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.

Sarfaraz K. Niazi, PhD

The FDA has released comprehensive guidance addressing promotional labeling and advertising considerations for prescription biological reference products, biosimilar products, and interchangeable biosimilar products. This 

 provides critical clarification for manufacturers navigating the complex landscape of biosimilar marketing communications.

FDA's new guidance clarifies promotional practices for biosimilars, ensuring accurate marketing and preventing misleading claims in the competitive landscape. | Image credit: digicomphoto - stock.adobe.com

The guidance underscores that all prescription biological products, whether reference products or biosimilars authorized under sections 351(a) or 351(k) of the Public Health Service Act, are required to adhere to the misbranding provisions stipulated in the Federal Food, Drug, and Cosmetic Act. Promotional communications must be accurate, not misleading, provide a balanced depiction of benefits and risks, and disclose all material facts pertaining to the products.

A fundamental principle underlying the guidance is the FDA's determination that licensed biosimilar products are highly similar to their reference products with no clinically meaningful differences in safety, purity, or potency. This scientific determination forms the basis for the FDA's recommendations on appropriate promotional practices.

The guidance stresses the importance of correctly and specifically identifying products in promotional materials. Biological products typically have three naming components: a proprietary (brand) name, a proper name (FDA-designated nonproprietary name), and a core name shared among related products. Firms must carefully evaluate each promotional communication to ensure accurate product identification, particularly when discussing risks that apply to both biosimilar and reference products or when presenting comparative information.

A critical aspect of the guidance addresses how firms should present clinical data in biosimilar promotional materials. When including information from studies that supported the reference product's licensure—data that appears in both products' FDA-approved labeling—firms should reference the biosimilar product's labeling. This approach ensures consistency with FDA's determination that the biosimilar can rely on the reference product's clinical data through the abbreviated licensure pathway.

For data not included in the biosimilar's FDA-approved labeling, such as biosimilarity demonstration studies, companies may present this information provided it remains consistent with the approved labeling and complies with the FDA's standards for medical product communications. Such presentations must include appropriate context regarding study design, methodology, the study's role in biosimilarity assessment, and any material limitations.

Comparative Claims and Competitive Positioning

The guidance provides crucial direction on comparative promotional communications between biosimilar and reference products. FDA explicitly warns against representations suggesting clinically meaningful differences between approved biosimilar products and their reference products. Claims of superiority—whether suggesting the reference product is safer or more effective than the biosimilar, or vice versa—are likely to be considered false or misleading.

For example, promotional materials cannot appropriately claim greater efficacy for a biosimilar based on numerically higher response rates from a biosimilarity study if those differences weren't statistically significant or clinically meaningful. Similarly, suggesting a biosimilar is inferior because it wasn't directly studied in each indication, while the reference product was, would be misleading.

The guidance addresses a particularly sensitive area: promotional communications regarding interchangeable designation. FDA clarifies that promotional materials should not suggest biosimilar products without an interchangeable designation are less safe or effective than those with such a designation. All biosimilar products, whether interchangeable or not, meet the same high standard of biosimilarity for approval.

Representations implying that patients currently treated with a reference product should not switch to a non-interchangeable biosimilar, or that healthcare providers should have safety concerns about prescribing non-interchangeable biosimilars, would be considered misleading.

A significant portion of the guidance addresses communications about different licensure pathways. Firms should avoid suggesting that biosimilar products are inferior because they followed an abbreviated licensure pathway rather than the whole development pathway of reference products. The guidance also cautions against misleading comparisons based on the number of approved indications, strengths, dosage forms, or routes of administration between biosimilar and reference products.

FDA recognizes that biological products naturally exhibit minor batch-to-batch variation without affecting safety, purity, or potency. Therefore, promotional communications suggesting biosimilars are inferior because they're not identical to reference products would be inaccurate and misleading.

The guidance provides concrete examples illustrating acceptable and unacceptable promotional practices. Acceptable communications might include claims that a biosimilar has the same route of administration, dosage form, and strength as the reference product for approved indications, or that healthcare providers can prescribe the biosimilar to both treatment-naïve and treatment-experienced patients.

Conversely, promotional materials that highlight numerical differences in response rates without disclosing lack of statistical significance, or that suggest interchangeable products are superior in safety and effectiveness to non-interchangeable biosimilars, would be considered misleading.

Firms seeking FDA feedback on promotional materials before dissemination should follow established procedures for submitting draft communications. Additionally, all promotional materials remain subject to postmarketing reporting requirements, requiring submission to the FDA at the time of initial dissemination along with Form FDA 2253.

