It is registered
Ministry of Justice of Ukraine
October 7, 2015
of July 23, 2015 No. 460
About modification of the Procedure for conducting examination of registration materials on medicines which move on state registration (re-registration), and also examinations of materials about modification of registration materials throughout action of the registration certificate and approval of the Procedure for test of the materials enclosed to the application for state registration of separate medicines concerning their amount
According to Item 2 of the Procedure for state registration (re-registration) of medicines approved by the resolution of the Cabinet of Ministers of Ukraine of May 26, 2005 No. 376, I order:
1. Make changes to the Procedure for conducting examination of registration materials on medicines which move on state registration (re-registration), and also examinations of materials about modification of registration materials throughout action of the registration certificate, No. approved by the order of the Ministry of Health of Ukraine of August 26, 2005 426, registered in the Ministry of Justice of Ukraine on September 19, 2005 for No. 1069/11349 (in edition of the order of the Ministry of Health of Ukraine of January 4, 2013 No. 3), having been reworded as follows it which is applied.
2. Ceased to be valid according to the Order of the Ministry of Health of Ukraine of 17.11.2016 No. 1245
3. To management of pharmaceutical activities and quality of pharmaceutical products () provide to Borodin S.A. in accordance with the established procedure provision of this order on state registration in the Ministry of Justice of Ukraine.
4. To impose control over the implementation of this order on the First Deputy Minister Pavlenko A. S.
5. This order becomes effective from the date of its official publication.
Approved by the Order of the Ministry of Health of Ukraine of August 26, 2005, No. 426
(in edition of the order of the Ministry of Health of Ukraine of July 23, 2015 No. 460)
1. This Procedure is developed according to the Laws of Ukraine "About medicines" and "About protection of the population against infectious diseases", the Procedure for state registration (re-registration) for medicines and the amount of collection for state registration (re-registration) of medicines approved by the resolution of the Cabinet of Ministers of Ukraine of May 26, 2005 No. 376.
2. This Procedure extends on:
active pharmaceutical ingredients, in particular in forms pellet, granulate and other forms of release;
finished pharmaceutical products;
medicines in packaging of in bulk;
medical immunobiological supplies;
the medical products containing substances which in the course of use arrive in system blood-groove.
3. This Procedure does not extend on:
the radio pharmaceutical medicines made according to instructions of the producer only of licensed sources of radionuclides, radio nuclide sets, precursors of radionuclides when using in accredited healthcare institutions;
medicines on the basis of blood and plasma which are fractioned from human donor blood according to instructions of the producer in the organizations accredited according to field of activity;
the active pharmaceutical ingredients (API), intermediate products, initial materials which are received by the producers in production process of finished pharmaceutical products and which are not intended for realization to other producers;
blood and plasma which are used for industrial production of ready medicines of blood;
4. To the homeopathic medicines having therapeutic indications or provided in dosage form which can represent risk that prevails over desirable therapeutic effect, it is necessary to apply the requirements to registration materials and their examination determined by this Procedure.
5. In case of registration of the medical immunobiological supplies or medicines received from human blood or plasma, the producer shall prove the capability to reach permanency of characteristics from series to series. In case of registration of the medicine received from human blood or plasma, the producer shall prove also lack of specific contamination by viruses in that degree which is possible in case of the modern level of technologies.
6. State registration of medicine is performed by the Ministry of Health of Ukraine (further - the Ministry of Health) based on the positive conclusions provided in the Ministry of Health for decision making concerning quality, safety and efficiency of the medicines constituted by the State company "State Expert Centre of the Ministry of Health of Ukraine" (further - the Center) by results of examination of registration materials (the registration file) according to Procedure.
7. The state re-registration of medicine the Ministry of Health based on the conclusions provided in the Ministry of Health for decision making about confirmation of positive ratio of the expected advantage to possible risk in case of use of medicine, the documents constituted by the Center by results of expert evaluation for ratio performs advantage/risk according to Procedure.
