Russia’s first three batches rule explained. State quality testing before a new drug reaches the market
When a new drug first appears on the Russian market, the manufacturer’s quality certificate is not the final step. The state initiates its own verification in an independent laboratory: the first three batches must undergo mandatory testing, and without a positive testing protocol the drug will not receive the right to move along the distribution chain. For companies that do not factor this procedure into their launch plans, it turns into an unexpected barrier with its own timelines, sample costs, and logistical requirements.
Federal Law No. 61-FZ «On the Circulation of Medicines» introduced Article 52.1 in 2018. Amendments made in January 2024 substantially overhauled it, adding new regimes, exceptions, and mitigation conditions. Government Decree No. 815 dated May 31, 2025 established the specific procedures and timelines. Below is a step-by-step breakdown.
How the System Worked Before
Prior to the introduction of Article 52.1, the requirements for placing new drugs into circulation essentially came down to manufacturer self-declaration. The company would submit a document confirming batch quality and an authorized person’s declaration to Roszdravnadzor; after that, the batch was considered introduced into circulation. No state laboratory was involved in the process.
The weakness of this approach is obvious: in practice, the first batches of a new drug can deviate from the declared quality. An unstabilized manufacturing process, unfamiliar climatic conditions during transportation, packaging materials new to the Russian market — all of this affects the outcome. Internal controls at the manufacturer, particularly one located abroad, do not always catch these deviations.
What Article 52.1 Changed
Article 52.1, as amended by Federal Law No. 1-FZ dated January 30, 2024, builds several tiers of control depending on the type of drug and the manufacturer’s reputational history.
Standard regime — three batches. For any drug manufactured in Russia for the first time or imported for the first time (regardless of dosage, under one marketing authorization (MA)), the manufacturer or importer is required to additionally submit a testing protocol for each of the first three batches to Roszdravnadzor. The protocol is issued by accredited Federal State Budgetary Institutions (FSBIs) subordinate to the Ministry of Health of Russia or Roszdravnadzor. Testing covers all quality indicators provided for by the normative documentation (ND) or EAEU requirements.
| Parameter | Standard Regime | Part 4.1 Regime |
|---|---|---|
| Number of batches under control | 3 | 1 |
| Condition for application | By default | RF/EAEU GMP + clean 3-year history |
| Type of testing | In-person at FSBI | In-person at FSBI |
| Testing protocol | For each batch | For one batch |
Concessional regime — one batch (Part 4.1). The law allows companies to limit themselves to a protocol for the first batch under two conditions. First: the manufacturer holds a valid GMP compliance certificate issued by a Russian authorized body or an authorized body of an EAEU member state, specifically for the site that manufactures the finished dosage form and performs batch release quality control. Second: within three years prior to the protocol issuance date, no information on quality non-conformances attributable to this manufacturer was published on the Roszdravnadzor website — covering all its sites involved in manufacturing and batch release.
In essence, this is a risk-based approach: a company with an impeccable history has fewer grounds to be subjected to expanded verification.
Exceptions — zero control of the first batches (Part 4.2). Protocols for the first batches are not required at all for two categories. The first is orphan medicinal products: their production volumes are small, and the speed of patient access is paramount. The second is advanced therapy medicinal products (ATMPs) obtained from the biological material of a specific person and intended solely for that person (personalized cellular therapy).
Special regime for other ATMPs (Part 4.3). Other advanced therapy products are controlled differently: a protocol is required for one batch per year, only during the first three years from the date of introduction into circulation, and exclusively in a remote format.
| Drug Category | Protocol Regime |
|---|---|
| Regular new drug | Three batches (standard) or one batch (Part 4.1) |
| Orphan drug | Not required |
| ATMP from patient bio-material | Not required |
| Other ATMPs | One batch per year, remote, first 3 years |
How the Procedure Works
The procedure for interacting with FSBIs is governed by Government Decree No. 815 dated May 31, 2025. There are five steps in total, each with a regulatory deadline.
