Fresenius Kabi Expands Biosimilar Pipeline With Deal for Next-Generation Molecules

Joining forces with a Chinese biologics company enabled Fresenius Kabi to obtain rights up for up to 37 biosimilar candidates over the next decade.

Fresenius Kabi, a serious player in the US biosimilar arena, had been seeking ways to bolster its biosimilar pipeline, and it made quite a splash earlier this week. The company signed an agreement with the Chinese-based WuXi Biologics, vastly expanding the Fresenius Kabi biosimilar pipeline. This comes after completing its acquisition of another biosimilar manufacturer last month.

Through October 2026, Fresenius owned several biosimilar approvals: adalimumab (Idacio), denosumab (Conexxence/Bomyntra), pegfilgrastim (Stimufend), rituximab (Zimrixby), tocilizumab (Tyenne), and ustekinumab (Otulfi)). PB016, a vedolizumab biosimilar in the Fresenius Kabi biosimilar pipeline through a partnership with Polpharma) is currently in FDA review. It also has Opdivo and Keytruda biosimilar candidates in development, among others.

Adding to the Fresenius Kabi Biosimilar Pipeline

The new deal will provide “exclusive option rights for up to 37 potential first-to-market biosimilar candidates,” expanding Fresenius’ present portfolio from 29 marketed and pipeline molecules “to up to 66 in the next decade.” According to Fresenius, this will provide a “next-generation portfolio” that covers “13 therapeutic areas and multiple biologic technologies, including monoclonal and bispecific antibodies, antibody–drug conjugates, and fusion proteins.”

No monetary value was placed on the agreement, but Fresenius disclosed that it will pay WuXi Biologics on a “fee-for-service basis for each biosimilar candidate that Fresenius selects for development.”

Fresenius also announced that it had purchased the remaining shares of mAbxience in October, completing its full acquisition of the company. This move had also added to Fresenius’ biosimilar pipeline.

This article was written by our Director of Content, Stanton Mehr. Stan has been writing commentary and reporting news about the biosimilar industry since the submission of the first biosimilar 351(k) application to the FDA 13 years ago. Since that time, BR&R has been tracking the US biosimilar marketplace, with the industry’s original, comprehensive and updated database of biosimilar filings with the FDA.

Lower Costs for Biosimilar Development Will Yield Myriad Benefits: Part 2

The removal of the phase 3 trial mandate for biosimilar manufacturers opens the door for lower development costs and for new biosimilar players. At last week’s Festival of Biologics program in Basel, sessions focused on pembrolizumab biosimilar activity driven by these lower costs.

Formycon’s Pembrolizumab Case Study

On October 13, the news had just been announced that the FDA had accepted Formycon AG’s 351(k) application for FYB206, marking the first pembrolizumab biosimilar candidate to reach that milestone. That day, Andreas Seidl, PhD, Chief Scientific Officer, Formycon AG, detailed why the company avoided comparative efficacy trials on FYB206.

This case study spoke to the scientific rationale for a pharmacokinetic (PK)-focused development program. The updated guidance from the FDA, said Dr. Seidl, specified that comparative efficacy studies (CESs) should only be conducted if they will provide meaningful additional information.

In the case of the reference product Keytruda, the molecule has high affinity for the target PD-1 receptor. The biology of pembrolizumab is well characterized, and its mechanism of action is well understood. It is a humanized IgG4 monoclonal antibody, and analytical similarity can be adequately demonstrated. As a result, any CES would not provide added value. Dr. Seidl stated, “At the approved dose, saturated target engagement and a flat exposure-response relationship limit the sensitivity of the comparative efficacy endpoints. A PK-focused program is proportionate when the integrated evidence sufficiently resolves residual uncertainty.”

Formycon’s FYB206 has comparable parameters, including PK and molecular weight, to the reference product, and their glycan profiles are highly similar. This translates into comparable neonatal Fc receptor (FcRn) binding. The company negotiated with FDA that a late-stage CES study was unneeded. Their PK study comprised 96 patients with completely resected stage II/III melanoma. This study also assessed the safety and immunogenicity of FYB206, as well as an exploratory efficacy endpoint.