1. According to the procedure the terms below are used in the following values:
1) active pharmaceutical ingredient (medicinal substance, active ingredient, substance) (further - AFI, active ingredient, substance) - any substance or mix of substances which is held for use in production of medicine and during this use becomes its active ingredient. Such substances have pharmacological or other direct impact on human body. As a part of ready forms of medicines they are applied to treatment, diagnostics or prevention of disease, to change of condition, structures or physiological functions of organism, to leaving, processing and relief of symptoms.
AFI can be: compact, covered with cover, granulated, crushed to certain degree or processed some other way are also provided under different names and in different forms (in particular in forms pellet, granulate and other forms of release);
2) safety of medicine - the characteristic of medicine based on comparative assessment of advantage of its application and potential harm which can be caused to the patient in case of use of this medicine by it;
3) bioveyver - the procedure of carrying out research of equivalence in vitro based on BSK for confirmation of equivalence of generic and reference medicines of system action in firm dosage form for oral application with immediate release for the purpose of registration of generic medicine without carrying out the researches in vivo;
4) bioavailability - the speed and degree with which active ingredient or its active component is absorbed (is soaked up) from dosage form and becomes available in the scene of action;
5) bioequivalence - bioekvivalentna medicines if they pharmaceutical are equivalent or pharmaceutical are alternative and if their bioavailability after introduction in the same molar dose it is similar to such degree that effects of these medicines by efficiency and safety are in fact identical;
6) biological medicines - the medicines containing the active ingredients of biological origin received by way of production from biological source (animal, human, vegetable, microbic or biotechnology);
7) the biopharmaceutical classification system (BCS) is scientific classification system of active ingredients on the basis of their solubility in water solutions and extent of complete absorption or extent of intestinal penetration;
8) interchangeable medicine - generic medicine which is equivalent to reference medicine and can replace it in medical practice;
9) the conclusion of the State MZ expert center by efficiency, safety and qualities of medicine - the generalized result of examination (preliminary and/or specialized) materials of the registration file on medicine with provision of recommendations concerning its state registration, modification of materials of the registration file on medicine during action of the registration certificate or its new registration or about refusal in registration, modification of materials of the registration file on medicine during action of the registration certificate;
10) high-technology (biotechnology) medicines the medicines containing the active ingredients received by means of methods of biotechnology, such as: genetically engineered technology, cellular engineering, gibridomny technology, engineering enzimologiya and engineering immunology and so forth;
11) secondary package - packaging in which medicine in primary package is made and which performs protective function concerning medicine and primary package;
12) generic medicine (the generic interchanged) (further generic) - medicine which has the same quantitative and high-quality composition of active ingredients both the same dosage form, and reference medicine and whose interchangeability with reference medicine is proved based on the corresponding researches;
13) genetically engineered medicines - the medicines received by technologies of recombinant DNA;
14) hybrid medicine - medicine which does not fall under determination of generic medicine or if its bioequivalence cannot be proved by bioavailability research, or has such distinctions with reference medicine: changes in operating substance(s), therapeutic indications, dosage, dosage form or way of introduction;
15) homeopathic medicine - any medicine made of products, substances or components which are called homeopathic raw materials according to the procedure of production of homeopathic medicine described in the State pharmacopeia of Ukraine (further - GFU), or the European pharmacopeia, or, in case of lack of such description, in the German homeopathic pharmacopeia (GHP), the Homoeopathic pharmacopeia of the USA (HPUS), the British homeopathic pharmacopeia (BHP), the Homoeopathic pharmacopeia Schwab.
