ORDER OF THE MINISTER OF HEALTH OF THE REPUBLIC OF KAZAKHSTAN

of April 14, 2023 No. 70

About modification and amendments in the order of the Minister of Health of the Republic of Kazakhstan of January 27, 2021 No. KR DSM-10 "About approval of rules of conducting examination of medicines and medical products"

I ORDER:

1. Bring in the order of the Minister of Health of the Republic of Kazakhstan of January 27, 2021 No. KR DSM-10 "About approval of rules of conducting examination of medicines and medical products" (it is registered in the Register of state registration of regulatory legal acts at No. 22144) the following changes and amendments:

state preamble in the following edition:

"According to items 4 and the 10th Articles 23, Item 3 of article 239 of the Code of the Republic of Kazakhstan "About health of the people and health care system", the subitem 1) of article 10 of the Law of the Republic of Kazakhstan "About the state services", with part one of Item 1 of Rules of registration and examination of safety, quality and efficiency of the medical products approved by the Decision of Council of the Eurasian Economic Commission of February 12, 2016 No. 46, and also Item 3 of Rules of registration and examination of the medicines for medical application approved by the Decision of Council of the Eurasian economic commission of November 3, 2016 No. 78 I ORDER:";

in rules of conducting examination of the medicines approved by appendix 1 to the specified order:

state Item 1 in the following edition:

"1. These rules of conducting examination of medicines (further – Rules) are developed according to items 4 and the 10th Article 23 and Item 3 of article 239 of the Code of the Republic of Kazakhstan "About health of the people and health care system" (further – the Code), article 14 of the Law of the Republic of Kazakhstan "About the state services" (further – the Law) and determine procedure for conducting examination of medicines including strategically important medicines (further – medicines), and also procedure for rendering the state service "Issue of the Conclusion about Safety, Quality and Efficiency of Medicines and Medical Products".";

state Items 6 and 7 in the following edition:

"6. The state expert organization involves specialists from the profile organizations performing activities in the field of service of blood to conducting examination of medicines of blood.

7. In these rules the following terms and determinations are used:

1) biosimilar medicine (bioanalogue, biosimilar medicine, биосимиляр) – biological medicine which contains the version of active ingredient, the registered biological original medicine or reference medicine and on which similarity (similarity) on the basis of comparative researches on indicators of quality, biological activity, safety and efficiency is shown;

2) bioavailability – the speed and degree with which active agent is soaked up from dosage form and becomes available in the scene of action;

3) biological medicine – medicine which active ingredient is made or emitted from biological source and the description of properties and which quality control requires combination of biological and physical and chemical methods of the analysis to assessment of production process and methods of its control;

4) biotechnological medicine – the medicine made by means of bioengineering procedures and application of methods with use of technology of recombinant deoxyribonucleic acid, controlled expression of the genes coding development of biologically active proteins, gibridomny technologies, monoclonal antibodies or other bioengineering procedures;

5) biopharmaceutical classification system (further – BSK) – scientific classification system of active agents on the basis of their solubility in circles with certain indicator of acidity (alkalinity) (pH) and extent of penetration through intestines wall;

6) biological equivalence (bioequivalence) – lack of significant distinctions on the speed and degree with which active ingredient or active part of molecule of active ingredient of pharmaceutical equivalents or pharmaceutical alternatives become available in the place of the action in case of introduction in identical molar dose in similar conditions in research with proper design;

7) original medicine – medicine with new active ingredient which was registered and placed by the first in the world pharmaceutical market, based on the file containing results of the complete preclinical (not clinical) and clinical trials confirming its safety, quality and efficiency;

8) the bioveyver procedure – the procedure according to which determination of equivalence of the reproduced medicine (generic) is carried out based on biopharmaceutical classification system and results of comparative researches out of organism (in-vitro) with testing use "Dissolution" and is applied to firm dosage forms of immediate release (1 and 3 class on biopharmaceutical classification system);

9) hybrid medicine – the medicine which is not falling under determination of the reproduced medicine in case of impossibility of confirmation of its bioequivalence by means of bioavailability researches and also if in this medicine there were changes of active ingredient (substances), indications to application, dosages, dosage form or way of introduction in comparison with original medicine;

