Chapter 7. Clinical Trials of Medicinal Products for Medical use, Clinical Trial Contract, Rights of Patients Involved in Trials

Table of contents

Chapter 1. General Provisions (articles 1-4)
Chapter 2. Powers of Federal Executive Bodies and Executive Bodies of Constituent Entities of Russian Federation with Respect to Circulation of Medicines (articles 5-6)
Chapter 3. State Pharmacopeia (article 7)
Chapter 4. State Control over Circulation of Medicines (articles 8-9)
Chapter 5. Development, Preclinical testing of Medicines and Clinical Trials of Medicinal Products for Veterinary Use (articles 10-12)
Chapter 6. Performance of State Registration of Medicinal Products (articles 13-37)
Chapter 7. Clinical Trials of Medicinal Products for Medical use, Clinical Trial Contract, Rights of Patients Involved in Trials (articles 38-44)
Chapter 8. Manufacture and Marking of Medicines (articles 45-46)
Chapter 9. Import of Medicines into the Russian Federation and Export of Medicines from the Russian Federation (articles 47-51)
Chapter 10. Pharmaceutical Activity (articles 52-58)
Chapter 11. Destruction of Medicines (article 59)
Chapter 12. State Regulation of Prices for Medicinal Products for Medical Use (articles 60-63)
Chapter 13. Safety Monitoring of Medicinal Products Being in Circulation in the Russian Federation (articles 64-66)
Chapter 14. Information on Medicinal Products (article 67)
Chapter 15. Liability for Violation of Legislation of the Russian Federation for Medicines Circulation and Compensation for Harm to Human Health Caused by Administration of Med (articles 68-69)
Chapter 16. Final Provisions (articles 70-71)

Article 38. Clinical Trials of Medicinal Products for Medical Use

1. Clinical trials of medicinal products for medical use, including international multicentre, multicentre, post-registration trial shall be conducted for the purpose of state registration of medicinal products and for any other purposes on one or more medical institutions as required by goods clinical practice approved by the authorized federal executive body for the following purposes:

1) to establish safety and/or tolerance of medicinal products for healthy volunteers, except for the trials of medicinal products manufactured outside the Russian Federation;
2) to select optimal dosages of medicinal product and course of treatment for patients with specific disease, optimal dosages and vaccination schemes of immunobiological medicinal products for healthy volunteers;
3) to establish safety and efficacy of a medicinal product for patients with specific disease, prophylactic efficacy for immunobiological medicinal products for healthy volunteers;
4) to study the possibility to widen the indication for medical use and identify earlier unknown side effects of registered medicinal products.

2. Generic medicinal products intended for medical use are subject to trials for bioequivalence and/or therapeutic equivalence in the procedure established by the authorized federal executive body.

3. Clinical trials of a medicinal product for medical use may be organized by:

1) developer of the medicinal product or by a person authorized by the developer;
2) educational institutions of higher and/or additional professional education;
3) research centres.

4. Clinical trials of medicinal products for medical use shall be conducted in the procedure prescribed by Articles 20 - 22 of this Federal Law under the permit to conduct the clinical trial of the medicinal product issued by the authorized federal executive body for the purposes specified in
Clause 1 of this Article. The authorized federal executive body shall maintain a register of issued permits to conduct clinical trials of medicinal products indicating the purpose or purposes thereof in the procedure established by such body.

5. In the event of state registration of a medicinal product, the state duty for expert examination of the documents required for obtaining permits to conduct clinical trials of a medicinal product for medical use and ethical expert examination, when an application is filed for state registration of the medicinal product for the purpose or purposes referred to in Clause 1 of this Article, shall be paid once.

6. The developer of a medicinal product may involve legal entities of any form of incorporation to organization of clinical trials of a medicinal product for medical use provided that these trials comply with the requirements of this Federal Law.

7. Clinical trials of medicinal products for medical use shall be carried out in medical institutions accredited by the authorized federal executive body in the manner prescribed by the Government of the Russian Federation.

