Biosimilars: Why Switching Is Safe — and What Changes in the Pen

Suddenly there is a different pack waiting at the pharmacy: same active ingredient, different name, different pen. A biosimilar is not a generic but a biologically manufactured successor product that is highly similar to the original — about as similar as two production batches of the same original preparation are to one another. On current evidence, efficacy and safety are regarded as comparable. What really changes when you switch is usually something quite practical: how the pen is handled and how it is stored.

1. What a biosimilar is

Biologics — also called biopharmaceuticals — are medicines whose active ingredient is not assembled chemically but produced by living cells. They include insulins, antibodies directed against inflammatory messengers, growth factors and many modern cancer medicines. The molecules are enormous and intricately folded; their three-dimensional structure determines how they work.

Once the patent protection of such an original preparation expires, other manufacturers may develop a successor product. Because they do not know the original's production process, and because a biological molecule cannot be copied exactly, what emerges is not an identical product but a highly similar one: a biosimilar.^¹

2. Generic or biosimilar? The decisive difference

Both are successor products that appear once a patent has expired, and both are cheaper than the original — but they come about in completely different ways.

A generic contains a chemically manufactured active ingredient. Molecules of that kind are small and can be reproduced exactly: a generic is chemically identical to the original. For approval it is therefore usually enough to demonstrate bioequivalence — that the active ingredient reaches the body in a comparable amount and at a comparable speed. How that works in everyday life, and why tablets can still look different, is explained in the guide Generics vs. brand-name medicines.

A biosimilar, by contrast, is produced by living cells — usually bacterial, yeast or mammalian cell cultures. Every cell line, every culture medium, every purification step influences the end product. That is why one cannot and may not speak of "identical" here, only of "highly similar". And that is why proof of bioequivalence is not enough: a biosimilar goes through a considerably more extensive approval procedure than a generic.

A rule of thumb for everyday life: what you swallow is usually a generic. What you inject or receive as an infusion is more likely to be a biosimilar. There are exceptions, but as a rough guide it carries you a long way.

3. What approval demands

In the European Union, biosimilars are approved centrally through the European Medicines Agency (EMA). The requirements are high — and they differ fundamentally from those for a generic.^²

At the heart of the procedure is the comparability programme: a step-by-step demonstration that the biosimilar does not differ from the original in any respect relevant to efficacy and safety.

1. Analytical comparison. Structure, folding, sugar side chains, purity and binding properties are set against the original molecule by molecule using high-resolution methods. This is the most demanding and the most informative part.
2. Functional comparison in the laboratory. Cell experiments check whether the molecule binds the same receptors and triggers the same biological effects.
3. Pharmacokinetics in humans. Studies show whether uptake, distribution and breakdown in the body match.
4. Comparative clinical study. In an indication that responds particularly sensitively to differences, efficacy, tolerability and immune reactions are compared directly against the original.
5. Immunogenicity. There is a targeted investigation of whether the body forms antibodies against the medicine — a central safety question with biologics.

Approval follows only when all the stages together produce a coherent picture. The underlying idea: a biosimilar does not have to prove its efficacy from scratch — the original has already done that. It has to prove that it matches the original.

4. Is switching safe?

That is the question on everybody's mind, and the answer is pleasingly clear: on current evidence, switching between an originator biologic and its biosimilar is regarded as unproblematic. Efficacy and safety are assessed as comparable — this is the shared position of the European regulators and of independent institutions such as IQWiG, Germany's institute for quality and efficiency in health care.^³

By now this has been examined extensively, among other things in switching studies in which people were moved from the original to the biosimilar and back again. No systematic loss of effect and no rise in side effects could be shown.

Even so, a switch is not a purely administrative act that you should simply let wash over you. There are good reasons to accompany it consciously:

• You should be told beforehand — a switch you first hear about at the pharmacy counter is a poor start.
• The handling often changes — and that is the point at which mistakes really do happen in everyday life.
• A switch in the middle of an unstable phase of illness is unfortunate — not because it would be dangerous, but because cause and effect can then no longer be told apart.

Whether and when a switch makes sense for you is decided by the practice treating you — together with you.

5. The nocebo effect: a real phenomenon

There is one observation that should be named honestly, because otherwise it comes across as a reproach: people who expect to get worse after a change of preparation experience exactly that more often. Specialists call it the nocebo effect — the negative counterpart to the placebo effect.

In studies it shows up in the fact that people who know about a switch and are sceptical about it stop the new preparation more often than people who knew nothing about it — even though objective disease parameters such as inflammatory markers stay unchanged. The symptoms are not imagined: pain, tiredness and malaise really are felt. What is influenced is not the perception itself but the way it is processed.

And the other direction matters just as much: the nocebo effect is not an explanation that allows genuine symptoms to be brushed aside. If you feel worse after a switch, that belongs in front of a doctor — not talked away.

6. What really changes: the pen in your hand

This is where the difference that matters most in practice lies — and it has nothing to do with the active ingredient but with the device. The injection systems of different manufacturers are built differently, and anyone who has used one particular pen for years has to get used to something new.

