The Email That Starts It All

It usually starts with an email. A neurologist at a university hospital in Leuven, Rotterdam or Zurich writes to your medical team. She has a patient who is too ill to wait for approval, doesn't qualify for your trial, and has run out of options. Can you help?

Saying yes feels obvious, and often it is the right answer. Early access programs (EAPs), also called compassionate use or named-patient programs, give patients with life-threatening, chronic or seriously debilitating conditions access to a medicine that isn't yet licensed in their country. For patients who are outside the trial criteria, or who need to stay on treatment after a trial ends, an EAP may be the only route.

But for a company that is new to rare disease, that first yes has consequences. It commits product, people and pharmacovigilance capacity. It creates a precedent with payers. And it puts an unlicensed medicine into routine clinical use, under national rules that differ from one European country to the next.

I've seen EAPs become the best part of a launch, and I've seen them cause trouble two years later in a reimbursement negotiation. The difference is almost always in the planning. Here are the four risks I'd look at before you open the program, and what to do about each. Where something is my practitioner judgement rather than how the system works, I'll say so.

Risk 1: Adverse Events

This is the obvious one. A serious adverse event in an early access patient can damage a product's reputation before it's even on the market, and it can follow you into the regulatory file.

Adverse event reporting is mandatory in every European market. Who carries liability is less uniform. In most countries it rests with the treating physician. In Germany, Sweden and Greece, the manufacturer is responsible. France and the UK distinguish between product quality, which sits with the company, and clinical use, which sits with the prescriber. If you are planning a multi-country program, map this country by country before you start.

What good looks like:

  • Strict patient eligibility. Write criteria that are clear and defensible, and stick to them. The hardest conversations come from exceptions made under pressure.
  • Train every healthcare professional involved: how to use the drug, how to administer it, and how and when to report adverse events. In a rare disease there may be only a handful of treating centres, so you can do this properly, centre by centre.
  • One pharmacovigilance system, including a patient registry. Collect, monitor and analyse all safety data and adverse event reports in one place, and make sure everyone knows how to use it. Emerging data that is easy to access lets you keep reassessing the benefit-risk profile, rather than discovering a signal months later.
  • Inform patients from day one. Patients and families should understand the potential risks, and why reporting side effects matters, before the first dose.

My practitioner view: companies new to rare disease often underestimate how much of this is relationship work. When an expert centre trusts your safety process, they report faster and more completely. That trust is worth building before anything goes wrong.

Risk 2: Supply, of Patients and of Product

This is the risk most often overlooked. Early access programs usually run alongside clinical trials, and that puts two kinds of supply at risk.

Patient supply. In a rare disease, every eligible patient matters to your trial. If the EAP is easier to get into, recruitment suffers. The answer is mutually exclusive inclusion and exclusion criteria for the trial and the EAP, so that an unlicensed medicine is only considered once all viable options, including trial participation, have been explored.

Product supply. You need to understand the level of unmet need in each target market and forecast how it might grow. That starts with agreeing on a definition of unmet need: which patients, and at what stage of disease, should be offered the product.

There is no obligation on a manufacturer to supply any patient. But a written definition helps a great deal if a dispute arises, and in rare disease, with active patient organisations and small, connected expert communities, disputes become public quickly.

You should also know how suitable patients and treating physicians will be identified, and whether access requests have already come in. In Benelux this is a short list. You can usually name the centres in Belgium and the Netherlands that will ask first, and Luxembourg patients are often treated at centres across the border.

A safety stock helps buffer against disruption and keeps treatment continuous for patients already on the program. With orphan products and small batches, that isn't always possible. If it isn't, plan for it openly rather than hoping it won't matter.

Risk 3: Different Rules in Every European Country

The EMA can authorise a medicine across the EU, but early access is largely national. Each country sets its own rules, and many have their own guidance on compassionate use programs. Before you launch an EAP anywhere in Europe, you need to understand the system in that country. Adverse event liability, described above, is just one example of how much they differ.

