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WHEN CHOICE ARRIVES: Competition & Consequences

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BIOSIMILAR APPROVALS

Sarfaraz K. Niazi, PhD, is an adjunct professor of biopharmaceutical sciences at the University of Illinois and the University of Houston, and founder of biosimilars companies Karyo Biologics and Adello Biologics. He also founded the biosimilar advisory company PharmSci.

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Skylar Jeremias is the Managing Editor for The Center for Biosimilars and The American Journal of Managed Care (AJMC).

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Explore the cost-effectiveness of ranibizumab biosimilars versus aflibercept in treating AMD and DME, revealing significant savings and treatment implications.

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The Center for Biosimilars connects professionals with insights on biosimilars, health economics, regulatory outcomes, and emerging treatment paradigms.

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Tony Hagen is senior managing editor for The Center for Biosimilars

Efforts to expand access to vision-saving therapies for people with diabetic eye disease increasingly depend on the availability of lower-cost biologic alternatives, and new comparative data add clarity to how one aflibercept biosimilar performs in routine clinical practice. A recently published retrospective analysis evaluated whether the aflibercept biosimilar QL1207 offered similar outcomes to reference aflibercept for individuals with diabetic macular edema (DME), a leading cause of vision impairment among people with diabetes.

The study was conducted to address a longstanding gap in real-world data. Although QL1207 was approved by China’s National Medical Products Administration in late 2023 based on structural and functional similarity to reference aflibercept, published comparative clinical information in DME populations remained limited. 

Given the high cost of originator anti-VEGF therapy and the chronic, injection-intensive nature of DME management, the investigators sought to determine whether the biosimilar performed comparably in anatomical and functional outcomes, macular perfusion metrics, injection burden, and safety.

The analysis included anonymized clinical data from 80 adults (80 eyes) with nonproliferative diabetic retinopathy and DME who were seen at a single ophthalmology department between June 2023 and April 2024. Participants were treatment-naïve and met diagnostic criteria outlined in the American Academy of Ophthalmology’s 2019 clinical guidelines. Individuals were excluded if they had other retinal diseases, a history of ocular procedures, proliferative disease, significant media opacity, or a hemoglobin A1c greater than 7%.

Demographic characteristics were balanced across treatment groups. The reference aflibercept group included 40 people (20 men and 20 women) with a mean age of 48.6 years. The QL1207 group included 40 people (19 men and 21 women) with a mean age of 46.7 years. Baseline HbA1c levels were similar, and no clinically meaningful differences emerged during the 12-month follow-up period.

All participants received 3 monthly loading doses followed by a pro re nata retreatment approach. Retreatment criteria included central retinal thickness (CRT) greater than 280 µm or a decrease of 5 or more Early Treatment Diabetic Retinopathy Study letters. Best-corrected visual acuity (BCVA), optical coherence tomography measures, and optical coherence tomography angiography parameters—including foveal avascular zone (FAZ) area and superficial and deep vascular density (SVD and DVD)—were collected at baseline and during follow-up. The investigators also recorded injection frequency and adverse events.

The study found no statistically significant differences between groups in BCVA or CRT at baseline or at 1, 3, 6, or 12 months. Both groups demonstrated significant improvement in BCVA relative to their own pretreatment values, as well as substantial reductions in CRT (

 < .05 for all within-group comparisons). At 12 months, mean CRT decreased from 447.1 µm to 280.4 µm in the reference group and from 441.0 µm to 290.3 µm in the QL1207 group. Injection burden was also similar, with mean injection counts of 3.58 in the reference group and 3.40 in the biosimilar group (

Macular microvascular outcomes also aligned closely across groups. FAZ area decreased significantly within each group, while both SVD and DVD increased, indicating improved or stabilized macular perfusion. None of these parameters differed significantly between groups at baseline or month 12.

