a copy of the monograph and used, if necessary, accompanied by the monographs included in the testing procedure validation and translation.
24. raw materials of animal origin, comply with the relevant requirements of the monograph, including European Pharmacopoeia Monographs and General chapters of the General. Tests and controls are applied to the raw materials concerned.
25. the application of the registration certificate shall be accompanied by documentation showing that the veterinary medicinal product, and the production of raw material complies with the requirements of the European Commission set out guidelines for animal spongiform encephalopathy agent spreading risk reduction products for human use and veterinary medicinal products, as well as the relevant monograph of the European Pharmacopoeia requirements. To demonstrate this compliance, you can use the European Directorate for the quality of medicines issued certificates of conformity with reference to the relevant monograph of the European Pharmacopoeia.
26. Raw materials not listed in the Pharmacopoeia, describes as follows: 26.1. raw materials of biological origin: 26.1.1. description provided in the form of monographs;
26.1.2. possible, vaccine production shall be based on a seed lot system and on established cell banks. If produce immunological veterinary medicinal products consisting of serums, medicine used in the production of animal's general health and immunological status. Certain raw materials used in production series;
26.1.3. Description and document the history and origin of raw materials, including geographic region. About genetically engineered materials, this information shall include the following information: output description cells or strains, vector design description (name, origin, function, replikon Activator Accelerator and other regulatory elements), effectively included in DNA (DNA) or RNA (RNA) sequences control plasmid vector in cells, the primer sequences in the plasmid, kotransfekcij added or removed genes, ready and the biological characteristics of the gene copy number and genetic stability;
26.1.4. tested the cultural material, including cell banks and raw serum preparation of Antisera to determine identity and extraneous agents;
26.1.5. provides information on all substances of biological origin used in each stage of the production process. This information includes detailed data about the resources, material processing, purification and inactivation, adding the process validation data and data on in-process control, as well as detailed information about the tests carried out for each substance series on pollution;
26.1.6. If foreign agents or suspected presence, of the following materials in the waste or extreme shifts in exceptional cases, if the further processing of the product provides a foreign agent or inactivation of the disappearance, the use of materials. In this case, the proof of foreign agents or inactivation of the disappearance;
26.1.7. when cell banks are used, the cell characteristics shall not reflect variability until the passage level used for the production at the highest level;
26.1.8. for live attenuated vaccines, provide evidence of the attenuation characteristics of the culture of stability;
26.1.9. the documentary argues that the inoculum, cell banks, serum series and other materials of animal origin, which concern the transmission of animal spongiform encephalopathies, meet the guidelines for animal spongiform encephalopathy agent spreading risk reduction products for human use and veterinary medicinal products, as well as the relevant monograph of the European Pharmacopoeia. European Directorate for the quality of medicines issued certificates of conformity with reference to the relevant monograph of the European Pharmacopoeia can be used to the showing of conformity;
26.1.10. If necessary, make organic raw materials or reagents used in the testing procedures, to medicine, a government agency can agree on a test;
26.2. the raw materials which do not originate in bio, a description in the form of a monograph, provide the following information: the name of the raw material 26.2.1. corresponding to paragraph 8 of this annex to the requirements of, add commercial or scientific synonyms;
26.2.2. Description of raw materials like the European Pharmacopoeia;
26.2.3. inputs function;
26.2.4. methods of identification;
26.2.5. Special precautions for storage of the substance out and, where appropriate, maximum storage time.
2.5. Control production process 27. to ensure the manufacturing process and the final product homogeneity, the certificate of registration of the application shall be accompanied by documentation of the production control tests that can be performed at an intermediate stage of production.
28. For inactivated or detoxified vaccines, inactivation and detoxification test each production cycle as quickly as possible after the inactivation or detoxification procedures are completed and after neutralisation, if it is made, but before the next production phase.

29. in order to carry out quality assessment, detailed description of the methods for the analysis of finished products. Documentation includes information on the control of the finished product. If you have the appropriate monograph, but use the test procedures and limit values, which are not recorded in the European Pharmacopoeia or national pharmacopoeia monographs used officially, the applicant presents evidence that, in the case of the final testing in accordance with those monographs will be appropriate in the relevant Pharmacopoeia quality requirements laid down in respect of a specific pharmaceutical form.
30. Application for receipt of certificate of registration specify the tests carried out in each of the final series on representative samples, as well as how often the tests are made which are not conducted for each series, and the series release.