A few examples closer to home:

  • Belgium. Compassionate use and medical need programs run through the federal medicines agency, FAGG-AFMPS. After approval, before reimbursement, some patients rely on individual requests to the Special Solidarity Fund. These routes work, but they have their own procedures and timelines.
  • The Netherlands. Named-patient supply through the hospital pharmacy is common, and the hospital budget is often part of the conversation.
  • Switzerland. Switzerland sits outside the EU system, so an EMA decision doesn't apply. Swissmedic runs its own procedures, including a temporary authorisation route for medicines for life-threatening diseases and a framework for compassionate use, and physicians can import unauthorised medicines for individual patients under strict conditions. Who pays is typically decided case by case with the patient's health insurer. If Switzerland is part of your European plan, treat it as a separate market from the start.

One rule is universal: you can't promote an unlicensed medicine anywhere in Europe. Every EAP has to be a response to an unsolicited request from clinicians, and you need to be able to show that.

The best protection is transparency about why you're running the program. Legitimate reasons include gathering more evidence of how the product performs, or an ethical commitment to improving access to orphan drugs. Write the aim down, and make sure medical, access and commercial teams describe it the same way.

Real-world data is not real-world evidence

EAP patients are usually closer to the patients who will use the drug after launch than trial patients are. Europe's diverse patient population makes that data even more interesting. But real-world data doesn't automatically become real-world evidence (RWE).

Decide upfront what you need to capture, and how it will turn into evidence that supports licensing and commercialisation. A specialist partner can help you get insight from the data and make sure capture and management meet European requirements, including the GDPR. Fixing the data model after the first fifty patients is expensive. Fixing it after five hundred is often impossible.

Risk 4: The Impact on Commercialisation

This is where companies new to rare disease most often get caught. An EAP is a medical and ethical decision, but it is also the first chapter of your commercial story in each country.

Think through every stage of the product life cycle before you start, including whether any target country will need extended compassionate use support while reimbursement is negotiated. In rare disease that bridge can last much longer than planned.

Pricing precedent. In some countries you can charge a nominal fee for product supplied through a named-patient program. That can help, but it also sets a precedent for future reimbursement discussions and can affect your price for years.

Who pays. In most European countries, the cost of compassionate use is picked up by patients, hospitals or national health insurance. In Austria, Greece and Spain, compassionate use products are expected to be provided free of charge. If you are planning a multi-country program, that difference belongs in the budget from day one.

Europe is not the US. Most European healthcare systems are publicly funded, and the path from early access to reimbursed supply looks completely different from a US launch. That said, real-world data from a well-run EAP can be very valuable alongside clinical trial data in a regulatory submission, and later in the HTA and pricing discussion.

Adherence and expectations. Poor adherence in an EAP can make a product look less effective than it is, and that impression can stick with physicians and payers. Patient expectations can also, understandably, be unrealistically high. Honest communication at the start protects patients and the product.

My practitioner view: an EAP without an exit plan is a commercial risk. Before the first patient starts, you should know how each country moves from early access to reimbursed supply, what you'll charge in between, and who will run those conversations locally. I wrote in May about why the standard launch playbook fails for rare disease drugs in Europe, and early access planned as a bridge is a big part of it.

Before You Say Yes: A Short Checklist

  1. Map liability and AE reporting rules in every country you'll open.
  2. Write eligibility and unmet-need definitions down, with trial and EAP criteria mutually exclusive.
  3. Forecast demand by centre, not just by country, and be honest about stock.
  4. Document the unsolicited request and the strategic aim of the program.
  5. Design the data model for RWE and GDPR before the first patient.
  6. Plan the exit to reimbursed supply, including fees and who pays, country by country.

How RareGenetics Helps

Most of the companies I work with are good at science and clinical development. What they often don't have yet is a team that has run an orphan launch in Europe: one that knows the expert centres by name, has managed early access alongside a trial, and has taken a product from compassionate use to reimbursement in Belgium, the Netherlands and beyond.

That's the work we do. We help with orphan drug launch planning across Europe, from early access strategy to market access and launch readiness. For companies entering Benelux, or a biotech launching its first European product, we also provide an interim Commercial Director for rare disease launches in Benelux: someone who has done it before, to set up the program, open the access route and hand over a working affiliate.

If you're weighing an early access program for an orphan product in Europe, Switzerland or Benelux, I'm happy to talk it through. You can reach me at tom.meuleman@raregenetics.be.