Homeopathic medicine also may contain more than one active ingredient;
16) the state re-registration of ready medicine - the procedure which is carried out according to requirements of the current legislation for the purpose of prolongation of the admission to medical application of medicine in Ukraine;
17) state registration of ready medicine - the procedure which is carried out according to requirements of the current legislation for the purpose of the admission of medicine to medical application in Ukraine and its entering into the State register of medicines of Ukraine;
18) state registration of AFI - the procedure which is carried out according to requirements of the current legislation for the purpose of reference of AFI of pharmaceutical products when importing to customs area of Ukraine and its entering into the State register of medicines of Ukraine;
19) permission to application of AFI in production ready medicinal sredstvutverzhdeniye according to requirements of the current legislation and the Procedure for data on AFI as a part of materials on ready medicine (module 3.2.S) in case of which production this AFI, and entering of the relevant data on AFI into the registration certificate on ready medicine is used;
20) equivalence research - research which determines equivalence between researched and reference medicines when using the researches in vivo and/or in vitro;
21) researches of equivalence in vitro based on BSK are complex researches which are based on classification of active ingredient according to BSK, and also include comparison of profiles of dissolution of the researched and reference medicines in three circles with values rn 1,2, rn 4,5 and rn 6,8;
22) the expert in examination of registration materials the Tsentrafizichesky person having appropriate level of qualification and knowledge of the legislation of Ukraine, rules and regulations of the European Union, WHO recommendations in the field of drug circulation, provisions of the International conference on harmonization of technical requirements to registration of medicines for the person. At the same time the expert shall not perform functions, including outside the Center which lead to conflict of interest;
23) examination of registration materials on medicine preliminary and specialized expert examination of registration materials on medicine for the purpose of preparation of motivated conclusions and recommendations about decision making of possibility of its state registration, re-registration, modification of registration materials or about refusal in state registration, in re-registration, modification of registration materials on medicine;
24) efficiency of medicine - favorable diagnostic, medical or preventive effect of medicine on establishment of nature of disease, its current, duration or correction of condition or physiological functions of human body according to the indications to application specified in the instruction for medical application;
25) the commonly accepted name - the international unlicensed name (further MNN) active ingredient recommended by the World Health Organization (further - WHO), or in the absence of such the regular commonly accepted name;
26) the applicant (the owner of the registration certificate) (further - the applicant) the legal entity or physical person which is responsible for efficiency, quality and safety of medicine according to the procedure determined by the current legislation, and has resources for implementation of pharmakonadzor in Ukraine, and also bears responsibility for accuracy of the information, containing in the registration materials provided to them;
27) changes, possible during action of the registration certificate, the changes offered by the applicant which concern the registered medicine;
28) the instruction for use of medicine (the instruction about use of medicine) (further - the instruction for application) - officially the approved information on medical application of medicine stated according to Procedure accompanying ready medicine;
29) confidential registration information - the scientific and technical information containing in registration materials on medicine including parts I-IV or modules of 1 - 5 materials of the registration file, medicine methods of quality control (except for information which is public, in particular information on reference medicine, information on the name of medicine, composition of active ingredients, action force which are provided in instruction limits for medical application, packaging, about the applicant and/or producer of medicine, the instruction for medical application, information on dangerous properties of medicine which can do harm to the patient during application)
30) phytogenesis medicine - any medicine containing exclusively operating substance(s) from one either more vegetable substances, or one or more vegetable medicines, or one or more vegetable substances in combination with one or more vegetable medicine;
31) the medicine made according to approved by copy-book - medicine which includes active ingredient with the medical application which is well studied in the territory of Ukraine, with certain efficiency, satisfactory degree of safety, copy-book on the approved MOZ;
32) the medicines received from blood or plasma of the person, the medicines on the basis of blood components made by industrial method at the state or private enterprises; such medicines include, in particular, albumine, factors of fibrillation and immunoglobulins of human origin;
33) medical immunobiological supplies (further - MIBP) - vaccines, anatoksina, immunoglobulins, serums, bacteriophages, other medicines, held for use in medical practice for the purpose of specific prevention of infectious diseases;
34) the name of medicine - the name given medicine which can be as the thought-up (producer), and commonly accepted or scientific that can be followed by the name of trademark or the name of the applicant (producer);
35) the independent expert - physical person which has appropriate level of qualification, special knowledge and to order the applicant performs scientific or scientific and technical examination and justification of recommendations according to requirements of task of the applicant of conducting examination answers to the applicant for reliability and completeness of the analysis, and is not the author, the researcher of object of examination; which does not work as the expert in the organizations or the organizations officially determined as expert bodies of objects of scientific and scientific and technical activities concerning drug circulation; or is not otherwise connected with official expert organs, the central executive body providing forming of state policy in the field of health care or the bodies authorized by it;
36) unauthorized use of registration information concerning safety and efficiency of medicine - references or other use of information on efficiency and safety of the medicine registered according to the complete and independent statement, earlier than in 5 years from registration date of such medicine in Ukraine for state registration of the appropriate generic medicine, except as specified, when the applicant according to the legislation acquired the right to refer and/or use registration information of reference/original medicine or submitted own complete registration information conforming to requirements to registration information of reference/original medicine.
