ORDER OF THE MINISTRY OF HEALTH OF UKRAINE

of July 12, 2012 No. 523

About introduction of amendments to the order of the Ministry of Health of Ukraine of September 23, 2009 No. 690

According to Articles 7, 8 Laws of Ukraine "About medicines", the Directive of the European Parliament and Council 2001/20 / Є With of April 04, 2001 "About approach of the laws, bylaws and administrative provisions of gosudarstvchlen concerning implementation of proper clinical practice when carrying out clinical testing of medicines for the use by the person" (with changes), and also for the purpose of further enhancement and ordering of carrying out clinical testing of medicines ORDER:

1. Make changes to the Procedure for carrying out clinical testing of medicines and examination of materials of clinical testing approved by the order of the Ministry of Health of Ukraine of September 23, 2009 No. 690, registered on October 29, 2009 for No. 1010/17026, having been reworded as follows it which is applied the Ministry of Justice of Ukraine.

2. Make changes to the Standard regulations on the commissions on questions of ethics approved by the order of the Ministry of Health of Ukraine of September 23, 2009 No. 690, registered on October 29, 2009 for No. 1011/17027, having been reworded as follows it which is applied the Ministry of Justice of Ukraine.

3. To provide to the head of department of development of the pharmaceutical sector of industry of health care submission of this order in accordance with the established procedure on state registration in the Ministry of Justice of Ukraine.

4. To impose control over the implementation of this order on the deputy minister - the chief of staff of Bogachyov R. M.

5. The order becomes effective from the date of its official publication.

 

Approved by the Order of the Ministry of Health of Ukraine of September 23, 2009, No. 690

(in edition of the Order of the Ministry of Health of Ukraine of July 12, 2012 No. 523)

Procedure for carrying out clinical testing of medicines and examination of materials of clinical testing

І. General provisions

1.1. This Procedure ICH GCP, the international ethical principles of biomedical researches with involvement of the person and the ethical code of the doctor is developed according to Articles 3, of 44 Bases of the legislation of Ukraine on health care, Articles 7, 8 Laws of Ukraine "About medicines", the Law of Ukraine "About personal data protection", taking into account requirements of Directives of the European Parliament and Council 2001/20 / Є With of April 04, 2001, 2001/83 / Є With of November 06, 2001, Resolutions of the European Parliament and Council 1901/2006 of December 12, 2006 and 1902/2006 of December 20, 2006.

1.2. This Procedure establishes the main requirements to carrying out clinical testing of medicines which can be carried out with the assistance of patients (volunteers) according to the complete or reduced program, including to bioavailability/bioequivalence testing, and also the international multicenter clinical testing.

1.3. This Procedure extends to all types of clinical testing of medicines, except for not intervention researches and clinical researches which are conducted without participation of the pharmaceutical companies within research works.

This Procedure does not extend to all types of clinical testing of fabric and cellular transplants, including barreled cells of chordate (funic) blood.

1.4. Conducting examination of materials of clinical testing, and also carrying out clinical audit of clinical testing of medicines is assigned to GP "State Expert Centre of the Ministry of Health of Ukraine" (далееЦентр).

ІІ. Determination of terms

2.1. In this Procedure terms are used in such value:

multicenter clinical testing (research) - testing of medicine according to the single protocol of clinical testing which is carried out more than in one venue of research;

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;

bioequivalence - two medicines are considered bioequivalent if they are pharmaceutical equivalent or pharmaceutical alternative and if their bioavailability after introduction in the same molar dose are similar to such degree that effects of these medicines concerning efficiency and safety will be in essence identical;

close relatives - and legal value in cases, stipulated by the legislation has physical persons between which natural communication is based on origin one from another or from general ancestors. Close relatives are the husband/wife, parents, children, relatives brothers and sisters;

the brochure of the researcher - abstract statement of preclinical and clinical data on the researched medicine which matter for its studying on the person;

producer of medicine - the legal entity who performs at least one of medicine production phases, including packagings;

