Biocon’s aflibercept biosimilar Yesafili became one of the first two products in its category to earn the FDA’s interchangeable designation in May 2024. It did not reach a single US patient until August 3, 2026 [1]. In the 27 months between those two dates, a competing biosimilar with no interchangeability designation at all — Amgen’s Pavblu — launched, captured shelf space, got its own reimbursement code, and became the product ophthalmology practices actually billed against Eylea [2][3]. Any formulary team that treated “interchangeable” as a proxy for “first to matter” spent more than two years waiting for the wrong drug.
The Short Answer: FDA interchangeability is a pharmacy-substitution mechanic governed by 42 U.S.C. § 262(i)(3) and state pharmacy law. It says nothing about patent litigation status, payer rebate contracts, formulary tier, or even whether the product has launched. Treating it as a formulary-readiness signal has caused real, dated, citable delays — and because commercial P&T committees meet quarterly and Medicare Part D locks its formulary a full calendar year in advance, a delay measured in weeks at the regulatory level routinely becomes a delay measured in a full plan year at the benefit-design level.
What “Interchangeable” Actually Means Under the BPCIA — and What It Doesn’t
The Biologics Price Competition and Innovation Act created two distinct FDA determinations for a follow-on biologic, and pharma content routinely collapses them into one. A biosimilar must show it is “highly similar” to the reference product with “no clinically meaningful differences.” An interchangeable biosimilar must clear a third, additional bar: the FDA must find it “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product” [42 U.S.C. § 262(i)(3)].
The Three-Part Legal Test for Interchangeability
A biosimilar seeking interchangeability must demonstrate, first, that it is FDA-approved as biosimilar; second, that it is expected to produce the same clinical result as the reference product in any given patient; and third — for products administered more than once — that alternating or switching between the biosimilar and reference product carries no greater safety or efficacy risk than staying on the reference product alone [4]. Only the third element is unique to interchangeability. The first two are already required for ordinary biosimilar approval.
What Interchangeability Does Not Determine: Formulary Coverage
Interchangeability is a permission slip for a pharmacist, not an instruction to a payer. A PBM builds its formulary and negotiates net cost independently of whether a given SKU carries the interchangeable label — biosimilars are negotiated the same way competing brand-name drugs in a therapeutic class are negotiated, on rebates and formulary position, not on regulatory designation [5]. A biosimilar can be interchangeable and formulary-excluded. A biosimilar can be non-interchangeable and formulary-preferred. Both have already happened, repeatedly, in the same therapeutic class.
The Eylea Timeline: How an Interchangeable Biosimilar Lost Two Years to a Non-Interchangeable One
Aflibercept is the cleanest natural experiment available because litigation forced interchangeable and non-interchangeable versions of the same molecule onto two completely different launch clocks.
May 2024: FDA Approves Two Interchangeable Aflibercept Biosimilars
On May 20, 2024, FDA approved Biocon’s Yesafili (aflibercept-jbvf) and Samsung Bioepis’s Opuviz (aflibercept-yszy) as the first two interchangeable biosimilars to Regeneron’s Eylea, both cleared for neovascular age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy [6][7].
June 2024: A Permanent Injunction Freezes Yesafili
Interchangeability did not touch the underlying patent dispute. The US District Court for the Northern District of West Virginia had already found in December 2023 that Yesafili infringed method-of-treatment claims in Regeneron’s US Patent No. 11,084,865, and on June 11, 2024 — three weeks after the interchangeable designation — the court entered a permanent injunction blocking Biocon and Mylan from launching Yesafili until the patent’s anticipated June 2027 expiration [8][9]. The FDA’s interchangeability determination and the district court’s infringement finding were decided on entirely separate tracks, and the second one controlled market access.
October 2024: The Non-Interchangeable Competitor Launches First
Regeneron also sued Amgen over its aflibercept biosimilar, Pavblu (aflibercept-ayyh) — approved without an interchangeability designation and carrying a skinny label that carved out Eylea’s retinopathy-of-prematurity indication [10]. Regeneron sought a preliminary injunction against Pavblu; the court denied it, and Amgen launched Pavblu in the United States in October 2024 [11][12]. For roughly two years, Pavblu was the only meaningfully available aflibercept biosimilar in the US market, and it carried no interchangeability designation at all.
