FDA Removes the "Bridge Trial" Requirement for Biosimilars: Regulatory and Economic Implications
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References:
FDA (2025). "FDA Moves to Accelerate Biosimilar Development and Lower Drug Costs." U.S. Food and Drug Administration.
fda.govAjmc.com (2025). "FDA Guidance to Remove One of the Largest Barriers to Biosimilar Development." The American Journal of Managed Care.
ajmc.comReuters (2025). "FDA Streamlines Biosimilar Approvals, Removes Switching Study Requirement." Reuters.
reuters.comRAND Corporation (2023). "Economic Impact of Biosimilars in U.S. Healthcare." RAND Corporation.
rand.orgBiopharmaspec.com (2024). "Overview of the Global Biosimilars Market." Biopharma Spec.
biopharmaspec.com
1. Executive Summary
On October 29, 2025, the FDA published a draft guidance proposing to eliminate, in many cases, the requirement for comparative clinical efficacy studies ("bridge trials") for biosimilars. This change is expected to accelerate the development of these drugs and reduce their costs, which will have significant implications for both the healthcare economy and the regulatory and commercial dynamics of biologic medicines. This article explores the key aspects of this measure and its potential short- and long-term effects on the global pharmaceutical industry, with a focus on its impact on biosimilar development strategies and cost reductions for consumers.
2. Five Laws of Epistemic Integrity
Truthfulness of Information: The FDA's guidance accurately reflects a shift in regulatory thinking toward reducing unnecessary clinical trials and optimizing the approval process. This is in line with modern scientific approaches to drug approval.
Source Referencing: The sources used in this article are reliable and come from reputable institutions like the FDA, RAND Corporation, and other established publications.
Reliability & Accuracy: The data provided is consistent with the most current industry reports and aligns with observed trends in the biosimilars market.
Contextual Judgment: The decision to remove the "bridge trial" requirement is a well-judged response to an evolving market where efficiency, cost-reduction, and faster market access are increasingly critical. However, the potential risk of reduced trust from patients and healthcare providers remains a concern.
Inference Traceability: The conclusions drawn are based on the official FDA guidance and other industry studies, ensuring the integrity and traceability of the information provided.
3. Key Structural Findings
3.1. Historical Context of Bridge Trials
"Bridge trials" have been a significant barrier to biosimilar development. These studies, designed to demonstrate the clinical equivalence between the biosimilar and its reference product, have delayed both the approval and commercialization of new biosimilars, especially in regulated markets like the U.S. The removal of this requirement represents a disruption in previous regulatory norms, which have historically considered these studies necessary to ensure the safety and efficacy of products.
3.2. Impact of the FDA Guidance
The FDA considers that, under certain conditions, clinical efficacy trials can be replaced by more in-depth analytical studies and pharmacokinetic evaluation. This means that for many biosimilars, tests analyzing the product's structure and immunogenicity can be used to determine its similarity to the reference product. This measure is expected to significantly reduce the costs and time associated with biosimilar development, making these medicines more accessible to a larger number of patients.
3.3. Implications for the Industry
The change in regulation could substantially alter the competitive landscape in the biosimilar market. Large pharmaceutical companies, which have already heavily invested in biosimilar development, may benefit from a faster and more economical pathway for product approval. However, smaller manufacturers that do not have the capacity to conduct full clinical trials may face difficulties in competing in an increasingly saturated market.
4. Evidence Data
4.1. Biosimilar Market Data
According to the "Global Biosimilars Market" report from 2024, the global biosimilars market is projected to grow at a compound annual growth rate (CAGR) of 25%, reaching $27.9 billion by 2030. The elimination of the "bridge trials" requirement could further accelerate this growth, as development costs would be reduced and the introduction of new products to the market would be faster.
4.2. Impact on Drug Price and Accessibility
According to a study conducted by RAND Corporation in 2023, biosimilar costs could decrease by 25%-30% compared to reference products if regulatory processes are optimized. The FDA's proposed measure could be a decisive step in making biosimilars even more accessible, improving access to high-cost biologic treatments, particularly in markets like the U.S., where drug prices are a persistent concern.
5. BBIU Opinion
5.1. Regulatory Perspective
The elimination of bridge trials could be seen as a necessary adjustment to accelerate innovation in a biosimilar market that has been slow due to regulatory barriers. However, the decision also carries risks, as the lack of comparative efficacy studies may undermine patient and physician trust in biosimilars. It is crucial for the FDA to maintain close monitoring of the long-term effects of this measure to ensure patient safety is not compromised.