researched (the subject of research) - the patient (the healthy volunteer) who according to the operating procedure takes part in clinical testing;

the researched medicine - dosage form of active substance or placebo which is studied or used for comparison in clinical testing, including medicines on which the registration certificate is already issued, but they are used or produced (are constituted or packed) in a different way in comparison with the registered dosage form, or are used on the unregistered displays, or used for more information on the registered medicine form;

the researcher / соисследователь - the doctor who has sufficient professional training and experience of treatment of patients, knows rules of proper clinical practice and the corresponding regulatory legal acts. The researcher bears responsibility for carrying out in the place of research of clinical testing of medicine. If clinical testing is carried out by group of persons in certain venue of research, one of researchers is determined by the responsible head of research group and can be called the responsible researcher;

the file of the researched medicine - information concerning quality of each researched medicine, including medicines of comparison and placebo, and also supplied preclinical researches and the information on the previous clinical testing or clinical use of the researched medicine;

examination of materials of clinical testing - check, the analysis and assessment of materials of clinical testing of medicine for the purpose of preparation of the motivated conclusions concerning carrying out clinical testing / rather essential amendment;

health care institution (treatment-and-prophylactic institution) (further - LPZ) the legal entity of any pattern of ownership and form of business or its separate division which main objectives is ensuring medical attendance of the population on the basis of the corresponding license and professional activity of health (pharmaceutical) workers;

legal representatives are parents, adoptive parents, parents tutors, guardians, custodians, representatives of institutions who fulfill duties of guardians and custodians;

the applicant of clinical testing - physical person or legal entity (for example, the sponsor, the contractual research organization) which submits the application to the Center for receipt of the conclusion concerning carrying out clinical testing / rather essential amendment. The applicant, if he is not sponsor, can submit the application only in the presence of the order issued by the sponsor with accurately certain delegated powers;

the report on clinical testing - the results of clinical testing reported in writing and their analysis;

identification code researched / number - the unique identifier which is appropriated by the researcher to each subject of testing for ensuring its anonymity and is used instead of surname in materials of clinical testing;

individual registration form (further - IRF) - the printing, electronic or optical document intended for entering into it of all information provided by the protocol of clinical testing which is subject to transfer to the sponsor, concerning each researched;

the informed consent - the decision to take part in clinical testing which shall be constituted in writing, dated and is signed is accepted voluntarily after proper notification about nature of clinical testing, its value, influence and risk, is appropriately documentary drawn up by person who is capable to agree, or his legal representative (close relative); in exceptional cases, if it is insolvent to write the corresponding person, it can give oral assent in the presence of at least one witness who certifies the consent of the subject of research in the written informed consent;

clinical testing (research) of medicine - nauchnoissledovatelsky work which purpose is any research with the assistance of the person as the subject of research, intended for identification or confirmation clinical, pharmacokinetic, phracodynamic and/or other effects, including for studying of absorption, distribution, metabolism and removal of one or several medicines and/or identification of collateral reactions to one or several researched medicines for the purpose of assessment of its safety and/or efficiency;

clinical audit of clinical testing - the procedure of official check of materials (documents) of clinical testing by the Center, rooms, the equipment and equipping, records, systems of security guarantee, quality and other resources which are related to clinical testing and which can contain in lechebnoprofilaktichesky institution, laboratories, rooms of the sponsor or the kontraktnoissledovatelsky organization, etc.;

the commission concerning ethics in case of treatment-and-prophylactic institution (daleekomissiya concerning ethics) - independent body which is effective in case of health care institution (treatment-and-prophylactic institution) where clinical testing which includes medical/scientific specialists, persons of other specialties, the public representatives who exercise supervision of observance of the rights, safety, wellbeing of the researched patients (healthy volunteers), ethical and moral legal principles of performing clinical trial are carried out.

