Decree No. 13 / 2010 Coll.
Decree amending Decree No. 228 / 2008 Coll., on the Registration of Medicinal Products
Valid
Effective from 05.02.2010
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13
DECLARATION
of 8 January 2010
amending Decree No. 228 / 2008 Coll., on the Registration of Medicinal Products
The Ministry of Health and the Ministry of Agriculture provides, pursuant to § 114 (2) of Act No. 378 / 2007 Coll., on Medicines and on amendments to certain related laws (Act on Medicines), as amended by Act No. 296 / 2008 Coll., ("the Act '):
Decree No. 228 / 2008 Coll., on the Marketing Authorisation of Medicinal Products, is amended as follows:
1. footnote 1 shall read:
"(1) Directive 2001 / 83 / EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. Directive 2002 / 98 / EC of the European Parliament and of the Council of 27 January 2003 laying down quality and safety standards for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001 / 83 / EC. Commission Directive 2003 / 63 / EC of 25 June 2003 amending Directive 2001 / 83 / EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use. Directive 2004 / 24 / EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001 / 83 / EC on the Community code relating to medicinal products for human use, as regards traditional herbal medicinal products. Directive 2004 / 27 / EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001 / 83 / EC on the Community code relating to medicinal products for human use. Directive 2001 / 82 / EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products. Directive 2004 / 28 / EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001 / 82 / EC on the Community code relating to veterinary medicinal products. Commission Directive 2009 / 9 / EC of 10 February 2009 amending Directive 2001 / 82 / EC of the European Parliament and of the Council on the Community code relating to veterinary medicinal products. Commission Directive 2006 / 130 / EC of 11 December 2006 implementing Directive 2001 / 82 / EC of the European Parliament and of the Council as regards the establishment of criteria for the exemption of certain veterinary medicinal products for food-producing animals from the veterinary prescription requirement. Directive 2009 / 35 / EC of the European Parliament and of the Council of 23 April 2009 on colours which may be added to medicinal products. ';
2. Article 7, including the title, reads:
Documentation submitted with application for registration of veterinary products
(1) Data and documentation shall be submitted with the application for registration of the veterinary medicinal product, the content and the breakdown of which are set out in Annexes 2 to 5 to this Decree. These Annexes shall also apply to the submission of data and documentation for the purposes of mutual recognition of registrations under Section 41 (1) of the Act. The scope of the dossier submitted with the application corresponds to the knowledge of the veterinary medicinal product, its nature, the therapeutic benefits it brings and the risks associated with its use and the current level of scientific knowledge and technical progress in the field of veterinary medicine.
(2) The application shall contain all information concerning the evaluation of the veterinary medicinal product concerned, whether favourable or unfavourable to the veterinary medicinal product. In particular, all relevant details of any incomplete or interrupted test or evaluation concerning the veterinary medicinal product shall always be provided.
(3) A separate application is supported by a complete dossier as set out in Annex 2 to this Decree. In the case of a literary application, the requirements set out in Annex 2 to this Decree shall apply mutatis mutandis to applications supported by experimental data.
(4) For applications using a reference, the reports prepared by experts in accordance with Title VI of Annex 2 to this Regulation shall not be submitted for parts of the dossier for which reference is made to the results of pharmacological and toxicological tests, the residue safety tests and the results of clinical trials already submitted in the context of another marketing authorisation procedure by another marketing authorisation holder. Where appropriate, the documentation necessary for the assessment of the safety and efficacy issues of the veterinary medicinal product which are not included in the dossier referred to shall be submitted for the applications referred to in Article 4 (c); the essential similarity of the veterinary medicinal product for which registration is sought, in relation to the veterinary medicinal product to which reference is made, must be demonstrated, for example, by a proof of bioequivalence or pharmaceutical, pharmacodynamic or therapeutic equivalence. In the case of applications using a reference, the proposed Summary of Product Characteristics usually corresponds to the current Summary of Product Characteristics referred to; However, where derogations exist in the proposed text, they shall be indicated in the proposal and justified. Where an appropriate reference product is registered, reference may not be made to a product registered in another Member State. The European reference product shall only be used if the appropriate reference product is not or has not been registered. Information is required on the country of origin of the European reference product and on the countries in which it is applied. The application submitted with the consent of the original holder shall be accompanied by such consent.