31. when a sample of the finished product tests, use the European Pharmacopoeia chemical and biological reference (reference) material. If you use other reference preparations and standards of reference, it identifies and describes in detail.
32. the Final determination of the General characteristics of the finished product tests average masses and maximum deviations, to mechanical, physical control and chemical tests, tests for physical properties (such as density, pH, viscosity). The applicant in each particular case by the specifications with the tolerance limits for each of these characteristics.
33. to identify the active substance, where necessary, carry out identification tests.
34. The series title or potency of each series determines the quantity of the active substance, demonstrating that each series contains the appropriate title and potency of safety and efficacy of the finished product.
35. the identification and assessment of excipients do, in so far as testing procedures are available, checking (through) and components of excipients the quantity and nature of the finished product.
36. identification of constituents of the excipient and evaluation shall be carried out in accordance with the following conditions: 36.1. as far as necessary, the excipient identification tests carried out;
36.2. performing an upper and lower limit test for preservatives;
36.3. the upper limit of compulsory tests shall also be carried out on other adjuvant components that may cause side effects.
37. in addition to the results of the tests made in accordance with this annex, Chapter 3 (safety checks), provided detailed information on safety inspections of the series. These tests are studies of veterinary medicine overdose, not less than one of the most sensitive target species and at least at the entry way, posing the greatest risk. The welfare of the animals may not take a regular series of safety checks, if there is a sufficient number of produced successive product series, which meet the conditions of the test.
38. Sterility and purity test shall be carried out to make sure that the product is not contaminated with extraneous agents or other substances. It will be carried out taking into account the nature of the immunological veterinary medicinal product (type), manufacturing method and conditions. If less regularly test each product series, than being down in the European Pharmacopoeia, the tests carried out are important (critical) role to ensure compliance with the monograph. Therefore provide evidence that the immunological veterinary medicinal product satisfies the requirements if they are tested in accordance with the monograph.
39. each freeze-dried product series take the residual humidity.
40. Inactivated vaccines tested end product primary packaging, thus validating the inactivation of the vaccine, if one test is carried out in the course of production as late as possible in the production stage.
41. in order to ensure constant product quality in all product series and show compliance with specifications, provides a complete protocol for three consecutive series, produced in showing all the tests performed in the course of production and finished product test results.
2.6 stability tests 42. Information on stability tests and documents, in accordance with the provisions of 13.6 and 13.9. section added to the application, of the registration certificate shall be made in accordance with the following requirements: 42.1. the description of the performed to verify the applicant's defined expiration date. These tests are real time studies carried out with sufficient product series, produced in accordance with the described production process and with the products stored in the final packaging. Take the biological and physico-chemical stability tests.
26.2. the opinion indicates the results of analyses, justifying the proposed validity period all proposed storage conditions;
26.3. veterinary medicinal products used for animal feed, provide information on the validity of the veterinary medicinal product in various animal feed and veterinary medicine mixing phases, if they mixed in accordance with the operating instructions;
26.3. If the final product before use, need to prepare or ready for use in veterinary medicinal products intended for Administration to (use) with drinking water, provides detailed information on the preparation of medicines, their period of validity is based;
26.4. the stability data set for the combined products, you can use as preliminary data regarding the derivative products that contain one or more of the same ingredients;
26.5. justify the use of the product expiry date;
26.5. demonstrate any preservative system efficiency. You can use information about the preservative effect of the same manufacturer's similar immunological veterinary medicinal products.
3. Safety Testing 3.1 General requirements 43. Safety test determines the possible risks that can lead to the immunological veterinary medicinal product to animals under the proposed conditions of use.
44. If the immunological veterinary medicinal product composed of living organisms, particularly those that can spread the vaccinated animals, assess the potential risk of infection of unvaccinated animals belong to the same or to a different medicine may subject species.
45. Safety inspections shall be carried out in the target animal species. The use of the veterinary medicinal product is recommended dose and safety examination halls to be taken from the series, produced in accordance with the application described in part II of the production process.

46. If the immunological veterinary medicinal product composed of living organisms, the laboratory tests to be used, the quantity of doses as described in this annex, paragraph 48 and 49 shall correspond to the quantity of the dose of medicines containing the maximum titre. The Antigen concentration can be adjusted to obtain the desired dose. Inactivated vaccines, medications used are recommended to use the maximum quantity of Antigen-without justification.
47. Safety Inspection assessed the potential risks that the veterinary drug effects may arise, people such as you enter it during the animal.