April 2025–August 2026: The Interchangeable Product Finally Arrives
Biocon and Regeneron settled in April 2025; the West Virginia court vacated the permanent injunction on April 22, 2025, and the settlement cleared Biocon to launch Yesafili in the US in the second half of 2026 [1][9][13]. Biocon commercially launched Yesafili on August 3, 2026 — becoming, in the trade press’s own description, only “the second aflibercept 2 mg biosimilar to actually reach the US market” [14]. The first interchangeable biosimilar to Eylea reached patients after the second-to-market, non-interchangeable one.
A formulary or GPO team that built its aflibercept biosimilar strategy around “wait for the interchangeable option” missed every P&T cycle, every annual bid cycle, and every buy-and-bill contracting window between October 2024 and August 2026 — more than two full Medicare Part D plan years.
Why Pharmacy Benefit Managers Don’t Rank Formularies by Interchangeability
The adalimumab category shows the same disconnect play out without any litigation at all — through simple rebate economics.
CVS Caremark’s April 2024 Humira Switch Skipped the Interchangeable Option
On April 1, 2024, CVS Caremark removed brand Humira from its major national commercial template formularies and installed biosimilars in the preferred position — 97% of adalimumab scripts were filled with a preferred biosimilar within weeks [15]. The products CVS Caremark placed in the preferred position were Sandoz’s Hyrimoz and an unbranded, low-list-price version of adalimumab-adaz [16]. Boehringer Ingelheim’s Cyltezo — the first adalimumab biosimilar ever granted interchangeability, on the market since July 2023 — was not among them on the primary national formularies; some smaller “value” formularies included Organon/Samsung Bioepis’s Hadlima alongside the Sandoz products instead [17][18]. CVS Caremark’s own public accounting of the switch never once cites interchangeability as a selection criterion — the stated rationale is list price and rebate structure [16].
Cigna Made the Opposite Bet
Cigna’s PBM removed Amgen’s Amjevita — the first-to-launch Humira biosimilar, but never granted interchangeability — from its formulary in September 2023, and installed Cyltezo (the interchangeable option) alongside Sandoz’s Hyrimoz-HC as the preferred alternatives [19]. Two of the three largest US PBMs made opposite decisions about whether an interchangeability designation earned formulary preference, in the same category, within months of each other. If interchangeability itself explained formulary outcomes, that shouldn’t be possible.
Interchangeability Is Granted by Strength and Device, Not by Brand Name
The adalimumab category surfaces a finding that is easy to state and rarely stated precisely: interchangeability is not a single yes/no attribute of a branded biosimilar — it is granted supplement-by-supplement, strength-by-strength, and device-by-device. Sandoz’s Hyrimoz received interchangeability for select low-concentration strengths in a May 2023 sBLA approval, then for additional 10 mg, 20 mg, and 80 mg high-concentration-formulation prefilled-syringe strengths in an April 5, 2024 sBLA approval [20][21]. As of the most recent adalimumab interchangeability approvals, Hyrimoz’s most commonly prescribed dose — the 40 mg high-concentration autoinjector pen — still did not carry an interchangeability designation, even though other Hyrimoz strengths and delivery formats did [22]. A pharmacist evaluating whether to substitute “Hyrimoz” for Humira cannot answer that question from the brand name alone; the answer depends on which strength, which concentration, and which device the prescription specifies. Any formulary communication, benefit-design document, or content asset that states a biosimilar brand is simply “interchangeable” without qualifying strength and device is describing a partial truth at best.
What a Missed Formulary Cycle Actually Costs
“Formulary cycle” is not a figure of speech; it maps to two specific, dated institutional processes, and missing either one has a fixed, calculable cost in time.
