Decree No. 171 / 2010 Coll.
Decree amending Decree No. 228 / 2008 Coll., on the Registration of Medicinal Products, as amended by Decree No. 13 / 2010 Coll.
Valid
Effective from 15.06.2010
171
DECLARATION
of 21 May 2010
amending Decree No 228 / 2008 Coll., on the Registration of Medicinal Products, as amended by Decree No 13 / 2010 Coll.
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 (the Law on Medicines):
Decree No. 228 / 2008 Coll., on the Registration of Medicinal Products, as amended by Decree No. 13 / 2010 Coll., 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. Commission Directive 2009 / 120 / EC of 14 September 2009 amending Directive 2001 / 83 / EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use, as regards advanced therapy medicinal products. '
2. Part IV of Annex 1 reads as follows:
PREPARATIONS FOR MODER TERAPY
1. Advanced therapy products are defined in Article 2 (1) (a) of Regulation (EC) No 1394 / 2007. Applications for their registration shall comply with the format requirements described in Part I of this Annex.
For modules 3, 4 and 5, the technical requirements for biological medicinal products set out in Part I of this Annex shall apply. The specific requirements for advanced therapy medicinal products described in Sections 3, 4 and 5 of this Part of the Annex provide for how the requirements set out in Part I of this Annex apply to advanced therapy medicinal products. In addition, additional additional requirements for these products have been laid down in this Part of the Annex, where appropriate and taking into account the specific characteristics of advanced therapy medicinal products.
Due to the specific nature of advanced therapy medicinal products, the level of quality and non-clinical and clinical data to be included in the application for authorisation may be determined on the basis of a risk analysis and in accordance with scientific guidance on the quality, safety and efficacy of medicinal products.
The following risk factors may also be taken into account in the risk analysis: the origin of cells, i.e. autologous, allogenic, xenogenic, proliferation and differentiation and immune response, cell-level manipulation, combination of cells with bioactive molecules or structural materials, nature of gene therapy medicinal products, degree of replication in viruses or micro-organisms used in vivo, level of inclusion of nucleic acid or genes into the genome, long-term exposure, risk of oncogenicity and route of administration or use.
The risk analysis may also take into account relevant non-clinical and clinical data available or experience with other related advanced therapy medicinal products. Any deviations from the requirements of this Annex shall be scientifically justified in Module 2 of the application dossier. The above risk analysis shall also be provided and described in Module 2 where applicable. In this case, the methodology used, the nature of the risks identified and the consequences of the risk analysis approach for the development and evaluation programme should be specified and any deviations from the requirements of this Annex resulting from the risk analysis should be described.
2. Definitions
For the purposes of this Annex, in addition to the definitions set out in Regulation (EC) No 1394 / 2007, the following definitions shall apply:
2.1. Medicinal products for gene therapy (18), which mean biological medicinal products, with the exception of vaccines against infectious diseases, having the following characteristics:
(a) contain or consist of an active substance that contains or contains recombinant nucleic acid used in humans or administered to people for the control, repair, replacement, addition or elimination of a genetic sequence; and
(b) their therapeutic, prophylactic or diagnostic effect applies directly to the recombinant nucleic acid sequence they contain or to the genetic expression product of that sequence;
2.2. Medicinal products for somatic cell therapi18) which mean biological medicinal products having the following characteristics:
(a) contain cells or tissues which have been the subject of primary manipulation, thereby altering biological properties, physiological functions or structural properties relevant to the intended clinical use, or cells or tissues which are not intended to be used for the same essential function in the recipient and donor, or consisting of such cells or tissues, and in particular the manipulation referred to in Annex 1 to the directly applicable European Union Regulation 19 shall not be considered as essential manipulation; and
(b) are presented in such a way that they have characteristics for the treatment, prevention or diagnosis of diseases based on the pharmacological, immunological or metabolic action of their cells or tissues, or are used for this purpose in humans or given to humans.
3. Specific requirements concerning Module 3
3.1. Special requirements for all advanced therapy medicinal products
The application for a marketing authorisation for a advanced therapy medicinal product shall be accompanied by a description of the traceability system which the marketing authorisation holder intends to establish and maintain in order to ensure the possibility of monitoring an individual product and its source materials and raw materials, including all substances in contact with the cells or tissues it may contain, from the source, to the manufacture, packaging, storage, transport, to the delivery to the medical establishment where it is used.