10) homeopathic medicine – the medicine made on homeopathic technology with use of homeopathic raw materials according to requirements of pharmacopeias of the Republic of Kazakhstan and (or) the Eurasian Economic Union or in case of their absence according to requirements of homeopathic pharmacopeias;

11) medicine – the means representing or containing the substance or combination of substances coming into contact with human body, intended for treatment, prevention of diseases of the person or recovery, correction or change of its physiological functions by means of pharmacological, immunological or metabolic impact or for diagnosis of diseases and condition of the person;

12) the conclusion about safety, quality and efficiency of medicine – the document containing results of examination declared on state registration, re-registration or modification of the registration file of medicine;

13) irrational combination of composition of medicines – the composition of medicine which is not corresponding to expected pharmacological properties and action;

14) the instruction on medical application of medicine (leaf insert) – the document containing information for the consumer and accompanying medicine in packaging;

15) the regulating document on quality of medicine – the document establishing requirements to quality control of medicine during the post-registration period based on the carried-out expertize of medicine in case of its registration and containing the specification, the description of analytical techniques and testing of medicine or the reference to such testing, and also the corresponding eligibility criterions for quality indicators;

16) standard samples of medicinal substances and their impurity – the comparison substances used when conducting examination of examinees of medicines;

17) producer of medicines – the organization which is performing activities for production of medicines and having the license for production of medicines;

18) medicinal vegetable raw materials – the fresh or dried-up plants, seaweed, mushrooms or lichens or their parts, integral or crushed, used for production of medicines;

19) general characteristic of medicine - the document approved by authorized body in case of state registration of medicine, containing information for health workers on safe and effective use of medicine;

20) medicine with well studied medical application – medicine which active agent is well studied during medical application at the same time its efficiency and acceptable degree of safety confirmed with detailed bibliographic references to the published data on post-registration and (or) epidemiological researches are acknowledged and there passed at least 10 years from the date of the first systematic and documentary use of active ingredient (active ingredients) of this medicine;

21) medicines of the advanced therapy (further – LPPT) - the medicines of medical application which are medicines of gene therapy, therapy by somatic cages, tkaneinzhenerny medicines or the combined medicines for the advanced therapy;

22) immunological medicine (immunobiological medicine) – the medicine intended for forming of active or passive immunity or diagnostics of availability of immunity, or diagnostics (development) of the specific acquired change of the immunological answer to allergiziruyushchy substances;

23) the risk management plan – the detailed description of risk management system;

24) the periodic updated report on safety – the report of the holder of the registration certificate of medicine for certain period of time during the post-registration period provided for ratio assessment "advantage – risk" medicine;

25) the reproduced medicine (generic) – medicine which has the same quantitative and high-quality composition of active ingredients and the same dosage form, as original medicine and which bioequivalence to original medicine is confirmed by the corresponding researches of bioavailability. Different salts, ethers, isomers, mixes of isomers, complexes or derivatives of active ingredient are recognized the same active ingredient if their safety and efficiency significantly do not differ. Different dosage forms for intake with immediate release of substances are recognized within the bioavailability researches the same dosage form;

26) the countries of the region of the International conference on harmonization of technical requirements to registration of medicines for medical application (ICH) (АйСиЭйч) – the states which regulatory bodies are part of founders and permanent members of ICH (the country of the European Union, Great Britain, the United States of America, Japan, Switzerland, Canada) (further – the countries of the region of ICH (АйСиЭйч));

27) Advisory council of the state expert organization (further – Advisory council) – the collegiate organ created in the state expert organization for consideration of matters of argument in results of examination, the bases (reasons) of issue of the negative conclusions about safety, quality and efficiency of medicine or medical product and to acceptance of the final decision;

28) orphan (rare) medicine – the medicine intended for diagnostics, etiopatogenetichesky or pathogenetic treatment of orphan (rare) diseases which frequency does not exceed officially certain level in the Republic of Kazakhstan;

