Package Leaflet Readability Testing Under EAEU Rules. When It Is Required and How to Run It
A company submits a registration dossier for an insulin analogue. Patients with a chronic condition administer it themselves at home. Eight months after registration, the expert organization sends an inquiry: where are the results of the package leaflet user readability testing? The company is hearing about this requirement for the very first time. They urgently commission testing, losing another six months. Yet the issue could have been settled before submitting the dossier.
User readability testing of the package leaflet (PL) is one of those topics that has been discussed at industry conferences for several years, but in practice, many regulatory specialists encounter it for the first time only when they receive an official request. Let us break down when it is actually needed, how the procedure is structured, and what must be included in the dossier.
The Regulatory Background
The legal basis is established by the Decision of the Council of the Eurasian Economic Commission (EEC) No. 88 dated November 3, 2016, «On Approval of the Requirements for the Instructions on Medical Use of a Medicinal Product and the Summary of Product Characteristics of a Medicinal Product for Medical Use» (hereinafter referred to as Decision No. 88). In February 2025, the EEC Council adopted amendments (Decision No. 18 dated February 21, 2025), which updated the requirements for the content of sections and the testing procedure.
The SmPC (Summary of Product Characteristics) is written for physicians: it contains the complete technical picture of the drug — indications, dosing regimens, and interactions. The PL is drafted on the basis of the SmPC, but rewritten so that a patient without medical training can understand what to do. This is precisely where the question arises: do patients actually understand what is written?
The results of user readability testing, when available, are placed in Module 1 of the registration dossier. The protocols, questions, answers, interviewer’s observations, and all tested versions of the PL are included specifically in Subsection 1.3.4.
When Testing Is Required and When It Is Not
In practice, this is the first question that arises, and the answer turns out to be non-obvious for those primarily familiar with European practice.
Decision No. 88 establishes that testing is conducted at the discretion of the applicant. Regulators are not entitled to demand the application of any specific methodology. They evaluate data confirming that potential users of the PL are able to find the necessary information and apply it correctly.
At the same time, the document identifies four categories of products for which testing «should be provided»:
a) medicinal products with new active substances or fundamentally new dosage forms (original/innovative drugs under the EAEU procedure);
b) products whose dispensing conditions have changed;
c) products whose current SmPC has been updated with significant new safety information that substantially alters indications, contraindications, or the method of administration;
d) products with expanded indications covering new patient populations (e.g., pediatric use).
For all other situations, the picture is as follows:
| Situation | Testing Requirement |
|---|---|
| Categories a–d from Paragraph 7.3 of Decision No. 88 | Testing is recommended («should be provided») |
| Bringing into compliance with the Union’s requirements (into a new member state) | May be requested by the expert organization |
| Bringing into compliance (into already covered member states) | Not required; at the applicant’s initiative |
| Generic drug / biosimilar | Not required; the text of the reference drug’s PL with the same INN is used |
| Drug administered by healthcare professionals in inpatient settings | Not required; at the applicant’s initiative or upon request by the expert organization |
| Post-authorization period (high risk of medication error under Paragraph 116 of the Registration Rules) | May be established within one year following registration |
If testing results are not submitted, the applicant includes a letter in Module 1 of the dossier indicating the source of information used to compile the PL.
How Testing Is Conducted
Conducting the testing correctly is in the company’s own interest. Accepted results open the way to PL approval; unaccepted results mean redrafting the document and conducting additional rounds.
Who Conducts It
The testing is organized by the marketing authorization holder (MAH) or a specialized contract research organization. The interviewer must possess interviewing skills and have a thorough understanding of the PL structure. The specialist who drafted the package leaflet may accompany the testing to ensure accurate information transfer.
When developing the test, it is permissible to involve patient associations or expert patients. This is particularly useful for drugs in rare or highly specific therapeutic areas.
Participants
The standard sample size is 20 participants, divided into two groups of 10. This structure allows for the PL to be adjusted after the first group and for the changes to be verified with the second. The sample includes representatives of the target patient population. Individuals with a medical or pharmaceutical background are not recruited for testing: their professional experience skews the perception of the document. The same participant cannot be included in such testing more than once every six months.
Mock-up
Testing is conducted on a full-color mock-up of the PL, the same version with which the drug will be marketed. The color, font, and paper must match the commercial product. Testing the text in a Word file without final layout is unacceptable: the design and physical characteristics of the paper directly affect how easily a patient can find information. If the PL is multilingual, the language version being tested must also correspond to the commercial mock-up.
Questionnaire
Usually, 12 to 15 questions are sufficient, but there may be more if the drug has several significant safety aspects. The questions must cover key safe-use information from Sections 1 to 4 of the PL. Simple questions that «ensure success» by being too easy are unacceptable: the expert organization will also evaluate the quality of the questions themselves.
