On December 23, 2024, FDA approved the first generic of a once-daily liraglutide injection, a synthetic peptide used to treat type 2 diabetes. In its fiscal 2025 report to Congress1, the agency singled the approval out, saying the peptide's structure "required sophisticated analytical approaches to accurately characterize its molecular structure and impurity profiles." A conventional generic tablet needs nothing of the kind.
Approvals like that are no longer one-offs. In the eight weeks from September 4 to October 27, 2026, original generic approvals recorded in openFDA's Drugs@FDA data7 included a metered-dose beclomethasone inhaler, a liposomal amphotericin B injection, a transdermal estradiol and levonorgestrel film, and peptide injections of lanreotide and teriparatide. Each falls into a category FDA treats as complex. GxRadar's approvals tracker lists them as they arrive.
Most generics still copy simple pills, where a blood-level study in a few dozen volunteers can show the copy behaves like the brand (the logic is laid out in GxRadar's piece on bioequivalence and the 80-125 rule). Complex products do not fit that model, and they are the main reason some medicines stay brand-only, or have a single generic, long after their patents expire.
What FDA counts as complex
The working definition comes from the GDUFA II commitment letter2, the agreement FDA and industry reached in 2016 for the second round of generic drug user fees, covering fiscal 2018 to 2022. It groups complex products as follows.
| Category | What makes it hard | Examples given in the GDUFA II letter |
|---|---|---|
| Complex active ingredient | The ingredient is hard to fully characterize | Peptides, polymeric compounds, complex mixtures of active ingredients, naturally sourced ingredients |
| Complex formulation | Drug release depends on a built structure | Liposomes, colloids |
| Complex route of delivery | The drug acts locally, so blood levels say little about whether it works | Dermatological products; ophthalmic and otic suspensions, emulsions or gels |
| Complex dosage form | The product's physical design controls the dose | Transdermals, metered-dose inhalers, extended-release injectables |
| Complex drug-device combination | The device affects how much drug reaches the body | Auto-injectors, metered-dose inhalers |
| Other | Uncertainty about the approval pathway | Products that would benefit from early scientific engagement with FDA |
Some products sit in two rows. A metered-dose inhaler is both a dosage form and a device, and it acts locally in the lungs. A long-acting injectable depends on how its slow-release formulation is built and made.
Why so few generics reach the market
The hard part is proving sameness. For a cream or an eye drop, very little drug reaches the blood, so the usual pharmacokinetic study tells FDA little. A developer may need a mix of laboratory tests of the product's physical structure, specialized drug-release studies and, in some cases, a clinical study in patients with the condition. Those cost more and take longer than a standard bioequivalence study.
Inhalers add a device problem: the copy has to deliver a matching dose and particle size, and patients have to be able to use it without new training. Liposomal and long-acting injectables depend on manufacturing steps that are difficult to reproduce, often under sterile conditions. Peptides and other complex ingredients require analytical work to show the copy contains the same components in the same proportions, which is the problem the liraglutide approval had to solve. (Larger protein drugs go through a separate pathway altogether, covered in biosimilars and generics.)
Economics compound the science. Higher costs and longer timelines mean fewer companies try, and a market with one or two generics behaves very differently from one with 10, as GxRadar's analysis of prices and competitor counts shows. FDA's fiscal 2025 report1 describes some complex topical products as "practically unfeasible to develop generics for" before its research program produced new testing methods.
Product-specific guidances
A product-specific guidance, or PSG, is FDA's written recommendation for how to show a generic matches one particular brand: which studies, which measurements, which statistics. For a complex product, a published PSG can remove years of guesswork about what the agency will accept. FDA keeps them all on its PSG database page4, and GxRadar's explainer on product-specific guidances walks through what one contains.
As of September 30, 2025, FDA had published 2,288 PSGs, according to the same report1. It issued 925 in fiscal 2025, but that number is inflated: most were revisions of more than 826 guidances for immediate-release oral drugs, updated to match the international ICH M13A bioequivalence standard that FDA finalized in October 2024. Only 49 of the fiscal 2025 PSGs covered complex products.
New guidances still arrive in batches. FDA's August 21, 2026 release6 contained 55 PSGs, 24 new and 31 revised. Eighteen were for complex products (seven new, 11 revised), and more than 30 covered products with no approved generic at all, 15 of them complex.
