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Producing peptide- and protein-based biologicals traditionally relies on living cells, bringing complexity to development and manufacturing. HORIZON-HLTH-2027-01-IND-01: “Development of cell-free protein synthesis platforms for discovery and/or production of biologicals” looks at another route: cell-free protein synthesis (CFPS). The call aims to advance CFPS towards more streamlined development and production of biologicals, with potential benefits for availability, affordability and decentralised manufacturing. Following the recently published official Horizon Europe Cluster 1 Health Work Programme 2026-2027, applicants should plan for the 17 February 2027 single-stage deadline. Below, we outline the main requirements from the call topic and how to address those in the proposal.

Call topic	Type of Action	Budget (EUR million)	Budget/project	Exp. number of funded projects
HORIZON-HLTH-2027-01-IND-01: Development of cell-free protein synthesis platforms for discovery and/or production of biologicals	RIA	24.5	€ 6 to 8 million	4

Why cell-free protein synthesis?

CFPS has been used in fundamental biological research for decades, but its potential for drug development and manufacturing has gained attention more recently. Instead of relying on intact living cells, CFPS uses cell lysates or fully synthetic systems containing the molecular machinery required to produce functional proteins.

The EC highlights several potential advantages of this approach:

• easier handling and scalability;
• on-demand production;
• rapid switching between products;
• simplified purification;
• facilitated standardisation and quality control;
• lower energy requirements and a smaller manufacturing footprint;
• production of proteins that may have toxic effects on living cells.

Different CFPS systems can be based on prokaryotic or eukaryotic cell lysates, including mammalian cells, or on fully synthetic systems. Mammalian cell-based systems are particularly relevant for proteins requiring post-translational modifications, such as human-like glycosylation.

Tip: Do not present CFPS as innovative simply because it avoids living-cell production. Define the concrete limitation of the current development or manufacturing process and show how your CFPS platform can overcome it.

At least two development areas must be addressed

Proposals under HORIZON-HLTH-2027-01-IND-01 must address at least two of these three areas:

• Improve CFPS for large-scale use: tackle bottlenecks such as quality-by-design, lysate characterisation and links between process parameters and product quality.
• Design and screen new biomolecules: use synthetic biology to create de novo biomolecules and develop cell-free systems for high-throughput screening.
• Move towards clinical-grade production: develop or optimise CFPS platforms for GMP-compliant production of material suitable for clinical trials.

Tip: Choose the areas that best match your platform’s maturity and show clearly how they connect.

AI and synthetic biology can accelerate discovery

The call explicitly links recent advances in synthetic biology and Machine Learning/Artificial Intelligence (ML/AI) with growing opportunities for CFPS.

In particular, generative deep learning and AI can support the de novo design of biomolecules with therapeutic or preventive properties. CFPS can then provide a platform for increasing the throughput of screening these newly designed molecules.

Potential applications are broad. The Work Programme points towards:

• therapeutics for infectious diseases;
• therapeutics for non-communicable diseases;
• vaccines;
• antibody fragments;
• antigens and virus-like particles;
• cytokines, enzymes and antimicrobial peptides;
• proteins containing non-natural amino acids.

However, AI is presented as an enabling opportunity rather than a mandatory component of every proposal.

Tip: Include AI because it solves a defined design or screening problem, not simply because the call mentions it. Make the connection between computational design, CFPS-based experimental validation and the targeted biological clear.

Think beyond the platform towards industrial uptake

HORIZON-HLTH-2027-01-IND-01 sits under the Horizon Europe destination “Maintaining an innovative, sustainable, and competitive EU health industry”. Its expected outcomes therefore extend beyond scientific advancement.

The EC expects results to contribute to:

• streamlined development and production processes for peptide- or protein-based biologicals;
• enhanced or decentralised production systems for innovative health technologies;
• better access, availability and affordability of pharmaceuticals based on biologicals.

Participation of start-ups, micro-enterprises and SMEs is specifically encouraged. This reflects the industrial orientation of the topic and the need to connect platform development with realistic routes towards exploitation and uptake.

Where applicants envisage clinical studies, they should also provide the required information in the dedicated clinical study annex.

Tip: Build the exploitation pathway around the platform and its use case. Show who could adopt the CFPS technology, what additional validation or scale-up would be needed and how the project moves the platform closer to industrial application.