3.2. Laboratory tests 48. safe use of one dose tested and description in accordance with the following requirements: 29.9. immunological veterinary medicinal products used and recommended dose in each of the proposed administration of the target species and category of animals, including the animals with the minimum age for the use of the product. The animals shall be observed and investigated to determine whether they appear systemic and local reactions. Where appropriate, carry out a detailed post-mortem macroscopic and microscopic investigation of the injection site. Also describes other objective criteria, such as rectal temperature and total value of the animals (productivity) indicators;
48.2. the animals shall be observed and investigated until no expected response, but not a shorter period than 14 days after the use of the investigational medicinal product;
48.3. the use of a single dose study may be part of a repeated-dose safety study of use in accordance with this annex, paragraph 50. The study can be omitted if, in accordance with this annex, paragraph 49 of the overdose, the results do not indicate a systemic or local reaction.
49. One overdose (enter quantity of veterinary medicinal products in excess of the recommended dose) safety tested and described in accordance with the following conditions: 30.5. immunological veterinary medicinal products, which are made up of living organisms, overdose;
30.6. the immunological veterinary medicinal product shall be carried out in each of the overdose recommended Administration most sensitive target species, if not justified in entering a sensitive type selection from several similar administration. If the immunological veterinary medicinal products shall be entered in the form of injections, dose and route of Administration is chosen, taking into account the maximum quantity you can enter in one injection site. The animals after administration of at least 14 days observed and investigated to determine whether they appear systemic and local reactions. Describes the other objective criteria, such as rectal temperature and total value (productivity);
30.6. where appropriate, this study includes a detailed post-mortem macroscopic and microscopic examination of the injection site, if such research is not carried out in accordance with this annex, paragraph 47.
50. Given the repeated use of tested and described in accordance with the following conditions: 50.1. If the immunological veterinary medicinal product enters more than once (as part of the basic system of vaccination), study on the reuse of the dose taken to detect side effects caused by repeated use. These studies will be carried out in the target species more sensitive categories (e.g., certain varieties, age groups) through each of the recommended route of administration;
50.2. the animals after administration of investigational medicinal product at least 14 days observed and investigated to determine whether they appear systemic and local reactions. Describes the other objective criteria, such as rectal temperature and total value (productivity) measurements.
51. Effects on reproduction functions check if raw material to the veterinary medicinal product may be a potential risk factor. Effects on reproduction test, enter the recommended dosage of the medicinal product in the form of men entering sensitive animals and pregnant female animals. Study the harmful effects on the progeny, as well as teratogenic and abortion-inducing effects. These studies can be performed simultaneously by this annex 48, 49 and 50 point safety studies mentioned in paragraph 58 above, or field research.
52. The effects on the immunological functions check if the immunological veterinary medicinal products may have harmful effects on the progeny of vaccinated animal or immune response. Appropriate tests shall be carried out by checking the immunological functions.
53. Special requirements for live vaccines: 53.1. the study of the spread of the vaccine strain from vaccinated to unvaccinated target animals, grass, entering its intended route, which can lead to a rapid spread of the vaccine strain. If necessary, study the spread of animal species other than the target species and which may be sensitive against the live vaccine strain;
53.2. to detect the spread of the vaccine strain in vaccinated animals, investigate its milk, eggs, droppings, urine, and other body secretions. If necessary, investigate the spread of the vaccine strain of the animal's body, paying special attention to the body, which the body prone to replication. If for zoonoses under the laws governing the occurrence of zoonoses and zoonotic agents, live vaccines used on animals to food, these studies will take particular account of the persistence of the organism injection site;
53.3. attenuated vaccines virulence strain of researching the reversion in culture. If the strain culture is not available in sufficient quantities, investigates below the passage level used for the production of the strain. The use of another passage. The initial vaccination shall be carried out using the proposed route of administration that is the quickest way to lead to reversion to virulence. Serial passages make the target animal species sequentially five animal groups, unless there are grounds to take a more arcade or body won't disappear from the animals used in the study as soon as possible. The body in the case of low replication taking so passage as possible in the target species;
53.4. biological properties of the vaccine strain. Other tests may be used to more accurately determine the specific vaccine strain biological characteristics (e.g. neurotropism);
13. rekombinēšan or strain genome rearrangement. Appearance or genomic reassortment of upgrading opportunities for field or other strains.