With Changes to the Phase 3 Trial Mandate, the Race is on for New Biosimilar Manufacturers

Bert Thomas, PhD, Senior Vice President of Business Development, Bio-Thera Solutions, emphasized that removing the late-stage CES requirement has been a priority point of discussion at the Festival of Biologics meetings for years. “Once the dam broke, pretty much everyone else followed, because the science is there.

“The hope is lower prices through lower development costs, faster development timelines, and more competition.” As a result of these efforts, he said it may be possible to start considering biosimilar competition for lower-revenue biologics. “The promised land is filling the biosimilar void,” proclaimed Dr. Thomas.

Based on the high costs of development, Bio-Thera had exited the oncology biosimilar arena. They re-entered the field with a pembrolizumab candidate (BAT3306), only because the phase 3 trial mandate was removed.

“We all go after biosimilars for the same high revenue targets. In reality, after the phase 3 clinical trial mandate was removed, there are many new players,” said Dr. Thomas. He stated there are more than 30 pembrolizumab biosimilars globally, and at least 15 dipliumumab biosimliars in various stages of development. “Most of these players don’t have an existing FDA or EMA approval—there is a learning process there. Do they know how to get a phase 3 waiver? How do they ask questions of the regulator? Do they have the capacity to support global launches? And the intellectual property challenge with originators is not getting easier or cheaper,” he pointed out.

The change to the phase 3 trial mandate has also changed the outlook of major biosimilar players: Samsung Bioepis, Celltrion, and Sandoz all announced significant pipeline expansions in the past year alone. These moves will also carry their commercialization partners (e.g., Teva, Harrow, Hikma, and Accord to name just a few) into more product areas.

Lower Costs for Biosimilar Development Will Yield Myriad Benefits: Part 1

At last week’s Festival of Biologics program in Basel, biosimilar attendees were treated to a preponderance of sessions involving streamlined biosimilar development—specifically, the removal of the phase 3 trial mandate by major regulators.

Although BR&R is keenly focused on the US biosimilar market, this year, we wanted to get a global perspective, by attending the Festival of Biologics European conference. Perhaps unsurprisingly, our colleagues on the continent are focused on the same hot topics that drive us in the US: development costs, competition, access, and government regulation.

At last week’s program in Basel, sessions featured the implications of streamlined requirements for biosimilar development—specifically, the removal of the phase 3 trial mandate by major regulators. Speakers addressed the cost savings resulting from this sea change in registration requirements, how it can spur activity within the biosimilar void, and what it means for biosimilar competition overall.

Biosimilars’ Value and Cost Savings to Shine With Lower Development Costs

Amidst the pressures on market access and pharmaceutal pricing, “Biosimilars are one of the clearest examples of how to create value for the whole healthcare system,” said Isabel Remus, Global Head of Biosimilars, Sandoz.

“The opportunity ahead is unlike anything we’ve seen before,” she stated, based on value of biologics that will lose exclusivity in the next decade.

With the cost of healthcare innovation continuing to rise, health systems in each country need to be funded in a sustainable way. “Biosimilar competition is a key lever for value,” said Ms. Remus. Across different healthcare systems, there is strong evidence on how biosimilars create value. For example, in the EU, biosimilar competition generated 75 billion euros in cumulative savings, over 9.2 billion patient-days of utilization. In comparison, the US health system saw $56 billion in savings. These savings can contribute to both broader access to valuable biologic medicines as well as funding innovation for new disease treatments.

However, not all patients benefit equally from biosimilar access. Adoption remains uneven between countries and regions, she pointed out. Some reference products attract a lot of biosimilar competition, whereas some generate very little or none. “Removing key barriers can materially reshape what is achievable in biosimilar development,” Ms. Remus said. “We’re trying to get the time of biosimilar development down to 4-6 years at a cost per program down to $60 million to $150 million. Regulatory evolution can open future opportunities and open opportunities previously thought to be closed.”

This may be one of the most important periods in the history of biosimilars, she concluded. The environment is becoming more complex. “Success will require not only flawless execution but the ability to anticipate policy changes.”