The traceability system is to be complementary and compatible with the requirements laid down in Act No. 296 / 2008 Coll. on human tissues and cells, as amended, and by Decree No. 422 / 2008 Coll. on establishing closer requirements to ensure the quality and safety of human tissues and cells intended for human use, as regards human cells and tissues other than blood cells, and in Act No. 378 / 2007 Coll. on medicinal products, as amended, and its implementing rules as regards human blood cells.
3.2. Special requirements for gene therapy medicinal products
3.2.1. Final product, active substance and starting materials
3.2.1.1. Medicinal product for gene therapy containing recombinant nucleic acid sequence or genetically modified micro-organism or virus.
The final medicinal product consists of a sequence of nucleic acid or a genetically modified micro-organism or virus in the final container, modified for intended medical use. The final product may be combined with a medical device or an active implantable medical device.
The active substance consists of a sequence of nucleic acid or a genetically modified micro-organism or virus.
3.2.1.2. Gene therapy medicinal product containing genetically modified cells
The final product consists of genetically modified cells in the final container, as modified for intended medical use. The final product may be combined with a medical device or an active implantable medical device.
The active substance consists of genetically modified cells of one of the products described in point 3.2.1.1.
3.2.1.3.
In the case of preparations consisting of viruses or viral vectors, the parent materials of the component from which the virus vector is derived are the matte inoculum of the virus or viral vector or plasmids used to transfect host cells and the bank of primary cells from those host cells.
3.2.1.4.
In the case of products consisting of plasmids, non-viral vectors and genetically modified micro-organisms, except viruses or viral vectors, the starting materials are the ingredients used to generate the production cell, i.e. plasmid, host bacteria and the bank of basic cells of recombinant microbial cells.
3.2.1.5.
In the case of genetically modified cells, the starting materials are those used to obtain genetically modified cells, which are the starting materials for the production of vector, vector and human or animal cells. The principles of good manufacturing practice shall apply from the system of the bank used for the production of the vector.
3.2.2. Specific requirements
In addition to compliance with the requirements set out in sections 3.2.1. and 3.2.2. of Part One, Part Two, Even this Annex, the dossier submitted for the application for authorisation of a gene therapy medicinal product contains:
(a) information on all starting materials used in the manufacture of the active substance, including the preparations necessary for the genetic modification of human or animal cells and, where appropriate, subsequent cultivation and preservation of genetically modified cells, taking into account the absence of purification steps,
(b) data on genetic modification, sequential analysis, attenuation of virulence, tropism for specific tissues and cell types, dependence of the micro-organism or virus on the cell cycle, pathogenicity and characteristics of the parent strain for preparations containing the micro-organism or virus
(c) in the relevant sections of the dossier, a description of the manufacturing process impurities and product-related impurities, in particular viral contaminants capable of replication, unless the vector is capable of replication;
(d) for medicinal products consisting of plasmids, data on the quantification of different forms of plasmids throughout the period of application of the medicinal product,
(e) in the case of genetically modified cells, an evaluation of the results of tests on the characteristics of the cells before and after genetic modification and, where appropriate, subsequent freezing or storage procedures.
In the case of genetically modified cells, in addition to the specific requirements for gene therapy medicinal products, the quality requirements for somatic cell therapy medicinal products and tissue engineering products referred to in Section 3 shall apply.
3.3. Specific requirements for somatic cell therapy medicinal products and tissue engineering products
3.3.1. Final product, active substance and starting materials
The final medicinal product consists of the active substance in the immediate packaging, as modified for intended medical use and in the final combination in the case of combined advanced therapy medicinal products.
The active substance is composed of modified cells or tissues.
Additional substances, in particular carrier structures, matrices, medical devices, biomaterials, biomolecules and other components, in combination with manipulated cells of integral part, may be considered as starting materials for the final medicinal product, while not being of biological origin.
Materials used in the manufacture of the active substance, in particular culture media, growth factors not to be part of the active substance, shall be considered as raw materials.