29) the production site – territorially isolated complex of the producer of medicines, medical products intended for accomplishment of all production process of medicines, medical products or its certain stages;

30) the applicant – the developer, the producer, the holder of the registration certificate or their authorized representative, authorized to submit the application, documents and materials and to perform the operations provided by the power of attorney of the principal on conducting examination in case of registration, re-registration and modification of the registration file of medicines;

31) radio pharmaceutical medicine – the medicine containing in condition, ready for application, one or several radionuclides (radioactive isotopes) as active ingredient or as a part of active ingredient;

32) reference medicine – medicine which is used as medicine of comparison and is standard by which are determined properties of medicine (are normalized);

33) strategically important medicines and medical products – the medicines and medical products intended for medical application in conditions:

military operations and liquidation of their effects;

origins, preventions and mitigations of consequences of emergency situations;

threats of origin, spread of new especially dangerous infectious diseases and liquidation of their effects;

prevention, diagnostics, treatment of the diseases and defeats received as a result of impact of adverse chemical, biological, radiation factors, and also liquidation of their effects;

absence or threat of lack of medicines or medical products in the markets of state members of the Eurasian Economic Union in the conditions of introduction of rationing economic arrangements concerning at least one of state members;

34) proper production practice – the component of system of quality assurance guaranteeing production and quality control of medicines according to standards according to their purpose and requirements of the registration file;

35) the registration file – the set of documents and materials of the established content represented to the statement for examination;

36) the holder of the registration certificate – the legal entity who is the resident or the nonresident of the Republic of Kazakhstan addressed to whom the registration certificate on medicine is issued;

37) modification of the registration file – the changes made by the applicant to the registration file during action of the registration certificate, which are not influencing negatively safety, quality and efficiency of medicine and subject to examination according to these rules;

38) pharmaceutical substance (active pharmaceutical substance) – the medicine intended for production and production of medicines;

39) equivalence research – research which determines equivalence between generic and original (reference) medicine when using researches in-vivo (in organism) and (or) in-vitro (out of organism);

40) medicinal vegetable medicine – the medicine containing in quality of active components exclusively medicinal vegetable raw materials and (or) medicines on its basis;

41) dosage – amount (content) of active ingredient in unit of dosage form, and also in unit of mass or medicine amount, significant for the correct identification and use of medicine;

42) authorized body in the field of health care (further – authorized body) – the central executive body performing management and cross-industry coordination in the field of protection of public health of the Republic of Kazakhstan, medical and pharmaceutical science, medical and pharmaceutical education, sanitary and epidemiologic wellbeing of the population, drug circulation and medical products, qualities of rendering medical services (help);

43) state body in the field of drug circulation and medical products (further – state body) – the state body performing management in the field of drug circulation and medical products, control of drug circulation and medical products;

44) the state expert organization in the field of drug circulation and medical products (further – the expert organization) – the subject of the state monopoly performing production economic activity in the field of health care on safety, efficiency and qualities of medicines and medical products.";

state Items 12 and 13 in the following edition:

"12. In case of examination of orphan medicines the applicant reports the research program which results are the basis for revaluation of ratio "advantage risk", with observance of use of medicine under strict observation of the doctor and immediate provision of maps messages about undesirable reactions, serious undesirable reactions and about lack of efficiency of medicine according to the order of the Minister of Health of the Republic of Kazakhstan of December 23, 2020 to No. KR DSM-320/2020 "About approval of rules of carrying out pharmakonadzor and monitoring of safety, quality and efficiency of medical products" (it is registered in the Register of state registration of regulatory legal acts at No. 21896).

13. The list of the main requirements to rendering the state service including characteristics of process, form, content and result of rendering and also other data taking into account features of provision of the state service is provided in the List of the main requirements to rendering the state service "Issue of the Conclusion about Safety, Quality and Efficiency of Medicines and Medical Products" according to appendix 5 to these rules.";

state Item 17 in the following edition:

"17. The state expert organization provides entering of data on stage of rendering the state service into information system of monitoring of rendering the state services according to the subitem 11) of Item 2 of article 5 of the Law and quarterly, no later than the 25th day of the first month of the next quarter, sends the relevant information to state body.

