The European Medicines Agency (EMA) has published guidelines on quality documentation for medicinal products when used with a medical device.

The provisions of the guidance are based on the following regulations:

  • Directive 2001/83/EC (the Medicinal Products Directive) and Regulation (EC) 726/2004 (as amended),
  • Regulation (EU) 2017/745 on Medical Devices amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009, and repealing Council Directives 90/385/EEC and 93/42/EEC.

At the same time, the agency mentions that the actual scope of the guidelines and recommendations provided herein should not be limited to the aforementioned regulations. Rather, they cover all applicable legislation adopted in the European Union.

General Principles 

According to the general principles, in the case of products containing both medicines and medical devices, the assessment of a medical device should be conducted with regard to its use together with the medicine the product also contains. Apart from this, all other features and characteristics of a medical device should be considered. It is stated that the documentation submitted by the applicant with regard to the medicine should also cover the impact caused by the device on the Quality Target Product Profile (QTPP), Critical Quality Attributes (CQA) and overall control strategy of the medicinal product. 

It is important to mention that in the case of medicine supplied together with or intended to be used with a medical device, the conformity assessment body responsible for the assessment of medicine will also carry out an assessment of safety-related aspects with regard to the medical device as well. However, the present document does not provide clarifications regarding how such an evaluation should be carried out but outlines the scope of information to be submitted to the conformity assessment body for initial review. At the same time, the scope of the guidance does not cover the obligations of medical device manufacturers with regard to their products. Hence, it is actually limited to the scope of applications related to medicinal products. 

The agency additionally encourages the applicants to provide samples of the products subject to review in order to facilitate the process and reduce the time the assessment body would need to request and obtain samples as they would be reasonably necessary to evaluate all the important aspects related to safety and effectiveness of the product in question. 

Data Submission 

According to the present guidance, information related to a medical device that is a part of a medicinal product should be provided in a structured way. In particular, the eCTD format[2]  should be used. It is stated that the information to be provided by the applicant should cover all the aspects that could potentially impact the safety, quality, or effectiveness of the product – this information is vitally important for the conformity assessment body to be able to carry out the benefit/risk analysis. If the applicant already possesses clinical data related to the medical device the product contains, such data should be provided as supplementary materials. This also applies if the medical device in question has already been approved for such use. 

At the same time, the agency explicitly states that the present guidance is not exhaustive and does not cover all possible regulatory issues. Consequently, in complex cases, applicants are encouraged to contact conformity assessment bodies to get product-specific advice and recommendations regarding the content of the dossier to be submitted. 

Integral Medicinal Products 

As stated in the guidance, information related to integral medicinal products should comply with the regulatory requirements set forth by Directive 2001/83/EC or Regulation (EC) 726/2004. In particular, it is not necessary to provide detailed information about the medical device part of the product, including information about the medical device manufacturer or its EU-based authorized representative, as well as the unique device identifier. At the same time, all information about the medical device part that is reasonably necessary to ensure that the product will be used in a safe and efficient way should be provided in the package leaflet supplied with the product. 

In particular, the information to be provided with regard to the integral medicinal product should include the following elements:

  • Description and composition, including extensive information about the medicine component and brief information about the medical device. This section should also contain a description of the functionality of the product in general and its components in particular. 
  • Pharmaceutical development section should describe the reasons behind including a medical device in the product subject to review. Additionally, this section should also contain details about the risk assessment of the overall product in question. It is also necessary to provide information about the intended use of the product and the role to be played by the medical device. 
  • With regard to medical devices, this section should contain information about the design of the device part, its functionality, and also the target population of the product. In case of changes made to a medical device part, a summary of such changes should be provided in this section as well, together with the assessment of impact caused by such changes to the safety and effectiveness of the overall product. 
  • In terms of the manufacturing process, the applicant shall provide information about the general manufacturing processes and also on the sterilization methods used. Additionally, the agency expects the applicant to provide information about the development of the product, including pivots. 
  • In the case of Container Closure System (CCS), the applicant shall also provide a brief description, which should cover such aspects as:
  1. Rationale for the container/medical device (part) and materials of construction;
  2. Critical functional parts e.g. dose-setting mechanism;
  3. Features to enhance user safety for dose delivery (e.g. audible click), sharps injury prevention features, safety/lock-out features to prevent over-dosage, safe disposal information, etc
  4. For implantable/transdermal device (part), information on the matrix and reservoir, including mechanism of drug release etc;
  5. If the device (part) includes a graduation marking, the requirements of the Quality of Medicines, Questions and Answers, on the EMA website should be considered. 
  • In the case of medical products supplied sterile, together with the description of the sterilization process, the applicant shall provide evidence demonstrating the product remains sterile within its whole lifecycle. 
  • Special attention should be paid to compatibility matters. In particular, it is necessary to demonstrate compatibility for any and all materials contacting medicinal products. This applies to physical and chemical compatibility, as well as the stability of the materials used. 

In summary, the present EMA guidance addresses the most important aspects related to the information to be submitted by the applicant with regard to medical devices intended to be used with the medicinal product. The document outlines the scope of information to be included in the submission in order to ensure the conformity assessment body would have sufficient information to conduct benefit/risk evaluation and assess the overall safety and performance of the product subject to review. 


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