According to Regulation (EU) 2017/745, clinical evaluation is an ongoing, methodologically defined process by which a manufacturer systematically identifies, assesses, generates, and analyzes clinical data pertaining to their product. Article 61, Paragraph 1 requires that this process be planned, conducted, and documented in accordance with the Article and Annex XIV Part A. The objective is to demonstrate that the relevant general safety and performance requirements are met under normal conditions of use, that undesirable side effects have been assessed, and that the benefit-risk ratio is acceptable. The term thus refers to the activity throughout the entire product lifecycle, not the document summarizing its outcome.
Legal Basis and Process Flow
Article 61, Paragraph 1 sets out two requirements: the manufacturer must specify and justify the necessary scope of clinical evidence, and this scope must be appropriate to the characteristics of the product and its intended purpose. Annex XIV Part A, Section 1 then divides the activity into five tasks: establishing and updating a clinical evaluation plan, identifying available clinical data and gaps in clinical evidence through systematic literature review, assessing the suitability of this data, generating new or additional data through appropriately designed clinical investigations, and analyzing all relevant data to draw conclusions on safety, clinical performance, and clinical benefit.
Section 2 additionally obliges the manufacturer to ensure thoroughness and objectivity: favorable and unfavorable data must be considered equally, and the scope and depth of the evaluation must match the product’s nature, classification, intended purpose, and risks. Article 61, Paragraph 3 describes the methodological foundation, namely the critical evaluation of relevant scientific literature, the critical evaluation of all available clinical investigations, and the consideration of other available treatment options.
The Clinical Evaluation Plan as a Steering Document
The clinical evaluation plan is the first step in the process and not an appendix to the final report. It defines which intended purpose, indications, target groups, and requirements from Annex I are to be supported by clinical data, which endpoints and acceptance criteria apply, which search strategy will be used for the literature, and how identified gaps will be addressed. From this plan, the clinical development plan is derived, which describes the sequence of proprietary data collection up to post-market clinical follow-up.
Because the evaluation is ongoing, the plan is updated throughout the product lifecycle. New literature, vigilance reports, market surveillance results, changes in the state of the art, or changes to the product and its intended purpose each trigger a renewed evaluation round. For Class III products and certain Class IIb products, Article 61, Paragraph 2 allows for consultation with an expert panel on the clinical development strategy before evaluation and investigation; the consideration of these viewpoints is documented.
Distinction Between Process, Report, and Data Source
The process and its outcome document are legally separate: the Clinical Evaluation Report (CER) is the summary and assessment of the data situation at a specific cut-off date, while the process is the continuous activity that generates and updates this report. A current report without a documented plan and without traceable data identification therefore does not comply with Annex XIV Part A. Similarly, clinical evaluation must be distinguished from its data sources: a clinical investigation according to Article 62 generates data but does not replace the evaluation.
The process must also be distinguished from the equivalence consideration according to Annex XIV Section 3, which merely formulates a condition for the use of third-party data, and from the benefit-risk assessment, which, although based on the results of the evaluation, is managed within risk management. For implantable products and Class III products, Article 61, Paragraph 4 generally requires proprietary clinical investigations; the exceptions regulated therein concern the data basis, not the obligation for evaluation itself.
Relevance for clinical trials
The understanding of the process dictates the sequence of study planning: first, the clinical evaluation plan identifies the open questions, then it is decided whether a clinical investigation, a post-market follow-up study, or an analysis of existing data will close the gap. Endpoints, inclusion and exclusion criteria, sample size assumptions, and follow-up duration of an investigation should be directly derived from the acceptance criteria formulated in the plan, so that the subsequent results genuinely support the evidence.
Upon completion of an investigation, the results flow back into the same evaluation loop, triggering the update of the plan, report, technical documentation, and risk management. Full-service CROs like Mediconomics support manufacturers in integrating the evaluation plan, literature methodology, study design, and documentation in such a way that data collection closes the evidence gaps defined in the plan and results can be consistently incorporated into the regulatory submission documents.
Frequently Asked Questions (FAQ)
Is the clinical evaluation concluded with the evaluation report?
No. The evaluation is an ongoing process throughout the product lifecycle. The report documents a status and is updated as soon as new clinical data, vigilance information, or product changes become available.
Which legal bases directly regulate the process?
Article 61 of Regulation (EU) 2017/745 and Annex XIV Part A. Article 61 regulates the obligation, scope, and methodology, while Annex XIV Part A covers the process steps including the plan, data identification, assessment, data generation, and analysis.
Does every manufacturer have to generate their own clinical data?
Not necessarily. The scope depends on the product and its intended purpose. However, for implantable products and Class III products, clinical investigations are the rule, from which deviations are only possible under the conditions of Article 61, Paragraph 4.
Regulatory References
- Regulation (EU) 2017/745, Article 61 – Obligation, scope, and methodology of clinical evaluation.
- Regulation (EU) 2017/745, Annex XIV Part A – Process steps including the clinical evaluation plan.
- Regulation (EU) 2017/745, Annex XIV Section 3 – Demonstration of equivalence as a condition for using third-party data.
- Regulation (EU) 2017/745, Article 61, Paragraph 4 – Clinical investigations for implantable products and Class III products.
- Regulation (EU) 2017/745, Annex I Sections 1 and 8 – Reference requirements for benefit-risk assessment and side effects.