54. Description of safety of users include discussion of the impact of this annex, the manner in which the immunological veterinary medicinal product to the people, and to what extent it is happening, to develop appropriate warnings to users and prepare other risk management measures.
55. The immunological veterinary medicinal product residues checking is not performed, except in the cases referred to in paragraph 56.
56. In the manufacture of immunological veterinary medicinal products, if it was used in the production process of the excipient or preservatives, there is a possibility that the processed food of animal origin can remain in the residues. If necessary, check the exposure of such residues, make recommendations regarding the withdrawal period of the organism and assess compliance with the period for any kind of testing that is performed before the trial.
57. the examination of the reliability of the context, describes the interaction with other medicinal products known, if the description of the investigational medicinal product is for compatibility with other immunological veterinary medicinal products.
3.3. Field studies 58. data on field studies that use the product series under the application of the registration certificate manufacturing process described in the documentation that accompanied the results of laboratory tests, if it is not supported elsewhere. You can check the field studies of the immunological veterinary medicinal product: 58.1.;
58.2. efficacy.
3.4. Environmental risk assessment 59. environmental risk assessment shall be carried out to assess the use of immunological veterinary medicinal products the potential harmful effects on the environment and determine the necessary precautions to reduce the risk.
60. The first phase of the environmental risk assessment shall be carried out in accordance with instructions drawn up. It finds use in veterinary medicinal products, the potential effects on the environment and with such exposure related risk level, especially when describing the following: 60.1. target species and the proposed pattern of use;
60.2. method of application, in particular the extent to which the veterinary medicinal product is to get into the environmental system;
60.3. the veterinary medicinal product and the active substances possible withdrawal from handling the animals come in the environment, the conservation of such discharges into the environment;
60.4. unused veterinary medicinal product or waste disposal.
61. The possible human risks assessed, if live vaccine strain is potentially zoonotic.
62. The second phase of the environmental risk assessment shall be carried out if, after the first phase of the evaluation findings point to a possible effect of veterinary medicinal products on the environment. Assesses the potential risks that the veterinary medicinal product may cause to the environment. If necessary, make further studies on the effects of the veterinary medicinal product on the environment (e.g., effects on soil, water, air, aquatic organisms, species other than the target species).
63. If the immunological veterinary medicinal product contains genetically modified organisms, the application shall be accompanied by documents required in accordance with the movement of genetically modified organisms in the regulatory requirements of the law.
4. Efficacy testing 4.1 General conditions 64. to confirm the efficacy of the immunological veterinary medicinal product, the efficacy of the tests carried out. The applicant information about drug effects and features, use confirmed by the results of the tests that are described in the application for a certificate of registration to the accompanying documentation.
65. The efficacy of the tests carried out in accordance with the specific details of the test set out in a protocol that registers in writing before the start of the test. The trials and tests the animals used provide veterinary supervision, as well as to comply with the requirements of animal welfare: 65.1. using pre-established, systematic written procedures for the Organization of the test effectiveness, conduct, data collection, documentation and verification;
65.2. field studies are conducted in accordance with the developed principles of good clinical practice, unless there is good reason to act otherwise.
66. Before undertaking field studies, agreed with studies of animals used owner (holder) and documented his consent to the use of animals in research in the field. The owner of the animal shall be informed in writing of the study animals used in the conditions and restrictions of food of animal origin products from animals used in research. The animal's owner signed and dated copy of the certificate included in the study documentation.
67. Studies using medicines labelled according to regulations on the labelling of the veterinary medicinal product requirements if one field study conducted using "blind" method. In any case, in clear and indelible markings indicate the phrase "for use only in veterinary field studies".
4.2. Basic studies and tests 68. Antigen or vaccine strain selection, based on the epizootol logical data.
69. the Laboratory efficacy studies are controlled studies, the use of untreated control animals, unless this is justified by the animal welfare requirements and efficacy may not prove otherwise. Research description in accordance with the following conditions: 69.1. laboratory studies complemented with field studies, including untreated control animals;
EB 69.2. research description in sufficient detail to enable them to repeat after the request of the State Agency in the controlled studies. The investigator declares all the study methodology involved validation;
69.3. report on the results obtained, whether favourable or unfavourable.
70. the efficacy of the immunological veterinary medicinal product shall be indicated for each category of target species recommended for vaccination, by each recommended route of administration of the medicinal product and graphic. If the effect of the vaccine – immunity – has a passive way or antiparticle derived from parent, such a possibility according to be evaluated and described. Signs of return and duration of immunity is determined and added to the study data, if these facts are not reasonably in advance.
