Adverse Event Monitoring for Biosimilars: How Safety Surveillance Works Today

When a patient gets a biosimilar instead of the original biologic drug, how do doctors and regulators know if something goes wrong? It’s not as simple as tracking a generic pill. Biosimilars are made from living cells, not chemicals. Even tiny changes in how they’re manufactured can affect how the body reacts. That’s why adverse event monitoring for biosimilars isn’t just important-it’s a complex, high-stakes system built to catch problems early.

Why Biosimilars Need Special Safety Tracking

Generics are copies of small-molecule drugs. They’re chemically identical to the original. Biosimilars? They’re highly similar, but not identical. Think of it like two handmade leather jackets from the same designer. They look the same, but the stitching, dye batch, or hide source might differ slightly. Those small differences can trigger immune responses in some patients-something called immunogenicity. That’s the biggest safety concern.

Unlike generics, biosimilars can’t be tested for every possible variation before approval. Clinical trials involve thousands, not millions, of patients. Rare side effects-like severe allergic reactions or autoimmune flare-ups-might only show up after thousands more people start using the drug. That’s why post-approval monitoring isn’t optional. It’s required.

How Adverse Events Are Reported

Most reports start with doctors, nurses, or patients. If someone has an unexpected reaction-rash, fever, joint pain, or worse-they or their provider file an adverse event report. In the U.S., that goes into the FDA’s FAERS system. In Europe, it’s EudraVigilance. Canada uses its Canada Vigilance Program.

But here’s the catch: these systems don’t automatically know if the drug was the reference product or the biosimilar. If a patient gets Amjevita (a biosimilar to Humira) and has a reaction, the report might just say “adalimumab.” That’s useless. You can’t tell if the problem came from the biosimilar or the original.

That’s why product identification matters. The FDA started requiring unique four-letter suffixes in 2017-like “-abp21” for Amjevita. But not all countries do this. Health Canada relies on brand names. In Spain, electronic health records now include the manufacturer’s name. In the U.S., a 2022 survey found 63% of doctors were confused about how to document which version the patient received.

The Two-Track Monitoring System

There are two main ways to track safety: passive and active.

Passive monitoring is spontaneous reporting. It’s the backbone of most systems. Healthcare providers report reactions as they come in. The FDA requires serious events to be reported within 15 days. Non-serious ones within 90 days. But this system has gaps. A 2021 IQVIA analysis showed that biosimilar-specific reports made up only 0.3% of all biologic reports-even though biosimilars accounted for 8.7% of prescriptions. That means most reactions are either missed or misattributed.

Active monitoring fixes that. Systems like the FDA’s Sentinel Initiative pull data from millions of electronic health records, insurance claims, and pharmacy databases. They look for patterns: Is there a spike in liver enzyme levels after switching to a specific biosimilar? Are patients on one biosimilar having more infections than those on another? This isn’t just waiting for reports-it’s hunting for signals.

Global Differences in Rules

Every country has its own rules. The European Medicines Agency (EMA) treats biosimilars the same as reference products under its pharmacovigilance framework. No extra rules. The U.S. takes a middle path: biosimilars must have a risk management plan (RMP) that includes immunogenicity monitoring and detailed reporting protocols. Health Canada goes further-it explicitly requires manufacturers to explain how they’ll tell biosimilar reports apart from reference product reports.

Traceability is where things get messy. In the U.S., biosimilars have suffixes, but many hospitals still don’t have systems to capture them. In Canada, brand names are required. In Spain, electronic records include the manufacturer. In India, manufacturers must submit safety reports every six months for two years after launch. In the EU, it’s annual.

And then there’s the problem of multiple biosimilars for the same drug. In 2022, the U.S. approved 10 new biosimilars for just one reference product. Now you’ve got six different versions of the same drug. If a patient has a reaction, which one caused it? Current systems struggle with this.

Real-World Challenges for Doctors and Pharmacies

Healthcare workers are on the front lines. A 2022 survey of 1,247 U.S. physicians found that hematologists and oncologists-the ones most likely to prescribe biosimilars-had the highest confusion rates. One doctor on Medscape said: “I now document both the brand and the specific manufacturer. Otherwise, I can’t tell what caused the reaction.”

Pharmacists are equally caught in the middle. A 2021 study showed only 37.8% of U.S. pharmacists knew exactly what information to include in a biosimilar adverse event report. Many don’t know if they’re supposed to write the brand name, the generic name, the suffix, or the manufacturer. One pharmacist in Barcelona said switching to mandatory manufacturer tracking in electronic records boosted reporting accuracy from 58% to 92%.

Patients don’t help much either. A 2022 Arthritis Foundation survey found 41.2% of patients on biosimilars didn’t know whether they got the reference product or the biosimilar. How can they report a reaction accurately if they don’t know what they took?

Technology Is Changing the Game

Manual reporting isn’t enough anymore. AI is stepping in. In 2022, the EMA launched VigiLyze-an AI tool that scans 1.2 million new safety reports every year. It flags potential signals with 92.4% accuracy. Companies like ArisGlobal and Oracle Health Sciences now offer cloud-based platforms that automate data collection, reduce reporting errors, and speed up analysis.

But it’s expensive. Implementing an AI-driven system costs between $250,000 and $500,000 for a mid-sized company. Most small manufacturers can’t afford it. That creates a gap: big players have advanced monitoring. Smaller ones rely on outdated methods.

Another innovation? Lot-level tracking. Right now, most reports just say “adalimumab.” What if every vial had a unique lot number, like a serial number on a phone? That way, if a batch causes a spike in reactions, you can pull it off the shelf fast. The International Pharmaceutical Regulators Programme is pushing for a global UDI-like system for biologics by 2026. Early pilots in Switzerland showed it could cut attribution errors by 73.5%.

Costs and Future Pressures

Monitoring biosimilars isn’t cheap. The Tufts Center estimates it costs $2.1 million per year to run pharmacovigilance for a single biosimilar in the U.S. That’s 18.3% of all post-approval spending. As the market grows-projected to hit $34.9 billion by 2028-these costs will climb.

And the pressure is building. The WHO predicts over 300 biosimilars will be on the market by 2030, targeting just 30 reference products. Current systems weren’t built for that scale. Regulatory agencies are already warning that they’ll need a complete redesign.

One thing’s clear: if we want biosimilars to keep lowering drug costs, we need safety systems that are smarter, faster, and more precise. Right now, we’re relying on patchwork solutions. The next decade will decide whether we can scale this properly-or if patients will pay the price.

What’s Next for Biosimilar Safety?

The FDA’s 2023 draft guidance on interchangeable biosimilars now requires post-marketing studies to track what happens when patients switch back and forth between the reference product and biosimilar. That’s new. That’s important. Because if switching causes more reactions, we need to know before it becomes widespread.

Health Canada’s 2023 rule requiring clear manufacturer identification in every report is a step in the right direction. Non-compliance can cost up to $500,000. That’s a strong incentive.

But the real solution isn’t just better rules. It’s better systems. Electronic health records that auto-populate the manufacturer name. Pharmacy software that forces the right selection. Patient apps that tell them exactly what they’re getting. And global standards so a report from Germany can be understood by a regulator in Canada.

For now, the system works-mostly. A 2016 Danish study found no difference in safety between biosimilars and their reference products. But that was five years ago. The number of biosimilars has tripled since then. The rules are catching up. The technology is improving. But the human factor-documentation, training, awareness-is still the weakest link.

Until every provider knows which product a patient received, and every patient can tell you what they were given, the safety net will always have holes.