Adverse Event Monitoring for Biosimilars: How Safety Surveillance Works in Real-World Use

When a patient gets a biosimilar instead of the original biologic drug, they shouldn’t have to worry about hidden risks. But here’s the catch: biosimilars aren’t like generic pills. You can’t just swap them in like you would with a $5 version of a brand-name painkiller. They’re made from living cells, not chemicals. That means tiny differences in how they’re made can affect how the body reacts - especially when it comes to immune responses. That’s why safety monitoring for biosimilars isn’t optional. It’s built into the system from day one.

Why Biosimilars Need Special Monitoring

Generics are copies of small-molecule drugs. Their chemistry is simple enough that labs can confirm they’re identical to the original. Biosimilars? Not even close. They’re complex proteins, often made in living cell cultures. Even small changes in temperature, pH, or manufacturing steps can alter their shape. And in biology, shape matters. A slightly different protein might trigger an immune reaction - something the original drug didn’t do. That’s why regulators don’t treat biosimilars like generics. They require extra layers of safety checks after approval.

Take filgrastim, a drug used to boost white blood cells after chemotherapy. The original, Neupogen, has been used for decades. Amjevita, its biosimilar, was approved in 2016. Both work the same way. But if a patient develops antibodies after switching, was it because of the biosimilar? Or because their body changed over time? Without precise tracking, you can’t tell. That’s the core challenge: distinguishing signals between the reference product and its biosimilar copies.

How Safety Systems Track Problems

Two main systems work together to catch problems: spontaneous reporting and active surveillance.

Spontaneous reporting is what happens when a doctor, nurse, or patient reports a bad reaction. In the U.S., that’s the FDA’s FAERS system. In Europe, it’s EudraVigilance. These databases collect millions of reports each year. But here’s the problem: if a pharmacist substitutes a biosimilar without telling the patient or documenting it, the report might just say “filgrastim.” No one knows if it was the original or the copy. That’s why labeling matters.

Since 2017, the FDA has required biosimilars to have a unique four-letter suffix - like filgrastim-sndz for Zarxio. That helps link a reaction to the exact product. Canada doesn’t use suffixes. Instead, they rely on brand names. If a patient gets Amjevita, the report must say “Amjevita,” not just “filgrastim.”

Active surveillance is more proactive. The FDA’s Sentinel Initiative pulls data from millions of electronic health records and insurance claims. It looks for patterns - like a spike in severe rashes or autoimmune reactions after a new biosimilar hits the market. It doesn’t wait for someone to report it. It finds it.

Global Differences in Tracking

Not every country does this the same way.

In the European Union, biosimilars follow the same rules as the original biologics. No extra requirements. The EMA believes if the drug is highly similar, the safety system should be too. But in Canada, the rules are stricter. Their 2022 handbook says biosimilar manufacturers must include detailed plans for monitoring immunogenicity - and show how they’ll separate reports for their product from others.

The U.S. takes a middle path. Manufacturers must submit safety reports every six months for the first two years, then annually. They also have to use the suffix system. But enforcement isn’t perfect. A 2022 survey found that 63% of U.S. doctors were confused about how to report biosimilar reactions. Some didn’t even know the suffix was required.

Spain, on the other hand, made a smart move in 2020. They forced electronic health records to include the exact biosimilar name and manufacturer. Result? Adverse event reporting accuracy jumped from 58% to 92% in just two years.

The Big Problem: Underreporting

Even with all these systems, we’re probably missing a lot.

IQVIA found that in 2021, biosimilars made up 8.7% of all biologic prescriptions in the U.S., but only 0.3% of adverse event reports came from them. That’s a huge gap. Why? Because patients don’t know what they’re getting. A 2022 survey by the Arthritis Foundation showed that 41% of patients on biosimilars couldn’t say whether they received the original or the copy. Pharmacists often switch without telling them. Doctors don’t always document it.

And it’s not just patients. A 2021 study found only 38% of U.S. pharmacists knew what information was needed to report a biosimilar adverse event correctly. That’s not a failure of the system - it’s a failure of training.

What’s Being Done to Fix It

Change is coming - slowly.

Canada started enforcing strict traceability rules on January 1, 2023. Now, every adverse event report must include the manufacturer’s name. Fines for non-compliance can hit $500,000 CAD. That’s a strong incentive.

Technology is helping too. The EMA launched VigiLyze in 2022 - an AI tool that scans 1.2 million reports a year and spots safety signals with 92% accuracy. It can detect patterns humans might miss, like a cluster of rare liver reactions tied to a specific lot number.

Some companies are using AI to scan unstructured clinical notes. If a doctor writes “patient had swelling after switch,” the system can flag it, even if the exact drug name wasn’t typed in. But this tech isn’t cheap. Setting it up costs between $250,000 and $500,000 for mid-sized firms.

Looking ahead, the World Health Organization is pushing for a global tracking system - something like a barcode for every batch of biologic or biosimilar drug. By 2026, they want every vial to have a unique identifier. Pilot studies in Switzerland show this could cut attribution errors by 73%.

What This Means for Patients

As a patient, you don’t need to become an expert in pharmacovigilance. But you do need to know this: if you’re on a biosimilar, you should know exactly what you’re taking. Ask your pharmacist. Check the label. Write it down.

If you feel something unusual - fatigue, rash, fever, joint pain - tell your doctor. And if they ask what drug you’re on, don’t say “the biosimilar.” Say the brand name. Or the suffix. Be specific.

Because safety isn’t just the job of regulators and manufacturers. It’s yours too.

What’s Next for Biosimilar Safety

The market is exploding. In 2022, the global biosimilar market was worth $7.3 billion. By 2028, it’s expected to hit $35 billion. More drugs. More manufacturers. More confusion.

Right now, the U.S. has approved 35 biosimilars. The EU has 43. But by 2030, experts predict over 300 biosimilars will be on the market - all targeting just 30 original biologics. That’s a nightmare for tracking.

Regulators are already planning for it. The FDA’s 2023 draft guidance on interchangeable biosimilars now requires post-marketing studies to test what happens when patients switch back and forth between products. That’s new. That’s important.

But without better labeling, better training, and better tech, we’re setting ourselves up for failure. The systems we have now work - but they’re not built for the scale coming next.

Key Takeaways

• Biosimilars aren’t generics - they need extra safety tracking because of their complex biology.
• Unique identifiers (like four-letter suffixes) and brand-name reporting are critical to link reactions to the right product.
• Underreporting is a major issue - patients and providers often don’t know which product was given.
• Active surveillance using real-world data is becoming as important as spontaneous reports.
• AI tools like VigiLyze are improving signal detection, but adoption is slow and expensive.
• Global standards are emerging, but systems still vary widely between countries.
• By 2030, current systems may not handle the volume of biosimilars coming to market.