Under the GDUFA III commitment letter3, FDA set deadlines for complex brands approved on or after October 1, 2022: PSGs for 50 percent of them within two years of the brand's approval and 75 percent within three years. For complex brands approved before that date there is no numeric target, only a commitment to keep developing guidance. That leaves many older complex products without a published roadmap. GxRadar's explainer on GDUFA covers how the fee agreement funds this work.
Meetings before the application
Because complex products rarely fit a template, FDA offers formal meetings before a company files its abbreviated new drug application (ANDA). These make up what FDA calls the pre-ANDA program5 (our piece on pre-ANDA meetings has more on how they run), and the GDUFA III letter3 attached timelines to them.
| Interaction | Purpose | GDUFA III goal (90% of cases) |
|---|---|---|
| Product development meeting | Scientific discussion of study design or alternative approaches during development | Grant or deny within 14 days; hold within 120 days of granting |
| Pre-submission meeting | Walk FDA through unusual data before filing the ANDA | Grant or deny within 30 days; hold within 60 days of the request |
| Controlled correspondence, Level 1 | Written answer to a specific technical question | Respond within 60 days |
| Controlled correspondence, Level 2 | More involved questions needing more review | Respond within 120 days |
| Pre-submission PSG meeting | Discuss an approach other than the one a PSG recommends, before filing | Grant or deny within 14 days; schedule within 120 days of the request |
These meetings let a developer test an unconventional approach before spending money on studies FDA might reject. They help the agency too, since a better-designed application needs fewer review cycles. The broader approval sequence is in GxRadar's guide to how a generic drug gets approved.
What the approval record shows
FDA's fiscal 2025 report lists liraglutide alongside a first generic of iron sucrose injection, approved in August 2025, as examples of complex products reaching the market. Each tends to arrive after years of method development, often after FDA has published or revised a PSG for that product. Thin complex markets are also where FDA's competitive generic therapy designation is most often used.
For patients, the gap shows up as an inhaler, cream or injectable that still has no generic long after the brand's patents ran out. Whether a generic exists for a specific product, and whether FDA rates it as substitutable, is listed in the Orange Book8; a pharmacist can look it up, and GxRadar's guide to therapeutic equivalence codes explains the ratings.
Sources and notes
- FDA (2026). Generic Drug User Fee Amendments FY2025 Performance Report to Congress
www.fda.gov/media/191187/download - FDA (2016). GDUFA Reauthorization Performance Goals and Program Enhancements, FY2018-2022 (commitment letter)
www.fda.gov/media/101052/download - FDA (2021). GDUFA III Performance Goals and Program Enhancements, FY2023-2027 (commitment letter)
www.fda.gov/media/153631/download - FDA (2026). Product-Specific Guidances for Generic Drug Development
www.fda.gov/drugs/guidances-drugs/product-specific-guidances-generic-drug-development - FDA (2026). GDUFA III Enhancements to the Pre-ANDA Program
www.fda.gov/industry/generic-drug-user-fee-amendments/gdufa-iii-enhancements-pre-anda-prog - FDA (2026). FDA publishes new product-specific guidances to facilitate generic drug development (August 21, 2026)
www.fda.gov/drugs/drug-alerts-and-statements/fda-publishes-new-product-specific-guidances- - openFDA (2026). Drugs@FDA API
open.fda.gov/apis/drug/drugsfda/ - FDA (2026). Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book)
www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivale
Superscript numbers in the text link to these sources. GxRadar data (NADAC histories, recall and shortage counts) come from CMS and FDA files described on the sources page. Researched and drafted with AI assistance and checked against the sources above. Information current as of Nov 3, 2026 and may change. Spot an error? It will be corrected once confirmed.
Drug data in this article
Estradiol 1 mg tabletCited by
ANDA review goal dates and how often generics clear the first cycleGeneric drug approvals in 2025, by the numbersPre-ANDA meetings and FDA's advice program for complex genericsQ1/Q2 sameness, the recipe rule for generic injectables, eye drops and creamsSpecialty pharmacies, limited distribution and how they differ from the drugstoreBioequivalence and the 80-125 ruleHow a generic drug gets approvedWhat therapeutic equivalence codes like AB, AA and BX meanThe brand-generic gap in NADACFDA's product-specific guidances, the study plans behind each genericGDUFA, the user fees that pay for generic drug reviewPatent thickets, evergreening and the Orange BookWhy some generics have only one makerNot health advice. GxRadar is for general information only. Nothing here is medical, pharmacy, legal or financial advice. Do not start, stop or change any medicine based on this site. Talk to your pharmacist or prescriber about your own situation. Laws, prices and program rules described here can change; confirm current details with the official source.