Fifty Percent Savings in Total Cost of Biosimilar Development Is Possible When Avoiding the Phase 3 Trial

According to Mourad Rezk, MD, MSc, MBA, CEO, RezMed Consulting, the impact of waiving comparative efficacy studies (CESs) could be game changing for developers. He believes that the lower cost to bring a biosimilar to market may make it possible to consider reference product targets with far lower revenues than in the past, perhaps as low as $350 million per year.

Consider that CESs went from being a default requirement to only being required in exceptional situations within 5 years, starting with the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) in 2021. Since that time, the major pharmaceutical regulatory agencies “have come to the same conclusion but are not yet fully aligned on wording of their guidances. We need more harmonization,” said Dr. Rezk.

He outlined the few instances when a CES may still be required for regulatory approval:

If the molecule is heterogeneous or poorly characterizable
If the mechanism of action is not completely understood or it may have multiple mechanisms of action
If the molecule is locally acting, and pharmacokinetic studies are not informative
If the compound carries a high risk of immunogenicity or carries severe consequences if immunogenicity occurs
If the biosimilar is the first applicant for a complex reference molecule

Some companies have chosen to continue their phase 3 studies, particularly with pembrolizumab biosimilar candidates. But with 50% savings potentially obtained through the avoidance of these CESs, some new players may decide to join the fray, Dr. Rezk believes. When you start to consider lower-revenue reference drug targets, it may be possible to “avoid the [biosimilar] void.” It may also be a boon for biosimilars in the rare disease space, he hoped.

Does the Direct-to-Employer Route for Biosimilars Make Sense?

Employers have strongly indicated that they would like to move away from the big 3 PBMs for cost transparency and the ability to capture as much of the savings as possible themselves. Going the direct-to-employer route, as Waltz Health and Fresenius Kabi are doing, would seem a natural option.

Waltz Health, a digital health company, has announced that it has agreed to team with Fresenius Kabi to help supply its three biosimilars in a direct-to-employer arrangement through its existing Waltz Connect platform.

First reported by Fierce Healthcare, the biosimilars that will be available direct-to-employer will be Fresenius Kabi’s Idacio (adalimumab), Tyenne (tocilizumab), and Otufli (ustekinumab). Waltz Health already has direct-to-employer arrangements with Eli Lilly and Novo Nordisk for their GLP-1 products.

By using Waltz Connect, corporate members can avoid traditional wholesaler and pharmacy benefit manager arrangements (and thus avoid rebate contracts). As the products are still delivered through specialty pharmacies, the typical provider and patient supports can still be provided.

The Direct-to-Employer Benefit for Biosimilars

This channel would appear to assure that patients directly benefit from discounts received by the corporate employer. In Fierce Healthcare, Fresenius Kabi’s President of Biopharma Sang-Jin Pak, MD, stated, “As we continue to expand our biosimilars portfolio, we remain focused on innovative partnerships that help employers and payers access high-quality treatment options.”

Employer benefit consultant F. Randy Vogenberg, PhD, told BR&R, “Making the costly drug purchase experience easier and engaging for the consumer as patient remains important. Leveraging biosimilar solutions could further the value to employers and their plan beneficiaries (patients) as other market forces change coverage affecting access to treatment options.” Dr. Vogenberg, Principal, FRV Health Strategy Advisory, Greenville, SC, said, “Addressing economic coverage gaps can be a win–win short-term solution for multiple stakeholders.”

Assuming that the employers signing onto Waltz Health have access to the same pricing for biosimilars as PBMs and others do, this seems a natural option. In surveys, employers have strongly indicated that they would like to move away from the big 3 PBMs for cost transparency and the ability to capture as much of the savings as possible themselves.

In Other Biosimilar News

Teva Pharmaceuticals received its second FDA approval for its denosumab biosimilar. After receiving its approval for Ponlimsi in March, referencing Prolia, to prevent osteoporosis, Degevma, referencing Xgeva, will be prescribed to prevent skeletal-related complications in patients with multiple myeloma or bone metastases. Teva plans to launch both products “in the coming months.” It joins a crowded field of 9 manufacturers with both denosumab indications.