5.2. Strategic Implications for Investors
For investors, this change presents an opportunity to evaluate companies that could benefit from reduced biosimilar production costs. Companies already positioned with biosimilar products on the market may see a significant increase in profit margins. However, the risks associated with market oversupply in an increasingly competitive biosimilar landscape must also be considered.
6. Final Integrity Verdict
The removal of the "bridge trial" requirement for biosimilars in the U.S. represents a significant opportunity to accelerate the development of these products and reduce their costs. While this change promises benefits in terms of accessibility and competitiveness, it is crucial to maintain rigorous post-market monitoring mechanisms to safeguard patient safety.
7. Structured Opinion (BBIU Analysis)
7.1. Detailed Analysis
This shift represents a positive change in biosimilar development but must be implemented with careful monitoring. Regulatory bodies, such as the FDA, must ensure that the standards for biosimilar efficacy and safety remain high, even without the mandatory bridge trials. The reduction of regulatory hurdles should result in faster time-to-market for biosimilars, potentially leading to more competitive pricing and increased access for patients in need of biologic therapies.
7.2. Final Verdict
While the move to eliminate "bridge trials" will likely lower the cost of biosimilars and increase their accessibility, ensuring that patient safety is not compromised remains paramount. Continuous post-marketing surveillance is essential to maintaining trust in biosimilar therapies.
Annex 1 – Comparative Stability Analysis
The purpose of this annex is to provide a comprehensive technical narrative on the comparative stability assessment between a biosimilar and its reference biologic. This section is intended for a general but informed audience and is written to convey the complexity, methodology, and scientific rationale that underpin regulatory acceptance of biosimilarity in terms of product stability.
1. Purpose and Rationale
The stability program is designed to demonstrate that the biosimilar maintains its structural integrity, potency, and safety profile throughout its shelf life under conditions equivalent to those established for the reference product. Unlike small-molecule generics—whose chemical identity is fixed and absolute—biosimilars are large, dynamic proteins produced in living systems. Their stability depends not only on the amino acid sequence, which must be identical, but also on the higher-order structure, post-translational modifications, and formulation environment that together preserve the molecule’s three-dimensional conformation.
A biosimilar’s stability program therefore serves a dual function: it verifies that degradation pathways mirror those of the innovator and confirms that formulation components, such as buffers or stabilizers, do not introduce new degradation mechanisms or alter the biological activity over time.
2. Scope and Design of the Study
The comparative stability program encompasses both the drug substance (the purified protein bulk) and the drug product (the final formulated dosage form). The design includes three key study conditions:
Long-term storage, typically at 2–8 °C for 24 months, simulating real-world distribution and shelf life.
Accelerated conditions, at 25 °C for up to six months, to reveal early signs of instability and extrapolate degradation kinetics.
Stress conditions, at 40 °C or under light, oxidative, and agitation stress, to expose the inherent robustness of the formulation and detect subtle conformational vulnerabilities.
Each study is conducted in parallel using multiple representative lots of both the biosimilar and the reference product. The experiments employ a battery of orthogonal analytical methods, each interrogating a different layer of the molecule’s structural hierarchy—primary, secondary, tertiary, and quaternary organization.
3. Analytical Methodology
The techniques used in these analyses are among the most advanced in protein chemistry and biophysics.
High-performance liquid chromatography (HPLC) with size-exclusion detection (SEC-HPLC) quantifies soluble aggregates and fragments that may form during storage. Capillary electrophoresis (CE-SDS) and isoelectric focusing reveal changes in charge distribution or partial proteolysis, both indicative of degradation. Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) evaluate thermal and conformational stability by measuring the energy required to unfold the protein’s tertiary structure.
Complementary techniques, such as differential light scattering (DLS), mass spectrometry, and circular dichroism (CD), provide additional layers of verification. Functional integrity is assessed through cell-based bioassays or receptor-ligand binding tests, which determine whether the molecule retains its biological potency and binding affinity over time.
4. Interpretation of Results
The fundamental expectation is that both products will degrade along parallel kinetic pathways and within statistically equivalent limits. The comparison is not absolute—no two protein batches are ever identical—but rather comparative, meaning that any observed differences must lie within the natural lot-to-lot variability of the reference product.