The order of questions in the questionnaire should differ from the sequence of information in the PL: this prevents guessing answers based on the document’s structure. A good question places a person in a specific scenario and tests their understanding of the correct course of action. The difference between «What is the maximum dose?» and «You missed your evening dose — what do you do?» is precisely about this.
If the drug requires complex manipulations (injections, inhalers), it is recommended to use mock-ups of the primary packaging, with participants demonstrating the preparation and administration process.
The «90 out of 90» Criterion
The test result is considered acceptable if the PL information is understood by 90% of participants from the 90% who found it. In practice, this means that 16 out of 20 participants (across both groups combined) must successfully locate the answer to each question and correctly explain what they need to do.
This criterion is applied to each question individually. Averaging results across the testing as a whole is not permitted. If the result for a single question falls below the threshold, the corresponding section of the PL must be revised, regardless of how well the other questions performed.
One more point worth knowing: if the expert organization has already issued comments on the draft PL, subsequent rounds of user testing are not conducted. The text is then agreed upon within the process of addressing those comments — at that stage, the dialogue is with the regulator, not a focus group.
Bridging Study — When a Repeat Test Is Not Needed
If a company is launching a line of products with the same active substance in different strengths or dosage forms, conducting a full test for each PL would be redundant. Decision No. 88 provides for a bridging study (Section 7.4).
The principle is as follows: if the «daughter» PL closely resembles the «parent» PL (which has already undergone testing) in terms of safe-use content and design, the testing results of the parent document can be transferred. For this, the daughter PL must have the same design, layout, and style of presentation as the parent. If this condition is not met, the expert organization has the right to reject the bridging.
The document also allows for «multiple bridging»: a daughter PL can draw on the testing results of several parent documents simultaneously. For example, the instructions for an inhalable drug can bridge to the PL of a drug with the same active substance (regarding pharmacological information) and to the PL of another drug with an identical administration device (regarding the inhaler instructions for use).
Repeat testing is not required when making changes to the PL that do not affect items «c» and «d» from the list in Paragraph 7.3 (new safety information and new patient populations), nor when changing only the design or layout.
What Must Be in Module 1.3.4
If testing was conducted, the report in Subsection 1.3.4 is structured as follows:
1. Safe-use information identified before the start of testing, with justification for the choice of questions.
2. Selection of participants and their demographic characteristics (gender, age, education level, exclusion criteria).
3. Analysis for each tested group with graphical representation of results by question.
4. Feedback from participants and a list of amendments made to the PL based on that feedback.
5. All versions of the PL that underwent testing.
6. Summary of participants’ oral responses (submitting raw interview transcripts in full is not required).
During the review of Module 1.3.4, the expert systematically evaluates the PL’s compliance with the structural requirements of Decision No. 88, the design and layout, the alignment of the questions with the declared safe-use information, and the demographic characteristics of the sample.
If testing was not conducted, the applicant includes a letter in Module 1 stating the source of information used to compile the PL.
What to Do
Determine if your drug falls under categories a–d. An original drug with a new active substance, a change in dispensing conditions, significant new safety data, or expansion to pediatrics: each of these scenarios means that testing is recommended and the expert organization is likely to expect it.
Check whether a bridging study is possible. If your portfolio already contains a tested PL and the new document is close in content and design, prepare a comparative analysis instead of commissioning a new test from scratch.
Prepare a full-color mock-up in advance, before beginning the interviews. The final layout must fully correspond to the commercial packaging: color, font, paper type. Testing draft text in Word carries no regulatory weight.
Form two groups of 10 participants. Correct the PL after the first group if needed, then verify the changes with the second group. Develop 12–15 questions in a random order, covering safe-use information from Sections 1–4.
Document everything according to Paragraphs 7.2.2.1–7.2.2.6. Participant demographics, group-by-group analysis, PL versions, and a summary of responses: without this, Module 1.3.4 will not pass evaluation. If testing is not conducted, prepare a justification letter for Module 1.
Preparation for testing takes time: developing the mock-up, selecting the sample, conducting the interviews, analyzing the results, and potentially revising the PL. From the start of the project to the final report, the process takes an average of two to three months. For drugs in categories a–d, this timeframe should be factored into the registration plan long before submitting the dossier.
Regulatory framework:
1. Decision of the Council of the EEC No. 88 dated November 3, 2016, «On Approval of the Requirements for the Instructions on Medical Use of a Medicinal Product and the Summary of Product Characteristics of a Medicinal Product for Medical Use» (as amended by Decision of the Council of the EEC No. 18 dated February 21, 2025), Sections 7.2–7.4
2. Decision of the Council of the EEC No. 78 dated November 3, 2016, «On Approval of the Rules of Registration and Examination of Medicines for Medical Use» (as amended in 2025), Paragraph 116