The authorized body sends information on the made changes and (or) additions to these rules to the operator of information and communication infrastructure of "the electronic government", the service provider and to Single contact center within three working days from the date of state registration in judicial authorities.";

state Item 19 in the following edition:

"19. Expertize is carried out with use of the information system integrated with the single database "Management System of Provision of Medicines" of the Unified information system of health care.

The applicant obtains information on procedure and the status of rendering the state service in the mode of remote access by means of "personal account" of information system, and also single contact – the center for questions of rendering the state services.

At the same time the applicant's term on provision of the answer and required materials on requests of the expert organization is estimated of signature date of the outgoing request certified by the electronic and digital signature.";

state Item 27 in the following edition:

"27. Specialized examination of medicine includes assessment of safety, quality and efficiency and ratio advantage risk of medicine based on the analysis and examination of data in documents of the registration file, the analysis of the report on results of pharmaceutical inspection in case of state registration, re-registration or modification of the registration file of medicines, and also assessment of rationality of combination of active ingredients as a part of medicine according to the List of irrational combinations of medicines according to appendix 9 to these rules.";

state Item 34 in the following edition:

"34. Laboratory researches of medicine are performed in test laboratories of the state expert organization for the purpose of confirmation of conformity of indicators of safety and quality of medicine and include:

1) the analysis of the analytical regulating document of medicine regarding techniques of carrying out testing;

2) laboratory testing on compliance to requirements of the regulating document for quality;

3) determination of reproducibility of analytical techniques of quality control.

Testing of samples of medicines with use of complex of physical and chemical, biological researches is directed to determination of quantitative and qualitative content acting and excipients, impurity, and also degree of biological safety (microbiological purity, toxicity, pyrogenicity).";

state Item 55 in the following edition:

"55. The state expert organization after modification of the instruction of original medicine or, in the absence of registration of original medicine in the Republic of Kazakhstan, in case of identification on the international sources and results of pharmakonadzor about changes in general characteristic of original medicine informs through information resources of all holders of registration certificates of generic medicines on need of entering of corresponding changes into the instruction on medical application (leaf insert) and general characteristic of medicine through the procedure of modification of the registration file within ninety calendar days after modification of the instruction of original medicine of information on safety from the date of placement of information on the website of the expert organization.

The holder of the registration certificate of original medicine makes changes to the instruction on medical application (leaf insert) and general characteristic of medicine based on the state expert organization of information on the discrepancies revealed as a result of pharmakonadzor and on official international sources within ninety calendar days from the date of placement of information on the website of the expert organization placed on information resource.

Holders of registration certificates submit the application for modification of the registration file within ninety calendar days from the date of placement of the harmonized information on the website of the expert organization for the registered medicines in general characteristic of medicine and the instruction on medical application of medicine (leaf insert) (further – OHLP and the Instruction of HP) medicines with the same international unlicensed name or with the same active ingredient.";

add with Items 65-1, 65-2, 65-3, 65-4, 65-5 of the following content:

"65-1. The holder of the registration certificate provides the declaration that in the OHLP projects and the Instruction of HP of the reproduced, hybrid or biosimilar (biosimilar) medicine there are no differences from the operating OHLP and the Instruction of HP of original (reference) medicine, except for differences of information on the producer, expiration date, composition of excipients and distinctions in bioavailability or pharmacokinetics.

65-2. The holder of the registration certificate provides line-by-line (located in parallel on one leaf) comparison of the operating OHLP and the Instruction of HP of original (reference) medicine and the OHLP projects and the Instruction of HP of the reproduced, hybrid or biosimilar (biosimilar) medicine with allocation and reasons for all differences.

65-3. The holder of the registration certificate in case of filing of application on modification of OHLP and Instructions of HP provides the sheet of changes with indication of line-by-line located comparison of the text of the made changes with the text of the approved version.

65-4. The expert organization initiates the procedure of reduction in compliance (harmonization) of information on the registered medicines in OHLP and the Instruction of HP of medicines with the same international unlicensed name or with the same active ingredient.

