RMP Deficiencies in EAEU Registration — What Changed Under GVP Decision No. 81 and How to Avoid Them
Deficiencies raised during expert evaluation at the Scientific Centre for Expert Evaluation of Medicinal Products (SCEEMP) do not solely stem from weak clinical data or an incorrect Module 3. One of the most frequent sources of assessor queries is Module 1.8.2 — the Risk Management Plan (RMP). For years, companies copied the RMP from their global EMA or FDA dossiers and inserted it into the EAEU registration package with practically no modifications. Until 2022, this approach somehow worked. After 2022, it no longer does.
EEC Council Decision No. 81 of May 19, 2022, «On Amendments to the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union» (hereinafter: Decision No. 81), which entered into force on December 6, 2022, altered the very logic of working with pharmacovigilance documents. The RMP and the Periodic Safety Update Report (PSUR) are no longer archival checkbox exercises. Today, they are active tools for managing a drug’s safety throughout its entire lifecycle. In parallel, a new pharmacovigilance procedure was introduced in Russia: Roszdravnadzor Order No. 3518 of June 17, 2024, established new reporting timelines.
In this article, we examine how the RMP differs from the PSUR, what Decision No. 81 specifically changed, and why half of the typical deficiencies raised during expert evaluation are entirely predictable.
What Is an RMP and Why Is It in the Registration Dossier
An RMP is mandatory for the majority of medicinal product registration applications in the EAEU. Within the Common Technical Document (CTD) dossier structure, it is placed in Module 1.8.2. Its legal definition is established in Paragraph 52.2 of Article 4 of Federal Law No. 61-FZ of April 12, 2010, «On the Circulation of Medicines»: an RMP is a detailed description of pharmacovigilance activities aimed at identifying, evaluating, and preventing or minimizing risks associated with medicinal products, including the evaluation of the effectiveness of those activities.
Stepping away from legal language: the RMP answers two questions. What can go wrong when this drug is used? And what does the company plan to do about it? A well-written RMP describes not only known risks but also what data the company currently lacks and how it intends to obtain them.
The PSUR is submitted after a drug’s registration at a specified frequency. It analyzes all accumulated safety data during the reporting period: spontaneous adverse drug reaction (ADR) reports, study data, and signals from scientific literature. The primary question for every new PSUR is whether the benefit-risk balance has changed since the previous report.
While the RMP describes the risk management work plan, the PSUR records its outcomes. Each new PSUR must assess how effectively the measures prescribed in the RMP have worked. If they have not, the RMP must be updated.
PSUR submission frequency is determined by the EAEU list of reference dates — an analogue of the EURD list used in the EU. The standard schedule is every 6 months during the first two years following the drug’s first global registration (the International Birth Date, or IBD), and annually thereafter. The data lock point (DLP) for each PSUR now has a formal regulatory definition under the updated EAEU GVP, which eliminates disputes about which events belong in a given report and which carry over to the next period.
How Requirements Looked Before 2022
The foundational document for pharmacovigilance in the EAEU is the Rules of Good Pharmacovigilance Practice (GVP), approved by EEC Council Decision No. 87 of November 3, 2016, «On Approval of the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union» (hereinafter: EAEU GVP).
In the 2016 version, the requirements for the RMP and PSUR were less detailed than those of the EMA. Companies frequently submitted RMPs that closely mirrored the EMA GVP Module V template without adapting them to the population characteristics of the Union’s member states. Safety specifications contained lists of identified and potential risks; however, the «missing information» section — covering groups excluded from clinical trials (CTs), such as pregnant women, patients with renal or hepatic impairment, and paediatric patients — was often reduced to a single phrase: «Data are not available.» Nothing else. No plan to obtain the data, no justification for why doing so was impossible.
During that period, the PSUR was perceived by many marketing authorization holders (MAHs) as an archival report: a list of ADRs, a comparison with the previous period, and a general conclusion about a satisfactory safety profile. Evaluation of the effectiveness of the risk minimization measures (RMMs) outlined in the RMP was practically absent from PSURs. Responses to identified safety signals were routinely deferred until the next scheduled report.
