Clinical trial documents in Russia face two reviews in 25 working days. What to align before you file them
The clinical trial (CT) protocol and the investigator’s brochure (IB) go through two reviews at once: an examination of documents at the expert institution (an organization to which the Ministry of Health of the Russian Federation assigns the examination of documents) and an ethical review by the Ethics Council (the body that assesses the ethical soundness of a trial). The patient information sheet (PIS, a document with information about the trial that the participant signs personally) is checked by the Ethics Council only. Both reviews see a discrepancy between the protocol and the IB, and the Ethics Council sees a discrepancy between these documents and the PIS.
Under Federal Law No. 61-FZ «On the Circulation of Medicines», both reviews together have up to 25 working days from the date the assignment is sent. A request from the Ministry of Health to clarify the information suspends the period for verifying the information, and the applicant has up to 90 working days to respond. Since 10 March 2026, documents are prepared under the new edition of the Rules of Good Clinical Practice (GCP) of the Eurasian Economic Union (EAEU), the GCP Rules, and since 28 December 2025 the PIS may be on paper or in electronic form.
Who reads each document
Clinical trials of medicinal products in Russia are conducted under the rules of good clinical practice approved by the Eurasian Economic Commission (EEC), as 61-FZ provides. The EEC approved these rules by Decision of the Council No. 79 of 3 November 2016 «On Approval of the Rules of Good Clinical Practice of the Eurasian Economic Union». The GCP Rules are based on the ICH E6 (R2) guideline of the International Council for Harmonisation. The numbering of the main sections matches the international guideline, except for the section with definitions, so almost any requirement can be checked against the English original.
61-FZ sets the list of documents for obtaining a trial authorization. The applicant submits the following through the unified portal or a personal account in the unified state healthcare information system (the unified system):
- an application signed with an enhanced qualified electronic signature;
- the protocol and the IB (for a product registered under EAEU rules, the IB may be replaced by the approved Summary of Product Characteristics (SmPC) if use in the trial does not contradict it);
- the PIS;
- information on the investigators’ work experience;
- a copy of the compulsory insurance contract stating the maximum number of patients;
- information on the composition of the product (except biological medicinal products);
- documents on the quality of the product manufactured for the trial, including a manufacturer’s document with quality indicators;
- information on preclinical safety and efficacy data that justify the use of the product, the routes of administration and the dosages (this requirement was introduced by Federal Law No. 324-FZ of 4 August 2026 and applies from 15 August 2026);
- information on the manufacturing licence or the manufacturer’s Good Manufacturing Practice (GMP) compliance conclusion.
Biological medicinal products also need the documents and information provided for by the EAEU rules for studies of biological medicinal products.
The expert institution was created as a federal state budgetary institution to support the powers of the Ministry of Health to issue trial authorizations and to register medicinal products. The work of the Ethics Council is regulated by 61-FZ. 61-FZ also divides the documents between the two bodies (Table 1).
Table 1. Which documents go to the expert institution and the Ethics Council
| Document | Expert institution | Ethics Council |
|---|---|---|
| Protocol | Yes | Yes |
| Investigator’s brochure | Yes | Yes |
| Patient information sheet | No | Yes |
| Information on investigators and the insurance contract | No | Yes |
| Composition of the product, quality documents, preclinical data | Yes | No |
Besides the Ethics Council, documents are assessed at the level of the trial site by the institutional review board (IRB), also called the independent ethics committee (IEC). The IRB/IEC reviews the protocol, the informed consent form, the IB, materials for patients, information on payments and the investigator’s CV. Before the trial starts, the investigator receives the IRB/IEC’s written, dated approval, and the sponsor does not supply the product to the site until it has received all the required documentation, including the approval of the IRB/IEC and of the authorized bodies. The protocol, the IB and the PIS go through two ethical assessments: the federal one by the Ethics Council and the local one by the IRB/IEC.
Clinical trial protocol
The protocol describes the objectives, design, methodology, statistical methods and organization of the trial. The GCP Rules set out the structure of the protocol: general information, rationale for the trial, objectives and tasks, design, selection and withdrawal of subjects, treatment, efficacy assessment, safety assessment and statistics. Part of the information may be placed in other documents to which the protocol refers, for example the IB. Information about a single site may be on separate pages or in an agreement with the site.
The summary of preclinical and clinical results is taken from the IB, and the description of known and potential risks and benefits is repeated later in the PIS. Randomization and blinding, together with the rules for breaking the code, determine what the patient is told about the chance of being assigned to a particular group. The non-inclusion criteria and the procedure for reporting adverse events rely on the IB data on the risks of the product, so they are checked against the IB.