The Commercial P&T Quarterly Cadence
Pharmacy and therapeutics committees — the independent physician-and-pharmacist bodies that build and revise formularies — meet no less than quarterly to review new drugs, new indications, and market changes [23][24]. A biosimilar whose interchangeability status, launch date, or patent-litigation posture changes between two P&T meetings does not get a formulary decision until the next quarterly cycle, a minimum three-month wait purely as a function of committee scheduling.
The Medicare Part D Annual Bid Deadline
Medicare Part D runs on a single annual formulary-lock date. Under 42 C.F.R. § 423.265, every Part D sponsor must submit its bids, formularies, and benefit designs to CMS by the first Monday in June for the following plan year [25][26]. Formulary negotiations between plans and manufacturers begin months earlier — typically the preceding late summer or early fall [27]. A biosimilar that clears FDA review, launches, or resolves its patent litigation after that June deadline has already missed the entire negotiating window for the next calendar year’s Part D formularies; the next opportunity is the following June, for coverage that doesn’t begin until the January after that.
Calculating the Cost of a Missed June Deadline
Layer the two clocks together and the arithmetic is direct. A biosimilar that becomes commercially available in, say, July — one month after the Part D submission deadline — does not merely wait one month. It waits through that plan year’s entire enrollment period, contract year, and utilization cycle, then re-enters formulary negotiations the following late summer, for a formulary that locks the following June, for coverage that begins 18 months after the original July launch. That is the mechanical anatomy of “a full formulary cycle”: a several-week regulatory or litigation delay, multiplied by the distance to the next annual lock date, compounds into 12 to 18 months of lost coverage — not because anyone made an error, but because formulary calendars only reset once a year.
Adalimumab biosimilars illustrate the downstream effect: even after 2023’s wave of Humira biosimilar launches, Medicare Part D coverage of adalimumab biosimilars from 2023 through 2025 remained more limited than coverage of the brand, and cost-sharing for the biosimilars leaned on coinsurance rather than the flatter copays typically associated with preferred generics [28].
The First-Interchangeable-Exclusivity Trap
A second, less-discussed mechanic compounds the timing problem: the BPCIA does not let the FDA approve a second interchangeable biosimilar to the same reference product right away, even if the second applicant is ready.
How 42 U.S.C. § 262(k)(6) Works
The statute blocks FDA from making a second interchangeable biosimilar’s approval effective until the earlier of one year after the first interchangeable product’s first commercial marketing, or 18 to 42 months after specified patent-litigation milestones tied to the first interchangeable applicant, depending on whether that applicant was sued and how the litigation resolved [29][30][31]. This first-interchangeable exclusivity (“FIE”) exists to reward the first company willing to clear the higher interchangeability bar — but it also means the second, third, and fourth interchangeable candidates in a molecule can be fully data-ready and still statutorily blocked from approval.
The Pfizer v. Boehringer Ingelheim Dispute Over Cyltezo’s Exclusivity Window
When Cyltezo became the first interchangeable adalimumab biosimilar, the exact expiration date of its FIE became a live legal question. Pfizer — pursuing interchangeability for its own adalimumab biosimilar, Abrilada — petitioned FDA arguing that Cyltezo’s exclusivity should expire 18 months after its interchangeability licensure, hinging the calculation on whether Boehringer Ingelheim had been “sued” within the meaning of BPCIA subsection (l)(6) given the May 14, 2019 dismissal of AbbVie’s suit against BI [32]. The dispute required an FDA legal memorandum to resolve which statutory clock applied. A formulary team relying on a public approval date to predict when a second interchangeable competitor could legally enter the market was relying on a calculation that the FDA’s own attorneys needed a formal memo to settle.
The FDA Is Quietly Narrowing the Distinction It Created
The interchangeable/non-interchangeable line that formulary strategy has been built around for a decade is also actively eroding at the regulatory level — which changes the planning horizon for every product still working through the older, stricter pathway.
2019: The Switching-Study Mandate
FDA’s May 2019 interchangeability guidance told sponsors it expected dedicated switching-study data — clinical trials specifically designed to test alternating a patient between the biosimilar and reference product — to support an interchangeability claim [33].
