Top 10 Reference Biologics with the Most FDA-Approved Biosimilars

For healthcare data analysts and formulary teams, the purple book FDA database is the authoritative starting point for understanding which reference biologics have attracted the greatest number of biosimilar approvals. The September 2026 snapshot shows a concentrated competitive landscape: adalimumab, pegfilgrastim, and trastuzumab lead the ranking by approved biosimilar licenses.

This guide identifies the top 10 reference biologics by the number of approved biosimilar biologics license applications (BLAs), explains the counting methodology, and highlights how to interpret Purple Book records without confusing regulatory approvals with commercial activity.

Important: This ranking counts unique approved 351(k) BLAs associated with each reference product. It does not count package sizes, dosage forms, NDC codes, market share, dispensing volume, or commercial availability.

Table of contents

• What the Purple Book measures
• Counting methodology
• Top 10 reference biologics by approved biosimilar BLAs
• How to use these counts in formulary analysis
• Data-quality checks for Purple Book extracts
• Why license-level ranking matters
• Sources

What the Purple Book measures

The FDA Purple Book is a database of FDA-licensed biological products. It includes reference products, biosimilars, interchangeable biosimilars, and other licensed biological products regulated by FDA centers.

For biosimilar analysis, the key regulatory designation is section 351(k) of the Public Health Service (PHS) Act. Purple Book listings record biosimilar licensure under section 351(k), distinguishing those products from reference biologics licensed under section 351(a).

That distinction matters when building a reproducible dataset. A product’s brand name, nonproprietary name, presentation, or package configuration may appear more than once in a data extract. The BLA number is the more reliable unit for counting approved biosimilar licenses.

For background on the database structure, terminology, and search workflow, see the FDA Purple Book Guide.

Counting methodology

This ranking evaluates unique 351(k) BLAs, rather than individual package presentations or NDC codes.

The method is:

1. Identify the reference biologic and its core name in the Purple Book.
2. Retrieve associated biological products classified as biosimilar or interchangeable.
3. Filter records to products licensed under section 351(k).
4. Deduplicate records by BLA number.
5. Count each unique 351(k) BLA once for the relevant reference product.
6. Rank reference biologics from the highest count to the lowest.

This approach avoids overstating competition when the same BLA appears repeatedly for different strengths, vial sizes, delivery devices, dosage forms, or other package presentations.

A single 351(k) BLA license can contain both biosimilar and interchangeable presentations. Consequently, analysts should not treat every displayed status or presentation as a separate license. The BLA remains the appropriate regulatory-level unit for this comparison.

The resulting count is a measure of approved regulatory licenses associated with a reference product. It is not a measure of products currently marketed, payer coverage, utilization, dispensing volume, price, or market share. Approval and commercial launch are separate events, and a Purple Book record should not be interpreted as evidence that every approved product is actively available in every market channel.

Top 10 reference biologics by approved biosimilar BLAs

The table below summarizes the September 2026 Purple Book snapshot.

Counts reflect unique approved 351(k) BLA numbers in the September 2026 snapshot. The ranking is based on FDA licensure records, not on launch timing or utilization.

1. Adalimumab: 10 approved biosimilar BLAs

Adalimumab, marketed as Humira, ranks first. As of the September 2026 Purple Book snapshot, adalimumab Humira leads with 10 approved unique 351(k) biosimilar BLAs.

The size of the adalimumab group makes it especially important to deduplicate records correctly. A search can return repeated rows for the same BLA because a product may have multiple presentations or because biosimilar and interchangeable information is displayed across related records.

For formulary teams, the adalimumab category is often the most complex to monitor because product status, presentation, payer policy, and contracting arrangements may differ even when products share the same reference biologic. The FDA record establishes licensure; it does not by itself establish formulary placement or operational availability.

Analysts building a Humira biosimilar list should therefore retain the BLA number, product name, biosimilar or interchangeable designation, dosage form, and presentation as separate fields. This preserves both the regulatory license count and the product-level detail needed for downstream analysis.

2. Pegfilgrastim: 6 approved biosimilar BLAs

Neulasta, the reference product for pegfilgrastim, ranks second with 6 approved biosimilar BLAs.

Pegfilgrastim illustrates why reference-product analysis should be conducted at the active ingredient and reference-product level rather than by brand-name text alone. Different presentations may appear in the database, but they should not automatically be counted as separate biosimilar licenses.

For healthcare data teams, pegfilgrastim records can support several analyses:

• mapping the competitive set around a reference product;
• identifying interchangeable designations;
• comparing delivery presentations;
• monitoring the growth of approved competition over time; and
• connecting regulatory records to separate contracting or utilization datasets.

Those uses require careful separation between FDA approval data and market data. A licensed product may have a different availability profile from another product in the same category.

3. Trastuzumab: 5 approved biosimilar BLAs

Herceptin ranks third, with 5 approved biosimilar BLAs.

Trastuzumab is a clinically important example of a complex biologic category in which analysts may need to track multiple indications, dosage forms, and administration settings. The Purple Book supplies the regulatory relationship between reference product and biosimilar, while clinical policy and formulary systems provide additional context.

A robust data model should preserve:

• the reference product;
• the biosimilar product name;
• the BLA number;
• the 351(k) legal pathway;
• any interchangeable designation;
• dosage form and strength; and
• the date of the relevant regulatory record, where available.