These requirements do not interfere with the subject to perform the corresponding development of medicine during this period, including to conduct researches on equivalence between generichny and reference medicines and to submit the registration file to regulatory body for receipt of the registration certificate after execution of five years from registration date in Ukraine of the reference medicine determined in the previous paragraph;
37) original (innovative) medicine - medicine which for the first time in the world was registered on the basis of complete set of documents concerning its quality, safety and efficiency (complete registration information);
38) patent medicine - medicine which arrives in the address under own name of the producer (applicant), the right to production (production) which realization and application it is protected by the legislation of Ukraine on protection of intellectual property rights;
39) primary package - individual packaging which directly contacts to medicine and promotes preserving its main properties;
40) similar biological medicine (biosimilyar) - biological medicine, similar on quality, efficiency and safety to the registered reference biological means which period of patent protection expired. Similarity of quality, efficiency and safety of such medicine of reference biological means shall be proved by the corresponding comparative researches on quality, comparative preclinical and clinical trials;
41) the applicant's representative (the authorized person acting on behalf of the applicant) (further - the applicant's representative) - legal entity or physical person to which based on the corresponding order the applicant granted the right to represent its interests when holding procedures of registration, re-registration and/or modification of registration materials in the territory of Ukraine and which is responsible as well as the applicant, for accuracy of the information, containing in the materials of the registration file provided to them in the Center;
42) radionuclide precursor - any radionuclide intended for introduction of radioactive tag in other substance before its application;
43) medicine of limited application (orphan medicine) - the medicine intended for diagnostics, prevention or treatment of rare disease, that is disease, life-threatening or which leads to disability no more than 5 people from each 10000 inhabitants for date of filing of application about state registration;
44) in bulk products - any medicine which passed all stages of engineering procedure, except for stages of packing and/or final packaging and marking;
45) copy-book (monograph) - information on structure, the production technology, quality control and use of medicine;
46) radio nuclide set - any medicine which shall be integrated or mixed with radionuclides in ready radio pharmaceutical medicine, as a rule, before its application;
47) radio pharmaceutical medicine - any medicine which contains one or several radionuclides (radioactive isotopes) entered into it in the medical purposes in condition, ready for application;
48) regularly updated report on safety of medicine (the regular report) - the written report containing regularly updated information on safety of medicine;
49) registration information - the scientific and technical information in any form and type kept on any carriers, including illustration (cards, charts, organograma, drawings, schemes, etc.), the photos and any other documentary data containing in registration materials on medicine;
50) the registration certificate on medicine (medical immunobiological supply) - the document which contains information on medicine (medical immunobiological medicine), registered in Ukraine and entered in the State register of medicines of Ukraine and the interdepartmental database about the medicines registered in Ukraine;
51) registration number - the specification symbol which is appropriated to medicine in case of state registration and remains behind medicine invariable for the entire period of stay of medicine in the pharmaceutical market of Ukraine;
52) registration materials (materials of the registration file) - set of the documents submitted for state registration, re-registration, modification of registration materials of medicine based on which it is possible to draw valid conclusion on its efficiency, safety and quality;
53) reference medicine - medicine to which medicine is compared and which is, first of all, original (innovative) medicine with the proved efficiency, safety and quality;