Step 1. Application. The manufacturer or importer sends an application to one of the accredited FSBIs — by post or in electronic form. The application is accompanied by a batch quality document and the authorized person’s declaration (as required by Parts 1 and 2 of Article 52.1), a copy of the normative documentation, and — for drugs registered under EAEU rules — packaging mock-ups.
Step 2. Verification and sample calculation (3 working days). The FSBI registers the application, verifies its completeness, and — if everything is in order — determines the required quantity of drug samples and materials for duplicate reproduction of quality control methods: reference standards, reagents, test strains. The testing fee is communicated at the same time. If the documentation is incomplete, the institution sends a request; the applicant must respond within 30 working days.
Step 3. Sample submission (up to 90 working days). The timeline runs from the day the FSBI receives the application. The applicant submits the samples and proof of payment. If the materials for reproducing quality control methods need to be purchased or imported from abroad, the deadline is extended by an additional 45 working days upon a separate application.
Step 4. Testing (up to 30 working days). Testing is conducted in person at the FSBI. When the ND methodology requires procedures with fixed time points — for example, stability tests — the timeline is extended by the duration of those procedures.
Step 5. Protocol (3 working days). After testing is complete, the institution issues a testing protocol in written or electronic form.
The fee for issuing the protocol is 1,200 rubles. The fee for the testing itself is calculated separately, according to the methodology of the Ministry of Health of Russia, individually for each drug.
When Remote Testing Is Permitted
By default, samples are delivered to the FSBI in person. Government Decree No. 815 provides for four situations where a remote format is possible:
The FSBI lacks specialized equipment for the required methodology.
The samples cannot physically be transported or stored under Russian laboratory conditions.
The drug’s characteristics do not allow testing to be conducted on Russian territory without damaging the entire batch.
The specification contains indicators that, per the ND, can only be verified at the manufacturer’s site.
In situations 2–4, the applicant initiates the remote format independently by submitting a justified application concurrently with the main application. The FSBI makes a decision within 5 working days. Remote testing is conducted either with FSBI specialists traveling to the site, or in an online format using video materials and primary equipment data.
For other ATMPs (except personalized ones), the remote format is mandated directly by law, without requiring additional approval.
After the First Batches — Annual Protocol
Passing the first batches does not mean exiting the control system. Annually, no later than April 1, the manufacturer or importer is required to submit a testing protocol for one batch (one trade name, one dosage form, one strength) from the preceding year to Roszdravnadzor. Testing for the annual protocol may be conducted by FSBIs or by any accredited testing laboratory. For orphan drugs, the frequency is reduced to once every three years.
A year in which a protocol was submitted under Part 4 or 4.1 counts toward the annual obligation. No additional protocol is required for that same year.
If the annual protocol is not received by April 1, Roszdravnadzor has the right to suspend the civil circulation of all batches of that drug introduced into circulation in the preceding year.
Shortages and Prices — How Government Decree No. 1771 Works
Introducing the first batches to the market is connected to the price regulation system through the mechanism established by Government Decree No. 1771 dated October 31, 2020 (valid until September 1, 2030; last amended April 8, 2025). For drugs included in the List of Vital and Essential Drugs (VED), specific rules apply to the regulation of maximum manufacturer prices in the event of a shortage or a risk of shortage arising from pricing constraints.
If delays during testing of the first batches create a threat of temporary shortage for a VED drug, the manufacturer has the right to initiate a price reregistration. Roszdravnadzor monitors the shortage risk and, upon confirmation, forwards the information to the Federal Antimonopoly Service (FAS). The reregistered price is valid for one year and allows the manufacturer to offset increased costs related to quality control and sample logistics.
Initiating this mechanism is justified only when there is a genuine shortage risk confirmed by data from the drug movement monitoring system (MDLP, «Chestny Znak»). The FAS verifies that the proposed price does not exceed the minimum level in reference countries.
How to Plan the Budget
The cost of the procedure comprises several items, and underestimating any of them can delay the launch.