The commission on questions of ethics in case of health care institution (lechebnoprofilaktichesky institution) based on assessment ethical and moral legal principles approves carrying out clinical testing directly in the place of its carrying out which is located based on LPZ in case of which it is created and this commission is effective;

the contractual research organization - physical person or legal entity which within the agreement with the sponsor carries out one or more its functions (powers) in clinical testing and acts on the basis of the order issued by the sponsor with accurately certain delegated powers;

medicines - substances or their mixes of natural, synthetic or biotechnological origin which are applied to the prevention of pregnancy, prevention, diagnostics and treatment of diseases of people or change of condition and functions of organism;

the venue of testing (further - MPI) - the place where the main activities connected with clinical testing (inclusion of patients, treatment, observation, etc.) in treatment-and-prophylactic institution are directly carried out;

the monitor - person designated by the sponsor or the contractual research organization who controls carrying out clinical testing according to the protocol of clinical testing;

not intervention research - research in which medicines are appointed regular method according to the approved instruction on medical application. Involvement of the patient with certain method of treatment in the protocol of clinical trial is not provided previously in group, and prescription of medicine is dictated by modern practice and does not depend on the decision to include the patient in testing. Do not apply supplementary diagnostic or monitoring procedures concerning patients, and for the analysis of collected data use epidemiological methods;

unpredictable collateral reaction - collateral reaction, nature or weight of which is not approved with the available information on medicine (for example, with the brochure of the researcher for the unregistered medicine or with the instruction for medical application / the short characteristic for the registered medicine);

the patient (the healthy volunteer) - person who can be attracted as the medicine researched to clinical testing;

source medical documents - original documents, data and records (for example, medical records of inpatients, medical records of outpatients, laboratory records, service records, the diaries researched or questionnaires, magazines of issue of medicines, the printouts of devices verified and verified copies or disaggregations of soundtracks, microfiches, photographic negatives, microfilms or magnetic carriers, x-ray pictures, administrative documents, records which are stored in drugstore, laboratory and in department of tool diagnostics, persons who take part in clinical testing, etc.);

collateral reaction - within clinical testing of medicine (original/generic) or its studying on new use, especially if therapeutic doses of medicine are not established, it is necessary to carry all negative and unpredictable responses to introduction of medicine of any dose to collateral reactions to medicine. The term "response to medicine introduction" means that there is at least admissible reliability of cause and effect relationship between use of medicine and collateral reaction, that is the interrelation cannot be excluded.

Concerning the registered medicines this term means all negative or unpredictable reactions connected using medicine in regular doses for the purpose of prevention, diagnostics or treatment of diseases, renewal, adjustment or influence on physiologic functions;

by-effect - any adverse medical manifestation at researched which not necessarily has causal relationship using medicine. Any undesirable and unpredictable manifestation (including changes of laboratory data), symptom or disease which match on time using (researched) medicine irrespective of, it is connected with acceptance (researched) medicine can be by-effect or not;

the amendment to the protocol of clinical testing - the written description of changes or formal explanation of the text of the protocol of clinical testing;

the protocol of clinical testing - the document which describes tasks, methodology, procedures, statistical aspects and the organization of clinical testing, and also data which, as a rule, are earlier obtained concerning the researched medicine and reasons for clinical testing;

serious collateral reaction or serious by-effect - any adverse medical manifestation in case of use of medicine (irrespective of dosing) which leads to death; poses threat of life; requires hospitalization or prolongation of term of the existing hospitalization; results in long-term or considerable disability or disability, to congenital anomalies or malformations;

the sponsor - legal entity or physical person which bears responsibility for initiation and the organization of clinical testing of medicine and/or its financing;

the essential amendment to the protocol of clinical testing - the amendment to the protocol of clinical testing is considered essential if it can have significant effect on safety or physical or mental condition of the patient (the healthy volunteer) who takes part in clinical testing or to affect scientific value of research;

the authorized person on quality (producer) - the physical person designated by the producer which is responsible for guarantee that each series of medicine is made with respect for the basic principles of proper production practice, is checked according to specifications on medicine and grants permission for realization or for clinical trials of each series of medicine.