Safety outcomes were consistent with the known safety profile of intravitreal anti-VEGF therapy. Mild events—including transient intraocular pressure elevations, corneal epithelial damage, and subconjunctival hemorrhage—occurred infrequently and at similar rates in both groups. No individuals experienced endophthalmitis, glaucoma, vitreous hemorrhage, cataract progression, or systemic cardiovascular or cerebrovascular events during the follow-up period.

The authors noted several limitations, including the retrospective design, relatively small sample size, nonrandomized treatment assignment, and 12-month follow-up period. In addition, while statistically significant changes in OCT angiography parameters were documented, their clinical significance remains uncertain. Longer, prospective, randomized studies will be needed to validate long-term comparability between QL1207 and reference aflibercept in DME.

Even with these limitations, the findings contribute to growing real-world evidence showing that aflibercept biosimilars may offer an effective and potentially more affordable option for individuals living with DME. As biosimilar adoption grows globally, studies like this may help inform formulary decisions and support broader access to sight-preserving therapy.

Zhai G, Liu N, Wang S, Zhang X. Comparative efficacy of intravitreal aflibercept biosimilar QL1207 versus reference aflibercept in the treatment of diabetic macular edema. 

. 2025:12:1662735. doi:10.3389/fmed.2025.1662735

Clinical

In 2009, Congress created a regulatory pathway for biosimilars to encourage competition and address rising spending on biologic drugs. One barrier to adopting biosimilars in the US is that the FDA has traditionally required additional testing for biosimilars to be deemed interchangeable with the original biologic. This analysis reviews the history and current status of biosimilar regulation in the US, concluding that changing the FDA’s interchangeability standards—as proposed by some policy makers—is a potentially useful but likely insufficient step to improve biosimilar competition in the US. Other policy options include more state laws allowing pharmacists to automatically substitute biosimilars, addressing strategies by payers and pharmacy benefit managers that inhibit biosimilar competition, and implementing more widespread education of clinicians and patients to build confidence about biosimilars. Other policies to ensure the affordability of biologic drugs include expanding Medicare’s price negotiation to cover biologics with or without biosimilar competition.

Congress created an expedited approval pathway for biosimilar drugs to compete and lower costs of biologic medications, but biosimilar use has been characterized by slow uptake.

Currently, not all biosimilars are deemed interchangeable with the original biologic, and some policy makers have proposed changing the biosimilar interchangeability laws to improve competition in the biosimilar market.

Such a change is a useful first step, but other changes are needed, including amending state laws to allow greater automatic pharmacist substitution, addressing strategies by payers and pharmacy benefit managers that inhibit biosimilar competition, and ensuring more education of clinicians and patients to build confidence about biosimilars.

Biologic drugs—complex products often synthesized from living cells—make up only 2% of prescriptions in the US but account for approximately half of prescription drug spending.

 To address these high costs, Congress passed the Biologics Price Competition and Innovation Act (BPCIA) in 2009. This law created a framework for the FDA to approve biosimilars, which are biologics made by different manufacturers with no clinically meaningful differences from already-approved biologic drugs.

 The goal was to spur competition between biosimilars and biologics to lower costs, just as generic competition has done for small-molecule drugs. In the decade after the passage of the BPCIA, however, the biosimilar marketplace was characterized by delays in biosimilar approval and availability, slow biosimilar uptake,

Challenges to biosimilar competition include limited interchangeability and lack of automatic pharmacist substitution. The FDA certifies nearly all generic drugs as therapeutically equivalent to the original brand-name drugs, and state laws allow—and often mandate—pharmacists to substitute therapeutically equivalent generics in place of brand-name drugs.

 This automatic pharmacist substitution facilitates rapid adoption of generics.

 By contrast, the BPCIA set additional standards for biosimilars to be deemed interchangeable with the originator biologic, and most state pharmacy substitution laws are more restrictive for biosimilars than generics.