The sponsor provides in the protocol or another agreement for the investigator’s duty to ensure direct access to source data for monitoring, audit, IRB/IEC review and inspections, and makes sure that each subject has agreed in writing to such access, so direct access is described in both the protocol and the PIS. The signatures of the investigator and the sponsor on the protocol, or a separate contract, confirm that the parties agree to conduct the trial under this protocol.
The new edition of the GCP Rules contains quality management requirements that concern the protocol. The protocol, case report forms (CRFs, the forms in which data on each subject are recorded) and other documents must be clear, concise and internally consistent, and unnecessary procedures and the collection of excess data are to be avoided. Already when developing the protocol, the sponsor identifies the processes and data that are significant for the protection of subjects and the reliability of results. Biostatisticians, clinical pharmacologists and physicians are involved in the development.
The sponsor itself chooses the monitoring strategy: on-site monitoring, a combination of on-site and centralized monitoring or, if justified, centralized monitoring only. The choice is justified in writing, for example in the monitoring plan. The plan describes the strategy, the allocation of duties and the methods, as well as control of the data and processes that are significant for the protection of subjects.
Investigator’s brochure and the definition of unexpected reactions
The investigator’s brochure contains a summary of the clinical and non-clinical data on the investigational product. Before signing the contract with the investigator, the sponsor gives the investigator the protocol and the current edition of the IB and allows time to study them. Under 61-FZ, the investigator and sub-investigators become familiar with the results of the preclinical studies from the IB and with the draft protocol, and under the GCP Rules the investigator studies the rules for using the product set out in the protocol, the current IB and the SmPC.
An adverse reaction is considered unexpected if its nature or severity is not consistent with the known information about the product: for an unregistered product this is the IB, for a registered product the instructions for medical use (package leaflet) or the SmPC. For all reactions that are both serious and unexpected, the sponsor informs all investigators, the IRB/IEC and the authorized bodies as soon as possible. The GCP Rules set the procedure and deadlines for these reports: no later than 7 calendar days from the date the information is received if the reaction led to death or was life-threatening, and no later than 15 calendar days in other cases. To decide whether a reaction was expected, the version of the IB that was in force on the date the reaction was identified is used.
The IB is updated as significant new information appears. If new data may adversely affect the safety of subjects, the sponsor immediately notifies all investigators and the authorized bodies. The investigator submits the new edition of the IB to the IRB/IEC. The IB is reviewed as planned at least once a year, and especially important new information is communicated to investigators, the IRB/IEC and the authorized bodies even before the new edition is issued. The title page of the IB gives the sponsor’s name, the product identifiers, the edition date, the version number, and the number and date of the previous edition.
If non-clinical data show an effect of the product on reproductive function, this is reflected in all three documents. The IB describes such data in the section on reproductive toxicity, the protocol enters them in the non-inclusion criteria, and the PIS includes them in the list of expected risks to the embryo, fetus or infant. Under 61-FZ, pregnant and breastfeeding women cannot be included in a trial unless the product is intended for them.
Patient information sheet and informed consent
The GCP Rules define informed consent as the process of voluntary confirmation of participation, documented by signing and dating the consent form. In 61-FZ, the information about the trial and the patient’s consent are combined in one document, the PIS. The patient or the patient’s legal representative confirms voluntary consent by signing this sheet.
Under Federal Law No. 504-FZ of 28 December 2025 (in force from 28 December 2025), the PIS may be drawn up on paper or as an electronic document. The patient or the patient’s legal representative signs an electronic PIS with an enhanced qualified, enhanced non-qualified or simple electronic signature through the unified identification and authentication system. A patient can also be informed in writing in two ways: on paper or in electronic form.
The PIS contains information from two lists. The GCP Rules list 20 items, which can be divided into six groups (Table 2).