71. the Multivalent and combined immunological veterinary medicinal products, the components of each exposure. If the medicinal product is recommended for use in combined or simultaneously with any other veterinary medicinal products, their compatibility.
72. If the immunological veterinary medicinal product forms part of a vaccination scheme recommended by the applicant to reflect the drug early or dynamic effects or effects of vaccination in the common system.

73. use the medications used in the recommended quantity and potency testing used in the series are taken from the series, produced in accordance with production process as described in part II of the application.
74. If the medicine is in the summary statement of compatibility with other immunological medicinal products, check the efficacy of the settlement. Describes other known interactions with other veterinary medicinal products. Use addition or with any other veterinary medicinal products is permissible if it is based on relevant studies.
75. For immunological veterinary medicinal products used for the diagnosis of animal diseases, the applicant shall specify how to interpret the animal's response to a medication.
76. On vaccines intended to distinguish vaccinated animals from infected animals (marked vaccines) and efficacy scores based on in vitro diagnostic tests, the applicant provided data on diagnostic tests, to be able to assess the appropriate to the plotted characteristics requirements.
4.3. the lab tests the efficacy of 77. demonstrate under controlled laboratory conditions, indicating that the response of the target animal provokes the immunological veterinary medicinal product of the proposed use of the product. As far as possible, the conditions which make a provocation, reflects a natural infection conditions. Detailed information on the stump and provocations. Live vaccines used in the series, containing the minimum titre or potency, unless there are reasons to do otherwise. Other immunological medicinal products used in the series, which contain the minimum active content, unless it is justified to act otherwise. Lists and describes the immune mechanism (cell fluid, a local class of immunoglobulin) which is proposed to target animals after administration of the immunological veterinary medicinal product, using the recommended route of administration.
4.4. Field studies 78. laboratory test results, accompanied by field research data using serial, produced according to the manufacturing process described in the application. Safety and efficacy of the medicinal product can be verified in the same field of study.
79. Field studies using laboratory tests, if it is not possible to substantiate the efficacy of the medicinal product.
5. Information and documents 5.1 General requirements 80. Documentation on safety and efficacy studies shall include an introduction defining the subject, pointing to tests and studies carried out in accordance with this annex, Chapter 3 and 4, as well as summary with detailed references to published literature. The summary shall include an objective discussion of the results obtained and noted the conclusions of the immunological veterinary medicinal product safety and efficacy. If you do not make any of the following tests or studies, and in the argument.
5.2. details of laboratory tests On laboratory tests 81. provide the following information: 81.1. Summary;
81.2. the name of the authority that carried out the tests;
81.3. a detailed experimental protocol giving a description of the methods, apparatus and materials used, provides detailed information about animal species or categories of animal, breed, animal, ID and the number of housing conditions and feeding conditions (in determining whether the animals are free from specific pathogenic organisms or specific antibodies, indicating the feed additive on the characteristics and quantity), use the dosage, route of administration, schedule and dates, the statistical methods used in the description and justification;
81.4. control animals, indicate whether they have received a placebo or not received any treatment;
81.5. provide information about the animals which have been treated with the drug, the test and, where appropriate, whether they are received in the test or other authorised medicinal products in the Member States;
81.6. description the General and individual observations and results obtained (with averages and standard deviations), both favourable and unfavourable. The data provide enough detail to be able to critically evaluate the results regardless of how it is interpretation by the author. Raw data reflect the table. Explaining and illustrating the results, you can add to, for example, to record the playback, microfilm, photographs;
81.7. Description of the characteristics of the observed effects, frequency, and duration;
81.8. indicate the number of animals withdrawn prematurely from the tests, and the reasons for such withdrawal;
81.9. statistical analysis of the results reflect, if necessary, in accordance with the test programme, and variance within the data;
81.10. additional description of disease incidence and progress, if any;
81.11. provides information for veterinary medicinal products other than investigational medicinal products, if their use was necessary in the course of the study;
81.12. provides an objective discussion of the results obtained, making conclusions about the investigational medicinal product safety and efficacy.