(5) The application for the simplified registration of a veterinary homeopathic product shall be accompanied by the documentation provided for in Title V of Annex 2 to this Regulation for the application for the simplified registration of veterinary homeopathic products.
(6) All relevant articles, including general articles and general chapters of the European Pharmacopoeia, shall be used for the dossier submitted with an application for authorisation of a veterinary medicinal product other than an immunological veterinary medicinal product for the part of the registration dossier affecting quality. All relevant articles, including general articles and general chapters of the European Pharmacopoeia, shall apply to immunological veterinary products for parts of the registration dossier which affect quality, safety and efficacy. With regard to the use of colouring matters in the veterinary preparation, the requirements laid down in Title VIII of Annex 2 to this Regulation shall apply.
(7) The dossier submitted with the application for registration of the veterinary medicinal product shows that the manufacturing processes of the veterinary product are carried out in accordance with the requirements for good manufacturing practice. The dossier further demonstrates that pharmacological, toxicological, residue and safety tests were carried out in accordance with the requirements of good laboratory practice.
(8) The dossier submitted with an application for registration of a veterinary product containing or consisting of a genetically modified organism contains an evaluation of the risk associated with the placing on the environment of a genetically modified organism under another regulatory provision (9).
(9) The dossier submitted with the application for registration of a veterinary medicinal product intended for minor species or for minor indications may not always contain all the information required in Annex 2, provided that this is provided for in the relevant Commission or Agency instructions.
(10) A single sample of the product shall be submitted with the application for a marketing authorisation or, where appropriate, before the marketing authorisation is granted, from each type of immediate packaging or, in agreement with the Veterinary Institute, models of all the internal and external packaging in which the veterinary product is to be placed on the market; a sample of the veterinary product may also be submitted from developmental batches whose characteristics correspond to those of the veterinary product which is the subject of the application. ';
3. the following Section 7a is inserted after Section 7, including the title:
Criteria for classification as reserved veterinary products, for assessing the interchangeability of the names of veterinary products and for deciding on classification with regard to the issue for veterinary products intended for animals from which animal products for human consumption are obtained
(1) The veterinary medicinal products reserved for use may be:
(a) absorption antidiarrhoic agents;
(b) anti-septic medicinal products intended to treat the skin surface of the animal or from outside mucous membranes, including those where the skin or mucous membranes show signs of inflammation or are present with minor injuries; are also veterinary products intended for the treatment of pups of neonatal pups and skin derivatives of animals, veterinary products intended for the preparation of an operating field and intended for use on the mammary gland of bovine animals in order to prevent or treat mastitis,
(c) dermatology;
(d) derivatives;
(e) insecticidal or acaricide preparations intended for external administration, including veterinary medicinal products for the development of external parasites;
(f) oral rehydration solutions,
(g) vitamin and mineral preparations;
(h) dietetic preparations;
(i) oral antivirals that have an effect on their physical-chemical activity.
(2) When assessing the interchangeability of names under § 31 (5) (a) (4) of the Act, it shall be taken into account in particular whether the name in the printed, manuscript or pronounced form is not interchangeable with the name of another veterinary medicinal product. The assessment shall take into account the likelihood of a risk to public health, animal health or the environment.
(3) The conditions under which a marketing authorisation may provide that a veterinary medicinal product intended for animals from which animal products for human consumption are obtained may be issued without a prescription are laid down in Title VII of Annex 2 to this Decree. '
4. Paragraph 10 (1) reads as follows:
"(1) A code shall be assigned to the marketing authorisation holder for each package size or type of packaging (Section 32 (5) of the Act). A new code shall be assigned in the case of type I changes listed in Annex 7, under points 2, 41 and, where applicable, 29. The new code shall also be assigned for changes defined in points 41 and 29 of Annex No 7, but which do not comply with the type I classification and thus are type II changes and in the case of transfer of registration, take-over and simultaneous importation. '
5. In the first sentence of Article 13 (3), the words' or, where appropriate, on its internal packaging 'are deleted.
6. In Article 18 (1), the words "the treating physician shall be given in writing or in electronic form to the address' shall be replaced by the words" the treating physician shall be given in electronic form or in writing to the address of the Institute '.