8. The list of medical institutions entitled to conduct clinical trials of medicinal products for medical use and the register of issued permits to conduct clinical trials of medicinal products shall duly be published and placed on the official web-site by the authorized federal executive body.

Article 39.  International Multicentre Clinical Trial of Medicinal Product for Medical Use or Post-registration Clinical Trial of Medicinal Product for Medical use

1. An international multicentre clinical trial of a medicinal product for medical use in the Russian Federation or a post-registration clinical trial of a medicinal product for medical use shall be carried out under a permit to conduct a clinical trial of the medicinal product issued by the authorized federal executive body upon the results of the expert examination of the documents required for obtaining a permit to conduct an international multicentre clinical trial of the medicinal product or post-registration clinical trial of the medicinal product and ethical expert examination.

2. To obtain a permit to conduct an international multicentre clinical trial of a medicinal product for medical use or a post-registration clinical trial of a medicinal product for medical use, the applicant shall submit to the authorized federal executive body:

1) application for obtaining a permit to conduct an international multicenter clinical trial of a medicinal product for medical use or a post-registration clinical trial of a medicinal product for medical use;
2) documentary proof to confirm payment of the state duty for issuance of a permit to conduct an international multicentre clinical trial of a medicinal product for medical use, or the state duty for issuance of a permit to conduct a post-registration clinical trial of a medicinal product for medical use;
3) report on preclinical testing of the medicine and a report on earlier clinical trials of the medicinal product for medical use (if any);
4) clinical trial draft protocol for the medicinal product for medical use;
5) investigator's brochure;
6) information sheets of the patients enrolled in the clinical trials of the medicinal product for medical use;
7) data about the investigators’ work experience in the relevant specializations and their clinical trial experience;

7¹) the details of medical organizations which are scheduled to conduct clinical trial of medicinal product for medical use (full and brief names of medical institution, legal form of medical institution, the seat and business location of medical institution, telephone, telefax, email address);
(as amended by Federal Law of November 29, 2010, No. 313-FZ)
7²) estimated terms of the clinical trial of the medicinal product for medical use;
(sub-clauses 7² introduced by Federal Laws of October 11, 2010, No. 271-FZ)

8) the copy of contract of compulsory insurance, made in accordance to the standard rules for compulsory insurance, with specifying the maximal number of patients involved in clinical trial of medicinal products for medical use;
(as amended by Federal Law of November 29, 2010, No. 313-FZ)
9) composition of the medicinal product required for obtaining a permit to conduct an international multicentre clinical trial of the medicinal product for medical use;
10) the document created by manufacturer of the medicinal product, which contains data on parameters (qualitative indicators) of the medicinal product for medical use, produced for conducting of clinical trials.
(as amended by Federal Law of November 29, 2010, No. 313-FZ)

3. In the period not longer than five business days on filing the application referred to in Sub-clause 1, Clause 2 of this Article and the appropriate documents, the authorized federal executive body shall:

1) check the data contained in the applicant’s documents for completeness and accuracy;
2) make a decision on expert examination of the documents to issue a permit to conduct an international multicentre clinical trial of the medicinal product for medical use or a post-registration clinical trial of the medicinal product for medical use and ethical expert examination, or on rejection of such expert examinations;
3) notify the applicant of the decision in writing or, in the event of rejection, indicate the reasons of such rejection.

4. Failure to submit a full package of documents prescribed in Clause 2 of this Article, or lack of sufficient list of appropriate details or information to be presented in the documents shall be a reason for rejection of expert examination of the documents required for issuance of a permit to conduct an international multicentre clinical trial of a medicinal product for medical use or a post-registration clinical trial of a medicinal product for medical use and ethical expert examination.