54) vegetable medicines - the medicines received as a result of processing of vegetable substances by pulling, distillation, extraction, crushing, cleaning, concentration and fermentation. Here the pounded or powdery vegetable substances, tinctures, extracts, essential oils, the wrung-out juice and the processed extracts enter;
55) vegetable substances - the whole, crushed or cut plants, parts of plants, seaweed, mushrooms, lichens in the raw, usually dried up form, sometimes fresh. The certain extracts from plants (for example, pitches) which are not intended for treatment are also considered as vegetable substances. Vegetable substances are accurately determined by morphological part of plant which is used, and its botanical name according to binomny system (sort, type, version and source);
56) force of effect of medicine - content of operating substance (substances) in quantitative expression per unit of dose, either unit of volume, or unit of mass according to dosage form;
57) the generalizing report - the written report which generalizes information on safety of the medicine containing in two or more regularly updated reports on safety of medicine;
58) pharmaceutical alternative medicines - medicines which contain different salts air, esters, isomers, mixes of isomers, complexes or derivatives of the same active component of molecule of active ingredient or differ in dosage form or force of action;
59) pharmaceutical equivalent medicines - the medicines containing the same molar amount of the same active ingredient (the same active ingredients) in the same dosage form conform to requirements of the same or comparable standards and are entered in the same way. Pharmaceutical equivalence not necessarily assumes bioequivalence because of distinctions in excipients and/or the production technology which can result in distinctions in the speed of dissolution and/or absorption of active ingredient;
60) quality of medicine - set of properties which provide to medicine capability to satisfy consumers according to the appointment and meet the requirements established by the legislation.
2. Other terms used according to the procedure are used in the values given in the legislation.
Types of medicines and the requirement to forming of registration files for the purpose of their state registration according to each of types are below included.
1. In case of medicine registration the applicant shall specify the bases for the choice like medicine to which there shall correspond the set of the available registration documents. The applicant shall provide registration form of medicine for one of the following types:
medicine according to the complete file (the autonomous file);
generic, hybrid medicine or biosimilyar;
medicine with well studied medical application;
medicine with the fixed combination;
other types of medicines as it is specified in Item 2 of this Section.
Registration files on all given types of medicines, irrespective of their nature and other features, shall conform to general requirements to materials of the registration file (in format of the general technical document (further - OTD)) taking into account stated below in this Section. At the same time in registration files of separate types of medicines, such, as: the medicines received from plasma, vaccines, radio pharmaceutical medicines and precursors, homeopathic medicines, herbal remedies, medicines gene and somatoklitinno of therapy and products of fabric engineering, medicines of limited application (orphan medicines), the special requirements stated in annexes to the Procedure are applied.
1.1. Medicine according to the complete file (the autonomous file)
Medicine on complete the registration file is medicine which contains new active ingredient or the known operating substance(s) that is part of other registered medicine.
For these medicines registration files contain: complete modules 1 and 2 in the module 3 - results of own pharmaceutical testing (physicochemical, biological or microbiological), in modules 4 and/or 5 - or results of own preclinical testing (pharmacological and toxicological) and clinical trials, or own limited preclinical testing (pharmacological and toxicological) and clinical trials and detailed bibliographic data, or only detailed bibliographic preclinical and/or clinical data.
Any variations from general requirements to the registration file, in particular lack of reports on certain researches / testing, are proved concerning why lack of this information is acceptable.
Reasons are given in the corresponding reviews of preclinical and clinical data in the module 2 registration files. The provision of general reasons concerning lack of one report or more reports on researches on condition of specification of the fact that reasons concern several reports is allowed.