7. in Annex No 1, point 3.2.2.4, the sentence "In order to verify the purity criteria, analytical methods shall be used to verify compliance with the purity criteria for certain additives used in foodstuffs."
8. Annex No 2, including the title and footnotes 13a to 13f, reads:
"Annex No 2 to Decree No 228 / 2008 Coll.
Requirements for registration documentation for veterinary products
REQUIREMENTS FOR VETERINARY PRODUCTS OTHER THAN IMMUNOLOGICAL VETERINARY PRODUCTS
Unless otherwise specified in Title III, the provisions of this Title shall apply to veterinary products other than immunological veterinary products:
SUMMARY OF MARKETING AUTHORISATION DOCUMENTATION
A. ADMINISTRATIVE DATA
The veterinary medicinal product which is the subject of an application for authorisation is identified by its name and the name of the active substance (s) together with its strength and pharmaceutical form, route and route of administration and description of the final packaging of the product, including packaging, labelling and package leaflet.
The name and address of the applicant shall be given together with the name and address of the manufacturers and sites involved in the various stages of manufacture, testing and release (including the manufacturer of the finished product and the manufacturer or manufacturers of the active substance or active substances) and, where appropriate, the name and address of the importer.
The applicant shall indicate the number and indication of bundles of documentation submitted with the application and, where samples are provided, indicate which.
The administrative data shall be accompanied by a copy of the manufacturing authorisation for all the manufacturing sites involved in the manufacture of the product concerned, together with a list of the countries in which the marketing authorisation was granted, copies of all the summaries of the product characteristics referred to in Article 3 (1) of the Act as approved by the Member States and a list of the countries in which the application was submitted or rejected.
B. SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
The applicant shall propose a summary of the product characteristics according to Annex 3 to this Regulation.
The proposed text of the labelling on the inside or outside packaging shall be submitted in accordance with Annex 5 to this Decree, together with the package leaflet in accordance with Annex 4 to this Decree, if required under Section 37 (3) of the Act. In addition, the applicant shall submit one or more samples or designs of sales packaging of all the inner and outer packaging in which the veterinary medicinal product is to be marketed in the Czech language, in justified cases in one of the official languages of the European Union. In agreement with the Veterinary Institute, draft sales packages may only be presented in black and white and in electronic form.
C. DETAILED AND CRITICAL SUMMARY
In accordance with Article 26 (6) of the Act, detailed and critical summaries of the results of pharmaceutical (physico-chemical, biological or microbiological) tests, safety and residue tests, pre-clinical testing and clinical trials and tests to evaluate the potential risks of the veterinary medicinal product to the environment shall be submitted.
Each detailed and critical summary shall be drawn up taking into account the state of scientific knowledge at the time of application. Each such summary shall include an evaluation of all tests and evaluations constituting the dossier for the application for a marketing authorisation and shall address any questions which may be relevant for the assessment of the quality, safety and efficacy of the veterinary medicinal product. The summary shall always contain detailed test and evaluation results and precise references to published data.
All relevant data shall be summarised in the Appendix, including modification to tables or graphs where possible. Detailed and critical summaries and additions shall always contain precise cross-references to the information contained in the main dossier.
Detailed and critical summaries are always signed and dated and are always accompanied by information on education, training and professional experience of the author. The author's professional relationship with the applicant shall be indicated.
Where the active substance is contained in a human product authorised in accordance with the requirements of Annex 1 to this Regulation, the total quality summary referred to in Module 2 of Section 2.3 of this Annex may, if necessary, replace the summary concerning the dossier related to the active substance or preparation.