5. Expert examination of the documents required for obtaining a permit to conduct an international multicentre clinical trial of a medicinal product for medical use or a post-registration clinical trial of a medicinal product for medical use and ethical expert examination, and issuance of a permit to conduct an international multicentre clinical trial of medicinal product for medical use or a post-registration clinical trial of medicinal product for medical use shall be performed in the procedure established in articles 20 - 22 of this Federal Law.

6. Decision on rejection of expert examination of the documents required for obtaining a permit to conduct an international multicentre clinical trial of a medicinal product for medical use or a post-registration clinical trial of a medicinal product for medical use and ethical expert examination and on rejection of issuance of a permit to conduct an international multicentre clinical trial of a medicinal product for medical use or a post-registration clinical trial of medicinal product for medical use may be appealed in the manner prescribed by the laws of the Russian Federation.

Article 40. Procedure for Clinical Trial of Medicinal Product for Medical use

1. The head of the medical institution conducting a clinical trial of a medicinal product for medical use shall appoint an investigator responsible for the clinical trial of the medicinal product for medical use, which investigator shall have a medical qualification corresponding to the clinical trial of the medicinal product to be conducted, with at least five-year experience on programs of clinical trials of medicinal products, and at his/her suggestion appoint fellow investigators from among of the physicians of this medical institution.

2. The investigator shall select patients who may be enrolled in the clinical trials of that medicinal product for medical use based on the medical indications.

3. The investigator and co- investigators shall be familiarized with the results of the non-clinical trial of the medicine contained in the investigator’s brochure, a clinical trial draft protocol of the medicinal product for medical use prepared by the developer of the medicinal product or any other legal entity engaged in organization of the clinical trial of the medicinal product for medical use, and with other materials of the clinical trial.

3¹. Within not later than three business days on the start of the clinical trial of a medicinal product for medical use the head of the medical institution shall notify the the authorized federal executive body, which issued the permit to conduct such clinical trial about this according to the prescribed form.
(clause 3¹ introduced amended by Federal Law of November 29, 2010, No. 313-FZ)

4. The institutions that organize a clinical trial of the medicinal product for medical use and referred to in Clause 3, Article 38 of this Federal Law, shall, if the draft protocol of the clinical trial of the medicinal product for medical use needs to be amended, notify the authorized federal executive body, which issued the permit to conduct such clinical trial, according to the prescribed form.
(as amended by Federal Law of October 11, 2010, No. 271-FZ)

4¹. The form of notice of on amending the protocol of the clinical trial of the medicinal product for medical use should contain the following data:

1) the name, ID number and the date of the protocol of the clinical trial;
2) the date of amendments to the protocol of the clinical trial;
3) the name and location of the applicant;
4) the name of organization involved by the developer of the medicinal product for medical use to arrange the conducting of the clinical trial (if any);
5) the names and locations of medical center for conducting of the clinical trial of the medicinal product  for medical use;
6) date of issue of permit for the conduct of the clinical trial and the number of the permit;
7) the amendments to the protocol of the clinical trial.
(clause 4¹ introduced by Federal Laws of October 11, 2010, No. 271-FZ)

5. Within thirty business days of receipt of the notice referred to in Clause 4 of this Article, the authorized federal executive body shall review this notice in the procedure which has established and make a decision on amending the draft protocol of the clinical trial of the medicinal product for medical use or on rejection of such amendment.

6. A clinical trial of a medicinal product for medical use may be suspended or terminated if proving a danger to the patients' health and life while in progress. In the event of a danger to the life or health of the patient involved in the clinical trial of a medicinal product for medical use, the investigators shall notify the head of the medical institution and/or the institution, which obtained a permit from the authorized federal executive body to organize a clinical trial of the medicinal product. A decision to suspend a clinical trial of a medicinal product for medical use shall be made by the head of the medical institution and/or the institution, which obtained a permit from the authorized federal executive body to organize a clinical trial of the medicinal product. A decision on termination of such trial shall be made by the authorized federal executive body on the basis of the written notice received form the head of the medical institution or institution, which obtained a permit from the authorized federal executive body to organize a clinical trial of the medicinal product for medical use.