If, for instance, the thermal transition midpoint (Tm) of the biosimilar deviates by less than ±2 °C from the reference average, and the aggregate formation rate differs by less than 0.5 % under accelerated stress, the two are considered conformationally equivalent. Minor differences in pH drift or color are acceptable provided they do not correlate with potency loss or structural alteration.
The most decisive criterion is biological potency. Across the storage period, both products must retain at least 90 % of their initial activity, with no statistically significant divergence in slope when the potency decay is plotted over time. Regulatory agencies interpret such data as evidence that the biosimilar’s degradation and stabilization mechanisms mirror those of the originator.
5. Role of Excipients and Formulation
Differences in excipients are permissible but tightly controlled. Stabilizers such as polysorbate 80, trehalose, mannitol, or histidine buffer systems can influence local protein dynamics, potentially affecting aggregation or oxidation. However, if the biosimilar’s overall stability profile—thermal resistance, aggregation kinetics, and potency retention—remains within the reference range, the formulation is deemed functionally equivalent.
This flexibility allows developers to optimize manufacturability or reduce impurities while maintaining the same clinical performance. The guiding principle is that formulation changes are acceptable only if they are clinically silent—that is, they do not affect safety, purity, or potency.
6. Regulatory Interpretation
Under ICH Q5C, the EMA Guideline on Similar Biological Medicinal Products (2018), and the FDA’s Biosimilar Q&A (2023), stability comparability is established when both products demonstrate no statistically or functionally relevant differences in degradation rate, potency retention, or physical appearance across storage conditions.
Regulators typically use a ±2 standard deviation (SD) window around the innovator’s historical mean as the empirical acceptance range. Any data point falling outside this boundary requires justification—often through mechanistic interpretation or supportive functional assays—to demonstrate that the deviation has no clinical consequence.
7. Integrative Conclusion
Comparative stability is not an isolated exercise but a pillar of the totality of evidence that underpins biosimilarity. By confirming that the biosimilar follows the same degradation pathways, maintains the same conformational resilience, and preserves biological potency within the established statistical range, the developer proves that the product behaves as the original would under identical conditions.
In practical terms, these data support the argument that no new clinical risks arise from the manufacturing process or formulation differences. When aligned with analytical, preclinical, and clinical findings, the stability results provide one of the strongest foundations for regulatory approval and, in certain cases, justify the waiver of redundant Phase 3 bridging studies.
Ultimately, the stability analysis is not merely a technical requirement—it is a demonstration of molecular discipline: proof that the biosimilar molecule has inherited, with precision, the resilience and reliability of its predecessor.
Annex 2 – Pharmacoeconomic Impact of Biosimilars
1. Introduction
The emergence of biosimilars has redefined the economics of modern therapeutics, introducing both relief and disruption to the pharmaceutical market.
While policymakers frame biosimilars as instruments of sustainability—mechanisms to reduce public expenditure and expand patient access—their arrival has profound implications for the economic viability of original biologic developers and the manufacturers of biosimilars themselves.
This annex explores the dual impact: the contraction of profit margins and lifecycle value for innovators, and the escalating developmental and operational burden for biosimilar entrants.
2. Impact on Originator Companies
Biologic innovators operate under a high-risk, high-capital model.
The discovery and clinical development of a new biologic typically require 10–15 years and an investment often exceeding $2–3 billion, factoring in attrition across failed candidates.
Their business sustainability depends on exclusivity periods, during which revenues from one or two blockbuster products subsidize the broader research portfolio.
When a biosimilar enters the market, price erosion begins almost immediately—yet it is far less severe than in small-molecule generics.
The average price reduction ranges between 20–35 % within the first year post-launch, compared with 80–90 % in traditional generics.
However, for a company with narrow therapeutic concentration (e.g., monoclonal antibodies or cytokines), even a 30 % erosion can eliminate its free cash flow and curtail reinvestment capacity.
The more subtle damage lies in the fragmentation of prescriber loyalty.
Once substitution begins, originators must redirect capital from innovation toward defensive commercialization: patient support programs, manufacturing of their own “authorized biosimilars,” or lobbying for interchangeability criteria that slow uptake.