3.3.2. Specific requirements
In addition to the requirements set out in Sections 3.2.1. and 3.2.2 of Part I of this Annex, the dossier for the registration of somatic cell therapy medicinal products and tissue engineering products complies with:
3.3.2.1. source materials consisting of:
(a) summary information on donation, collection and examination of human tissues and cells in accordance with the provisions of Act No. 296 / 2008 Coll., as amended, and Decree No. 422 / 2008 Coll., used as source materials; if non-healthy cells or tissues, in particular cancerous tissue, are used as starting materials, their use should be justified,
(b) in the case of a mixture of allogeneic cell populations, from a description of the way in which mixtures are produced and measures to ensure their traceability;
(c) as part of the validation of the manufacturing process, characterisation of the active substance and the finished product, development of tests, specification and stability, where it is necessary to take into account potential variability caused by human or animal tissues and cells;
(d) in the case of xenogenic products derived from animal cells from the provision of information on the origin of animals, in particular geographical origin, the breeding of animals, their age, specific criteria of acceptance, measures to prevent and monitor infections in animal donors, testing animals for the presence of infectious agents, including vertically transmitted micro-organisms and viruses, and information on evidence of the suitability of breeding establishments;
(e) for products derived from genetically modified animal cells, a description of the specific characteristics of the cells related to genetic modification, giving a detailed description of the method of production and characterisation of the transgenic animal;
(f) in the case of genetic modification of cells from the technical requirements referred to in Section 3.2.
(g) a description and justification for testing any other substance, in particular supporting structures, matrices, medical devices, biomaterials, biomolecules or other components, which are combined with modified cells of which they are integral components;
(h) in the case of supporting structures, matrices and medical devices covered by the definition of a medical device or an active implantable medical device, information required under section 3.4 for the evaluation of a combined advanced therapy medicinal product.
3.3.2.2. a production process consisting of:
(a) validation of the process to ensure compliance between batches and compliance of processes, functional integrity of cells throughout production and transport up to the time of application or administration and appropriate state of differentiation; and
(b) for cells cultivated directly within the matrix, carrier structure or medical device or on the matrix, carrier structure or medical device, information on the validation of the cell culture process as regards cell cultivation, function and integrity of the combination.
3.3.2.3. characterisation and control strategy consisting of:
(a) relevant information on the characterisation of the cell population or a mixture of cells with regard to identity, purity, in particular foreign microbial agents and cellular contaminants, viability, efficacy, karyology and tumoriginity and eligibility for intended therapeutic uses, including demonstration of genetic stability of cells;
(b) qualitative and, where possible, quantitative data on product-related impurities and manufacturing process impurities and on all materials which could cause the presence of decomposed products during manufacture, including justification for the extent of the determination of impurities;
(c) a justification where certain tests for release cannot be carried out on the active substance or the finished product but only on key intermediate products or as tests during the manufacturing process;
(d) characterisation of the impact of bioactive molecules such as growth factors and cytokines and their interactions with other active substance components, where these bioactive molecules are part of a product derived from cells;
(e) information on the state of differentiation, the structural and functional arrangements of the cells and, where appropriate, the extracellular matrix, if a three-dimensional structure is part of the intended function; the information is part of the characterisation for those preparations derived from cells; If necessary, physical-chemical characterisation shall be supplemented by non-clinical trials.
3.3.2.4. Excipients
In the case of excipients used in cellular or tissue medicinal products, in particular components of the transport medium, the requirements for new excipients set out in Part I of this Annex shall apply, unless there is data on interactions between cells or tissues and auxiliary substances.
3.3.2.5. Development Studies
The description of the development programme shall relate to the choice of materials and processes, in particular with regard to the integrity of the cell population in the final composition.
3.3.2.6. reference materials
A reference standard which is essential and specific to the active substance and the finished product is documented and characterised.
3.4. Special requirements for advanced therapy medicinal products containing medical devices
3.4.1. Advanced therapy medicinal product containing medical devices referred to in Article 7 of Regulation (EC) No 1394 / 2007.
Part of the dossier submitted for the application for authorisation of a advanced therapy medicinal product containing medical devices
(a) a description of the physical characteristics and effect of the preparation;
(b) a description of the methods of development of the preparation, a description of the interaction and compatibility between genes, cells or tissues and structural components.
3.4.2. Combined advanced therapy medicinal products as referred to in Article 2 (1) (d) of Regulation (EC) No 1394 / 2007
For the cellular or tissue part of the combined advanced therapy medicinal product, the specific requirements for somatic cell therapy medicinal products and for tissue engineering products referred to in section 3.3 and, in the case of genetically modified cells, the specific requirements for gene therapy medicinal products referred to in section 3.2 shall apply.
A medical device or active implantable medical device may be an integral part of the active substance. Where a medical device or active implantable medical device is combined with the cells at the time of manufacture, application or administration of the finished product, it shall be considered as an integral part of the finished product.