Table 2. Information for the PIS under the GCP Rules
| Group | What is stated |
|---|---|
| Nature of the trial | Experimental nature, objective, experimental aspects, duration of participation, approximate number of subjects |
| Treatment and procedures | Treatment options and the probability of random assignment to a group, all trial procedures, including invasive ones, the subject’s duties |
| Risks and benefits | Expected risks and inconveniences and, where necessary, risk to the embryo, fetus or infant; expected benefit (if no medical benefit is expected, this is stated directly); alternative treatments with their benefits and risks |
| Financial terms | Compensation and treatment for harm to health, planned payments to the subject and the subject’s expenses |
| Rights and data | Voluntary participation and the right to leave the trial without penalty, direct access of monitors, auditors, the IRB/IEC and authorized bodies to source records, confidentiality |
| Communication and support | Timely information about new findings, contacts for questions and in case of harm to health, grounds for ending participation |
The second list is in 61-FZ. From it the PIS also includes the terms of compulsory life and health insurance and what the patient should do in the event of unforeseen effects of the product. The insurance terms are set in 61-FZ. The organization that received the authorization insures the risk of harm to the patient’s life and health at its own expense. The insurance payment for each patient is RUB 2,000,000 in case of death. In case of Group I, II and III disability it is RUB 1,500,000, RUB 1,000,000 and RUB 500,000 respectively, and for deterioration of health without disability it does not exceed RUB 300,000. The insurance contract cannot be shorter than the trial. A patient cannot take part without such a contract.
The text of the PIS must contain as few specialist terms as possible and must not, directly or indirectly, induce the subject to waive legal rights or release the investigator and the sponsor from liability for negligence. Before signing, the subject is given enough time and full answers to questions. The subject and the person who conducted the discussion sign and date the form before participation begins, and if the subject cannot read, an impartial witness attends the discussion. The signed copy is given to the subject before inclusion in the trial.
The IRB/IEC checks the amount and procedure of payments to prevent undue inducement of subjects. The amount of payments is set in proportion to participation and cannot depend only on whether the subject completes the trial. The methods, amount and procedure of payments are stated in the consent form.
Financial terms are set in the sponsor’s contract with the investigator (the medical organization). Under 61-FZ, such a contract is concluded by the organization that holds the authorization and the medical organization, and it states the terms and timelines of the trial, the total cost of the programme with the amount of payments to investigators and sub-investigators, and the form for submitting results to the Ministry of Health.
Children may take part only with voluntary consent in a PIS signed by parents or adoptive parents, and only in the cases listed in 61-FZ. The child, if able, signs and dates the consent form. Under 61-FZ, orphans and children without parental care, military personnel (with exceptions), law enforcement officers, persons in places of deprivation of liberty and persons in custody cannot be included in a trial.
What changed in the document set since 2025
Decision of the EEC Council No. 63 of 1 August 2025 restated the GCP Rules in a new edition. The Decision entered into force 180 calendar days after official publication, and the new edition applies from 10 March 2026. The basis remains the ICH E6 (R2) guideline. The Rules were supplemented with provisions on the risk-based approach and centralized monitoring, and the requirements for electronic records and essential documents were updated (Table 3).
Table 3. What changed in the GCP Rules and in 61-FZ
| Parameter | Before (GCP Rules before 10 March 2026) | After (new edition of the GCP Rules) |
|---|---|---|
| Definition of a clinical trial | A study was considered clinical if it met at least one condition: a strategy assigned in advance outside routine practice, the decision on the product is taken together with the decision to include the subject, additional diagnostic or monitoring procedures | Any study in humans to identify or confirm clinical and pharmacological effects, identify adverse reactions or study pharmacokinetics |
| Quality management | The sponsor was responsible for quality assurance and quality control systems with standard operating procedures (SOPs) | A quality management system covering all stages of the trial and based on risk assessment has been added |
| Monitoring | Sites were as a rule visited before the trial, during it and after it; monitoring without visits was allowed in exceptional cases | The general rule on visits is kept. The sponsor chooses on-site, combined or, if justified, centralized-only monitoring and documents the choice |
| Title page of the IB | Indicating the version number and the number and date of the previous edition was recommended | These details are mandatory |
| Notice of trial start | The sponsor informed the authorized body of the start of the trial as set by the law of the member state, and the list of essential documents included the sponsor’s notice of the start of the trial | The sponsor submits applications to the authorities before the trial starts. There is no sponsor duty to inform the authority of the start, and no such document in the list of essential documents. Under 61-FZ, the head of the medical organization reports the start of the trial to the Ministry of Health within 3 working days |
| Form of the PIS (61-FZ) | An electronic document signed by the patient with an enhanced qualified or simple electronic signature through the unified identification and authentication system | A paper document signed by the patient, or an electronic document with an enhanced qualified, enhanced non-qualified or simple electronic signature (61-FZ as amended by Federal Law No. 504-FZ of 28 December 2025, in force from 28 December 2025) |
Review periods and grounds for refusal
After the documents are submitted, the Ministry of Health checks within 3 working days that the information is complete and reliable and decides whether to order the reviews. The examination of documents and the ethical review take up to 25 working days from the date the assignments are sent, and the Ministry of Health spends another 3 working days assessing the conclusions and deciding whether to issue the authorization. Without requests, this comes to up to 31 working days.