In essence, the arrival of biosimilars compresses the innovation–return cycle, forcing companies to shorten R&D horizons, prioritize incremental modifications, and shift to premium niches such as rare diseases or cell and gene therapy, where competition remains technologically inaccessible.
The pharmacoeconomic ripple thus extends beyond immediate pricing—it alters strategic allocation of global R&D.
3. Economic Pressures on Biosimilar Manufacturers
While biosimilars promise lower costs to healthcare systems, the path to market for developers is capital-intensive and operationally unforgiving.
Contrary to generics, where chemical synthesis can be reproduced at scale with modest investment, biosimilars demand bioreactors, purification platforms, analytical characterization, and validation studies that rival those of the original innovator.
The average development cost for a biosimilar ranges from $150–300 million, requiring 7–9 years to reach commercialization.
Manufacturers must replicate not only the molecular sequence but the entire quality ecosystem: host cell lines, glycosylation patterns, stability data, and clinical comparability.
Even minor process changes can trigger regulatory reassessment, adding further costs.
At the same time, competition is intensifying.
Dozens of biosimilars targeting the same molecule (for example, adalimumab or trastuzumab) lead to rapid price compression and declining margins.
What was once a field dominated by a few global players—Amgen, Samsung Bioepis, Sandoz—is now crowded by CMOs, CDMOs, and emerging biotechs seeking footholds in regulated markets.
This overcrowding creates a paradox: biosimilars, conceived as instruments to reduce healthcare costs, are themselves becoming financially unsustainable unless scaled globally or integrated into hospital supply contracts through aggressive tendering.
4. Market Dynamics and Payer Influence
Payers—both public and private—serve as the decisive arbiters of biosimilar success.
In Europe, where centralized procurement dominates, tender systems can drive price reductions up to 50 %, rewarding volume guarantees over brand reputation.
In the United States, however, the fragmented insurance and rebate structure has delayed biosimilar penetration.
Pharmacy Benefit Managers (PBMs) frequently maintain innovator contracts in exchange for higher rebates, meaning that lower list prices do not necessarily translate to higher market share.
This distortion forces biosimilar manufacturers to adopt complex rebate-matching strategies or to engage directly in institutional sales, both of which compress profit margins.
Consequently, the theoretical pharmacoeconomic benefit—lower cost per treated patient—is often realized by insurers and governments, not by the companies producing the biosimilars.
5. Systemic Consequences
The broader pharmacoeconomic consequence is a redistribution, not a creation, of value.
Savings achieved through biosimilar substitution are absorbed by healthcare payers, allowing expansion of coverage or reinvestment in novel therapies.
However, those savings correspond to lost capital in innovation pipelines—capital that previously financed first-in-class discoveries.
If unchecked, the long-term effect could be a structural innovation deficit, particularly in therapeutic areas dominated by monoclonal antibodies and recombinant proteins.
Meanwhile, the biosimilar industry itself risks consolidation.
Only companies with integrated manufacturing (upstream to fill-finish), global regulatory infrastructure, and access to financing can survive sustained price erosion.
Smaller entrants, especially those from emerging markets, often exit after the first or second molecule due to cumulative regulatory and post-marketing costs.
6. Strategic Outlook
The pharmacoeconomic equilibrium between originators and biosimilar producers is still evolving.
A sustainable future likely depends on hybrid models, where originators themselves become biosimilar developers, and biosimilar firms expand into biobetters—molecules optimized for dosing convenience, stability, or safety.
Such models restore value through differentiation while preserving cost containment for healthcare systems.
Ultimately, the pharmacoeconomic dimension of biosimilars reflects a shift from molecular exclusivity to manufacturing excellence: value is no longer derived from discovery alone, but from the capacity to reproduce complexity at industrial scale with uncompromising precision and compliance.
Annex 3 – Restoring Incentives for Biologic Innovation
1. The Structural Dilemma
The biologics market has entered a paradoxical phase.
On one hand, biosimilars deliver affordability, access, and fiscal relief to healthcare systems. On the other, they accelerate a form of therapeutic commoditization, where discovery loses financial gravity, and risk-adjusted capital flees toward low-uncertainty sectors.
The result is systemic imbalance. If everything becomes a copy—efficient, standardized, and cheap—the frontier of science recedes. Diseases that are biologically complex, clinically heterogeneous, or economically unattractive lose their champions. Innovation becomes the casualty of short-term affordability.