Keeping these dimensions separate allows analysts to answer different questions without collapsing license counts and presentation counts into one measure.

4. Bevacizumab: 4 approved biosimilar BLAs

Avastin has four approved unique 351(k) biosimilar BLAs in the snapshot. Bevacizumab analysis can be especially sensitive to presentation and indication details, so a license-level count should be supplemented with product and clinical metadata when used for formulary work.

5. Rituximab: 4 approved biosimilar BLAs

Rituxan also has four approved biosimilar BLAs. As with other oncology biologics, teams should avoid assuming that an approved biosimilar has identical operational use across all institutions. Approval establishes the FDA-recognized regulatory status; local policy, contracting, administration requirements, and clinical protocols remain separate considerations.

6. Infliximab: 4 approved biosimilar BLAs

Remicade has four approved biosimilar BLAs in the September 2026 snapshot. Teams reviewing an infliximab biosimilar list should distinguish unique BLA licenses from individual package configurations.

Infliximab is also a useful category for demonstrating how regulatory records connect to practical data questions. A formulary analyst may need to know how many biosimilar licenses exist, which products are designated interchangeable, which presentations are approved, and whether a product is operationally available. These are related but distinct questions and should be answered with appropriately scoped data.

7. Ranibizumab: 3 approved biosimilar BLAs

Lucentis has three approved biosimilar BLAs. Ranibizumab records demonstrate the value of preserving presentation-level details even when the headline metric is license-level: the BLA count supports competitive-landscape analysis, while presentation data supports clinical and procurement workflows.

8. Filgrastim: 3 approved biosimilar BLAs

Neupogen has three approved biosimilar BLAs. Filgrastim is an established biologic category, making it useful for longitudinal analyses of how biosimilar competition develops after reference-product approval.

When comparing categories, analysts should use consistent inclusion criteria. Mixing product presentations for one reference biologic with unique BLAs for another can create misleading rankings.

9. Epoetin alfa: 2 approved biosimilar BLAs

Epogen and Procrit are associated with two approved biosimilar BLAs in this snapshot. Because epoetin products may be represented through different brand and product naming conventions, normalization of reference-product names is important before aggregation.

10. Etanercept: 1 approved biosimilar BLA

Enbrel has one approved biosimilar BLA in the September 2026 snapshot. Its position illustrates that a reference biologic may have a relatively small approved biosimilar group even when it is clinically prominent or widely used.

How to use these counts in formulary analysis

The ranking is most useful as a regulatory competition indicator. It can help teams prioritize categories for deeper review, identify reference products with substantial biosimilar activity, and structure monitoring dashboards.

However, the count should not be used alone to infer:

• market share;
• dispensing volume;
• product uptake;
• payer coverage;
• net price;
• launch timing;
• supply reliability; or
• substitution behavior.

A complete formulary intelligence workflow typically joins Purple Book records with additional sources, such as claims, purchase data, wholesaler availability, payer policies, institutional preference lists, and contracting information. Each source answers a different question.

For example, the Purple Book can establish that a product has an FDA license under section 351(k). A claims dataset may show utilization. A purchasing dataset may show acquisition activity. A formulary file may show preferred status. None of those measures should be substituted for another.

The same principle applies to interchangeable status. Interchangeability is a regulatory designation, but substitution rules and pharmacy practice requirements are governed by applicable law and policy. Analysts should therefore retain the designation as a field rather than treating it as an automatic utilization outcome.

Data-quality checks for Purple Book extracts

Before publishing a ranking or using it in a dashboard, perform these checks:

Deduplicate by BLA number

Repeated rows do not necessarily indicate separate licenses. Deduplicate the 351(k) records by BLA number before counting.

Separate pathway from presentation

Confirm that the record is licensed under 351(k). Do not combine reference-product records licensed under 351(a) with biosimilar records.

Preserve interchangeable status

A 351(k) BLA can include biosimilar and interchangeable presentations. Keep that status visible without counting the license twice.

Normalize reference names

Brand names, proper names, and related biological product labels may vary. Create a controlled reference-product field before aggregation.

Record the snapshot date

Purple Book data changes over time. Every ranking should include its extraction or snapshot date so users understand the temporal scope.

Link back to FDA records

Retain the BLA number and source URL wherever possible. This supports auditability and makes later updates easier.

For a broader overview of approved products and regulatory terminology, see FDA-Approved Biosimilars.

Why license-level ranking matters

Counting unique 351(k) BLAs produces a defensible view of the number of approved biosimilar licenses associated with each reference biologic. It is more stable than counting package presentations and more transparent than relying on product-name strings alone.

The approach also makes comparisons reproducible. Analysts can explain exactly what was counted, which records were excluded, and why repeated presentations were not treated as additional approvals. That clarity is essential when regulatory data is used in executive reporting, formulary reviews, procurement planning, or public-facing intelligence.

The September 2026 snapshot shows a clear concentration of approved biosimilar activity around adalimumab, pegfilgrastim, and trastuzumab. Yet the ranking should be read as a map of FDA-approved regulatory licenses—not as a proxy for commercial success or patient use.

Explore Purple Book biosimilar records in QOPE.

Sources

• FDA Purple Book Database
• FDA-Approved Biosimilars
• Explore Purple Book data in QOPE