Where the Veterinary Institute provides by guideline that chemical, pharmaceutical and biological / microbiological information on the finished product may only be included in the registration dossier in the format of a common technical document, a detailed and critical summary of the results of the pharmaceutical tests may be submitted in the form of an overall summary of the quality.
Where the product is intended for minor animal species or for minor indications, the format of the overall quality summary may be used without prior approval of the Veterinary Institute.
PHARMACEUTICAL (PHYSICAL-CHEMICAL, BIOLOGICAL OR MICROBIOLOGICAL INFORMATION (QUALITY)
General principles and requirements
The particulars and documents which must accompany the marketing authorisations referred to in Article 26 (5) (i) (1) shall be submitted in accordance with the following requirements.
Pharmaceutical (physico-chemical, biological or microbiological) data for the active substance or active substances and for the final veterinary product shall contain information on the manufacturing process, characteristics and characteristics, quality control procedures and requirements, stability as well as a description of the composition, development and presentation of the veterinary product.
All articles, including the general articles and general chapters of the European Pharmacopoeia, or, if not mentioned therein, the pharmacopoeia of the Member State shall apply.
All test procedures must meet the criteria for analysing and checking the quality of the starting materials and the finished product and should take into account the guidelines and requirements introduced. Results of validation studies shall be submitted.
All test procedures shall be described in sufficient precision and detail to enable them to be repeated in the control tests carried out at the request of the Veterinary Institute; any special instruments and equipment which may be used shall be described in sufficient detail, where appropriate with the drawing attached. The composition of the laboratory reagents shall be supplemented, if necessary, by the preparation method. In the case of the test procedures referred to in the European Pharmacopoeia or pharmacopoeia of a Member State, this description may be replaced by an accurate reference to the pharmacopoeia concerned.
Where appropriate, chemical and biological reference materials of the European Pharmacopoeia shall be used. Where other reference products and standards are used, they shall be identified and detailed.
Where the active substance is contained in a human product authorised in accordance with the requirements of Annex I to Directive 2001 / 83 / EC in the current version (1), the chemical, pharmaceutical and biological / microbiological information referred to in Module 3 of this Directive may, if necessary, replace the dossier concerning the active substance or the finished product.
Chemical, pharmaceutical and biological / microbiological information for the active substance or the finished product may be included in the registration dossier in the format of the common technical document only if the Veterinary Institute so provides in the Veterinary Institute's Guidance.
Where the product is intended for a minor animal species or for a minor indication, the format of the common technical document may be used without prior approval of the Veterinary Institute.
A. QUALITATIVE AND QUANTITATIVE COMPOSITION PARTICULARS
1. Qualitative
"Quality data 'of all components of a medicinal product means a description or description of:
- active substances or active substances,
- excipients, whatever their nature or quantity, including dyes, preservatives, adjuvants, stabilisers, thickeners, emulsifiers, flavourings,
- the components of the outer layer of veterinary preparations intended for ingestion or other administration to animals - capsules, gelatine capsules.
This information shall be supplemented by any relevant information on the inner packaging and, where appropriate, the outer packaging and, where appropriate, the method of sealing it, together with details of the means by which the veterinary medicinal product will be used or administered and which will be supplied with it.
2. Usual terminology (terminology)
The usual terminology to be used for the description of the components of veterinary medicinal products shall be without prejudice to the other provisions of Section 26 (5) (b) of the Act:
- in the case of ingredients listed in the European Pharmacopoeia or, in the absence thereof, in the pharmacopoeia of one of the Member States, the main name of the relevant Article, referring to the pharmacopoeia,
- in the case of other components, an international non-proprietary name recommended by the World Health Organisation (WHO), which may be accompanied by another non-proprietary name, or, in the absence of such names, a precise scientific designation; ingredients which do not have an international non-proprietary name or precise scientific indication shall be described by data on how and from which they are prepared, adding any other relevant details where appropriate,
- in the case of "E" colours, by a code assigned to them under another legislation 13a).