5.3. Posts for field studies in the news field 82. studies include the following: 82.1. Summary;
82.2. the investigator's last name, address, title and qualifications;
82.3. place and time of the study, the identification code, that can be attached to the animal owner's name and address;
82.4. detailed information about the research protocol giving a description of the methods, apparatus and materials used, provide information on the investigational medicinal product administration and treatment, dose and animal categories, the duration of observation, the serological response and other investigations carried out on animals after administration of investigational medicinal product;
82.5. indicate whether the control animals received placebo or not received any treatment;
82.6. processed and control animal identification (collectively or individually), such as species, breed or strain, age, weight, sex, physiological status;
82.7. animal breeding and feeding techniques, a short description of the additives contained in the feed type and quantity;
82.8. data on the observed facts, assessments and results (with averages and standard deviation). The individual data points, when tests and measurements are made to individual animals;
82.9. clinical research describes results, whether favourable or unfavourable, indicating the activity test objective observations and results, which are required for the evaluation of the product. Indicate the methods used and explain the results of variation (declination) significance;
82.10. describe the effect on value (productivity);
82.11. indicate the number of animals withdrawn prematurely from the studies and reasons for such withdrawal;
82.12. Description of the characteristics of the observed effects, frequency, and duration;
82.13. Description of additional disease incidence and progress;

82.14. provides information for veterinary medicinal products (other than the test drug) used drugs before the test or simultaneously with them or test animal at the time of observation. Provides information about the observed interaction;
82.15. provide an objective discussion of the results obtained, specifying the test conclusions about safety and efficacy of the medicinal product.
6. Bibliographical references 83. Details lists bibliographical references specified in Chapter 1 of this annex the summary referred to in, and submit copies of them. "
20. To supplement the provisions of this annex with the 3.1 version: "3.1 Annex Cabinet 18 July 2006 regulations no requirements for specific 600 submissions for registration certificate 1. Generic veterinary medicinal products 1. Submission, submitted in accordance with the provisions of paragraphs 22 and 23, add to annex 2 of these rules 1 and 2, the data referred to the environmental risk assessment and data demonstrating that the veterinary medicinal product having the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product as well as data showing bioequivalence with the reference medicinal product. If the reference medicinal product is a biological veterinary medicinal product, take into account this provision in annex 3 of the documentation requirements for similar biological veterinary medicinal products.
2. summaries of generic veterinary medicinal products for safety and efficacy of the focus on the following: 2.1 explanation and justification, if the generic veterinary medicinal product is substantially similar to the reference product;
2.2. Overview of impurities and, where appropriate, of the degradation products arising during storage, the active substance and the finished series of veterinary medicinal products which are intended to be placed on the market as product, as well as the evaluation of impurities;
2.3. the assessment of bioequivalence study or rationale not to carry out such studies in accordance with the instructions laid down;
2.4. If necessary, additional data supporting the active substances authorised in different salts, esters or derivatives of the equivalence of safety and efficacy. These data include evidence that the veterinary medicinal product have not been changed therapeutic pharmacokinetics, pharmaco-dynamics of part or toxicity, which may affect the safety or efficacy of the product.
3. If the generic description of the veterinary medicinal product contains an allegation of the known drug characteristics and for the correctness of this assertion is impossible to ascertain, pre-clinical or clinical research reports or summaries it based on publications and (or) additional studies.
4. For generic veterinary medicinal product intended for intramuscular or subcutaneous, transdermal, provide the following data: 4.1. evidence of equivalent levels or different release from entering the site, which may be based on the corresponding residue retention studies;
4.2. proof of tolerance target animals entered the site, which may be based on the appropriate target animal studies of tolerance.
2. Similar biological veterinary medicinal products 5. If, in accordance with the provisions of paragraph 23 of the biological veterinary medicinal product which is similar to a reference biological veterinary medicinal product does not meet the definition of generic medicinal products in these conditions, the applicant to submit information in accordance with the provisions of annex 2 or 3 1 and 2 (pharmaceutical, chemical and biological data). The information you submit is supplemented with data on veterinary medicinal products, and bioavailability bioequivalence, as well as additional data, particularly for the safety of the veterinary medicinal product and efficacy.
6. additional data types and volume (for example, toxicological and other safety studies, according to clinical studies) shall be determined on a case by case basis in accordance with relevant scientific guidelines.
7. Biological veterinary medicinal products, due to the diversity of the State Agency of medicines shall establish the necessary studies in accordance with the provisions of annexes 2 and 3 of Chapter 3 and 4, taking into account the biological veterinary medicinal product specific characteristics.
8. Use the General applicable principles that are specified by the European Medicines Agency guidelines, taking into account the biological characteristics of the veterinary medicinal product.