At the «RegLec-2022» conferences organized by the SCEEMP of the Russian Ministry of Health, experts documented several recurring errors across registration dossiers: inconsistencies between the RMP and other modules, a missing link between the safety specification and preclinical materials (Module 4), a superficial approach to RMMs, and complete disregard for the «Additional Union Requirements» section within the safety specification.
What Decision No. 81 Changed
Decision No. 81 affected nearly all key processes within the safety monitoring system. The changes go beyond formatting requirements — they concern the core logic of document preparation.
Data consistency. If the RMP states that a drug is hepatotoxic in a certain percentage of cases, this must be reflected in both Module 5 (clinical data) and the SmPC (Summary of Product Characteristics). Discrepancies between dossier sections have become a direct ground for deficiencies during evaluation and, in some cases, a trigger for an unscheduled GVP inspection.
Deeper requirements for «missing information.» Stating that pregnant women were not included in clinical trials is no longer sufficient. The company must either propose a concrete mechanism for obtaining such data — typically a Post-Authorisation Safety Study (PASS) — or provide a substantiated explanation of why this is impossible. Leaving the section empty is no longer an option.
Evaluation of RMM effectiveness is now a mandatory PSUR section. If an educational programme for physicians fails to reduce the frequency of a specific ADR, the RMP must be revised. The regulator expects evidence that measures are working, not merely a list of them.
Signal management with mandatory procedures. Section IX of the EAEU GVP (paragraphs 704–762) describes the complete signal processing cycle: detection, validation, prioritization, evaluation, recommendations, and information exchange. For urgent safety issues, the MAH must notify the competent authorities of the member states within no more than 3 business days of determining that a validated signal meets the definition (paragraph 756 of the EAEU GVP). For other confirmed signals, the regulator establishes action timelines individually, proportional to the severity and public health impact (paragraph 738 of the EAEU GVP).
Electronic PSMF. Decision No. 81 revised the requirements for the Pharmacovigilance System Master File (PSMF): an electronic version is now officially permitted, provided it includes bookmarks and a text search function. Sections describing the Qualified Person for Pharmacovigilance (QPPV) and local contact persons (LCPs) in the member states must clearly describe the interaction between the global and local levels.
EAEU population specifics. The updated rules require taking regional characteristics into account, including potential genetic differences in drug metabolism among the populations of the Union’s countries. For medicinal products with a narrow therapeutic index, this carries real practical weight.
| Parameter | Before Decision No. 81 | After Decision No. 81 |
|---|---|---|
| Consistency of RMP with other dossier modules | Recommended | Mandatory; verified during evaluation |
| «Missing information» section | Statement of fact | Plan to obtain data — or substantiated justification for its absence — is required |
| Evaluation of RMM effectiveness in PSUR | Not required | Mandatory section |
| Signal management | Procedure not detailed | Full cycle (paragraphs 704–762): urgent issues — 3 business days (para. 756); others — timeline set by regulator (para. 738) |
| PSMF format | Paper only | Electronic format with bookmarks is permitted |
| EAEU population specifics | Not required | Analysis of population characteristics of the Union’s countries |
Since March 1, 2025, Roszdravnadzor Order No. 3518 of June 17, 2024, «On Approval of the Pharmacovigilance Procedure for Medicinal Products for Medical Use» (registered with the Ministry of Justice under No. 79394) has been in force in Russia. The Order established specific timelines: MAHs must submit information on urgent safety issues (paragraphs 756–757 of the EAEU GVP) to ESI@roszdravnadzor.gov.ru within 3 business days, with mandatory duplication on paper. Healthcare organisations must report serious ADRs not involving a threat to life within 15 calendar days. PSURs and RMPs are submitted through the Automated Information System (AIS) of Roszdravnadzor, which registers them automatically. Failure to fulfil pharmacovigilance obligations is now a direct ground for suspending a marketing authorization (MA). The Order remains in effect until March 1, 2031.