June 2024: The Draft Guidance That Removed the Switching-Study Expectation
On June 20, 2024, FDA issued draft guidance stating that a sponsor could instead submit a written assessment explaining why its existing comparative analytical and clinical data already met the interchangeability switching standard, without a dedicated switching study [34][35]. FDA’s own stated basis: of the 13 interchangeable biosimilars approved as of that date, 9 had already been approved without additional switching-study data, undercutting the rationale for requiring it prospectively [36].
Approval Timelines Compressed From 798 Days to 364 Days
A retrospective analysis of the FDA Purple Book archive found that the average time from application to interchangeable-biosimilar approval fell from 798 days for applications dated in 2020 to 364 days for applications dated in 2024, and that since 2020 the FDA has approved 26 interchangeable biosimilars, 19 of them between January 2024 and September 2025 alone [37]. Manufacturers have also shifted strategy: 17 of the products in that analysis pursued interchangeability concurrently with initial biosimilar approval rather than filing a separate, delayed supplement [37].
Toward Automatic Interchangeability for All Non-Vaccine Biosimilars
An August 2025 study commissioned by HHS concluded that the biosimilar/interchangeable distinction itself has increased development time and cost without a commensurate safety benefit, and that eliminating the extra clinical requirement would materially increase manufacturers’ expected returns on biosimilar development [38]. Legal analysis of the resulting policy direction indicates FDA intends to finalize aligned guidance in early 2026 and may begin approving all non-vaccine biosimilars as interchangeable by default [38]. If that occurs, the interchangeable/non-interchangeable distinction — the entire subject of this article — would collapse for future approvals, though the first-interchangeable-exclusivity mechanics and the existing population of non-interchangeable biosimilars already on formularies would not disappear retroactively.
State Substitution Law Is a Second, Independent Patchwork
Even where a product’s interchangeability status is settled and unambiguous, whether a pharmacist may act on it is governed by state law, not federal law, and the state rules do not align with each other.
Four States (Plus Puerto Rico) Require Prescriber Sign-Off Regardless of Interchangeable Status
Forty-six of fifty states permit a pharmacist to automatically substitute an interchangeable biosimilar without contacting the prescriber, consistent with the federal standard. Alabama, Indiana, South Carolina, Washington, and Puerto Rico do not; in those jurisdictions, a pharmacist needs prior prescriber approval before substituting even an FDA-designated interchangeable product [39][40].
Several States Condition Substitution on Patient Cost
A subset of states — Arkansas, Idaho, Mississippi, North Carolina, Ohio, and California among them — only permit automatic substitution when the interchangeable biosimilar actually costs the patient less than the reference product, adding a cost-comparison step state law imposes on top of the federal interchangeability determination itself [39][41].
Notification Timelines and Recordkeeping Vary by State
Separately from the substitution decision itself, most states require the pharmacist to notify the prescriber that a substitution occurred, but the required timeframe, communication method, and documentation obligations differ state by state, and some state statutes are silent on timing altogether [39][42]. In all 50 states, a prescriber can override substitution entirely by writing “dispense as written” or an equivalent instruction on the prescription [43][42].
A Second Layer on Top of the Federal Determination
In every one of these fifty-plus jurisdictional variations, the FDA’s interchangeability determination is a necessary condition for substitution — but never a sufficient one. A national formulary or benefit-design document that describes substitution rules in a single sentence is describing, at best, the 40 states where no cost condition applies and prescriber sign-off isn’t required — not the patchwork that a multi-state health plan, PBM, or pharmacy chain actually has to operate under.
Denosumab: Interchangeability Arriving After the Formulary Decision Was Already Made
Denosumab biosimilars compress the entire thesis of this article into a matter of months rather than years.
Sandoz Set the Interchangeable Baseline
Sandoz’s Jubbonti (denosumab-bbdz, referencing Prolia) and Wyost (denosumab-bbdz, referencing Xgeva) were the first denosumab biosimilars FDA approved, in March 2024, and both carried interchangeability designations from the start; they launched in the US in June 2025 pursuant to an April 2024 settlement with Amgen [44][45][46].