Meitheal Pharmaceuticals announced September 28 that the FDA approved its high-concentration formulation of Yusimry, the company’s adalimumab biosimilar. The company will now be able to compete for prescriptions for this most-used adalimumab biosimilar formulation. “With this approval, we now have FDA approval for both low- and high-concentration formulations of Yusimry, marking an important step in expanding treatment options for patients with certain chronic autoimmune diseases,” said Tom Shea, Chief Executive Officer of Meitheal Pharmaceuticals. In July, the company had also received FDA approval for its insulin aspart biosimilar Garzulys, which is produced by Emerge Bioscience. Meitheal has marketing responsibility for this agent.

Is the 505(b)2 Pathway Viable for Biosimilars?

With regulators focused on streamlining the 351(k) biosimilar development, it makes sense to wonder if the 505(b)2 pathway is valid for biosimilar approval.

Can discussions about streamlining biosimilar development reach into abbreviated approval pathways for small molecules? Based on a Stat News webinar I attended yesterday, they already have. What exactly are the differences between the 351(k) pathway for biosimilar candidates and the 505(b)2 pathway for small molecules?

Biosimilar-Type Products Already Approved Through the 505(b)2 Pathway

The 505(b)2 pathway was used for some products that are considered by most as biosimilars today. For example, Basaglar, the first copy of insulin glargine, was approved in 2015 through this pathway; it was before insulins transferred to the biosimilar pathway for approval in 2020. Admelog was the first insulin lispro copy, approved in 2017 through the 505(b)2 pathway as well. However, Granix, the first filgrastim molecule launched that was not Epogen or Procrit, utilized the 351(a) pathway, meant for innovator biologics; it predated the implementation of the 351(k) route to approval.

With streamlining of biosimilar development—a major focus of regulators today—it makes sense to wonder if the 505(b)2 pathway is a valid goal for biosimilar manufacturers.

Infographic comparing 505(b)(2) drug approval and 351(k) biosimilar pathways

The 505(b)2 application pathway was implemented through the Hatch–Waxman Amendments of 1984. It was not meant as an abbreviated pathway for generics, but rather a streamlined way to bring new forms of existing innovative medications to market. These are commonly referred to as “follow-on” products. The basis for its use is that the innovator product on which the follow-on molecule is based has a truckload of patient experience proving its safety and efficacy. The manufacturer would simply have to show that its product was very much like the innovator. Its application could range from new formulations, strengths, to other modifications that wouldn’t be expected to affect the structure or anticipated effectiveness.

According to Drug Patent Watch, development cost of a 505(b)2 product might be anywhere from $8 million to $20 million, and the timeline to reach the market (not counting patent litigation) could be as short as 3 years. The 505(b)2 pathway allows a manufacturer to utilize the innovator product’s preclinical and clinical data, requiring little more than comparability studies and bridging pharmacokinetic studies to reach the FDA application stage. The FDA may still require a phase 3 trial, which would change the costs dramatically, but it appears attractive in any case.

Of course, biosimilars require a bit more consideration, as they are far more complex than small molecules, for which the 505(b)2 pathway was intended. With the push to streamline biosimilar development, including waiving the phase 3 trial mandate, eliminate separate testing for interchangeability (and eliminate the designation itself), and drop the need for bridging studies, it is not difficult to visualize movement in this direction.

The Difference With Insulin as a Biosimilar

Yet, insulin is a relatively simple biologic molecule. It has decades of use and clinical experience supporting its safety and efficacy. When the 505(b)2 pathway was used to approve Basaglar and Admelog, few considered this a big risk (it may have helped that the first biosimilars were already approved and in clinical use).

Biosimilars are not follow-on products, unlike typical 505(b)2 agents. Rather, biosimilar manufacturers strive to make their candidates as close a copy as possible to the innovator (but realizing an exact match is impossible). Logically, it might seem that the biosimilar approval process should be at the same level of proof as the 505(b)2 pathway. No, that can never be the case—the structure of biosimilars will always be a little different than the innovator agent. And the structure will always change a bit over time (as will the innovator biologic).

