EMA Concept Paper - Interface between Companion Diagnostics and Medicines Development

August 2017

Personalised medicine aims to tailor treatments to individual patients based on their predicted response or risk of disease. It can avoid unnecessary treatment, improve drug-development success rates and reduce costs. Biomarker-based assays have become key tools in the personalised medicine arsenal. A companion diagnostic compares the effect of a medicinal product in patients with and without a particular biomarker.

Current Guidance

Back in August 2014, the US Food and Drug Administration (FDA) issued guidance to assist sponsors with the development of a therapeutic product for which the use of an in vitro companion diagnostic device (or test) is essential for the therapeutic product’s safe and effective use or vice versa [1]. This has been followed in July 2016 by a draft of its Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product [2].

Guidance from the European Medicines Agency (EMA) had been notably lacking for many years since its reflection paper on co-development of pharmacogenomics markers and assays in the context of drug development [3] which was issued in June 2010. That position has changed following the adoption of the In Vitro Diagnostic Medical Devices Regulation [4] on 5 April 2017, although the Regulation will only apply after a 5 year transitional period. The Regulation specifically defines a companion diagnostic as:

a device which is essential for the safe and effective use of a corresponding medicinal product to:

(a) identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product; or

(b) identify, before and/or during treatment, patients likely to be at increased risk of serious adverse reactions as a result of treatment with the corresponding medicinal product.

Notably the Regulation will bring the medicinal product and medical device regulatory regimes together. So, for instance, the applicable notified body will be required to consult the EMA or a competent authority designated by the Member States in accordance with Directive 2001/83/EC on the Community code relating to medicinal products for human use.

Concept Paper

The European Medicines Agency has also now issued a Concept Paper [5] which it intends to develop into a guideline providing recommendations on the interface between predictive biomarker-based assays including companion diagnostics, and the development and lifecycle of a medicine.  Public consultation on the Concept Paper will finish on 25 November 2017 [6] with a draft guideline anticipated to be available 9-12 months afterwards.

The Concept Paper sees it as useful to have “a close knit development programme” linking the development of the medicinal product and its companion diagnostic, and use of clinical trials to generate evidence required to support validation of the diagnostic. The diagnostic must also be adequately validated and sufficiently quality assured.

Issues which the Concept Paper anticipates the ultimate guideline may cover include:

  • whether the biomarker status affects study entry, subject eligibility and treatment allocation;
  • the timing of the assay development in relation to drug development;
  • the interchangeability of assays that have been co-developed with more than one drug, but measure the same predictive biomarker;
  • the information provided in the Summary of Product Characteristics (SmPC) of the medicinal product regarding predictive biomarker-based assays that were used during the pivotal study;
  • the role of the risk management plan for medicinal products to be used in conjunction with a predictive BM assay if there could be important risks associated with incorrect patient selection.


The Concept Paper is a welcome move by the EMA. It may, however, be almost the end of 2018 before we see anything more concrete. The FDA’s List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools) [7] already shows 36 approved companion diagnostic devices, some of which have been approved with more than one medicinal product. The lack of any specific approval regime within the European Union for some time to come remains a possible cause for concern.

[1] In Vitro Companion Diagnostic Devices - https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM262327.pdf

[2] https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM510824.pdf

[3] http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/07/WC500094445.pdf

[4] Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017

[5] http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2017/07/WC500232420.pdf

[6] Comments to be submitted on a template form to pgwpsecretariat@ema.europa.eu

[7] https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm

This update was prepared by HGF Partner Janet Knowles.  If you would like further advice on this or any other matter please contact Janet or your usual HGF representative or visit our Contact page to get in touch with your nearest HGF office.