65-5. The holder of the registration certificate in case of development of OHLP and the Instruction of HP of the reproduced, hybrid or biosimilar (biosimilar) medicine in case of filing of application for examinations in case of registration, and also in case of re-registration and introduction of changes is guided (harmonized) information on OHLP and the Instruction of HP on the international unlicensed name or composition of the active ingredients posted on the website of the expert organization in the Kazakh and Russian languages brought into accord.";

state Item 68 in the following edition:

"68. Examination of medicine in case of modification of the registration file like ІА, type ІБ and type II with laboratory testing is carried out in time, not exceeding ninety calendar days, including:

1) initial examination of medicine – fifteen calendar days;

2) specialized examination – forty calendar days of calendar days, (including, confirmation of authenticity or transfer into Kazakh of OHLP and the Instruction of HP, prototypes of marking of packaging, labels, stickers);

3) laboratory researches – twenty five calendar days;

4) forming of the conclusion about safety, efficiency and quality – ten calendar days.";

add with Item 68-1 of the following content:

"68-1 Examination of medicine in case of modification of the registration file like IA which are not requiring assessment of safety, quality and efficiency and ratio advantage risk of medicine (specialized examination) is carried out in time, not exceeding thirty calendar days, including:

1) initial examination of medicine – ten calendar days;

2) forming of the conclusion about safety, efficiency and quality and confirmation of authenticity or transfer into Kazakh of general characteristic of medicine and the instruction on medical application (leaf insert), prototypes of marking of packaging, labels, stickers – twenty calendar days.";

3) of Item 72 to state the subitem in the following edition:

"3) time of the organization and conducting pharmaceutical inspection.

The applicant within 60 (sixty) calendar days from the date of receipt of the notification on need of conducting inspection provides the letter of consent;

Duration of the organization and conducting inspection of production does not exceed 120 (hundred twenty) calendar days from the date of receipt by the applicant of the notification on need of its carrying out.";

in the List of the provided materials of the registration file depending on medicine type, the approved appendix 4 to the above rules:

state Item 2 in the following edition:

"2. The reproduced medicine

For the reproduced medicines data of pharmaceutical development are represented in comparison with original or reference medicine.

For the proof of equivalence of generic with original (reference) medicine in the Module 5 of the OTD format or part IV of the List of the documents provided for examination by producers of the Republic of Kazakhstan (further – the List) in the registration file of generic results of researches according to the Rules of carrying out researches of bioequivalence of medicines within the Eurasian Economic Union approved by the Decision of Council of the Eurasian economic commission of November 3, 2016 No. 85 are reported.

In the Module 1 or Part I of the List the applicant provides the summary (to 5 pages) the reasons and the facts showing that medicine is the reproduced medicine of the corresponding original medicine. The specified summary contains information on medicine, its high-quality structure and quantitative content in it active agent, its dosage form and profile of safety and (or) efficiency of its active agent in comparison with active agent of original medicine, and also data on biological availability and bioequivalence of this medicine.";

in Item 5:

the second to state part in the following edition:

"For examination of biosimilar medicine data of comparative researches it with original (reference) biological medicine according to the Rules of carrying out researches of biological medicines within the Eurasian Economic Union approved by the Decision of Council of the Eurasian economic commission of November 3, 2016 No. 89 are provided.";

in Item 12:

3) to state the subitem in the following edition:

"3) the immediate notification of state body on any undesirable reactions which arose in case of use of orphan medicine, and the taken measures according to the order of the Minister of Health of the Republic of Kazakhstan of December 23, 2020 No. KR DSM-320/2020 "About approval of rules of carrying out pharmakonadzor and monitoring of safety, quality and efficiency of medical products" (it is registered in the Register of state registration of regulatory legal acts at No. 21896).";

1) of Item 17 to state the subitem in the following edition:

"1) the Accelerated examination of medicines is performed according to the decision of authorized body and carried out in cases:

purposes of medicines for prevention, treatment, diagnosis of rare diseases;

origins and elimination of effects of epidemic, pandemic of infectious diseases (the medicines of etiopatogenetichesky therapy applied in emergency situations in response to health hazards of the population (pandemic) and included in clinical protocols of treatment;

military operations and liquidation of their effects, origin, prevention and mitigation of consequences of emergency situations, threat of origin, spread of new especially dangerous infectious diseases and liquidation of their effects;

purposes of medicine, the foreign producer, for transfer of technologies on the production site in the territory of the Republic of Kazakhstan.";

in the Summary report of experts in medicine assessment approved by appendix 10 to the above rules:

state Item 35 in the following edition:

"1) the Short characteristic of system of pharmakonadzor of the holder of the registration certificate includes the following elements:

the proof that the holder of the registration certificate has at the order the authorized person for global pharmakonadzor the declaration signed by the holder of the registration certificate that it has system of pharmakonadzor for accomplishment of tasks and obligations on post-registration control of safety medicinal средств_________________________________________________

the reference to the place (address) where the master file of system of pharmakonadzor contact information of the authorized person for global pharmakonadzor is stored;

2) authorized (contact) person for pharmakonadzor in the Republic of Kazakhstan: the document confirming appointment of authorized (contact) person for pharmakonadzor in the Republic of Kazakhstan _______________

contact information of authorized (contact) person for pharmakonadzor in the Republic of Kazakhstan;

3) the Risk management plan in case of medical application of the medicine declared on registration (re-registration) or modification (for original medicines, biosimilyar, vaccines, blood medicines, to generic medicines of the requiring special control)

Note:

* noted Sections are filled in in case of re-registration

Conclusion:

positive negative (with reasons)

Receipt date of documents to the expert

Date of completion of examination of documents

All data provided in the expert opinion are authentic and conform to modern requirements that I confirm with the personal signature.

Head of the structural unit of _______ __________________

F.I.O'S signature (in case of its availability)

Expert of ________ __________________________

F.I.O'S signature (in case of its availability)

Date ______________";

appendix 2 to the specified Rules to be reworded as follows according to appendix 1 to this order;

appendix 3 to the specified Rules to be reworded as follows according to appendix 2 to this order;

appendices 5 to the specified Rules to be reworded as follows according to appendix 3 to this order;

appendix 18 to the specified Rules to be reworded as follows according to appendix 4 to this order;

in rules of conducting examination of the medical products approved by appendix 2 to the specified order:

state Item 1 in the following edition:

"1. These rules of conducting examination of medical products (further – Rules) are developed according to items 4 and the 10th Article 23 and Item 3 of article 239 of the Code of the Republic of Kazakhstan "About health of the people and health care system" (further – the Code), article 14 of the Law of the Republic of Kazakhstan "About the state services" (further – the Law) and determine procedure for conducting examination of medical products, including strategically important medical products (further – medical products), and also procedure for rendering the state service "Issue of the Conclusion about Safety, Quality and Efficiency of Medicines and Medical Products".";

state Item 6 in the following edition:

"6. In these rules the following terms and determinations are used:

1) medical products for in vitro of diagnostics of open type – medical products for diagnostics of in vitro which operation according to their functional purpose is possible when using reagents (reactants) of wide range of producers;

2) the software is medical product on condition of compliance to its all following criteria:

represents the computer program or its modules regardless of the used platform equipment room, and also methods of placement of the software and provision of access to it;

is not component of other medical product;

it is intended by the producer for delivery of health care;

the result of action of the software consists in interpretation in the automatic mode, including with use of technologies of artificial intelligence, or in the parameters set by the health worker influencing adoption of the clinical decisions, data set received from the medical products allowed to the address in accordance with the established procedure or entered by health workers for the purpose of delivery of health care;

3) consumable materials to the medical product in vitro of diagnostics of the closed type – the consumable materials providing its full functioning according to the set purpose and included in its komlektation for use with this medical product;

4) medical products for in vitro of diagnostics of the closed type – medical products for diagnostics of in vitro which operation according to their appointment is possible only when using special reagents (reactants) provided by the producer for this medical product and its modifications included in its picking;

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