1.2. Medicine according to the complete file of the mixed type
Modules 4 and/or 5 of the mixed registration files contain reports on limited preclinical and/or clinical researches which were conducted by the applicant, and detailed bibliographic data. All other modules are provided according to general requirements to materials of the registration file (in the OTD format).
The center accepts the file format offered by the applicant depending on each case for conducting examination.
Lack of reports on own testing / researches and provision instead of references to references shall be proved concerning why the given bibliographic references can replace reports on researches and how the provided materials guarantee compliance of the registration file to general requirements.
The necessary account on researches bibliographic given, replacing, are provided in the corresponding Items of the module 4 and/or 5 of the registration file and generalized in the module 2.
The bibliographic data provided in addition to reports on researches are provided in Sections OTD according to references and do not require generalization in the module 2 registration files.
For innovative medicines the Risk management plan is provided.
For each Item of modules 4.1 and 5.1 of the registration file the applicant specifies information on availability of results of preclinical researches or clinical testing in the form of detailed reports on the conducted researches and/or in the form of bibliographic references or such information is absent;
if reports on the conducted researches are provided and they include all requirements to the necessary Section, then further reasons from the applicant are not necessary;
if bibliographic references to certain Item are given, then reasons for why the given bibliographic references can replace reports on researches and as the provided results are provided guarantee compliance of the registration file to general requirements of materials of the registration file (in the OTD format);
if no reports for certain testing or research are provided, then reasons for why such reports are not submitted are provided and are considered executed general requirements to materials of the registration file (in the OTD format). The simple formulation, such as "is not applied", is not acceptable reasons.
For reasons for lack of reports on the conducted own researches in each Section the following principles are used:
special partial cancellation is provided in the current legislation;
careful attitude to animals (The directive of Council of November 24, 1986 86/609/EEC about rapprochement of the laws, rules and administrative provisions of the states of members on protection of the animals used for experimental and other scientific purposes) and the ethical questions (The Helsinki declaration of the World Medical Association "Ethical principles of medical researches with participation of the person as research object") which are followed by expert opinions on low-probability that further testing or researches will expand scientific knowledge in the studied area;
the expert opinion that repeated researches, most likely, will not bring new data in the researched area (for example, clinical experiment on use of active ingredient at the time of development will replace some preclinical researches);
the scientific argumentation about unacceptability of these or those testing and researches;
impossibility of provision of exhaustive data as it is specified in Item 8 of the Section IV of the Procedure (exceptional cases);
other proofs which are provided for reasons for lack of data on these or those testing and researches.
1.3. Generic, hybrid medicine or biosimilyar:
1) generic medicine
Generic medicine is medicine for which it is proved according to provisions of the Management of the European medical agency (further - EMA) on bioequivalence research (CPMP/QWP/EWP/1401/98 Rev. 1) or MZU 42-7.1 ST-N installations: 2014, that it is generic to reference medicine.
This type of medicine provides that the registration file contains the reference to the registration information containing in the file on reference medicine on condition of finishing their equivalence.
Generic is determined as medicine which has the same quantitative and high-quality structure of AFI and the same dosage form, both reference medicine, and whose equivalence of reference medicine was proved by the corresponding researches of bioavailability. Different salts, esters, simple air, isomers, mixes of isomers, complexes or derivatives of active ingredient will be considered as the same active ingredient provided that they significantly do not differ from the point of view of safety and/or efficiency. In such cases the applicant shall provide the additional information which proves safety and/or efficiency of different salts, air or derivatives of active ingredient. Different dosage forms for oral application will reckon with immediate release as the same dosage form. The research of bioequivalence will not be required from the applicant if he proves compliance of generic medicine to the established criteria.