The dossier submitted for the application for authorisation of a combined advanced therapy medicinal product shall include information concerning a medical device or active implantable medical device which is an integral part of the active substance or the finished product which is essential for the evaluation of the combined advanced therapy medicinal product. This information shall include:
(a) information on the choice and intended functioning of a medical device or implantable medical device with other ingredients;
(b) the demonstration of compliance of the medical device which is part of the whole with the essential requirements set out in Annex 1 to Government Regulation No 336 / 2004 Coll., laying down technical requirements for medical devices, as amended, or the compliance of the active implantable medical device which is part of the whole with the essential requirements set out in Annex 1 to Government Regulation No 154 / 2004 Coll., laying down requirements for active implantable medical devices, as amended,
(c) where applicable, proof of compliance of the medical device or implantable medical device with the requirements concerning TSE laid down in Act No. 22 / 1997 Coll., on technical requirements for products and amending and supplementing certain laws, as amended by Act No. 205 / 2002 Coll., and Government Decree No. 251 / 2003 Coll., amending certain government regulations issued for the implementation of Act No. 22 / 1997 Coll., on technical requirements for products and amending and supplementing certain laws, as amended, as amended by Decree No. 336 / 2004 Coll.,
(d) if available, the results of any assessment of the medical device which is part of the whole or of the active implantable medical device which is part of the whole carried out by the body in accordance with Act No. 123 / 2000 Coll. on Medical Devices, as amended, and its implementing provisions.
The body which has carried out the assessment referred to in point (d) of this section shall, at the request of the competent authority which assesses the request, provide all information relating to the results of the assessment in accordance with Act No. 123 / 2000 Coll., as amended, and its implementing rules. This may be information and documents contained in the request for conformity assessment concerned, relevant to the assessment of the combined advanced therapy medicinal product as a whole.
4. Specific requirements concerning Module 4
4.1. Special requirements for all advanced therapy medicinal products
Due to the unique and diverse structural and biological properties of advanced therapy medicinal products, the requirements of the I Module 4 of this Annex with regard to pharmacological and toxicological tests of medicinal products is always appropriate. The technical requirements in sections 4.1, 4.2 and 4.3 below explain how the requirements in Part I of this Annex apply to advanced therapy medicinal products. Where appropriate and taking into account the specific characteristics of advanced therapy medicinal products, additional requirements have been established.
The non-clinical summary shall explain and justify the justification for non-clinical development and the criteria used to select the relevant species and modules in vitro and in vivo. The selected animal model (s) may include animals with reduced immunity, animals with targeted inactivated knock-out gene, or animals humanised or transgenic. Consideration shall be given to the use of homologous models, in particular mouse cells analysed in mice or models mimicking the disease, especially for immunogenicity and immunotoxicity studies.
In addition to the requirements set out in Part I is the content of the dossier submitted for the registration of evidence of safety, suitability and biocompatibility of all structural components such as matrices, supporting structures and medical devices and any other substances such as cellular preparations, biomolecules, biomolecules and chemicals present in the final product. Their physical, mechanical, chemical and biological characteristics shall be taken into account.
4.2. Special requirements for gene therapy medicinal products
In order to determine the extent and type of non-clinical studies necessary to determine the appropriate level of non-clinical safety data, account shall be taken of the nature and type of the gene therapy medicinal product.
4.2.1. Pharmacology
The dossier submitted for the application for authorisation of gene therapy medicinal products shall include:
(a) in vitro and in vivo studies on the proposed therapeutic use of a pharmacodynamic approach study using models in the relevant animal species to demonstrate that the nucleic acid sequence achieves its intended target, i.e. target organ or cell and performs its intended function, i.e. expression and functional action. The study shall provide data on the duration of effect of the nucleic acid sequence and the proposed dosing schedules in clinical trials,
(b) studies to confirm the specificity and duration of action and efficacy in target cells and tissues where the gene therapy medicinal product is intended to act selectively or in a targeted manner.
4.2.2. Pharmacokinetic
(a) The biohazard study shall include evaluation of persistence, clearance and mobilisation. In addition, evidence of the risk of transmission via the germ line is also included in the biodarum study.
(b) Together with the environmental risk assessment, data on the evaluation of excretion and the risk of transmission to third parties shall be provided unless their failure is duly justified in the application on the basis of the product-type concerned.