 In recent years, the evidence required by the FDA to meet the interchangeability standards has evolved, and some at the FDA have proposed eliminating the separate interchangeability designation entirely.

 Improving the interchangeability of biosimilars could enhance biosimilar uptake in the US, although additional steps are needed to unlock further savings for patients and the health care system.

The BPCIA required the FDA to affirm that biosimilars have no clinically meaningful differences and are as safe and effective as the original biologic. In practice, this has meant that biosimilars are typically tested in head-to-head randomized clinical trials against the original biologic for at least 1 of the drug’s indications. By contrast, the bioequivalence determinations for generic small-molecule drugs are based on more limited pharmacokinetic and pharmacodynamic data from small studies of healthy volunteers.

For biosimilars to be designated as interchangeable, the FDA requires evidence that a biosimilar could be expected to yield the same results as the original biologic for any individual patient and that switching between the biosimilar and the original poses no additional concerns related to safety or diminished effectiveness. This was initially operationalized via switching studies run by biosimilar manufacturers that evaluated safety and efficacy when patients alternated between a biosimilar and its reference product.

One of the primary motivations for a separate interchangeability standard was concerns that minor differences between biologics and biosimilars could lead to antidrug antibodies when patients switch versions, which could diminish the effectiveness or lead to adverse effects through cross-reactivity with patients’ own proteins. These concerns were based on rare reports of treatment failure related to antidrug antibodies.

 Regulators in other countries, including the European Medicines Agency, did not include similar 2-tier regulatory systems for biosimilars,

 although automatic pharmacist substitution is not standard practice in these countries.

The FDA approved the first biosimilar in 2015, but it was not until 6 years later that the FDA approved the first biosimilar with an interchangeability designation, a version of long-acting insulin glargine-yfgn (Semglee) deemed interchangeable with the original version (Lantus). As of May 2025, the FDA has approved 75 biosimilars, 21 of which were granted interchangeable designations.

Recently, US regulators have signaled a shift in their approach to biosimilar interchangeability. In June 2024, the FDA released an updated draft guidance that eliminated the expectation for switching studies.

 The FDA defended this change based in part on a meta-analysis conducted by FDA scientists that revealed no differences in safety or immunogenicity among patients switching from a reference biologic to a biosimilar.

 These conclusions aligned with those from extensive postmarketing analyses conducted in the European Union and the global experience,

 reinforcing that the FDA’s “highly similar” standards for biosimilars were sufficient for determining interchangeability.

In response to shifting FDA guidance, some policy makers have proposed that Congress alter the BPCIA to eliminate the separate interchangeability standards.

 Such a policy was included in the Biden administration’s 2024-2025 fiscal year budgetand was publicly supported by some leaders at the FDA.

One goal of removing the separate interchangeability designation for biosimilars is to boost competition and further lower costs for biologic drugs in the US. This could be accomplished if the streamlined regulatory standards encourage more drugmakers to introduce biosimilars or if the improved interchangeability standards promote greater uptake of biosimilars by patients.

Key Barriers and Solutions Beyond Interchangeability

Even if Congress were to remove the interchangeability designation, competition in the biosimilar marketplace in the US could be further optimized by addressing state pharmacist substitution laws, reimbursement behavior by pharmacy benefit managers (PBMs), and skepticism from patients and clinicians. Simultaneously, it is sensible to enact alternative policies to ensure the affordability of biologic drugs after patent protection expires, such as expanding Medicare’s price negotiation to cover biologics with or without biosimilar competition.

 The rules about whether pharmacists can (or must) automatically substitute biosimilars in place of the original biologic are set by state legislatures in their oversight of the practice of pharmacists. For generics, substitution laws have been remarkably effective. Generics are used 97% of the time when available, and generic uptake is lower when state substitution laws are more restrictive.

After Congress passed the BCPIA, many state pharmacy substitution laws were modified to allow pharmacist substitution of FDA-designated interchangeable biosimilars. However, these laws were often stricter than the same state’s laws governing generic substitution; for example, many states required physician notification if a pharmacist substituted FDA-approved biosimilars.