Stoboclo and Osenvelt Launched as Ordinary Biosimilars, Then Became Interchangeable Three Months Later
Celltrion’s Stoboclo and Osenvelt were commercially launched in the US in July 2025 as biosimilars — without an interchangeability designation. FDA did not grant them interchangeability until October 29, 2025, roughly three months after launch [47][48]. Any hospital P&T committee, health-system formulary, or Medicaid preferred drug list that evaluated Stoboclo/Osenvelt for formulary placement in July, August, or September of 2025 was necessarily evaluating them as non-interchangeable products; a committee that deferred a coverage decision specifically to wait for interchangeability status missed at least one full quarterly review cycle waiting for a designation that arrived after the product had already been on the market and, in many health systems, already administered to patients under a buy-and-bill medical benefit that doesn’t turn on pharmacy-level substitution rules in the first place.
Five Denosumab Pairs Launched on Five Different Interchangeability Timelines
By the end of 2025, FDA had approved denosumab biosimilar pairs from Sandoz (interchangeable at approval, March 2024), Samsung Bioepis (Ospomyv/Xbryk, interchangeable at approval, February 2025), Celltrion (Stoboclo/Osenvelt, interchangeable three months post-launch, October 2025), Fresenius Kabi (Conexxence/Bomyntra, approved March 2024, litigation-delayed launch to mid-2025), and additional entrants through the fall of 2025 [45][49][50]. No two of the five pairs reached “interchangeable and commercially available” status on the same timeline, in the same order, or via the same mechanism.
Original Analysis: Measuring the Interchangeability-to-Access Gap
Methodology
The following table compares, for five documented biosimilars across three molecules, the date FDA granted (or the sponsor’s product ultimately received) an interchangeability designation against the date that biosimilar — interchangeable or not — actually became commercially available to write or dispense in the US. “Access gap” is calculated as the number of months between interchangeability designation and commercial launch where the interchangeable product lagged a non-interchangeable competitor in the same molecule, or, where interchangeability followed launch, the number of months the product was on the market before the designation existed. Dates are drawn from FDA announcements, court filings, and manufacturer press releases cited throughout this article; where a source gave a month and year rather than an exact day, the analysis uses the first of the month as a conservative placeholder. This is DrugPatentWatch-style timeline reconstruction applied specifically to the interchangeability question rather than to patent expiration, and it is intended to be reproducible by any analyst willing to walk the same public court dockets and FDA announcements.
Findings: Designation Date vs. Meaningful Market Availability
First meaningfully available aflibercept biosimilar; no interchangeability designation
[11][12]
Cyltezo (adalimumab-adbm)
Adalimumab
Oct 2021 (approval); launched interchangeable
Jul 2023
First interchangeable adalimumab biosimilar; still not preferred on CVS Caremark’s main formulary as of Apr 2024
[17][18]
Hyrimoz (adalimumab-adaz)
Adalimumab
May 2023 (select strengths); Apr 5, 2024 (additional strengths); 40mg HCF pen still not designated as of 2025
2018 (original); Jul 2023 (HCF)
Placed in CVS Caremark’s preferred formulary position in strengths that, in part, predated its own interchangeability
[16][20][21][22]
Stoboclo / Osenvelt (denosumab-bmwo)
Denosumab
Oct 29, 2025
Jul 2025
Launched ~3 months before interchangeability designation existed
[47][48]
Reading the Access-Gap Table
The pattern across all five rows is the same: the interchangeability designation date and the date the product actually mattered to a formulary decision are two different dates, and the direction of the gap is not consistent — sometimes interchangeability arrives years after a competitor has already captured the market, sometimes it arrives months after the product itself has already launched. No single column in the table — designation date, launch date, or gap direction — can be predicted reliably from any other column, which is itself the finding: interchangeability status carries no consistent lead-lag relationship to market availability that a formulary team could plan around as a rule of thumb.
A Taxonomy of How the Interchangeability Assumption Fails
Four distinct failure modes recur across the cases above, and distinguishing them matters because each calls for a different formulary-planning response.
