EMA Guidance: Regulating Innovation in Phage Therapy and Device–Drug Combinations

Sharan Murugan
Oct 26
2 min read

In October 2025, the European Medicines Agency (EMA) released two landmark drafts for public consultation. These documents collectively signal the Agency’s evolving regulatory stance toward precision biologics such as bacteriophage therapy and innovative device–drug integration approaches to simplify clinical bridging for biologics delivered subcutaneously.

1. Quality Guidance for Phage Therapy Medicinal Products (PTMPs)

The EMA draft guideline on phage therapy quality (October 2025) targets the clinical resurgence of bacteriophage therapy as a precision solution for antibiotic-resistant infections.

Key regulatory expectations include:

Scope:
Strictly covers lytic phages for human use, including genetically engineered variants, but excludes cell-free/ex-vivo made phages.
Manufacturing Controls:
Requires full genome sequencing for host cell banks and phage seeds, minimising risk from antibiotic resistance or toxin genes.
Characterisation:
Uses advanced analytical and genetic methods for detailed safety and identity profiling of active phage substances.
Impurities Management:
Defines strategies for controlling and removing manufacturing and product-related impurities (e.g., host cell DNA, proteins, pyrogens).
Finished Product:
Sets rules for phage cocktails, stability studies, and specific potency testing for each phage type. Post-approval changes to phage composition require a full regulatory extension.
Reference:
The guideline aligns with established European and ICH standards (e.g. Q5D, Q6B, Ph. Eur. 5.31).
The Consultation ends April 2026.

For Full guideline: EMA Phage Therapy Quality Guideline PDF

2. Qualification Opinion on Molecule-Independent Device Bridging Approach (MIDBA)

Issued on 24 October 2025, the Draft Qualification Opinion on the Molecule-Independent Device Bridging Approach (MIDBA) represents a regulatory innovation in how the CHMP evaluates drug–device combination products for subcutaneous biologics, especially monoclonal antibodies.

Objective

MIDBA aims to streamline device bridging studies by allowing developers to leverage existing pharmacokinetic (PK) data from other monoclonal antibodies (mAbs) delivered using the same autoinjector platform — eliminating the need for repeated molecule-specific clinical PK bridging.

In essence, MIDBA provides a qualification framework to waive new comparative PK studies if pre-established device and formulation equivalence criteria are met.

Context of Use

MIDBA specifically applies to YpsoMate 1.0 mL and 2.25 mL autoinjectors as alternative delivery systems for mAbs that:

Have been previously qualified through manual (handheld syringe or PFS) injection during pivotal trials.
Share equivalent formulation, concentration, and administration volumes.

Core Requirements for Applying MIDBA

To adopt this approach, applicants must demonstrate:

Same monoclonal antibody (including identical production process and control strategy).
Same dose, formulation, and injection volume as used in pivotal clinical trials.
Same injection site and absorption profile, with slow systemic absorption typical of mAbs (Tmax of 2–13 days).
Exposed needle length between 4–8 mm, ensuring comparable subcutaneous depth without accidental intramuscular delivery.

Validated PK comparability data from omalizumab and gantenerumab, used as reference mAbs, underpin this regulatory position. CHMP notes that while inter-subject PK variability exists, device-mediated differences are minimal when these parameters are controlled.