7. Within not later than five business days on completion, suspension or termination of the clinical trial of the medicinal product for medical use, the notice of the same shall be forwarded to the institutions refereed to in Clause 3, Article 38 of this Federal Law, and to the authorized federal executive body according to the prescribed form.

8. The form of notice of completion, suspension or termination of the clinical trial of the medicinal product for medical use shall include:

1) information about the medical institution(s) which has/have conducted this trial;
2) trial description;
3) investigator’s details (full name, place or employment, position, qualification, experience on programs of clinical trials of medicinal products, and list of clinical trials of medicinal products in which he/she participated (when) as an investigator or a co-investigator);
(as amended by Federal Law of October 11, 2010, No. 271-FZ)
4) trial results (trial completion/suspension/termination indicating their reasons and the effect on the reasons on the results assessment, risk assessment and anticipated benefit from the use of the medicinal product under investigation, as well as further supposed actions).

9. The authorized federal executive body shall publish and place on its official website a notice of completion, suspension or termination of the clinical trial of the medicinal product for medical use within five business days on its duly receipt.

10. The authorized federal executive body shall maintain a register of investigators who are conducting or conducted clinical trials of medicinal products for medical use in accordance with the rules approved by such body and duly place the register on its official web-site. Such register shall contain data as provided for in Sub-clause 3 of Clause 8 of this Article.

11. The institution mentioned in Clause 3 of Article 38 of this Federal Law shall prepare a report on the findings of clinical trial of a medicinal product for medical use on the basis of conclusions of the medical institutions involved in this trial, and submit it to the authorized federal executive body, which issued a permit to conduct the trial, within three months on the trial completion, suspension or termination in accordance with the procedure established by the authorized federal executive body.

12. Failure to follow good clinical practice, falsification of clinical trial results of a medicinal product for medical use shall entail liability as prescribed by the laws of the Russian Federation.

13. When conducting a clinical trial of a medicinal product for medical use, biological sampling in patients is permitted (biologic fluids, tissues, secretion and waste products, physiologic and pathologic discharge, smears, scrapes, washouts, microorganisms, bioptic materials) for study of the samples inside and/or outside the Russian Federation

14. The procedure for import into the Russian Federation and export outside the Russian Federation of biological materials obtained in a clinical trial of a medicinal product for medical use shall be established by the Government of the Russian Federation.

Article 41.  Contract for Clinical Trial of Medicinal Product for Medical Use

1. A clinical trial of a medicinal product for medical use shall be conducted in accordance with the contract for the clinical trial of the medicinal product for medical use to be concluded between the institution which obtained a permit from the authorized federal executive body for organization of such trial and medical institution conducting the clinical trial of the medicinal product.

2. A contract for a clinical trial of a medicinal product for medical use shall:

1) prescribe trial terms and conditions,
2) determine the total cost of the trial program indicating the amount to be paid to the investigators and co-investigators; and
3) determine the form in which the trail results are to be presented to the authorized federal executive body.

Article 42.  Finance Support of Clinical Trial of Medicinal Product for Medical Use

A clinical trial of a medicinal product for medical use shall be financed by:

1) federal funds,
2) funds of the institutions which have obtained a permit to conduct this trial, in accordance with the terms and conditions of the trial contract; and
3) other sources not prohibited by the laws of the Russian Federation.

Article 43.  Rights of Patients Involved in Clinical Trial of Medicinal Product for Medical Use

1. Participation of patients in a clinical trial of a medicinal product for medical use shall be voluntary.

2. The patient or his/her legal representative shall be informed in writing of the following:

1) medicinal product for medical use and the nature of the clinical trial of this medicinal product;
2) safety, anticipated efficacy of the medicinal product for medical use, and the degree of risk for the patient;
3) conditions of the patient’s participation in the clinical trial of the medicinal product for medical use;
4) objective(s) and duration of the clinical trial of the medicinal product for medical use;
5) patient's actions in the event of unforeseen effects of the medicinal product for medical use on the patient’s health;
6) terms and conditions of compulsory life and health insurance for the patient;
7) guarantees of confidentiality for the patient’s participation in the clinical trial of the medicinal product for medical use.

