New Draft EMA-Guideline On Clinical Development Of Fixed Combination Medicines

The European Medicines Agency (EMA) has recently published for public consultation its draft guideline on clinical development of fixed combination medicinal products (Draft Guideline), which is intended to replace CHMP/EWP/240/95 Rev. 1 (Existing Guideline). The Draft Guideline applies to fixed combination medicinal products containing two or more active substances within a single pharmaceutical form. The active substances may be known active substances or substances that have yet to be authorised in the EU.

An EMA concept paper on the Existing Guideline suggested that it be revised in order to suppress regulatory aspects and restrict it to the scientific requirements for clinical development of fixed combination products. The Draft Guideline therefore contains a number of changes from the Existing Guideline, including:

It no longer describes the applicable legal basis for approving marketing authorisation applications for fixed combination products. The Existing Guideline places a strong link between Article 10b of Directive 2001/83/EC and the development of fixed combination products. However, the Draft Guideline provides that “The legal basis for applications concerning fixed combination medicinal products may vary depending on the particularities of the active substances in combination and the development undertaken. The choice of legal basis lies with the applicant…” The Draft Guideline, as is the case with the Existing Guideline, does not discuss data exclusivity in respect of fixed combination products. The European Commission’s guidance contained in its Notice to Applicants, Volume 2 A continues to apply in this regard. It is worth noting that Teva has recently withdrawn its application and has discontinued proceedings in litigation before the General Court of the European Union (Case T-547/12) concerning regulatory data exclusivity for fixed combination products.

The Draft Guideline no longer addresses requirements for combination packs (i.e., where active substances are included in separate pharmaceutical forms marketed in the same package). The Existing Guideline states that scientific principles applicable to fixed combination products will also be applied in the assessment of combination pack medicinal products. However, the EMA has subsequently recognised that from a regulatory point of view combination packs are not the same as fixed-dose combinations. As such, reference to combination packs has been removed from the Draft Guideline.

The Draft Guideline contains more detail on the scientific aspects relevant for approval of fixed combination products. In summary, it provides that the basic requirements for a marketing authorisation application for a fixed combination product are: (1) justification of the pharmacological and medical rationale for the combination, (2) establishment of the evidence base for the: (a) relevant contribution of all active components to the desired therapeutic effect; and (b) positive risk-benefit for the combination, and (3) verification that the evidence base presented is relevant to the product applied for.

The deadline for submitting comments on the Draft Guideline is 15 November 2015. Comments should be sent to FDCguideline@ema.europa.eu, and should be submitted using this template.

Advising clients on a broad range of life sciences matters, Sarah Cowlishaw supports innovative pharmaceutical, biotech, medical device, diagnostic and technology companies on regulatory, compliance, transactional, and legislative matters.

Sarah is a partner in London and Dublin practicing in the areas of EU…

Sarah is a partner in London and Dublin practicing in the areas of EU, UK and Irish life sciences law. She has particular expertise in medical devices and diagnostics, and on advising on legal issues presented by digital health technologies, helping companies navigate regulatory frameworks while balancing challenges presented by the pace of technological change over legislative developments.

Sarah is a co-chair of Covington’s multidisciplinary Digital Health Initiative, which brings together the firm’s considerable resources across the broad array of legal, regulatory, commercial, and policy issues relating to the development and exploitation of digital health products and services.

Sarah regularly advises on:

obligations under the EU Medical Devices Regulation and In Vitro Diagnostics Medical Devices Regulation, including associated transition issues, and UK-specific considerations caused by Brexit;
medical device CE and UKCA marking, quality systems, device vigilance and rules governing clinical investigations and performance evaluations of medical devices and in vitro diagnostics;
borderline classification determinations for software medical devices;
legal issues presented by digital health technologies including artificial intelligence;
general regulatory matters for the pharma and device industry, including borderline determinations, adverse event and other reporting obligations, manufacturing controls, and labeling and promotion;
the full range of agreements that span the product life-cycle in the life sciences sector, including collaborations and other strategic agreements, clinical trial agreements, and manufacturing and supply agreements; and
regulatory and commercial due diligence for life sciences transactions.

Sarah has been recognized as one of the UK’s Rising Stars by Law.com (2021), which lists 25 up and coming female lawyers in the UK. She was named among the Hot 100 by The Lawyer (2020) and was included in the 50 Movers & Shakers in BioBusiness 2019 for advancing legal thinking for digital health.

Sarah is also Graduate Recruitment Partner for Covington’s London office.