Publication date: January 21, 2026
Every drug introduced to the EU market must obtain a permit from the competent authority. In Poland, this is the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products. EU regulations included in Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, implemented into Polish law by the Act of 6 September 2001 – Pharmaceutical Law provide for several procedures enabling drug registration, one of which is the so-called well-established medicine procedure (WEU). This is a special procedure for obtaining marketing authorization for medicines containing active substances with well-established medical use, i.e., medicinal substances known and systematically used in the EU for at least 10 years. The most important difference with this procedure is that there is no need to submit new clinical and pre-clinical studies, and the application can be based on available scientific studies that confirm the effectiveness and safety of the substance.
Most often, this procedure applies to herbal medicines and medicines containing commonly used substances that were already in use before the introduction of the drug registration requirement – examples include medicines containing paracetamol or aspirin.
Article 10 paragraph 1 of the Pharmaceutical Law governs the general requirements of an application for marketing authorization for a medicinal product, which should include:
Pursuant to paragraph 2, the application shall be accompanied by:
– together with a quality overall summary, a non-clinical overview and a non-clinical summary, and a clinical overview and a clinical summary;
As can be seen, any entity wishing to market a medicinal product must have extensive documentation to ensure its safe use after marketing authorization. The template for applications submitted to the Polish Office was published in the Regulation of the Minister of Health of January 10, 2014, regarding the template for applications for marketing authorization for medicinal products (consolidated text: Journal of Laws of 2018, item 593).
With regard to the application submitted under the WEU procedure, significant differences are introduced by Article 16 of the Act, according to which the marketing authorisation holder is not obliged to present the results of non-clinical or clinical trials if:
In this case, the results of non-clinical or clinical studies are replaced or supplemented publications from the scientific literature, and the application must be accompanied by a justification prepared by an expert regarding the use of scientific literature in accordance with the requirements set out in Annex I.
The publications to be submitted must include the full scope of non-clinical and clinical trial results required for new medicinal products. Furthermore, the wording of Article 16 of the Act contradicts Article 10a of the Directive, which only refers to the replacement of scientific studies with publications, not to their replacement or supplementation.
The above-mentioned conditions for applying the WEU procedure leave considerable room for interpretation and discretion in the issuance of marketing authorizations for medicinal products. Consequently, EU and national authorities have issued numerous guidelines on this topic.
Until March 30, 2007, detailed requirements for the WEU procedure were specified in the Regulation of the Minister of Health of January 16, 2003, regarding documentation of medicinal product test results, including veterinary medicinal products, and expert reports, which was repealed with the amendment to the Pharmaceutical Law. Currently, Polish regulations do not provide a binding interpretation of the concept of a substance with a well-established medical use.
The criteria for applying this concept can be found in Annex I to the Directive , according to which the following principles apply to demonstrate well-established medicinal use:
a/ The factors that should be taken into account in order to recognize the well-established medical use of the ingredients of medicinal products are as follows:
– how long a given substance has been used,
– the quantitative aspect of the use of a given substance,
– the degree of scientific interest in a given substance (as reflected in the published scientific literature) and
– consistency of scientific assessments.
b/ The documentation submitted by the applicant should cover all aspects of the safety and/or efficacy assessment and must include or refer to a review of the relevant literature, including pre- and post-marketing studies and published scientific literature on experience gained, in the form of epidemiological studies, and in particular comparative epidemiological studies. All documentation, both favorable and unfavorable, must be provided. In accordance with the provisions on “well-established medical use,” it is particularly necessary to clarify that “bibliographic references” to other sources of evidence (post-marketing studies, epidemiological studies, etc.), and not just data relating to tests and trials, can serve as valid evidence of the product’s safety and efficacy if the application satisfactorily explains and justifies the use of these sources of information.
c/ Particular attention must be paid to any missing information and an explanation must be provided as to why demonstration of an acceptable level of safety and/or efficacy can be supported despite the absence of some studies.
d/ Non-clinical and/or clinical reviews must clarify the relevance of any data submitted that relate to a product other than the product intended for marketing (so-called bridging data). A decision must be made as to whether the investigational product can be considered similar to the product for which marketing authorization has been applied for, despite existing differences.
e/ Post-marketing experience with other products containing the same ingredients is particularly important and the applicant should place special emphasis on this issue.
Furthermore, in July 2019, the European Commission issued guidance for applicants for marketing authorizations (Volume 2A, Chapter 1), which also addresses this procedure. The following indications follow from this guidance.
The Commission stressed that applications submitted under Article 10a of the Directive should not lower the level of safety and efficacy that a product with a well-established substance must also meet.
With respect to advanced therapy medicinal products (ATMPs), the Commission has determined that applications under this procedure are only permissible to the extent that the published scientific literature is relevant and sufficient to demonstrate the safety and efficacy profile of the medicinal product. Due to the specific nature of the ATMP manufacturing process, an application under this procedure will be admissible only exceptionally, provided that the manufacturing process for the product covered by the application is identical to the manufacturing process already described in the literature.
It is also worth noting that the term “medical use” does not necessarily mean use as an approved medical product, but evidence of the medicinal activity of a given substance must be provided. The 10-year period referred to in the regulations, in the case of a substance used in products authorised for marketing, does not have to cover the entire period during which a given country was a member of the EU or EFTA – this period also includes the years in which the product was authorised before the country joined the organisation in question.
The term “well-established use” refers to the use of a substance for a specific therapeutic purpose – if a well-known substance is to be used for a completely new therapeutic purpose for which no well-established use can be applied, it will not be possible to use this procedure.
It is the applicant’s responsibility to provide a detailed description of the strategy used to search for published literature and the rationale behind the selections made. The term “published” literature means that the text must be freely available in the public domain and published by a reputable, preferably peer-reviewed, source. Full texts of the research studies must be included in the application, along with any necessary translations.
European Medicines Agency (EMA) has also issued guidelines on this topic.
It is the applicant’s responsibility to demonstrate that the active substance contained in the medicinal product for which the application is submitted is identical to the substance described in the literature and to provide appropriate bridging data. Any studies submitted must support the efficacy and safety of the active substance.
The Agency stated that the applicant should submit a tabulated summary of data to support the assessment, including at least the following details:
For specific types of substances and products, EMA has also issued detailed guidance on the requirements for bridging data used to establish the well-established use of a specific substance.
Comparison of active substances in given products should be based on one or more of the following criteria:
Finally, it is worth emphasizing that if a medicinal product is authorized for the market under the WEU procedure, it may constitute a reference product when submitting applications for authorization to market equivalent products (as stated by the CJEU in its judgment of 23 October 2014 in case C-104/13).
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