Type 1: Litigation-Delayed Interchangeable
FDA grants interchangeability, but a district court injunction blocks commercial launch for years regardless of the FDA determination. Yesafili is the documented example. The planning response: track the BPCIA patent-dance litigation docket, not the FDA approval database, to predict actual launch timing.
Type 2: Rebate-Blocked Interchangeable
The interchangeable product is commercially available, but the PBM’s net-cost and rebate calculus prefers a non-interchangeable competitor for formulary placement anyway. Cyltezo’s absence from CVS Caremark’s April 2024 national preferred formulary is the documented example. The planning response: interchangeability status is not a formulary-outcome predictor in a rebate-driven market; net cost is.
Type 3: Retroactive Interchangeable
The product launches first as an ordinary biosimilar, and interchangeability arrives as a supplemental designation afterward, meaning any coverage or clinical decision made before the supplemental approval was necessarily made on non-interchangeable terms. Stoboclo/Osenvelt is the documented example. The planning response: a formulary committee should evaluate a biosimilar on the clinical and cost merits available at the time of review rather than deferring the review to wait for a designation that may arrive after the review would otherwise have concluded.
Type 4: Fragmented-by-Strength Interchangeable
The brand name carries an interchangeability designation for some strengths or device configurations but not others, so a blanket statement that “Product X is interchangeable” is accurate for only part of the actual prescribing and dispensing volume. Hyrimoz is the documented example. The planning response: any formulary communication or benefit-design document needs to specify strength and device, not brand name alone.
What This Means for Formulary and P&T Teams
A P&T committee that places a candidate biosimilar in “pending” status specifically to await an interchangeability designation is making a scheduling decision, not a clinical one — the underlying safety and efficacy data supporting ordinary biosimilar approval do not change when interchangeability is later granted. Given that commercial formularies revise quarterly and Medicare Part D locks annually in June, the committee should default to evaluating a biosimilar on its available biosimilarity data, litigation status, and net cost at the next scheduled review, and treat a subsequent interchangeability designation as a substitution-policy update rather than grounds to have delayed the original coverage decision.
What This Means for Biosimilar Manufacturers
Manufacturers pursuing interchangeability concurrently with initial biosimilar approval — now the majority strategy, at 17 of the products in the 2020–2025 Purple Book analysis, against 9 that pursued it as a delayed supplement — compress the Type 3 retroactive-designation problem, but they do not solve the Type 1 litigation-delay problem, since patent litigation runs on its own docket regardless of when the interchangeability application is filed [37]. A manufacturer’s launch-planning materials for payers should separate “regulatory designation timeline” from “expected patent-litigation resolution timeline” as two independent tracks, because conflating them is exactly the error the Yesafili case demonstrates.
Separating the Two Timelines in Payer-Facing Materials
A pipeline slide that lists a single “expected launch” date for an interchangeable candidate obscures the fact that two independent gating events — FDA’s interchangeability review and the reference manufacturer’s patent litigation — have to clear before that date is real. Presenting them as two separate rows, each with its own status and risk factors, gives a payer’s formulary team an honest basis for deciding whether to wait for the interchangeable candidate or move on a currently available non-interchangeable competitor instead.
What This Means for Payers and PBMs
Because 46 of 50 states already let pharmacists substitute without prescriber sign-off once FDA designates a product interchangeable, and CVS Caremark’s own experience shows a formulary switch to biosimilars can move 97% of a molecule’s utilization within weeks once the payer commits, the interchangeability determination functions best as a lever a payer pulls after choosing a formulary strategy on cost grounds — not as an input into which biosimilar to select in the first place [15][39].
Frequently Asked Questions
Does an interchangeable biosimilar have to be covered on formulary?
No. Interchangeability is an FDA pharmacy-substitution determination; formulary inclusion, tier, and prior authorization are set independently by each payer or PBM based on contracted net cost [5].
Can a non-interchangeable biosimilar be a PBM’s preferred product?
Yes, and it routinely is. CVS Caremark’s April 2024 national Humira formulary switch preferred non-interchangeable Sandoz adalimumab products over the interchangeable Cyltezo [16][17].