• Needle length and gauge: a different needle feels different and sometimes calls for a different angle or a different skin fold.
• Trigger mechanism: some pens are released by pressing a button, others by pressing the device onto the skin. If you do not know where the pressure point is, you release too early or not at all.
• Injection speed: autoinjectors deliver the liquid at different rates. Faster delivery can sting more for a moment — unpleasant, but not a sign of a problem.
• Hold time: the time the pen has to stay on the skin after it is released differs. Lifting it off too early means part of the dose does not arrive.
• Feedback: clicking sounds, viewing windows and colour markings differ from system to system — that too has to be learned to read all over again.

A second, often overlooked point: carry on rotating the injection sites systematically. Hardened areas in the subcutaneous fat develop regardless of the preparation and alter absorption — they are a common but avoidable reason for an apparently fluctuating effect after a switch.

7. Storage and the cold chain

Biologics are delicate protein molecules. Heat, frost and vigorous shaking can destroy them — and you cannot always tell by looking at the solution. Most pre-filled syringes and pens are therefore kept in the fridge, usually at two to eight degrees Celsius.

• Do not freeze: a biologic that has been frozen once has to be disposed of, even if it has thawed again. The back wall of the fridge and the coldest shelf, directly above the salad drawer, are the risk zones.
• Not in the fridge door: that is where the temperature fluctuates most.
• Let it warm up before injecting: many manufacturers recommend taking the pen out of the fridge some time before use. Cold liquid stings considerably more.
• Mind the time window outside the fridge: many preparations may be kept at room temperature for a limited period — how long is stated in the package leaflet and can differ between the original and the biosimilar.
• Keep it cool when travelling: a cool bag with a cold pack, but with no direct contact with the pack, and never in the car or in checked luggage.

All the other rules on temperature, light, humidity and shelf life are in the guide Storing medications correctly. This is exactly the point that deserves a second look when you switch: the storage requirements for a biosimilar are not automatically the same as for the preparation you are used to.

8. Where biosimilars are used

Biosimilars stopped being a niche topic long ago. They involve some of the most frequently prescribed biologics of all.

Anyone using insulin for diabetes has very probably held a biosimilar in their hand at some point. In rheumatology and gastroenterology, TNF inhibitors are the big field of application — in rheumatoid arthritis, psoriasis, Crohn's disease and ulcerative colitis. A biologic is frequently combined there with methotrexate; a switch to a biosimilar changes nothing about that underlying therapy.

9. Note the batch number — with biologics that is compulsory

Many people do not know about this point, and it is the most important organisational difference from tablets: with biologics it should always be traceable which preparation, from which batch, was given.

The reason lies in the manufacturing. Because the product comes from living cells, medicines safety has to be able to follow not just the active ingredient but the specific product and its production batch. European pharmacovigilance therefore explicitly requires that the brand name and the batch designation are documented for biologics — every single time they are used.^⁴

For the same reason, with biologics: do not rely on the name of the active ingredient alone. The original and its biosimilars share the active ingredient but carry different brand names. Both should be on your list — active ingredient and product name. How to build such an overview is set out in Keeping a medication list.

10. Costs, discount contracts and the pharmacy

Biosimilars are as a rule considerably cheaper than the original preparation. For you as someone with statutory health insurance in Germany that usually makes little difference to the co-payment — the effect is on what the health insurers spend, and the resulting price pressure often brings down the price of the original preparations as well.^⁵

Two mechanisms matter in practice. First, health insurers conclude Rabattverträge (discount contracts) with individual manufacturers; the pharmacy then dispenses that manufacturer's product by preference. Second, there are German rules on substitution in the pharmacy — the aut idem provisions — which are markedly more cautious for biologics than for tablets; and the prescribing practice can rule substitution out by ticking the aut idem box on the prescription if there is a medical reason for doing so.

The result in everyday life: it can happen that a repeat prescription brings you a different pack from the one you had last time. Ask at the pharmacy when that happens, and have it confirmed that the active ingredient is the same. If the injection system changes, instruction goes with it — even when the switch happens "only" for contractual reasons.

11. Symptoms after a switch: what to do now

You have felt worse since the changeover. That may be down to the preparation, to the nocebo effect, to the injection technique — or simply to the disease being more active at the moment. The only way to tell these apart is with data and a calm head.

1. Do not stop on your own. An abrupt end to biologic therapy can trigger a flare. Contact the practice treating you instead.
2. Write the symptoms down concretely. What exactly, since when, how severe, and how long after the injection. "I feel worse" gets nobody any further.
3. Have your technique checked. Very often a handling error is behind it: lifted off too early, wrong angle, injection into a hardened site, liquid too cold.
4. Compare the objective values. Inflammatory markers, blood glucose trends or disease activity scores show whether anything has changed measurably.
5. Report a suspected side effect. With the brand name and the batch number — through the practice, the pharmacy or directly.

If careful examination reveals no other reason, switching back is possible — that is for the practice treating you to decide. It is not a failure but a normal adjustment of therapy.

12. How brite helps you with a biosimilar switch

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