9. where a biological veterinary medicinal product of reference has more than one indication, like a biological veterinary medicinal product efficacy and safety, subject to the application of similarity, or, if necessary, separately for each indication, demonstrate the subject of the application.
3. the use of a well-established veterinary practice 10. veterinary medicinal products containing active substances included are well-established veterinary practice in accordance with the provisions of paragraph 28, subject to the following conditions: the applicant shall provide documentation 10.1. in accordance with the provisions of annex 2, Chapter 1 and 2;
10.2. the documentation in Chapter 3 and 4 safety and efficacy aspects, giving references to the relevant sources of information (detailed scientific bibliography).
11. to prove that veterinary medicinal products used in the active substance is generally recognized veterinary practice, describes the following: 11.1. length of time that the active substance is applied;
11.2. the active quantitative aspects of the use of the substance;
11.3. the level of scientific interest in the use of the active substance (reflect the published scientific literature);
11.4. the coherence of scientific assessments;
11.5. the evaluation of the period, since the respective active substance used in veterinary medicinal products. Different substances have different time periods to determine that they are universally recognized in veterinary practice. The time required to determine that the active substance is a well-established veterinary practice, must not be less than 10 years from the first systematic and documented use of that active substance in veterinary medicinal products of the European Community;

11.6. the dossiers shall apply to veterinary medicinal products, safety and efficacy aspects of the assessment for the proposed indication in the target species, using the proposed route of administration and dosage regimen. Documentation shall include a review of the relevant literature or reference to it in the light of studies before and after the placing on the market of the medicinal product, as well as the published scientific literature concerning experience in the particular epizootiological studies and comparative epizootiological studies. Information submitted, whether favourable or unfavourable. As regards the conditions for the "extensive use in veterinary practice" BIBLIO-grāfisk reference to other evidence of ces sources (such as post market research, epidemiological research, epizootiological), not only to the data associated with the tests and studies can be used as proof of the safety and efficacy of the product, if the documentation attached to this application information sources according to explain and justify;
7.3. If necessary, specify the information completeness and not a justification for why it can be considered that the degree of safety or efficacy is acceptable, despite the fact that some studies are missing;
11.8. the summaries on the safety and efficacy of providing an explanation of the relevance of any data submitted which concern veterinary medicinal products which are different from those provided for the trade in veterinary medicinal products. Assess whether the investigational medicinal products can be considered as similar to the veterinary medicinal products for which a certificate of registration of the application, despite the fact that there are differences between them;
7.4. the applicant specifically examine the experience gained after the other market veterinary medicinal products containing the same components that the investigational medicinal products.
4. the combined 12. veterinary medicinal products On the rules referred to in paragraph 31 combined veterinary medicinal products provides that the provisions of annex 2 or 3 1, 2, 3, and 4. the documentation referred to in section.
13. There is no need to conduct studies on each active substance safety and efficacy. The application can include information on certain substances in certain combinations.
14. The applicant shall submit the data of each individual active substance research for user safety, residue and clinical research into a specific combination of veterinary medicinal products, the appropriate reasons, may not be included in the data for the study of the combined veterinary medicinal products based on animal welfare and unnecessary animal testing, if one is not possible interactions that may lead to additional toxicity. If necessary, provide information on the location of production and safety assessment of possible agents.
5. Informed consent application 15., submitted an application in accordance with the provisions of paragraph 33, the content of these provisions Chapter 1 of annex 2 (summary of the dossier) data described, taking into account that the original of the veterinary medicinal product, the holder of the registration certificate (the owner) has allowed the applicant to use the references of the original documentation of the veterinary medicinal product in 2, 3 and 4 of chapter content. In this case, the applicant may not submit summaries of the quality, safety and efficacy.
6. Documentation requests 16. in exceptional cases a certificate of registration may be granted subject to certain specific requirements that the applicant to introduce specific procedures, in particular in respect of the veterinary medicinal product safety and efficacy if the applicant in accordance with the provisions of paragraph 57 of this can prove that the failure to provide comprehensive data on the efficacy and safety of medicinal products intended conditions of use. 
7. the certificate of registration of the application of composite 17. Mixed application of the registration certificate are submissions accompanied by documentation, Chapter 3 or 4 contents safety and efficacy studies conducted by the applicant, as well as bibliographical references.