3. The patient’s voluntary consent to participate in the clinical trial of a medicinal product for medical use shall be confirmed by his/her signature or signature of his/her legal representative on the patient information sheet.

4. The patient, or his legal representative, may withdraw from the clinical trial of a medicinal product for medical use at any stage of such trial.

5. A clinical trial of medicinal product for medical use with participation of children as patients shall only be permitted with written consent of their parents/adoptive parents. Children may only be considered as potential patients of such trial if the trial is required for promotion of children’s health or prophylaxis of infectious diseases in childhood, or where the objective of a clinical trial is to obtain data on the best dosage of medicinal product for treatment of children. In such cases the trial shall be preceded by a clinical trial of the medicinal product for medical use in adults.

6. It shall be prohibited to conduct a clinical trial of medicinal product for medical use in the following patients:

1) orphaned children/children without parental care;
2) pregnant and nursing women, except for clinical trials conducted on a medicinal product designed for said women where the information sought may only be obtained in respective clinical trials of medicinal products and when all the appropriate measures have been taken in order to exclude any risk of harm to the pregnant or nursing woman, the foetus or the baby;
3) military personnel, except where a clinical trial of a medicinal product specially designed for use in military operations, emergency situations, prophylaxis and treatment of diseases and damages resulting from the exposure to unfavourable chemical, biological or radiation factors. A clinical trial of such medicinal products may be conducted with participation of military personnel as patients, except for military personnel doing call-up military service, in accordance with the requirements established by this Federal Law with respect to civilians;
4) law enforcement personnel; and
5) individuals serving sentences at places of confinement, or individuals in custody at detention facilities.

7. It is allowed to conduct a clinical trial of a medicinal product for medical use designed for treatment of mental disorders in individuals with mental disorders recognized as disabled in accordance with the laws of the Russian Federation. A clinical trial of a medicinal product in this case shall be conducted subject to consent in writing having been given by legal representatives of said individuals.

Article 44.  Compulsory Insurance of Life and Health of the Patient Involved in Clinical Trial of Medicinal Product for Medical Use

1. The institution which has obtained a permit for organization of a clinical trial of a medicinal product for medical use shall insure the life and health of the patient involved in a clinical trial of a medicinal product at its own expense as an insurant by making a contract for compulsory insurance .

2. The object of compulsory insurance shall be the patient’s property interest connected with harm caused to the patient’s life or health as a result of a clinical trial of a medicinal product for medical use.

3. An insurance event under a compulsory insurance contract shall be the patient’s death or health impairment, including health impairment entailing disability in case of a cause-and-effect relationship between the occurring events and participation of this present in clinical trial of medicinal product.

4. Claims for compensation of harm caused to the patient’s life or health shall be satisfied within the limitation period established by the civil legislation.

5. The extent of benefits under a compulsory insurance contract shall be as follows:

1) in case of patient’s death - RUR Two million for each patient who participated in the clinical trial of the medicinal product;
2) in case of patient’s health impairment:

a) which caused first class disability - RUR One million five hundred thousand for each patient involved in clinical trial of a medicinal product;
b) which caused second class disability - one million roubles for each patient involved in clinical trials of a medicinal product;
c) which caused third class disability - RUR Five hundred thousand for each patient involved in clinical trials of a medicinal product;
d) which did not cause disability - not more than RUR Three hundred thousand for each patient involved in clinical trial of a medicinal product.

6. The extent of benefits may be increased by a court decision.

7. The term of a compulsory insurance contract shall not be less than the term of the clinical trial of a medicinal product.