4.2.3. Toxicology
(a) The final gene therapy medicinal product shall be evaluated for its toxicity. In addition, depending on the product-type, individual tests of the active substance and of the excipients shall be taken into account and the in vivo effect of substances derived from the expressed nucleic acid sequence not intended for physiological function shall be evaluated.
(b) Single dose toxicity studies may be combined with pharmacological and pharmacokinetic safety studies, such as for the evaluation of persistence.
(c) Repeated dose toxicity studies are reported when repeated dosing in humans is intended. The route and schedule of administration should correspond exactly to the planned clinical dosing. Repeated dose toxicity studies shall be considered when a single dose may cause prolonged activity in humans of nucleic acid sequences. The duration of the studies may be longer than for standard toxicity studies depending on the persistence of the gene therapy medicinal product and the expected potential risks. In this case, the justification for the duration of the study is given.
(d) A toxicity study demonstrates the evaluation of the gene therapy medicinal product for genotoxicity. However, standard genotoxicity studies shall be conducted only where they are necessary for testing certain impurities or components of the vector.
(e) A toxicity study shall support the evaluation of gene therapy trials for carcinogenicity. Standard lifetime carcinogenicity studies in rodents are not required. However, depending on the product-type, tumourigenic potential must be evaluated in appropriate in vivo or in vitro models.
(f) Reproductive and developmental toxicity: is documented by studies of effects on fertility and reproductive function, embryonal or foetal and perinatal toxicity and transfer across the germ line, unless their failure is duly justified in the application on the basis of the product type concerned.
(g) Supplementary toxicity studies
1. Integration studies:
Integration studies shall be provided for each gene therapy medicinal product unless the absence of such studies is scientifically justified, for example because nucleic acid sequences do not penetrate the cell nucleus. Integration studies shall be conducted for gene therapy medicinal products which, although not expected to be integrated, indicate a risk of transmission via the germ line.
2. Immunogenicity and immunotoxicity:
Part of the toxicity study is evidence of research into potential immunogenic and immunotoxic effects.
4.3. Specific requirements for somatic cell therapy medicinal products and tissue engineering products
4.3.1. Pharmacopoeia
(a) The primary pharmacological study is supported by evidence of conception. The interaction of products from cells with surrounding tissues shall be investigated.
b) The amount of product needed to achieve the expected effect is determined, that is the effective dose and depending on the type of product of the frequency of administration.
(c) Secondary pharmacological studies shall be taken into account to evaluate potential physiological effects that are not related to the anticipated therapeutic effect of the somatic cell therapy medicinal product and the tissue engineering product or other substances, as, in addition to protein monitoring, the elimination of biologically active molecules may occur, or the observed protein may have undesirable target points.
4.3.2.
(a) Conventional pharmacokinetic studies for the assessment of absorption, distribution, metabolism and excretion are not required when parameters such as viability, life expectancy, distribution, growth, differentiation and migration are evaluated, unless the non-evaluation is duly justified in the application on the basis of the product type concerned.
(b) In the case of somatic cell therapy medicinal products and tissue engineering products that produce systemically active biomolecules, the distribution, duration and level of expression of these molecules shall be evaluated.
4.3.3. Toxicology
(a) For the final medicinal product, its toxicity shall be assessed. Individual testing of the active substance, the excipients, other substances and any impurities from the production process shall be taken into account.
(b) Where the duration of observation is longer than in standard toxicity studies, the expected lifetime of the medicinal product shall also be taken into account, together with its pharmacodynamic and pharmacokinetic profile. In this case, the justification for the duration of the study is given.
(c) Conventional carcinogenicity and genotoxicity studies are required only in relation to the tumorigenic potential of the product.
(d) Research on the potential immunogenic and immunotoxic effects of the medicinal product shall be demonstrated.
(e) In the case of products originating from cells and containing animal cells, relevant specific safety issues, such as the transfer of xenogenic pathogens to humans, should be addressed.
5. Specific requirements concerning Module 5
5.1. Special requirements for all advanced therapy medicinal products
5.1.1. The specific requirements in this Section of Part IV are additional requirements to those set out in Module 5 of Part I of this Annex.
5.1.2. If the clinical application of advanced therapy medicinal products requires specific concomitant treatment and includes surgical procedures, the treatment process shall be evaluated and described as a whole, including information on the standardisation and optimisation of these procedures during clinical development.