2.2. Other terms in this Procedure are used in the values given in Bases of the legislation of Ukraine on health care, the Law of Ukraine "About medicines", the Family code of Ukraine and other regulatory legal acts.

ІІІ. General principles of carrying out clinical testing

3.1. All clinical testing are carried out according to the international ethical principles with ensuring protection of the rights, safety and wellbeing of researched. Clinical testing can be carried out only if the expected advantage justifies risk.

3.2. Clinical testing of medicines are carried out for the purpose of establishment or confirmation of efficiency and harmlessness of medicine. They can be carried out to LPZ which are determined by the Central executive body in the field of health care (further - TsOIV), based on positive experimental testimony of materials concerning carrying out clinical testing which is provided by the Center (further - the Conclusion) and TsOIV affirms.

3.3. All persons who join carrying out clinical testing shall have proper education, professional training and experience for accomplishment of the functions and obligations connected with clinical testing.

3.4. The choice of researchers and LPZ is assigned to the sponsor. Requirements to researchers and LPZ are provided in the Section V of this Procedure.

The sponsor can delegate any or all the functions of the contractual research organization. At the same time the sponsor remains responsible for initiation and carrying out clinical testing and for information which was collected as a result of clinical testing.

3.5. All clinical testing begin after receipt of the positive Conclusion approved by TsOIV, and the protocol of the commission(s) on questions of ethics in case of LPZ where clinical testing concerning approval of this clinical testing which is the basis for its carrying out directly shall be carried out.

3.6. Ensuring confidentiality of documents which can identify person of researched is necessary condition for protection of the rights researched.

3.7. Planning, carrying out and the reporting of all clinical testing, including researches on bioequivalence assessment, are performed with observance of requirements and the principles of Proper clinical practice (GCP).

3.8. If the researched medicine belongs to drugs, psychotropic substances or precursors, carrying out clinical testing is performed also with observance of requirements of the legislation on drugs, psychotropic substances and precursors.

3.9. For quality assurance of all aspects of clinical testing the system of certain procedures is used.

3.10. Registration, processing and preserving information obtained during clinical testing shall provide correct provision, interpretation and verification of data.

The list of the main documents of clinical testing which are stored in the LPZ/venue of testing and at the sponsor is given in appendix 1 to this Procedure, this documents shall be stored at least 15 years after completion of clinical testing in the archive room.

3.11. Production and preserving the researched medicine, and also the treatment of him are performed in the procedure established by the legislation with observance of requirements of the Proper production practice (GMP) and Proper clinical practice (GCP).

The main requirements to marking of the researched medicine are provided in the Section VI of this Procedure. The researched medicine is used only according to the approved protocol of clinical testing.

3.12. At any stage of clinical testing or after its completion the Center can book clinical audit of clinical testing according to the Section X ІІІ this Procedure.

ІV. Main requirements to protection of researched

1. General provisions about protection of researched

1.1. Protection of researched is provided by ratio assessment risk/advantage as before carrying out each clinical testing, including based on the previous conducted researches, and during its carrying out by observation from the Center and the commissions on questions of ethics in case of LPZ.

1.2. Special protection of patients who are insolvent to give the informed consent on participation in clinical testing is provided. Such patients do not join in clinical trial if it can be carried out with the assistance of persons who are capable to provide the informed consent personally.

Patients who are insolvent to give the informed consent join in clinical testing only when there are bases to expect that use of the researched medicine will bring direct benefit to the patient and it exceeds risk.

In cases when patients who owing to the clinical condition are insolvent to give personally the informed consent are involved in clinical testing, it is necessary to receive the informed consent of the legal representative, and in case of its absence - close relatives. In the protocol of clinical trial or in the amendment to it the procedure of receipt of the informed consent of the patient shall be described after it renews opportunity personally to give the informed consent.

1.3. Clinical testing can be carried out in case:

1.3.1 the expected risk and inconveniences were weighed concerning the expected advantage for researched (patients / healthy volunteers);

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