The Principle of Proportionality in the RMP
This is rarely discussed, yet it is one of the most practically significant innovations introduced by Decision No. 81. The scope of the RMP is now differentiated by application type.
For originator products with a full dossier, all parts and all modules of the safety specification are required. For generics, the scope is reduced: Part VI (the RMP Summary) is mandatory, while other parts are submitted only if the reference product has additional RMMs in place. Hybrid medicinal products occupy an intermediate position; the scope of the RMP depends on how they differ from the reference product.
| Drug Type | RMP Requirements |
|---|---|
| Originator (full dossier) | All parts (I–VII) and all safety specification modules |
| Generic | Part VI mandatory; other parts required only if the reference product has additional RMMs |
| Hybrid | Scope determined by the nature of differences from the reference product |
| Well-established use | Minimum requirements, subject to demonstrated safety |
A company that submits an RMP for a generic in the full scope of an originator RMP is making an error on the side of excess. An oversized document creates unnecessary work for the assessor and increases the risk of internal inconsistencies in the text. The principle of proportionality cuts both ways.
RMP Structure and What the Assessor Reviews
The EAEU GVP prescribes seven parts for the RMP.
| Part | Content |
|---|---|
| I | Product overview: composition, dosage forms, worldwide registration status |
| II | Safety specification (8 modules: preclinical, clinical, post-marketing, specific populations, drug interactions, overdose, missing information, additional EAEU requirements) |
| III | Pharmacovigilance plan: routine and additional activities, including PASS |
| IV | Post-Authorisation Efficacy Studies (PAES) plan |
| V | Risk minimization measures: routine and additional RMMs |
| VI | Public Summary of the RMP |
| VII | Annexes: questionnaires, study protocols, additional materials |
During evaluation, assessors primarily compare Part II (the safety specification) with Part VI (the summary) and the SmPC. A potential risk mentioned in the safety specification but absent from the summary will prompt a deficiency. A risk described in Part II for which Part V proposes no minimization measures is a guaranteed query.
The RMP Summary (Part VI) must be in Russian. When the full RMP is drafted in English, the summary must be detailed enough for the assessor to evaluate the validity of the conclusions without consulting the main text. A brief two-page abstract will not suffice.
Typical Errors in Preparing RMPs and PSURs
An analysis of past evaluation deficiencies and the RegLec-2022 conference materials reveals several recurring errors. What is notable is that most of these do not require deep expertise in the EAEU GVP — they require careful, diligent document work.
Error 1: Copying a global RMP without adaptation. A company takes an RMP prepared for the EMA and submits it to the EAEU unchanged, replacing only the title page. This document lacks the «Additional Union Requirements» section (Module CVIII of the safety specification), contains no analysis of the EAEU’s population characteristics, and has no Russian-language summary of the required depth. The assessor returns the RMP with deficiencies on all three counts.
Error 2: No link between the safety specification and preclinical documentation. Module CII of the safety specification must reflect the results of specific toxicology studies: genotoxicity, carcinogenicity, and reproductive toxicity. Many companies describe preclinical data in Module 4 of the dossier but fail to carry this through to the RMP. The assessor finds a risk in Module 4 that is absent from the RMP safety specification and raises a query.
Error 3: Superficial RMMs. The description of risk minimization measures in Part V is reduced to «the information is reflected in the SmPC» or «the prescribing information contains warnings.» This is a routine measure, not an additional one. If a risk is serious, the assessor expects to see exactly how the physician or patient will receive information about it: educational materials, a patient alert card, or controlled-access measures. Without this, the RMM looks purely declarative.
Error 4: PSUR submitted without a section on safety signals. The company submits a PSUR with detailed ADR tables but with no section covering safety signals — neither closed nor newly identified. Since Decision No. 81 entered into force, this deficiency is entirely predictable: both types of signals are now mandatory sections of the document.
Error 5: No evaluation of RMM effectiveness. The PSUR describes the measures taken during the reporting period but does not assess their outcome. An educational programme for physicians was launched — good. Whether it reduced the frequency of the relevant ADRs is nowhere mentioned. Without this evaluation, the PSUR fails to answer the central question of the updated GVP: is the risk management system actually working?