3. Quantitative data
3.1. When providing quantitative data on all active substances of veterinary medicinal products, it is necessary to indicate for each active substance the weight or number of units of biological activity, either in the unit of pharmaceutical form or in the unit of weight or volume, depending on the pharmaceutical form concerned.
Units of biological activity are used for substances that cannot be chemically defined. If defined by the World Health Organisation, an international biological activity unit is used. If no international unit has been defined, the biological activity units shall be expressed in such a way as to provide clear information on the activity of the substances whenever possible using European Pharmacopoeia units.
If possible, biological activity per unit of mass or volume shall be reported. The following information shall be added:
- in the case of unit dose products, the weight or units of biological activity of each active substance in one container, taking into account the usable volume of the product, where appropriate after reconstitution,
- in the case of veterinary medicinal products administered by drops of weight or units of biological activity of each active substance contained in one drop or in a number of drops corresponding to 1 ml or 1 g of preparation,
- in the case of syrups, emulsions, granulated products and other formulations administered in measured amounts of weight or units of biological efficacy of each active substance in measured quantities.
3.2 Active substances present in the form of compounds or derivatives are quantitatively described by their total weight and, if necessary or important, by the weight of the active part or active parts of the molecule.
3.3 For veterinary medicinal products containing the active substance that is the subject of an application for registration for the first time in a Member State, the active substance content shall be systematically expressed, if it is salt or hydrate, by the weight of the active part or active parts of the molecule. The quantitative composition of all veterinary medicinal products subsequently authorised in the Member States shall be indicated in the same way for the same active substance.
4. Pharmaceutical Development
An explanation shall be provided concerning the choice of composition, ingredients, immediate packaging, possible additional packaging or external packaging, the intended function of the excipients in the finished product and the method of manufacture of the finished product. This explanation shall be supported by scientific data on pharmaceutical developments. An overstatement shall be provided with its justification. The microbiological properties (microbiological purity and antimicrobial activity) and the instructions for use shall be shown to be suitable for the intended use of the veterinary medicinal product as specified in the dossier for the application for marketing authorisation.
B. DESCRIPTION OF PRODUCTION ELIGIBLE
The name, address and responsibility of each manufacturer and of each proposed manufacturing site or equipment involved in the manufacture and testing shall be indicated.
The description of the production method attached to the application for registration under Section 26 (5) (d) of the Act shall be given in such a way as to provide a sufficient overview of the nature of the operations carried out.
For this purpose, the description shall include at least:
- the indication of the individual stages of production in order to assess whether the processes used in the manufacture of the pharmaceutical form could cause an undesirable change in the ingredients,
- in the case of continuous production, full details of the measures taken to ensure the homogeneity of the finished product,
- the actual composition of the production batch with quantitative data on all the substances used, but the amount of the excipients may be expressed approximately if the pharmaceutical form so requires; all substances which may disappear during manufacture must be mentioned; any exaggeration must be indicated and justified;
- an indication of the stages of production in which sampling is carried out for the control tests during the manufacturing process and the limits laid down, where the information in the documentation accompanying the application indicates that such tests are necessary for the quality control of the finished product,
- experimental studies validating the production process and, if necessary, the validation plan for the production batch,
- for sterile preparations, provided that the conditions of the sterilisation process not mentioned in the pharmacopoeia are applied, details of the sterilisation processes used or aseptic procedures.
C. CONTROL OF EASTERN SURVINS
1. General requirements
The starting materials are all components of the veterinary preparation and, where appropriate, its immediate packaging, including its closure, as referred to in Section A (1) above.
The registration dossier shall contain specifications and information on the tests to be carried out to check the quality of all batches of starting materials.
Routine tests carried out on each batch of starting materials shall be consistent with those provided for in the application for registration. Where tests other than those mentioned in the pharmacopoeia are used, proof shall be provided that the raw materials comply with the quality requirements of the pharmacopoeia.
Where a certificate of conformity has been issued for a source raw material, active substance or excipient by the European Directorate for Quality of Medicines and Health Care, that certificate shall constitute a reference to the relevant article of the European Pharmacopoeia.
