Biosimilar Switching: What Regulators Settled and What You Still Have to Prove

The scientific argument about biosimilar switching was settled some years ago. In a joint statement issued in September 2022, EMA and the Heads of Medicines Agencies confirmed that biosimilars authorised in the EU are interchangeable with their reference medicine and with equivalent biosimilars. Yet uptake across Europe remains uneven, and the reason is rarely regulatory. The obstacle sits with prescribers, hospital committees and patients — and it is an evidence problem of a different kind.

What the regulators actually closed

The 2022 statement rested on the accumulated experience of biosimilars authorised in the EU since 2006, supported by safety data covering more than a million patient treatment years without new safety concerns emerging. Its conclusion was that a switch, made under the supervision of a prescriber, does not require additional systematic switching studies.

Two things it did not do are worth stating plainly:

• It did not create automatic substitution. Whether a pharmacist may dispense a biosimilar in place of what was prescribed, without consulting the prescriber, remains a national competence. Practice differs considerably across Member States.
• It did not remove the need for local persuasion. A hospital pharmacy and therapeutics committee is not bound by an EU-level scientific statement when it sets its own protocol.

The direction of travel has continued since. CHMP adopted a reflection paper on a tailored clinical approach in biosimilar development in March 2026, following a consultation that closed in September 2025, and work on ICH M18 is examining when comparative efficacy studies add value at all. Regulators are asking for less clinical data, not more.

Where the evidence gap genuinely sits

Systematic reviews and meta-analyses of switching between reference biologics and biosimilars have not identified an increased immunogenicity or safety risk. That body of work is now substantial for originator-to-biosimilar transitions.

It is thinner for two situations that are becoming routine:

• Biosimilar-to-biosimilar switching. As multiple biosimilars of the same reference product reach the market and tender outcomes change annually, patients are moved between biosimilars rather than from the originator. Published evidence for these switches is more limited, and reviewers have been cautious about drawing firm conclusions.
• Multiple sequential switches. A patient switched three or four times over several years is a real clinical scenario with comparatively little dedicated study behind it.

These are the questions clinicians now raise, and answering them with data about a single originator-to-biosimilar transition does not land.

The nocebo effect is an access issue, not a footnote

Comparisons of open-label and double-blinded switching studies have consistently found higher discontinuation in open-label settings — a difference attributed not to the molecule but to expectation. Patients told they are being moved to a different product report more adverse events and stop treatment more often.

For a company, a discontinued patient is lost volume; for a health system, it is a lost saving and a patient back on a more expensive therapy. The literature on mitigation points consistently at how the switch is communicated and organised: framing, clinician confidence, staff training, personalised information, and involving patients in the decision rather than announcing it.

Evidence that payers and hospitals will act on

• Local real-world data. Retention and persistence figures from comparable European settings are more persuasive to a hospital committee than a pivotal trial.
• Switch-programme outcomes, not just clinical equivalence. Committees want to know what happened to discontinuation rates when a switch was actually implemented.
• Budget impact modelled on realistic uptake. Projections that assume frictionless conversion overstate savings and lose credibility quickly.
• Materials built for the conversation. Prescriber and patient communication is part of the access strategy, not a marketing afterthought.

How PQRA helps

PQRA supports biosimilar developers and marketing authorisation holders across regulatory and market access. We advise on development and switching evidence strategy in light of the tailored clinical approach, build real-world evidence and budget impact arguments suited to Greek and EU payers, prepare hospital and tender-facing dossiers, and help design switch programmes that anticipate the behavioural barriers rather than discovering them after launch.

Interchangeability is established. Uptake still has to be earned. Talk to PQRA about the evidence your biosimilar needs to convert approval into use.