Error 6: Inconsistency between the DLP and the data included. The data lock point is formally stated, yet the PSUR includes events that occurred after it. Or, conversely, events that fell within the DLP period are deferred to the next report. Since Decision No. 81 gave the DLP a formal regulatory definition, such inconsistency is no longer a minor technical slip — it is a violation of the pharmacovigilance procedure.
What Needs to Be Done
Verify the current status of your RMPs. For every medicinal product with an active marketing authorization (MA) in the EAEU, open the RMP and confirm it was prepared in accordance with the updated GVP requirements (Decision No. 81, in force since December 6, 2022). If an RMP was prepared before 2023 and has not been updated since, it must be revised. For generics, also verify that the scope of the RMP complies with the principle of proportionality.
Cross-reference the RMP against other dossier modules. Go through the list of identified and potential risks in Part II and confirm that the same risks are reflected in the SmPC and the clinical summaries of Module 5. Check separately whether Part II references the key toxicology data from Module 4. This is a very common source of assessor queries.
Fill in the «missing information» section meaningfully. For each subgroup where data are lacking (pregnant women, lactating women, paediatric patients, elderly patients, patients with renal or hepatic impairment), answer the question: does the RMP include a plan to obtain these data, or a substantiated rationale for not doing so? The phrase «data are not available» on its own is no longer accepted.
Review your SOP on safety signal management. Section IX of the EAEU GVP details the complete signal handling cycle. Verify that your Standard Operating Procedure (SOP) covers each of the six stages: detection, validation, prioritization, evaluation, recommendations, and information exchange. Pay particular attention to the criteria for urgent safety issues: upon their identification, the MAH has exactly 3 business days to notify the regulator (paragraph 756 of the EAEU GVP). For other signals, the regulator sets the timeline in its request — but «timeliness» is directly anchored as a legal requirement (paragraph 730 of the EAEU GVP), and extended internal approvals without defined deadlines represent a tangible regulatory risk.
Update your PSMF. If the Pharmacovigilance System Master File has not been updated since December 2022, its structure likely does not conform to the new requirements. Review the description of the interaction between the global QPPV and the local contact persons (LCPs) in each EAEU country. An electronic format with bookmarks and text search is now officially permitted.
Align Russian processes with Order No. 3518 (in effect from March 1, 2025, to March 1, 2031). Check three things. First: all periodic reports (PSURs, RMPs) must be submitted exclusively through the AIS of Roszdravnadzor; the email address pharm@roszdravnadzor.gov.ru is a backup channel for technical failures only. Second: in the event of an urgent safety issue, the MAH has 3 business days to notify the regulator at ESI@roszdravnadzor.gov.ru with mandatory duplication on paper. Third: is your QPPV reachable 24/7? If not, this is an organisational risk, not a technical one.
December 31, 2025, was the final deadline for bringing registration dossiers into conformity with EAEU rules. Companies that failed to complete this process faced the risk of marketing authorization cancellation. The updated EAEU GVP and Russia’s national pharmacovigilance procedure function in tandem, and non-compliance in any area — pharmacovigilance documents, the PSMF, or reporting workflows — is equally visible during expert evaluation and routine GVP inspections. Most of these issues can be resolved not by revising the scientific position, but through diligent document updates.
Regulatory Framework:
1. Roszdravnadzor Order No. 3518 of June 17, 2024, «On Approval of the Pharmacovigilance Procedure for Medicinal Products for Medical Use» (registered with the Ministry of Justice September 5, 2024, under No. 79394; in effect from March 1, 2025, to March 1, 2031)
2. EEC Council Decision No. 87 of November 3, 2016, «On Approval of the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union» (as amended by Decision No. 81)
3. EEC Council Decision No. 81 of May 19, 2022, «On Amendments to the Rules of Good Pharmacovigilance Practice of the EAEU» (entered into force December 6, 2022)
4. Federal Law No. 61-FZ of April 12, 2010, «On the Circulation of Medicines» (as amended, 2025)