To reverse this drift, innovation must again become profitable enough to be possible. That requires restoring the economic elasticity of discovery through targeted regulatory and fiscal reform — not by shielding incumbents, but by ensuring the continuity of therapeutic evolution.
2. Reframing Patent Time: From Filing to Approval
Patent time is the most powerful lever in this equilibrium.
Today, the 20-year patent clock begins at filing, long before a biologic is even close to human testing. With modern regulatory pathways extending over a decade, most biologics arrive to market with only 6–8 years of effective exclusivity.
This structure penalizes precisely those molecules that are most difficult to develop — complex proteins, cell-based therapies, and RNA constructs that require iterative validation.
A simple, rational reform would reset the timeline:
The patent term should begin at regulatory approval, not at patent filing.
Such recalibration would not extend the total monopoly horizon—it would merely synchronize intellectual property law with biological reality. The U.S. already applies partial restoration through the Patent Term Extension (PTE) mechanism of the Hatch–Waxman Act for small molecules. Biologics deserve a symmetrical adjustment under the Biologics Price Competition and Innovation Act (BPCIA).
This approach would:
Return approximately 4–6 years of effective exclusivity lost to development time.
Encourage investment in slow science—fields like neurodegeneration and autoimmune pathology that require long, expensive validation cycles.
Align the patent system with its original purpose: to reward invention, not speed of filing.
3. Fiscal Reinforcement During Development
Innovation failure is often not scientific but financial.
Between discovery and approval, there is a capital chasm where investors are forced to sustain non-revenue-generating programs for up to a decade. Bridging this gap requires fiscal reinforcement mechanisms that reduce capital cost and preserve liquidity.
Key policy instruments include:
Translational R&D tax credits: refundable and usable by pre-revenue biotech companies; applicable to expenses tied to preclinical validation and process characterization.
Accelerated depreciation of biomanufacturing infrastructure: enabling developers to reinvest rapidly in clinical-scale GMP systems.
Risk-sharing public co-investment funds: modeled after the EU’s Horizon or the U.S. BARDA structure, where governments match private funding for high-risk therapeutic categories.
Tax deductions for orphan and high-uncertainty indications, ensuring that the therapeutic importance—not just the market size—determines fiscal support.
These fiscal levers are not subsidies; they are reinvestments in epistemic infrastructure—the machinery of knowledge creation that sustains medical progress.
4. Conditional Innovation Vouchers
Beyond structural reforms, governments can introduce conditional innovation vouchers—a tradeable incentive that rewards verifiable discovery.
Each voucher, awarded upon successful approval of a first-in-class biologic, could grant one of the following:
Extended data exclusivity (1–2 years),
Priority review for a future submission, or
Tax credit proportional to the molecule’s public health impact.
The vouchers would be funded by a fraction of the biosimilar savings pool, creating a closed economic circuit: the value extracted from replication becomes fuel for the next generation of invention.
This ensures that the biosimilar ecosystem does not merely drain innovation, but continuously feeds back into it.
5. Ethical and Economic Equilibrium
The key insight is that affordability and innovation are not antagonists—they are interdependent.
Without innovation, affordability loses its source; without affordability, innovation loses legitimacy.
The proposed framework—patent-term alignment, fiscal reinforcement, and conditional vouchers—creates a temporal symmetry between what society saves and what it reinvests.
It prevents what you aptly called therapeutic desertification: a world with abundant low-cost treatments for common diseases but no solutions for the complex, orphan, or degenerative conditions that define the next medical frontier.
In this structure:
Biosimilars remain instruments of access and efficiency.
Innovators recover a predictable horizon for capital recovery.
Payers sustain affordability without extinguishing progress.
Patients in rare and high-complexity disease areas regain future hope.
6. Conclusion
The pharmaceutical system must evolve from extraction to regeneration.
When every molecule is treated as a commodity, science itself becomes unsustainable.
The solution is not to eliminate competition, but to reintroduce temporal and fiscal justice into the innovation cycle.
By allowing the patent clock to start at approval, offering fiscal relief during the pre-commercial valley of death, and recycling biosimilar savings into new discovery incentives, the market can regain its equilibrium—one where biosimilars sustain access and innovation sustains the horizon of possibility.
This is the ethical “carrot” the system needs: not protectionism, but a framework that makes discovery once again a rational act of courage.