 Additionally, unlike the FDA’s generic therapeutic equivalence designations, interchangeable biosimilar designations only apply between each biosimilar and the original drug—the FDA does not certify that 2 biosimilars for the same drug are interchangeable. It remains unclear whether state laws would allow substitution between multiple biosimilars of the same drug.

Thus, current state substitution laws may undermine rapid biosimilar uptake, particularly if these laws do not permit substitution between different biosimilars of the same biologic drug. Even if Congress revises the FDA’s interchangeability standards, it is ultimately up to state lawmakers to determine the role of pharmacists in expanding biosimilar use.

 For pharmacists to freely substitute FDA-approved biosimilars, payers and their PBMs would need to adjust reimbursement policies to be agnostic to which version of a biologic drug patients receive. For generic drugs, public and private payers usually reimburse pharmacies based on a maximum allowable cost schedule, which incentivizes pharmacies to dispense the lowest-cost generic version.

By contrast, PBMs have generally treated biologics and biosimilars separately, negotiating rebates and formulary position with each manufacturer, similar to how they handle competition among multiple brand-name drugs in the same class. Thus, even if biosimilars are interchangeable, pharmacists must fill whichever version is preferred by a patient’s insurance formulary. Additionally, biologic manufacturers can leverage their rebates to block biosimilar competitors.

 For example, several biosimilar versions of the blockbuster drug adalimumab (Humira) entered the market in 2023. However, brand-name Humira continued to account for more than 98% of adalimumab prescriptions, likely because AbbVie offered substantial rebates to PBMs to maintain Humira’s advantage over biosimilars.

In August 2023, CVS Caremark, one of the 3 largest PBMs in the US, announced that it would stop covering Humira and instead cover a biosimilar that it would produce via a comarketing arrangement with the drug’s manufacturer. Three PBMs account for approximately 80% of all prescriptions in the US,

 so if other PBMs pursue a similar comarketing strategy, this could mean that only a limited number of biosimilar makers are able to secure such contracts and market their products successfully in the US. These arrangements may result in short-term savings for patients and the health system, but a market characterized by such agreements might dissuade companies from investing in developing future biosimilars without assurance that their product will generate sufficient sales to cover these costs.

Some members of Congress have asked federal regulators to scrutinize comarketing agreements between PBMs and biosimilar makers for anticompetitive behavior.

 Additionally, state and federal policy makers could consider prohibiting confidential rebates for biologic drugs once biosimilar versions become available in the US to improve price transparency and facilitate more direct price competition. For federal programs such as Medicare, this may require Congress to revise the safe harbor protections that currently exempt rebates from federal antikickback statute. For clinician-administered drugs, CMS could revise its Part B reimbursement rules to create bundled payment rates for biologics and biosimilars, like the current reimbursement rules for generics.

 A prerequisite for relying on pharmacist substitution to facilitate a competitive biosimilar marketplace is that patients and prescribers be comfortable freely switching between versions, even after they have initiated treatment. Switches between generic drug manufacturers are commonplace; although these changes are safe and effective,

 patients who experience a change in the size, shape, or color of their medication (eg, because they receive a version made by a different manufacturer) are more likely to stop taking it.

For biosimilars, regulators in the US and internationally have not found evidence that switching between versions poses risks in terms of safety or effectiveness. Still, surveys of prescribers have shown varying degrees of confidence; some prescribers have expressed concerns about patients switching to a biosimilar after achieving clinical stability with the original biologic.

 Although these concerns are well intentioned, they raise a fundamental question about whether prescribers (and patients) would accept widespread automatic biosimilar substitution. If regulations and laws allowed pharmacist substitution only for new users, for example, this would dramatically limit the ability to rely on substitution to promote competition between biologics and biosimilars.

