Bioequivalence study timeline

What the timeline consists of

A bioequivalence study has no single timeline: it depends on the product, the protocol and how ready the documents are. But the stages are always the same. Below is what each includes and which time limits are set by law.

Preparation and feasibility. The sponsor prepares the protocol; the clinic assesses whether it can be carried out: inclusion criteria, the sampling schedule, realistic recruitment rates. More in feasibility assessment.
Permit and ethics review. The Ministry of Health issues a permit after an expert review of the documents and an ethics review by the Ethics Council. The law limits the expert review of the documents and the ethics review to 25 working days (Article 39, Part 6); in addition, the Ministry checks the documents submitted for up to three working days (Part 3) and decides on the permit within up to three working days after the opinions (Part 7). If the material is insufficient, the Ethics Council sends the applicant a request (an expert may not request materials directly); the applicant has up to 90 working days to answer, and that time is not part of the ethics review period (Article 39.1, Parts 4.1–4.2). Changes to a protocol are decided within 28 working days (Article 40, Parts 4–5).
Recruitment and screening. Candidates can be lined up in advance, but people may be enrolled only after the ethics committee’s written approval (EAEU GCP Rules, clauses 3.3.6 and 4.4.1); informed consent is signed before participation begins (clause 4.8.8). Physicians examine candidates and check the protocol criteria. The head of the organisation notifies the Ministry of Health of the start within no more than three working days (Article 40, Part 3.1).
Clinical phase. Volunteers receive the products in periods separated by a break for elimination of the substance (by the start of the next period the substance should no longer be detectable; five half-lives is usually enough, clause 15 of the EAEU Rules). For example, with a half-life of 10 hours, five half-lives is 50 hours, a little over two days. Blood samples are taken to a schedule during the dosing periods.
Bioanalysis of samples. The concentration of the substance is measured in the samples with a validated method. This is a separate stage with its own schedule: it is carried out by an analytical laboratory, whose provider is agreed in the project.
Statistics and report. The measures and confidence intervals are calculated and the report is written: it is signed by the investigator and follows the structure of Annex 7 to the EAEU Rules (clause 116).

What lengthens a project

An incomplete package of documents or additional requests from the Ethics Council.
Slow recruitment: rare criteria, restrictions on medicines, strict health requirements.
A long half-life of the substance: the break between periods grows.
Repeat visits or several cohorts, if the number of volunteers is larger than the clinic can admit at one time.
Re-analysis of samples and agreeing deviations from the protocol.

How to shorten the timeline

Prepare the full package of documents before filing and decide in advance who answers the Ethics Council’s requests.
Carry out a feasibility assessment before approving the protocol: it shows which criteria will slow recruitment.
Calculate the group size with a dropout allowance in advance — the calculator gives a guide.
Agree with the laboratory on the sample transfer schedule and the analytical method.

A typical schedule for your project

The clinic names the real timelines by stage for a specific protocol. Send a synopsis or protocol, information on the products and your target timelines: we will assess feasibility and come back with a schedule. Send us a request or call us.

Sources

Federal Law No. 61-FZ of 12 April 2010 “On the Circulation of Medicines”: Article 39 (Parts 3, 6, 7), Article 39.1 (Parts 4.1–4.2), Article 40 (Parts 3.1, 4–5) — text on ConsultantPlus.
Ministry of Health Order No. 586n of 31 October 2024 — the period of ethics review (Annex 2, item 9).
EAEU Bioequivalence Rules — clauses 15 and 116 and Annex 7.

Questions and answers

What takes longest in a bioequivalence project?

It depends on the product and the preparation: the timeline is set by the documents and the permit, volunteer recruitment, the breaks between periods and the bioanalysis of samples. Which stage turns out longest can only be seen from the protocol.

What does the length of the clinical phase depend on?

On the number of periods and the breaks between them. The break must be long enough that the substance is no longer detectable at the start of the next period: five half-lives is usually enough (clause 15 of the EAEU Rules). If the substance is eliminated slowly, the break and the whole study get longer.

How quickly is a trial permit issued?

The expert review of the documents and the ethics review take no more than 25 working days (Article 39, Part 6 of Law No. 61-FZ). Before that the Ministry checks the documents for up to three working days (Part 3), and afterwards it decides on the permit within up to three working days (Part 7). The time between the Ethics Council’s request and the applicant’s answer is not counted in the ethics review period (Article 39.1, Part 4.2).