It is better, instead, that the 351(k) pathway is modified to reflect the real-life experience of the biosimilars approved to date by the FDA and the EMA, and that does provide ample opportunity for lowering the bar, and costs, of development.

First Opdivo Biosimilar FDA Application Submitted by Amgen

Amgen became the first manufacturer to submit an application to the FDA for a nivolumab (Opdivo) biosimilar. It also was the first to be sued for patent infringement.

Last week, Amgen became the first manufacturer to disclose that they submitted an application to the FDA for a nivolumab (Opdivo) biosimilar. In doing so, Amgen also became the first manufacturer to be sued by the reference manufacturer Bristol-Myers Squibb for patent infringement.

The company disclosed the 351(k) application during a business presentation on September 10. Amgen’s product, ABP 206, is one of several publicly disclosed nivolumab biosimilar candidates. The company reported, “...for ABP 206, our biosimilar candidate to OPDIVO, our Biologics License Application with the FDA has been submitted and accepted for review. We expect an FDA action on that BLA by end of the year.”

Net 2025 US revenues for Bristol-Myers Squibb’s PD-L1 inhibitor were $5.9 billion. The intravenously administered drug was first approved in 2014 (and market exclusivity ends this year), and its main patent expiration is expected to expire in 2028. Bristol-Myers Squibb also introduced a subcutaneously administered version of Opdivo in 2024, which is approved only for specific cancers. Among other manufacturers who have publicly disclosed potential nivolumab biosimilars Sandoz, Xbrane, Henlius, and mAbxience, are in various stages of development.

Patent Infringement Suit Filed Against Amgen’s Opdivo Biosimilar

Within days of the announcement of Amgen’s FDA biosimilar application for ABP 206, Bristol-Myers Squibb initiated a lawsuit claiming infringement on at least 7 patents on their product. We estimate the earliest expected launch date for intravenously administered nivolumab biosimilars to be in 2029 based on a main patent expiration in late 2028. Based on past experience, the likelihood of a settlement between the two parties may be lower than for other prospective biosimilar manufacturers, as Amgen has been willing to go at-risk for launch in the past (specifically for its aflibercept biosimilar Pavblu, a product with a similar market size as nivolimumab).

Of further interest, Opdivo is often prescribed in combination with Yervoy (ipilimumab), which is also the focus of considerable biosimilar research (also involving Amgen). Amgen also disclosed during its business presentation that it intends to file its biosimilar application for ABP 234, its biosimilar candidate to compete with Keytruda, before the end of the year.

The Second Entyvio Biosimilar Is Under Review at FDA

On July 31, Fresenius Kabi and Polpharma Biologics announced that its 351(k) application was accepted by both the FDA and the EMA for PB016, a proposed vedolizumab biosimilar candidate to Entyvio

The second vedolizumab biosimilar candidate is now under review by the US FDA. On July 31, Fresenius Kabi announced that its 351(k) application was accepted by both the FDA and the EMA for PB016, a proposed vedolizumab biosimilar candidate to Entyvio lyophilized vial for intravenous administration.

PB016, in-licensed from Polpharma Biologics S.A., is a proposed biosimilar to IV vedolizumab, an integrin-receptor antagonist indicated for the treatment of adults with moderately to severely active ulcerative colitis and Crohn’s disease in adults.

“FDA and EMA acceptances for review of IV vedolizumab biosimilar marks important milestones in the development program and underscores our commitment to improving patient access to high-quality, affordable biologic medicines,” said Dr. Sang-Jin Pak, President Biopharma at Fresenius Kabi. “With IV vedolizumab, we are advancing our autoimmune biosimilars portfolio and taking another step toward providing additional treatment options for patients living with chronic inflammatory diseases.”

The first biosimilar biologic licensing application was submitted in June by Alvotech and Teva.

In Other Biosimilar News

Amneal closed on its purchase of Kashiv Biosciences, a deal which “combines Kashiv’s biologics research, development and manufacturing capabilities with Amneal’s commercial scale, establishing biosimilars as a major long-term growth pillar within the Company’s Affordable Medicines business.”