Although FDA regulators are convinced that switching between different versions of a biologic is safe, more evidence or better communication of existing evidence is needed to educate patients and clinicians. Similar knowledge barriers existed in the early days of generics, when patients and clinicians expressed skepticism about the safety and efficacy of generic medications. Even as late as 2009, 23% of physicians surveyed harbored doubts about the effectiveness of generics, and 50% had concerns about their quality, leading more than 25% to avoid recommending generics as first-line therapy.

 Overcoming these barriers will require robust educational campaigns for patients and prescribers.

 Competition from low-cost generics has been remarkably effective in lowering costs of small-molecule drugs, in large part due to interchangeability and pharmacy substitution. If the same approach proves insufficient for biologic drugs, another option is regulation of prices after a period that allows biologics to earn sufficient sales revenue to recoup research and development costs. The Inflation Reduction Act of 2022 allows Medicare to negotiate prices for certain drugs and includes a statutory minimum price reduction of 60% lower than the nonfederal average manufacturer price after a drug has been on the US market for 16 years.

 Currently, Medicare’s ability to negotiate prices ends once generic or biosimilar competition begins, but Congress could amend this to continue leveraging Medicare’s negotiation authority to lower biologic prices rather than relying solely on biosimilar competition.

Changing the FDA’s interchangeability standards is a necessary step to improve biosimilar dissemination in the US market and thereby increase competition, reduce prices, and improve access to these medications. However, such a policy change would likely be insufficient on its own to optimize the uptake and affordability of biologic medications. So far, the evidence supports the safety and effectiveness of switching between a biologic and its biosimilars, but additional evidence and guidance from regulatory bodies, including the FDA, could help build confidence among providers and patients, which could pave the way for more flexible state pharmacy substitution laws. Policies are also needed to prevent payers and PBMs from inhibiting biosimilar competition and potentially to ensure that biologic prices fall after a period, regardless of biosimilar competition.

 Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (BNR, AB, ASK), Boston, MA.

 This project was funded by a grant from Arnold Ventures.

 Dr Rome and Dr Kesselheim have received consulting fees from Alosa Health and grant funding from the Elevance Health Public Policy Institute and the National Academy for State Health Policy. Dr Kesselheim has served as an expert on behalf of a class of payers in a case against Johnson & Johnson relating to patents on the biologic drug Stelara and on behalf of the Federal Trade Commission in a case against pharmacy benefit managers. Ms Bhaskar reports no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

 Concept and design (BNR, AB, ASK); drafting of the manuscript (BNR, AB); critical revision of the manuscript for important intellectual content (BNR, AB, ASK); obtaining funding (ASK); administrative, technical, or logistic support (AB); and supervision (BNR, ASK).

 Benjamin N. Rome, MD, MPH, Brigham and Women’s Hospital Division of Pharmacoepidemiology and Pharmacoeconomics, 1620 Tremont St, Ste 3030, Boston, MA 02120. Email: brome@bwh.harvard.edu.

The U.S. Generic & Biosimilar Medicines Savings Report

. Association for Accessible Medicines; September 2023. Accessed January 18, 2025. 

https://accessiblemeds.org/wp-content/uploads/2024/11/AAM-2023-Generic-Biosimilar-Medicines-Savings-Report-web.pdf

2. Implementation of the Biologics Price Competition and Innovation Act of 2009. FDA. Updated February 12, 2016. Accessed January 18, 2025. 

https://www.fda.gov/drugs/guidance-compliance-regulatory-information/implementation-biologics-price-competition-and-innovation-act-2009

3. Rome BN, Bhaskar A, Kesselheim AS. Use, spending, and prices of adalimumab following biosimilar competition. 

. 2024;5(12):e243964. doi:10.1001/jamahealthforum.2024.3964

4. Hong D, Kesselheim AS, Sarpatwari A, Rome BN. Biosimilar uptake in the US: patient and prescriber factors. 

5. Feng K, Russo M, Maini L, Kesselheim AS, Rome BN. Patient out-of-pocket costs for biologic drugs after biosimilar competition. 