Where reference is made to a certificate of conformity, the manufacturer shall guarantee the applicant in writing that the manufacturing process has not been modified since the certificate of conformity was granted by the European Directorate for the Quality of Medicines and Health Care.
The results of batch analyses for the starting materials shall be submitted to demonstrate compliance with the specified specification.
1.1. Active substances
The name, address and responsibility of each manufacturer and of each proposed manufacturing site or equipment involved in the manufacture and testing of the active substance shall be indicated.
In the case of a well-defined active substance, the active substance manufacturer or the applicant may make use of the possibility for the active substance manufacturer to provide the following information directly to the Veterinary Institute in the form of a separate document entitled Active Substance Master File:
(a) a detailed description of the production process;
(b) a description of the quality control during production;
(c) a description of the process validation.
In this case, however, the manufacturer shall provide the applicant with all the information necessary for the applicant to assume responsibility for the veterinary medicinal product. The manufacturer shall confirm in writing to the applicant that he will ensure compliance between lots and shall not change the production process or specifications without informing the applicant. The documents and data accompanying the application for such amendment shall be submitted to the Veterinary Institute. Such documents and data shall also be provided to the applicant in respect of part of the basic document on the active substance concerning the applicant.
In the absence of a certificate of conformity for the active substance, details of the method of manufacture, quality control and impurities, as well as evidence of molecular structure, shall be provided.
1. Information on the manufacturing process shall include a description of the manufacturing process of the active substance, which represents the applicant's obligation to produce the active substance. The list of all raw materials needed to produce the active substance or active substances shall be given, indicating at which stage of the process the raw material shall be used. Information shall be provided on the quality and control of these raw materials. It shall be demonstrated that the raw materials meet the standards appropriate for their intended use.
2. Quality control information shall include information on tests (including acceptance criteria) carried out at each critical step, information on quality and control of intermediate products and process validation or assessment studies, as appropriate. Where appropriate, it shall also contain validation data for analytical methods used in relation to the active substance.
3. The information on impurities shall indicate the expected impurities together with the content and characteristics of the impurities observed. Where relevant, information on the safety of such impurities shall also be provided.
4. In the case of biotechnology veterinary preparations, the molecular structure shall contain a schematic sequence of amino acids and a relative molecular weight.
1.1.1. Active substances listed in pharmacopoeia
The general and specific articles of the European Pharmacopoeia shall apply to all active substances listed therein.
If the ingredients comply with the requirements of the European Pharmacopoeia or pharmacopoeia of one of the Member States, the provisions of Section 26 (5) (h) of the Act shall be deemed to be fulfilled. In this case, the description of the analytical methods and procedures shall be replaced by a corresponding reference to the pharmacopoeia in each relevant section.
In cases where the specification referred to in Article European Pharmacopoeia or in a pharmacopoeia of a Member State is insufficient to ensure the quality of the substance, the competent authorities may require more appropriate specifications from the applicant, including limits on specific impurities with validated testing procedures.
The competent authorities shall inform the authorities responsible for the pharmacopoeia. The marketing authorisation holder shall provide the competent Pharmacopoeia authorities with details of the alleged insufficiency and the additional specifications used.
In cases where the active substance is not described in Article of the European Pharmacopoeia and where the active substance is described in the pharmacopoeia of a Member State, such Article may apply.
In cases where the active substance is not described in either the European Pharmacopoeia or the pharmacopoeia of a Member State, compliance with the article referred to in the pharmacopoeia of a third country may be recognised if its suitability is demonstrated; in such cases, the applicant shall submit a copy of the article together with, where appropriate, the translation. Data demonstrating the ability of the article to adequately control the quality of the active substance shall be provided.