Why did FDA remove the switching-study requirement for interchangeability?
FDA stated that of the 13 interchangeable biosimilars approved as of June 2024, 9 had already been approved without a dedicated switching study, undermining the case that such studies were still necessary to demonstrate switching safety [36].
How long does first-interchangeable exclusivity block a second interchangeable competitor?
Up to one year after the first interchangeable product’s first commercial marketing, or 18 to 42 months after specified patent-litigation milestones tied to the first applicant, whichever comes first under 42 U.S.C. § 262(k)(6) [29][30].
Do all states let pharmacists substitute an interchangeable biosimilar automatically?
No. Alabama, Indiana, South Carolina, Washington, and Puerto Rico require prescriber approval regardless of the FDA interchangeability designation; several other states additionally require the substitution to lower the patient’s cost [39][40][41].
Can one brand-name biosimilar be interchangeable in some strengths and not others?
Yes. Sandoz’s Hyrimoz has interchangeability for some low- and high-concentration strengths but, as of the most recent public reporting, not for its most commonly prescribed 40 mg autoinjector pen [21][22].
What happens when a biosimilar launches before its interchangeability designation is granted?
It is treated as an ordinary, non-substitutable biosimilar until the designation is granted, as happened with Celltrion’s Stoboclo and Osenvelt, which launched in July 2025 and were not designated interchangeable until October 29, 2025 [47][48].
Does interchangeability change reimbursement coding?
No. Each biosimilar, interchangeable or not, is billed under its own distinct HCPCS code rather than the reference product’s code; submitting a biosimilar under the reference product’s code results in denial [14].
Is FDA planning to make all biosimilars interchangeable by default?
Legal analysts tracking FDA’s 2026 guidance plans indicate the agency may move toward approving all non-vaccine biosimilars as interchangeable, following an August 2025 HHS-commissioned study concluding the separate interchangeability pathway increases cost and delay without a clear safety benefit [38].
How much total savings do biosimilars and generics currently generate in the US?
The 2026 AAM/IQVIA savings report found generic and biosimilar medicines together generated $496 billion in US savings in 2025 and more than $3.6 trillion over the preceding decade [51].
“Biosimilars have expanded patient access to care by nearly 571 million days of therapy,” according to the 2026 U.S. Generic & Biosimilar Medicines Savings Report, developed by the Association for Accessible Medicines and the Biosimilars Council in partnership with the IQVIA Institute [51].
Key Takeaways
FDA interchangeability is a pharmacy-substitution determination under 42 U.S.C. § 262(i)(3); it does not control formulary tier, rebate contracts, or patent-litigation outcomes.
Regeneron’s aflibercept litigation delayed the first interchangeable biosimilar to Eylea, Yesafili, until August 2026 — about 22 months after the non-interchangeable Pavblu had already launched and captured the category.
CVS Caremark’s April 2024 national Humira formulary switch preferred non-interchangeable Sandoz adalimumab products over the interchangeable Cyltezo, while Cigna made the opposite choice in the same category the same year.
Interchangeability is granted by strength and delivery device, not by brand name; Hyrimoz carries the designation for some configurations but, as of the most recent reporting, not for its most-prescribed 40 mg autoinjector pen.
Commercial P&T committees meet no less than quarterly, and Medicare Part D locks its formulary annually by the first Monday in June — meaning a several-week regulatory or litigation delay can compound into 12 to 18 months of lost coverage if it crosses either deadline.
The BPCIA’s first-interchangeable-exclusivity provision can statutorily block a second, data-ready interchangeable competitor for up to 42 months, independent of that competitor’s own regulatory readiness.
FDA’s June 2024 draft guidance removed the expectation of dedicated switching studies for interchangeability, cutting average approval timelines from 798 days (2020 applications) to 364 days (2024 applications), and the agency may move toward interchangeability as the default outcome for all non-vaccine biosimilars in 2026.
Denosumab biosimilars Stoboclo and Osenvelt launched as ordinary biosimilars in July 2025 and were not designated interchangeable until October 29, 2025 — proof that the sequence can run in either direction.
References
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