Biosimilar Bytes: Biocon’s Yesafili Launches and Dr. Reddy’s Rituximab Biosimilar Is Approved

Biocon announced the launch of its Yesafili biosimilar, in competition now with Pavblu, for the aflibercept market. Dr. Reddy’s and its marketing partner Fresenius Kabi have received FDA approval for its rituximab biosimilar.

Biocon Begins Marketing Its Aflibercept Biosimilar Yesafili

Shreehas Tambe, Chief Executive Officer and Managing Director of Biocon Limited, said, “The commercial launch of Yesafili in the United States is an important milestone in our efforts to improve access to high-quality biosimilar medicines. It strengthens our presence in ophthalmology and reflects our commitment to making advanced treatments more accessible and affordable for patients around the world.”

The second aflibercept biosimilar has reached the US market, as Biocon Biologics announced the launch of Yesafili. Initially approved in May 2024, along with a slew of other aflibercept biosimilars, launches were delayed by settlement agreements with the manufacturer of the reference product, Eylea.

Pricing information was not reported for Yesafili. Significant sales volume of the first marketed aflibercept biosimilar, Pavblu, was achieved with a relatively small wholesale acquisition cost discount (–16%). Amgen, in its second-quarter 2026 earnings, reported $280 million in US sales, putting it on pace to be the first billion-dollar biosimilar. It has largely driven Amgen’s overall biosimilar revenues, which are up 29% from the same quarter in 2025.

Dr. Reddy’s Readying Rituximab Biosimilar for Launch with Fresenius Kabi After FDA Approval

On August 1, 2026, Dr. Reddy’s Laboratories received FDA approval for its rituximab biosimilar. The brand name and nonproprietary name suffix were not announced at the time of posting.

Dr. Reddy’s entered into a commercialization agreement with Fresenius Kabi to market the monoclonal antibody biosimilar in the United States.

The agent was known as DRL_RI in clinical trials, is already commercialized in the European Union in the United Kingdom. It is sold under the brand name Ituxredi in those markets. A launch date has not been announced for this fourth rituximab biosimilar approved by the FDA.

Currently, two biosimilars (Truxima and Ruxience) lead the rituximab category, each with 35% market share by volume, based on IQVIA data.

Tracking Two Bills to Remove the Clinical Efficacy Study Requirement for Biosimilar Development

Proposals in the House and Senate, both titled the Expedited Access to Biosimilars Act, may officially remove the FDA’s requirement for clinical efficacy studies for biosimilar candidates.

On July 15^th, a new bipartisan bill was introduced into the House of Representatives that would expand access to biosimilars by modernizing the FDA’s biosimilar approval process. This could be paired with a similar proposal just reaching Senate Committee discussion. Both of these proposals seek to reduce the cost of biosimilar development through squeezing out the need for comparative efficacy studies.

As reported earlier, the FDA in October 2025 announced a draft guidance that would achieve the same end, to remove the mandate for late-stage clinical efficacy trials for biosimilar manufacturers. However, a final guidance has not yet been released.

Introduced by Representatives Nick Langworthy (R-NY) and Kim Schrier, MD (D-WA), the Expedited Access to Biosimilars Act (HR 9661) could codify long-awaited regulatory changes to comparative trial expectations in the 351(k) biosimilar pathway.

According to a press release from Congressman Langworthy’s office, the act would eliminate unnecessary regulatory hurdles while preserving the FDA’s authority to require additional studies whenever scientifically warranted. This supports the October 2025 announcement of a draft guidance for removal of a mandate for phase 3 clinical efficacy studies for biosimilars. A key stipulation of the proposal would be a requirement for FDA to notify manufacturers early in the review process if additional late-stage comparative efficacy studies will be required. The aim would be to provide greater certainty around the clinical trial resources required for a successful biosimilar application process as well as avoiding unnecessary delays in the application process.

A number of associations have express support for the legislation including the Association for Accessible Medicines, the American Society of Health-System Pharmacists, and America’s Health Insurance Plans, among others.