1.1.2. Active substances not included in the pharmacopoeia
Ingredients not included in any pharmacopoeia shall be described in the form of an article with the following items:
(a) the name of the ingredient meeting the requirements of the section; A point 2 shall be supplemented by all commercial or scientific synonyms;
(b) the definition of a substance in a form similar to that used in the European Pharmacopoeia shall be accompanied by all necessary explanatory evidence, in particular concerning the molecular structure. Where substances can only be described by the method of their manufacture, the description should be sufficiently detailed to characterise a substance which is stable both by its composition and by its effects;
(c) the identification methods may be described in the form of complete procedures as used for the manufacture of the substance and in the form of tests which should be carried out routinely;
(d) purity tests shall be described in relation to each expected individual impurity, in particular those which may have a harmful effect and, where appropriate, those which may have an adverse effect on the stability of the medicinal product with regard to the combination of the substances to which the application relates, or distort the analytical results;
(e) tests and limits for the control of parameters relevant to the finished product, for example, the particle size and sterility, and the relevant methods shall be described and, where appropriate, validated;
(f) in the case of complex substances of plant or animal origin, a distinction must be made between when multiple pharmacological effects make the chemical, physical or biological control of the essential constituents necessary and the case of substances containing one or more groups of constituents having similar activity for which a method setting the total content may be permitted.
These data shall demonstrate that the proposed set of test procedures is sufficient to control the quality of the active substance from a specified source.
1.1.3 Physical-chemical properties that may affect bioavailability
The following information on active substances, whether or not listed in the Pharmacopoeia, shall be submitted as part of the general description of the active substances, provided that the bioavailability of the veterinary medicinal product depends on them:
- crystalline form and solubility coefficients,
- particle size, possibly after dusting,
- degree of solvation,
- oil / water partition coefficient,
- pK / pH values.
The first three indents shall not apply to substances used in solution only.
1.2. Excipients
The general and specific articles of the European Pharmacopoeia shall apply to all substances listed therein.
Excipients comply with the requirements of the relevant Article of the European Pharmacopoeia. In the absence of such an article, reference may be made to the article of the pharmacopoeia of the Member State. Where there is no such article, reference may be made to the article of the third country's pharmacopoeia. In this case, the appropriateness of such an article should be demonstrated. Where necessary, the requirements of the Article shall be supplemented by additional tests to check parameters such as particle sizes, sterility, residual solvents. In the absence of a pharmacopoeia article, the design and justification of the specifications shall be provided. The specification requirements set out in sections 1.1.2 (a) to (e) for the active substance shall be complied with. The proposed methods and accompanying data on their validation shall be submitted.
Colouring matter added to veterinary preparations shall always comply with the requirements laid down in Title VIII, except for certain veterinary preparations for topical use, such as insecticide collars and ear tags for which the use of other colouring matters is justified.
Dyes shall comply with the purity criteria laid down in another legislation13b).
For new excipients, i.e. those used in the veterinary medicinal product for the first time or by a new route of administration, detailed information on production, detailed characteristics and details of controls with cross-references to additional clinical and non-clinical safety data shall be provided.
1.3. Internal packaging closure systems
Active substance
Information on the system of closing the immediate packaging for the active substance shall be provided. The level of information required is determined by the physical state (liquid, solid) of the active substance.
1.3.2. Final product
Information on the system for closing the immediate packaging for the finished product shall be provided. The level of information required is determined according to the route of administration of the veterinary medicinal product and the physical condition (liquid, solid) of the formulation.
Packaging materials shall comply with the requirements of the relevant Article of the European Pharmacopoeia. In the absence of such an article, reference may be made to the article of the pharmacopoeia of the Member State. In the absence of such an article, reference may be made to the article of the third country pharmacopoeia. In this case, the appropriateness of such an article shall be demonstrated.
In the absence of an article in the pharmacopoeia, the specification for packaging material should be proposed and justified.
Scientific data on choice and suitability of packaging material shall be provided.
For new packaging materials in contact with the product, information on their composition, manufacture and safety shall be provided.
Specifications and functional data for any device for dosing or administration of the veterinary medicinal product shall be provided.
1.4. Substances of biological origin
Where raw materials such as micro-organisms, tissues of plant or animal origin, cells or fluid (including blood) of human or animal origin or biotechnology cell structures are used in the manufacture of veterinary products, the origin and history of the starting materials shall be described and documented.