. 2024;5(3):e235429. doi:10.1001/jamahealthforum.2023.5429

6. Sacks CA, Van de Wiele VL, Fulchino LA, Patel L, Kesselheim AS, Sarpatwari A. Assessment of variation in state regulation of generic drug and interchangeable biologic substitutions. 

. 2021;181(1):16-22. doi:10.1001/jamainternmed.2020.3588

7. Rome BN, Lee CC, Gagne JJ, Kesselheim AS. Factors associated with generic drug uptake in the United States, 2012 to 2017. 

. 2021;24(6):804-811. doi:10.1016/j.jval.2020.12.020

8. Considerations in demonstrating interchangeability with a reference product: guidance for industry. FDA. Updated May 20, 2019. Accessed January 18, 2025. 

https://www.fda.gov/regulatory-information/search-fda-

guidance-documents/considerations-demonstrating-interchangeability-reference-product-guidance-industry

9. Mirkov S, Hill R. Immunogenicity of biosimilars. 

. 2016;32:532-538. doi:10.1007/s40267-016-0341-2

10. Biosimilar medicines: overview: interchangeability of biosimilar medicines in the EU. European Medicines Agency. Accessed January 18, 2025. 

https://www.ema.europa.eu/en/human-regulatory-overview/biosimilar-medicines-overview#interchangeability-of-biosimilar-medicines-in-the-eu-10279

11. Biosimilars approved in the US. Generics and Biosimilars Initiative. May 22, 2025. Accessed September 19, 2025. 

https://www.gabionline.net/biosimilars/general/biosimilars-approved-in-the-us

12. Considerations in demonstrating interchangeability with a reference product: update. FDA. Updated June 20, 2024. Accessed January 18, 2025. 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-demonstrating-interchangeability-reference-product-update

13. Cavazzoni P, Yim S. The science of biosimilars—updating interchangeability. 

. 2024;332(15):1235-1236. doi:10.1001/jama.2024.15225

14. Lee seeks increased competition in biological drug market. News release. US Senator Mike Lee. July 13, 2023. Accessed January 18, 2025. 

https://www.lee.senate.gov/2023/7/lee-seeks-increased-competition-in-biological-drug-market

15. DeGroot L. Biden administration proposes funding bump for FDA, nixing interchangeability requirement. Endpoints News. March 11, 2024. Accessed January 18, 2025. 

https://endpts.com/biden-administration-proposes-funding-bump-for-fda-nixing-interchangeability-requirement/

16. Rome BN, Sarpatwari A, Kesselheim AS. State laws and generic substitution in the year after new generic competition. 

. 2022;25(10):1736-1742. doi:10.1016/j.jval.2022.03.012

Realizing the Benefits of Biosimilars: Overcoming Rebate Walls

. Duke Margolis Center for Health Policy; 2022. Accessed September 4, 2025. 

https://healthpolicy.duke.edu/sites/default/files/2022-03/Biosimilars%20-%20Overcoming%20Rebate%20Walls.pdf

18. Cai C, Rome BN. Reforming pharmacy benefit managers – a review of bipartisan legislation. 

. 2023;389(18):1640-1643. doi:10.1056/NEJMp2309533

19. Wyden and Brown urge FTC to investigate emerging anti-competitive practices by PBMs. News release. US Senate Committee on Finance. October 1, 2024. Accessed January 18, 2025. 

https://www.finance.senate.gov/chairmans-news/wyden-and-brown-urge-ftc-to-investigate-emerging-anti-competitive-practices-by-pbms

20. Rome BN, Feldman WB, Desai RJ, Kesselheim AS. Correlation between changes in brand-name drug prices and patient out-of-pocket costs. 