If the information is incomplete or unreliable, the Ministry of Health sends a request for clarification. The applicant answers within 90 working days, and the verification period is suspended for that time. The reviews will be refused if the set of documents is incomplete, the applicant did not answer the request on time, the documents lack the exhaustive information required, or there is no proof that the state fee was paid.
How to change documents after submission
After submission, each type of change has its own approval procedure and its own deadline (Table 4).
Table 4. Approval and notification of changes
| What changes | What is approved and who is notified | Deadline |
|---|---|---|
| Protocol amendment | Sponsor’s agreement and prior written approval of the IRB/IEC, notice to the Ministry of Health in the established form | Decision of the Ministry of Health within 28 working days |
| Deviation to eliminate an immediate threat to subjects | Prior approval of the IRB/IEC is not required; a description of the deviation and its reasons is sent to the IRB/IEC, the sponsor and, if necessary, the authorized bodies | As soon as possible |
| New information added to the PIS | Approval of the IRB/IEC before the new edition is used, the subject is informed of the new information in good time, and this is documented | Before use begins; signed copies of the new editions are given to the subject |
| New safety data | The sponsor notifies all investigators and the authorized bodies, the investigator informs the IRB/IEC of changes that increase risk | Immediately; other safety information that changes the benefit-risk balance, within 15 calendar days |
| Clarifying data in the authorization | Request through the personal account with a justification | 28 working days |
The notice of an amendment to the Ministry of Health contains the name, number and date of the protocol, the date of the changes, information on the applicant and on the organization engaged in organizing the trial, the names and locations of the sites, the date and number of the authorization, and the changes themselves. To assess whether the changes are justified and how great the risk to patients is, the Ministry of Health may involve experts of the Ethics Council and the expert institution. If an amendment changes procedures or risks for the patient, this is new information that may affect the participant’s consent, and the PIS is supplemented.
What to do
Draw up a correspondence matrix before submitting the documents. List the figures that recur in several documents: doses and regimen, inclusion and non-inclusion criteria, risks, procedures and visits, insurance, payments. For each one, give the source document (the IB or the SmPC) and the places where it recurs in the protocol and the PIS. Return to the matrix before every amendment.
Write quality management into the protocol. Identify the processes and data that are significant for the protection of subjects and the reliability of results, involve a biostatistician and a clinical pharmacologist at the development stage, and justify the monitoring strategy in the monitoring plan.
Check the IB before it goes to investigators. Set a planned review at least once a year and make sure the title page shows the version number and the number and date of the previous edition. Check that the section on adverse reactions makes it possible to tell which reaction is unexpected. For a registered product, decide whether to submit the IB or the SmPC.
Prepare the PIS under the GCP Rules and 61-FZ and choose the format before submission. Check that the text contains information on insurance, payments, compensation for harm and direct access to source records. For the electronic format, decide in advance how the signed versions will be stored and who is responsible for the system. The GCP Rules set requirements for SOPs and for validation of electronic systems.
Set up the amendment process and bring SOPs and contracts into line with the new edition of the GCP Rules. Draw up a map of «change, whom to notify, by when» based on Table 4 and assign people responsible. Check that document templates and contracts with the sponsor, contract research organizations and sites match the edition of the Rules in force since 10 March 2026.
The protocol and the IB go through both reviews, the PIS is checked by the Ethics Council, and all three documents read as one description of the product. Discrepancies in figures and risks between them are removed before submission. After submission, a new edition of the PIS needs the approval of the IRB/IEC, and a protocol amendment needs both the approval of the IRB/IEC and the decision of the Ministry of Health within 28 working days.
Regulatory framework:
1. Federal Law No. 61-FZ of 12 April 2010 «On the Circulation of Medicines» (as amended on 4 August 2026)
2. Federal Law No. 504-FZ of 28 December 2025 (amendments to 61-FZ, in force from 28 December 2025)
3. Federal Law No. 324-FZ of 4 August 2026 (amendments to 61-FZ, in force from 15 August 2026)
4. Decision of the Council of the Eurasian Economic Commission No. 79 of 3 November 2016 «On Approval of the Rules of Good Clinical Practice of the Eurasian Economic Union» (as amended by Decision of the EEC Council No. 63 of 1 August 2025, in force from 10 March 2026)
5. For the «Before» column: Decision of the Council of the Eurasian Economic Commission No. 79 of 3 November 2016 before the amendments made by Decision No. 63 of 1 August 2025