8. Terms and conditions of contract of compulsory insurance, including insurance rates of compulsory insurance, the list of documents required to enable payment of benefits, the procedure of individual identification code of a patient, the procedure of informing the insurer by the insurant of the number of patients involved in clinical trial of the medicinal product for medical use, the procedure for the payment of the insurance premium, the procedure for exercising the parties' rights and obligations prescribed by by this Federal Law and other federal laws under the contract of compulsory insurance shall be established by standard rules for compulsory insurance.

9. If harm is caused to the life of a patient involved in clinical trials of a medicinal product, the beneficiary under the compulsory insurance contract shall be people entitled to compensation for harm in the event of death of the breadwinner in accordance with the civil legislation; if there are no such people, the beneficiary will be the parents, spouse, children of the deceased patient involved in clinical trials of the medicinal product; if the deceased patient involved in clinical trials of a medicinal product had been dependent, the beneficiary will be people on whom he/she depended; compensation for funeral expenses on the patient involved in clinical trials of a medicinal product will be paid to the person who has incurred such expenses.

10. Benefits for compensation of harm caused to the life of a patient involved in clinical trials of a medicinal product shall be distributed among the beneficiaries in proportion to their number in equal shares.

11. In case of an insurance event with the patient involved in clinical trial of a medicinal product, the beneficiary shall have the right to claim immediately to the insurer for compensation of the harm caused. The insurer shall pay benefits within thirty days on receipt of the appropriate documents. The patient involved in clinical trial of a medicinal product or the beneficiary shall be obliged to provide the insurer with the patient's identification code required to enable payment of benefits, established by the insurer in accordance to the standard rules for compulsory insurance.

12. Until the extent of harm to be indemnified is determined in full, the insurer may, on request of the patient involved in clinical trials of a medicinal product, or on request of the beneficiary, pay part of the insurance benefits corresponding to the actually determined part of the harm caused.

13. Benefits under the compulsory insurance contract shall be paid irrespective of any benefits payable on any other type of insurance.

14. The participation of a patient in a clinical trial of medicinal product without the contract of compulsory insurance shall be prohibited.

15. The federal executive body issuing permits to conduct clinical trials of a medicinal product for medical use shall control to make sure the institution, which has obtained a permit to conduct clinical trials of a medicinal product, for medical, fulfills its obligation on compulsory life and health insurance of a patient involved in clinical trials of medicinal product for medical use as stated in this Article. (as amended by Federal Law of November 29, 2010, No. 313-FZ)

Table of contents

Chapter 1. General Provisions (articles 1-4)
Chapter 2. Powers of Federal Executive Bodies and Executive Bodies of Constituent Entities of Russian Federation with Respect to Circulation of Medicines (articles 5-6)
Chapter 3. State Pharmacopeia (article 7)
Chapter 4. State Control over Circulation of Medicines (articles 8-9)
Chapter 5. Development, Preclinical testing of Medicines and Clinical Trials of Medicinal Products for Veterinary Use (articles 10-12)
Chapter 6. Performance of State Registration of Medicinal Products (articles 13-37)
Chapter 7. Clinical Trials of Medicinal Products for Medical use, Clinical Trial Contract, Rights of Patients Involved in Trials (articles 38-44)
Chapter 8. Manufacture and Marking of Medicines (articles 45-46)
Chapter 9. Import of Medicines into the Russian Federation and Export of Medicines from the Russian Federation (articles 47-51)
Chapter 10. Pharmaceutical Activity (articles 52-58)
Chapter 11. Destruction of Medicines (article 59)
Chapter 12. State Regulation of Prices for Medicinal Products for Medical Use (articles 60-63)
Chapter 13. Safety Monitoring of Medicinal Products Being in Circulation in the Russian Federation (articles 64-66)
Chapter 14. Information on Medicinal Products (article 67)
Chapter 15. Liability for Violation of Legislation of the Russian Federation for Medicines Circulation and Compensation for Harm to Human Health Caused by Administration of Med (articles 68-69)
Chapter 16. Final Provisions (articles 70-71)