18. all other parts of the documentation designed according to annex 2 of these provisions Chapter 1 describes the structure. "
21. To supplement the provisions of this annex with 3.2: "3.2 annex Cabinet 18 July 2006 regulations no 600 claims submissions for registration certificates for specific types of veterinary medicinal products in the annex sets out the requirements for specific types of veterinary medicinal products that are associated with the medicinal product contains active substances.
1. Immunological veterinary medicinal products 1.1. Vaccine Antigen master file (VAMF) 1. Specific immunological veterinary medicinal products has introduced Antigen immunological veterinary medicinal product to the concept of background documentation that define the exceptions to these rules in Chapter 2 of annex 3 (chemical, pharmaceutical and biological or microbiological information) requirements for active substances.
2. within the meaning of this annex of the immunological veterinary medicinal product is compiled of antigens of the immunological veterinary medicinal product certificate of registration of the documentation attached to the application for an individual part, which includes information on the quality of the active substance, which is the integral part of the veterinary medicinal product. Individual components may cover one or more monovalent or combined vaccine, submitted by the same applicant or holder of the registration certificate (the owner).
3. The applicant's use of the European Medicines Agency's scientific guidance on vaccine antigen presentation of background documentation and evaluation. The immunological veterinary medicinal product shall be submitted and compiled the Antigen shall be assessed in accordance with the procedures laid down in the European Commission published guidelines on medicinal products of the European Community legal framework document item volume VI, part B "applications for the applicants".
1.2. Daudzcelm vaccine documentation 4. Specific immunological veterinary medicinal products that contain multiple antigens (foot-and-mouth disease, avian influenza and Bluetongue case), has introduced the daudzcelm vaccine documentation (documentation, which contains a unique and in-depth scientific assessment of different strains and strain combinations possible) use a concept that defines exceptions to the provisions of this annex 3, Chapter 2 requirements for active substances.
5. Daudzcelm vaccine dossier submitted in order to receive permission to use the vaccine against antigēnisk in changing viruses.

6. In preparing the documentation for the daudzcelm vaccine, the applicant uses the European Medicines Agency's scientific guidance on vaccine daudzcelm submission of a dossier and evaluation. Daudzcelm vaccine dossier is submitted and evaluated in accordance with the guidelines of the European Commission published the European Community pharmaceutical legislative framework document item volume VI, part B "applications for the applicants".
2.7 Homeopathic veterinary medicinal products. This provision referred to in paragraph 40 of homeopathic veterinary medicine simplified registration in accordance with this provision, paragraph 43 and 44, to the requirements documentation submitted: 7.1 the homeopathic stock described in the Latin name correspond to the name used in the European Pharmacopoeia in Latin or, in the name used officially in the Member States. Where appropriate, each Member State applied traditional name;
7.2. data and documents for raw materials (for all materials, including raw materials and intermediates up to the final dilution to be included in the finished in homeopathic veterinary medicinal products) supplemented by data on homeopathic feedstock;
7.3. without prejudice to Regulation (EEC) No 2377/90, the provisions for substances included in homeopathic raw materials intended for food-producing animals to enter, follow that rule 2 of the annex Chapter 3 (safety and residue tests). If the information provided is incomplete, based on the safety level of evidence, why is acceptable, despite the fact that some studies do not.
8. the general quality requirements shall apply to all the raw materials, as well as on the intermediate stages of the manufacturing process up to the final dilution to be included in the finished in homeopathic veterinary medicinal products. If the homeopathic veterinary medicinal product containing a toxic component, this component shall be carried out in the final dilution (if that's possible). If it is not possible to control the high dilution factor due to toxic components out of control earlier in the production stage. Each stage of the manufacturing process from raw materials to the final dilution for inclusion in finished product detail description.
9. If included the dilutions, dilution carried out in accordance with a homeopathic manufacturing methods laid down in the relevant monograph of the European Pharmacopoeia or, failing this, used officially in the Member States.
10. the ready-made homeopathic veterinary medicinal products subject to general quality requirements. Any exception the applicant accordingly.
11. Identify and determine the toxicologically significant components. If the applicant argues that all the important components of the identification of toxicological or determination is not possible, for example, because of the high dilution factor present in the final product, the quality of the show with the production process of dilution and full validation.
12. The applicant demonstrates preparing a homeopathic veterinary medicinal product stability. If the active substance identification or detection is not possible due to the degree of dilution, can be taken into account in the form of the stability of the medicinal product data. "
Prime Minister v. dombrovsky, Agriculture Minister Minister of environment r. vējonis Editorial Note: regulations shall enter into force by 1 October 2009.