The description of the starting material shall include the production strategy, the purification / inactivation procedures with their validation and all control procedures during the manufacturing process intended to ensure quality, safety and conformity between the lots of the finished product.
Where cell banks are used, it should be demonstrated that the cell properties in the arcade used for production and the subsequent passage remain unchanged.
Inocula, cell banks, sera and, if possible, raw material sources must be tested for the absence of foreign agents.
Where starting materials of animal or human origin are used, a description of the measures to ensure the absence of agents that may be pathogenic shall be provided.
Where the presence of foreign agents which may be pathogenic is unavoidable, the relevant raw material may only be used if further processing ensures their removal or inactivation, which must be validated.
A dossier shall be submitted demonstrating that the inoculum, cell inoculum, serum batch and other raw materials of animal origin relevant for the transmission of TSE are in accordance with the Guidance for minimising the risk of transmission of animal spongiform encephalopathy agents through human and veterinary products, as well as with the relevant Article of the European Pharmacopoeia. Conformity certificates issued by the European Directorate for the Quality of Medicines and Health Care may be used to demonstrate compliance, with reference to the relevant Article of the European Pharmacopoeia.
D. CHECKING TESTS IMPLEMENTED AT THE SIZE OF THE INDUSTRIES
The registration dossier shall contain data concerning the control tests of the preparation which may be carried out in the manufacture at the intermediate stage to ensure compliance with the technical characteristics and production process.
These tests are necessary to verify the conformity of the veterinary medicinal product with the composition if the applicant, exceptionally, proposes an analytical procedure for testing the finished product which does not include the determination of the content of all active substances (or of all excipients subject to the same requirements as the active substances).
The same applies if the quality control of the finished product depends on the control tests during the manufacturing process, in particular if the substance is essentially defined by its production method.
Where an intermediate product may be stored before further processing or primary formulation, the period of application of the intermediate product shall be defined on the basis of data obtained from stability studies.
E. TESTS OF THE DEFINITIVE PRODUCT
For the control of the finished product, batches of the finished product shall comprise all units of the pharmaceutical form which are made from the same initial quantity of raw materials and have undergone the same series of production or sterilisation operations or, in the case of a continuous production process, all units produced within a given time interval.
The registration shall indicate the tests which are routinely carried out on each batch of the finished product. The frequency of tests not carried out routinely shall be reported. Specify the release limits.
The registration dossier shall contain data concerning the final product control tests on release. The data shall be submitted in accordance with the following requirements. The provisions of the relevant Articles and of the general chapters of the European Pharmacopoeia, or, in the absence thereof, of the pharmacopoeia of the Member State, shall apply to all preparations listed therein.
Where test procedures and limits other than those provided for in the relevant Articles and General Chapters of the European Pharmacopoeia are used or are not mentioned in the Pharmacopoeia of the Member State, proof shall be provided that the final product, if tested in accordance with those Articles, meets the quality requirements of the pharmacopoeia for the pharmaceutical form concerned.
1. General characteristics of the finished product
Certain tests on the general characteristics of the preparation must always be included among the tests on the finished product. These tests shall, whenever possible, concern checking of average masses and maximum deviations, mechanical, physical or microbiological tests, organoleptic properties, physical properties such as density, pH, refractive index. For each of these characteristics, the applicant shall determine the standards and permissible limits for each individual case.
If they are not indicated in the European Pharmacopoeia or in the pharmacopoeia of a Member State, the test conditions and, where applicable, the equipment or apparatus used and the standards must always be accurately described; The same applies where the methods prescribed by these pharmacopoeia are not applicable.
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Regulation Information
| Citation | Decree No. 13 / 2010 Coll., amending Decree No. 228 / 2008 Coll., on the Registration of Medicinal Products |
|---|---|
| Regulation Type | - |
| Author | - |
| Collection | Code of Laws |
| Date of Promulgation | 21.01.2010 |
|---|---|
| Effective from | 05.02.2010 |
| Effective until | - |
| Status | Valid |
The regulation text is for informational purposes only.
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