The Senate’s 2025 Proposal

A Senate proposal by the same name (S.1414), introduced in April 2025 by Senator Rand Paul (R-KY), seeks largely the same goals. It has languished in the Committee on Health, Education, Labor, and Pensions, without additional cosponsors, until now. A committee meeting is scheduled for July 22 to finally consider this legislative proposal. It has one co-sponsor (Sen. Mike Lee, R-UT).

We’ll be monitoring whether the Expedited Access to Biosimilars Act can break through for an eventual debate and vote on either the House or Senate floor.

When is a Biosimilar a Biosimilar?

In 2026, is the definition of a biosimilar the same for countries’ drug regulatory systems around the globe? A recently published scoping survey attempted to answer the question.

Although there has been a decade of interest in moving towards global biosimilar regulatory standards, we first must answer a more foundational question: Is the definition of a biosimilar the same worldwide?

You may suspect that the answer is obvious, but then again, why are we asking it? Is it a trick question? Years ago, the answer was not so simple. Those of us covering the biosimilar field in the 2010s will recall that some Indian companies, for example, were producing what might be considered “follow-on” medicines by the FDA’s regulatory standards, but were promoting them as biosimilars.

No Guidances by FDA on Follow-on vs. Biosimilar Products

The FDA’s own regulatory definition was not set in stone: Basaglar, the second insulin glargine product to receive FDA approval, is a biosimilar but technically not a biosimilar. Even today, there may be some confusion as to whether Basaglar is considered a biosimilar or a follow-on product. It was indeed approved by the FDA under a 505(b)2 application, principally because insulins were not considered eligible for the 351(k) approval pathway until 2020. The FDA would probably support that it is clinically equivalent to Lantus in any way that matters. Yet, from a regulatory perspective, it was not evaluated as part of the biosimilar pathway, so it cannot be designated a biosimilar.

The same can be said for Granix, the second filgrastim product approved by the FDA, which underwent its approval process before the 351(k) was implemented (and under which Zarxio was licensed). It is important to note that the FDA itself has not tried to improve clarity by announcing retrospectively that these agents can be considered either biosimilar or an equivalent.

A Survey of Biosimilar Definitions

So, is a biosimilar a biosimilar throughout the world? An article published in JAMA Health Forum described a survey of 19 countries’ biosimilar regulatory guidelines. These included 12 with emerging and developing economies and 7 with advanced economies, according to the World Health Organization classification. The authors, from the University of San Francisco and GlaxoSmithKline, found that most countries define “biosimilarity as the absence of differences in the medicine’s quality, safety, and efficacy compared with the RP. Sixteen countries explicitly required comparability exercises to demonstrate biosimilarity, and 13 countries specified that the same RP must be used in these studies.

“Of the 19 countries in the study sample, 17 (89%) have adopted the WHO’s biosimilar terminology; the exceptions were Indonesia, which uses the term follow-on biological in addition to biosimilar,and Tanzania, which uses the term similar biotherapeutic product. A total of 17 countries (89%; except India and South Korea) define biosimilarity according to the absence of differences in quality, safety, and efficacy between the biosimilar and the reference product, although in some countries (Egypt, Turkey, UK, and US), this is heavily implied rather than explicitly stated. Most countries (n = 16 [84%]) require comparability exercises (by definition), but 3 (Mexico, Indonesia, and China) do not explicitly include this requirement.”

The authors also stated that all advanced economies waived the need for clinical efficacy and immunogenicity testing when justifiable, but guidelines from emerging and developing economies differed on clinical study waivers.”

Interestingly, one of the areas of least consensus is that of biosimilar naming and labeling guidance provided. Countries such as France, Germany, Japan, and South Korea do not specify any requirements, whereas the UK, US, and Canada do, among the WHO advanced economic sector. Among countries in the emerging and developing economic region, China and Mexico do have naming and labeling guidelines, whereas Brazil, India, and Indonesia do not. The area of greatest agreement seemed to be in acceptance of extrapolation, with all but Saudi Arabia among the surveyed countries with published extrapolation guidelines.

Scoping surveys such as this are necessary steps in a march towards global regulatory standards for biosimilars. They show not only how far we’ve come in reaching basic agreements, but also how far we need to go. Perhaps, most importantly, they show us areas where a push for global standards would have the least likelihood of success.