If active ingredient of generic contains the same active component of molecule, as the original registered medicine, but in the form of other salt / air / complex / derivatives, it is necessary to confirm that at the same time the pharmacokinetics, pharmakodinamika and/or toxicity of that component of substance which is responsible for these properties do not change, and can change safety/efficiency profile. If such proofs do not exist, then this substance is new active ingredient;
2) gibridnon medicine
If medicine does not fall under determination "generic medicine" and is not medicine according to the complete file (autonomous or mixed) or if its bioequivalence cannot be shown by bioavailability researches, or in cases of changes in operating substance(s), therapeutic use, dosage, dosage form or ways of introduction, the applicant reports results of the corresponding toxicological and pharmacological researches and/or clinical testing.
If medicine is intended for other therapeutic use, or it is provided in other dosage forms, or has other ways of introduction, or is applied in other doses or in case of other nosology, results of the corresponding toxicological and pharmacological researches and/or clinical testing are reported.
Hybrid medicines differ from generic in the fact that for them results of the corresponding own preclinical researches and clinical testing are required in the following cases:
medicine does not fall under determination "generic medicine";
researches of bioavailability cannot be applied to bioequivalence confirmation;
changes of active ingredient, therapeutic indications, doses, dosage form or way of introduction in comparison with reference medicine.
At the same time results of testing and researches shall correspond to general to materials of the registration file (in the OTD format).
Registration files on hybrid medicines contain references to results of the preclinical researches and clinical testing of reference medicine added with results of own researches conducted by the applicant.
Registration files on generic and hybrid medicines shall correspond to structure of OTD.
Special requirements to these files are:
registration files on medicines which move without own preclinical and clinical data, the containing data described in modules 1 - 3, provided that the applicant has the consent of the owner of the registration certificate of reference medicine to opportunity to make the cross reference on content of modules 4 and 5 of its registration file,
registration files contain the data described in modules of 1 - 3 OTD and also the data proving bioavailability and bioequivalence with original medicine provided that the last is not biological medicine.
In Section 1.5.2 of the module of 1 registration file the brief information (amount to 5 pages) is provided in which all bases and proofs used for demonstration of the fact that the declared medicine is are summed up:
generic to reference medicine. This brief information contains data on medicine: high-quality and quantitative composition of active ingredients, dosage form; profile safety efficiency of its operating substance (substances) in comparison with the operating substance(s) of reference medicine, and also the questions connected with bioavailability and bioequivalence where it is applicable to generic medicine;
hybrid to reference medicine. This brief information shall contain data on medicine: high-quality and quantitative composition of active ingredients, dosage form; action force; therapeutic indications, way of introduction, if necessary - in comparison with reference medicine, and also the questions connected with bioavailability and bioequivalence where it is applicable to hybrid medicine.
In Section 1.5.2 of the module 1 the table "Overview of the Choice of Reference Medicine" is provided. The chosen reference medicine shall be, first of all, medicine with the proved safety and the efficiency registered based on the complete file.
All other requirements of the module 1 OTD are applied to generic and hybrid medicines.
If certain information is absent, the applicant in appropriate section provides reasons for why lack of this information in the registration file is considered acceptable.
The module contains 2 registration files: the general summary on quality, reviews of preclinical and clinical data. The summary of preclinical and clinical data can be provided, but this summary is obligatory if data on the conducted new additional researches are provided to documentation.
For these medicines preclinical/clinical resume reviews include the following elements:
reasons for the fact that medicine is generic;
the short description of the impurity which are available in batches of active ingredient and also in ready medicine (and, whenever possible, the disintegration products arising in case of storage) which is supposed to be used as the medicine intended for release together with assessment of these impurity;
assessment of researches of bioequivalence or reasons for why researches were not conducted according to the Management of EMA on research of bioequivalence CPMP/QWP/EWP/1401/98 Rev. 1 or MZU 42-7.1 ST-N installations: 2014;
the published literature on active ingredient and medicine. For this purpose it is possible to use the summary of Articles from scientific magazines on expert evaluation;
Disclaimer! This text was translated by AI translator and is not a valid juridical document. No warranty. No claim. More info
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