The fee for issuing the protocol is fixed: 1,200 rubles per document. The cost of the testing itself is calculated by the FSBI individually, based on the Ministry of Health methodology, and depends on the testing scope, labor intensity, and equipment used. The institution communicates this amount to the applicant within the same three working days when it calculates the sample requirements.
Drug samples are submitted to the laboratory free of charge. Their quantity always exceeds a standard commercial package: samples are needed for testing plus material for a duplicate run of quality control methods. For biological drugs and highly specialized molecules, the sample cost across three batches can represent a substantial share of the first commercial shipment.
A separate budget item covers reference standards, reagents, test strains, and cell cultures for reproducing quality control methods. If specific materials are unavailable at the FSBI, the applicant must procure and supply them independently. Imported reference standards require time for procurement, importation, and customs clearance — a separate logistical chain with its own timelines. For such cases, the law allows the sample submission deadline to be extended by up to 45 working days beyond the standard 90.
Transportation of cold-chain drug samples requires a qualified cold chain: specialized transport, calibrated temperature data loggers, and documentary proof of the storage regime at the time of handover. This expense should be budgeted separately from commercial distribution costs.
Finally, a contingency reserve for re-testing is prudent. If the results are inconclusive, the FSBI requests additional samples — a repeated submission, repeated timelines, repeated costs. Building this reserve into the budget from the outset, based on the cost of one batch of samples, is the practical approach.
What to Do
Plan testing well in advance. In a baseline scenario, approximately 120–130 working days elapse from application submission to protocol receipt: 90 days for sample submission (counted from the application date), 30 days of testing, and 3 days for protocol issuance. If the methodology requires long-duration procedures, the timeline expands. Start the procedure 6–7 months before the planned commercial shipment; for complex molecules, allow 9 months.
Verify the GMP status of all manufacturing sites. To qualify for the concessional regime under Part 4.1 (one batch instead of three), the GMP compliance certificate must cover the specific site that manufactures the finished dosage form and performs batch release — not only the active substance site. Check Roszdravnadzor publications for non-conformances over the past three years: any mention of any of the manufacturer’s sites blocks the concessional regime.
Calculate the budget before starting the procedure. The protocol fee is fixed (1,200 ₽, Government Decree No. 815); the testing fee is calculated by the FSBI individually. The bulk of the budget goes to samples and reagents for reproducing quality control methods. For drugs requiring non-standard reference standards or specialized reagents, add procurement and importation costs.
Assess the need for a remote format early. If the drug contains quality indicators that per the ND can only be verified at the manufacturer’s site, or requires equipment unavailable at Russian FSBIs — prepare the justification and file the remote testing application together with the main application. A late request will extend the timeline.
Synchronize batch introduction with MDLP. Every batch that has received a testing protocol must be recorded in the Chestny Znak system before moving along the supply chain. The absence of a confirmed status in MDLP halts the batch’s circulation regardless of whether a paper protocol exists.
The first three batches rule is a risk management tool at launch: the state does not rely solely on the manufacturer’s word when a drug is entering the market for the first time. Manufacturers with an impeccable GMP track record test one batch; everyone else goes through the full cycle. Roszdravnadzor has the right to suspend batch circulation within three working days of identifying missing documentation. This is the system’s standard operating mode, not an exception.
Regulatory Framework:
1. Government Decree No. 1771 dated October 31, 2020 «On Approving the Specifics of State Regulation of Maximum Manufacturer Prices for Medicinal Products Included in the List of Vital and Essential Drugs» (as amended April 8, 2025)
2. Federal Law No. 61-FZ dated April 12, 2010 «On the Circulation of Medicines» (as amended July 23, 2025), Article 52.1
3. Federal Law No. 1-FZ dated January 30, 2024 «On Amendments to the Federal Law ‘On the Circulation of Medicines’»
4. Government Decree No. 815 dated May 31, 2025 «On the Procedure for Introducing Medicinal Products for Medical Use into Civil Circulation»