If medical devices used during surgical procedures for administration, implantation or administration of a advanced therapy medicinal product could have an impact on the efficacy or safety of the advanced therapy medicinal product, information on these medical devices should be provided.
The specific competence required to perform the application, implantation, administration or follow-up measures shall be established. Where appropriate, a plan for the training of health professionals on procedures for the use, application, implantation or administration of these products shall be documented.
5.1.3. If, due to the nature of advanced therapy medicinal products, their manufacturing process changes during clinical development, additional studies may be required to demonstrate comparability.
5.1.4. During clinical development, the risks arising from potential infectious agents or the use of material of animal origin should be evaluated and measures taken to reduce such risks.
5.1.5. The choice of doses and schedule of use are based on dose studies.
5.1.6. The efficacy of the proposed indications is supported by appropriate results from clinical trials using clinically relevant parameters for the intended use. In certain clinical conditions, evidence of long-term efficacy and the provision of a long-term efficacy assessment strategy may be required.
5.1.7. The risk management plan shall include a strategy for long-term safety and efficacy monitoring.
5.1.8. In the case of combination advanced therapy medicinal products, safety and efficacy studies are designed and conducted for the combined product as a whole.
5.2. Special requirements for gene therapy medicinal products
5.2.1. Pharmacokinetic studies in humans
Pharmacokinetic studies in humans include the following aspects:
(a) exclusion studies to address the issue of the exclusion of gene therapy medicinal products;
(b) the biodesign study;
(c) pharmacokinetic studies of the medicinal product and functional groups responsible for gene expression, in particular expressed proteins or representative "signature" genome sequences.
5.2.2. Pharmacodynamic studies in humans
Pharmacodynamic studies in humans must address the expression and function of the nucleic acid sequence after administration of the gene therapy medicinal product.
5.2.3. Safety studies shall address the following aspects:
(a) the presence of a vector capable of replication;
(b) the occurrence of new strains;
(c) rearrangement of existing genome sequences;
(d) neoplastic proliferation due to advertising mutagenicity.
5.3. Special requirements for somatic cell therapy medicinal products
5.3.1. Medicinal products for somatic cell therapy for which the mode of action is based on the production of defined active molecules.
In the case of somatic cell therapy medicinal products for which the mode of action is based on the production of defined active molecules, the pharmacokinetic profile, in particular the distribution, duration and level of expression of these molecules, should be addressed where possible.
5.3.2. Biodiversity, persistence and long-term healing of the components of the somatic cell therapy medicinal product.
During clinical development, bioaccumulation, persistence and long-term healing of the components of the somatic cell therapy medicinal product should be addressed.
5.3.3. Safety study
Safety studies shall address the following aspects:
(a) distribution and healing after administration;
(b) by ectopic healing;
(c) oncogenic transformation and fidelity of cells or tissues to the respective line.
5.4. Specific requirements for tissue engineering products
5.4.1. Pharmacokinetic studies
If conventional pharmacokinetic studies are not relevant for tissue engineering products, biodegradation, persistence and degradation of components of tissue engineering products should be considered during clinical development.
5.1. Pharmacodynamic studies
Pharmacodynamic studies are always designed and adapted to take into account the specific properties of tissue engineering products, which are supported by evidence of compliance with the design and kinetics of the product to achieve the intended regeneration, reparation or replacement. Appropriate pharmacodynamic markers related to the intended function and structure shall be taken into account.
5.4.3. Safety study
Section 5.3.3 shall apply. ';
This Decree shall take effect on the 15th day following its publication.
Minister for Health:
Juraskova v. r.
Minister for Agriculture:
Ing. Shebesta v. r.
18) Commission Directive 2009 / 120 / EC of 14 September 2009 amending Directive 2001 / 83 / EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal products.
19) Regulation (EC) No 1394 / 2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001 / 83 / EC and Regulation (EC) No 726 / 2004. '
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Regulation Information
| Citation | Decree No. 171 / 2010 Coll., amending Decree No. 228 / 2008 Coll., on the Registration of Medicinal Products, as amended by Decree No. 13 / 2010 Coll. |
|---|---|
| Regulation Type | - |
| Author | - |
| Collection | Code of Laws |
| Date of Promulgation | 31.05.2010 |
|---|---|
| Effective from | 15.06.2010 |
| Effective until | - |
| Status | Valid |
The regulation text is for informational purposes only.
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