. 2021;4(5):e218816. doi:10.1001/jamanetworkopen.2021.8816

21. Kesselheim AS, Bykov K, Gagne JJ, Wang SV, Choudhry NK. Switching generic antiepileptic drug manufacturer not linked to seizures: a case-crossover study. 

. 2016;87(17):1796-1801. doi:10.1212/WNL.0000000000003259

22. Kesselheim AS, Bykov K, Avorn J, Tong A, Doherty M, Choudhry NK. Burden of changes in pill appearance for patients receiving generic cardiovascular medications after myocardial infarction: cohort and nested case–control studies. 

. 2014;161(2):96-103. doi:10.7326/M13-2381

23. Reilly MS, McKibbin RD. US prescribers’ attitudes and perceptions about biosimilars. 

. 2022;11(3):96-103. doi:10.5639/gabij.2022.1103.016

24. Kesselheim AS, Gagne JJ, Eddings W, et al. Prevalence and predictors of generic drug skepticism among physicians: results of a national survey. 

. 2016;176(6):845-847. doi:10.1001/jamainternmed.2016.1688

25. Hwang TJ, Kesselheim AS, Rome BN. New reforms to prescription drug pricing in the US: opportunities and challenges. 

. 2022;328(11):1041-1042. doi:10.1001/jama.2022.15268

Changing the FDA biosimilar interchangeability standards is a necessary but likely insufficient step to improve biosimilar competition in the US.

Business & Practice

Biosimilar Interchangeability and Substitution in the US: What Comes Next?

All things biosimilars

In the special video podcast episode, produced in partnership with the Association for Accessible Medicines (AAM), co-hosts Giuseppe Randazzo, senior vice president of sciences and regulatory affairs at AAM, and Alex Keeton, the new executive director of AAM's Biosimilars Council, break down one of the most consequential policy shifts in the biosimilar landscape in years: the FDA’s new draft guidance on comparative efficacy studies (CES) and interchangeability. 

Keeton opened the discussion by outlining how the agency’s updated scientific framework aims to streamline biosimilar development by reducing, and in many cases eliminating, the need for large, costly comparative efficacy studies. Instead, the FDA is formally recognizing that advanced analytical tools and pharmacokinetic data are often more sensitive and scientifically meaningful than clinical efficacy trials—an evolution that could save manufacturers years of development time and as much as $100 million to $300 million per program.

Randazzo emphasized the potential impact on access, noting that lower development costs can help expand competition and deliver more affordable biologic alternatives to patients. The hosts highlighted growing political momentum behind biosimilars following a recent press conference in which federal officials framed the guidance as a shift from bureaucracy to science. However, they also pointed to persistent policy gaps, including state-level substitution restrictions and the continued statutory existence of the interchangeable designation—an issue the hosts argued now requires Congressional action to align the law with current FDA science.

The conversation also addressed the “biosimilar void,” a term describing more than 100 biologics that are approaching patent expiration with no biosimilars in active development. Randazzo noted that reducing clinical trial requirements alone will not close this gap; challenges such as manufacturing complexity, market incentives, and payer-side barriers continue to slow progress.

Keeton and Randazzo closed by previewing a future episode dedicated entirely to payer dynamics, reinforcing that regulatory reform is only one piece of the broader effort to make biosimilars more accessible and sustainable across the US health care system.

To learn more about the FDA draft guidance regarding clinical efficacy studies for biosimilars and interchangeability, 

To read more about G's discussion with Sarah Yim, MD, from the FDA from the recent 2025 GRx+Biosims conference, 

To read more on Yim's perspectives on biosimilar policy harmonization, 

In this special video episode of Not So Different, co-hosts Giuseppe Randazzo and Alex Keeton from the Association of Accessible Medicines tackle the FDA's recent draft guidance on comparative efficacy studies (CES) and interchangeability for biosimilars, addressing some of the confusion around the new announcement and remaining action items for the agency.

Tony Hagen

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