This guidance represents the FDA's effort to ensure a level playing field in biosimilar marketing while maintaining scientific accuracy in promotional communications. By clarifying acceptable promotional practices, the FDA aims to prevent misleading comparisons that could undermine confidence among healthcare providers and patients in biosimilar products.

The guidance emphasizes that biosimilar products provide equivalent therapeutic benefits to reference products, thereby encouraging wider adoption of biosimilars while ensuring that promotional materials accurately represent the scientific rationale behind biosimilar approval. Manufacturers are advised to meticulously review their promotional strategies to ensure adherence to these comprehensive recommendations, especially when making comparative claims or addressing the biosimilar development process.

As biosimilar competition intensifies, this guidance provides essential guardrails to ensure that competitive positioning remains grounded in scientific evidence rather than creating artificial distinctions unsupported by clinical data. The ultimate goal is fostering an environment where biosimilars can compete effectively while maintaining the integrity of promotional communications in the biological products marketplace.


1. Promotional labeling and advertising considerations for prescription biological reference products, biosimilar products, and interchangeable biosimilar products. FDA. December 10, 2025. Accessed December 11, 2025. https://www.fda.gov/media/134862/download

Articles

FDA's new guidance clarifies promotional practices for biosimilars, ensuring accurate marketing and preventing misleading claims in the competitive landscape.

BioRationality: FDA Issues New Guidance on Promotional Communications for Biosimilar Products

A New Era Dawns for Biosimilar Development

Fifteen years have passed since the Biologics Price Competition and Innovation Act (BPCIA) transformed the biosimilar landscape. Today, we are at a crucial point: the FDA has finally removed clinical efficacy studies for all biosimilar molecules, marking the most significant regulatory change in biosimilars' history. 

On October 29, 2025, FDA Commissioner Marty Makary, MD, MPH, confirmed at GRxBiosims2025 that “we'll be releasing new draft guidance today to remove the comparative study requirement for biosimilar applications. It should shave off 3-4 years from the approval process.” I had recently obtained these waivers for products that I am personally working with, but this is the first time the FDA has announced a commitment to extending the waiver to all biosimilars.

One reason for the FDA possibly doing this now is to reduce barriers to new biosimilar filings. The industry's outdated playbook—those McKinsey estimates suggesting $100 to $300 million per biosimilar approval—belongs in the archives.

 With strategic regulatory reforms now in place, developers can realistically target development costs as low as $10 million.

Fifteen Years of Advocacy: Victories Achieved

My journey advocating for science-based biosimilar regulation spans over 40 peer-reviewed publications, 12 citizen petitions, and countless meetings with FDA scientists. The principle driving these efforts has never wavered: regulatory decisions must be grounded in scientific rationality, not tradition.

 — WAIVED for insulin (precedent for all molecules)

The Unfinished Agenda: Four Critical Reforms

While we celebrate these victories, our work continues. I'm actively collaborating with the US Senate and White House to advance four game-changing reforms:

1. Standardized Analytical Testing Through USP or Approved Labs

The FDA's historical opposition to USP biological monographs has created an unnecessary burden: developers must procure 10 reference product lots—a costly and complex endeavor. My solution? Enable US Pharmacopeia or FDA-approved commercial laboratories to establish standardized product release specifications and validated testing methods. This ensures consistency across all biosimilar products while dramatically reducing development barriers.

2. Eliminating Redundant Pharmacokinetic Studies

For intravenous products, pharmacokinetic studies offer zero scientific value, in my opinion. While some utility exists for controlled-release formulations, such as certain insulins, mandating these studies for all products constitutes unnecessary human exposure. I've petitioned the FDA to recognize this ethical consideration and eliminate these scientifically unjustified requirements.

3. Clarifying Immunogenicity Testing Requirements

The science is unequivocal: when analytical assessments match, immunogenicity testing adds no value beyond data manufacturers have already collected. All immunogenic differences stem from analytical variations. The FDA must explicitly state this principle, acknowledging that immunogenicity testing in small populations cannot predict causality in broader patient groups.

Here's a simple innovation that could transform the safety of biological drugs: requiring 0.2-micron filtration at the point of use. Larger aggregates—the primary culprits in immunogenicity—can form during storage and transportation. While recognized for its use in erythropoietin, this preventive measure should be standard for all biological drugs. It's a low-cost, high-impact safety enhancement that's inexplicably absent from current requirements.

The US Patent and Trademark Office (USPTO)'s past resistance to addressing double-patenting—a uniquely American obstacle—continues hampering biosimilar entry.

 Despite withdrawing supportive Senate legislation under pressure from the pharmaceutical industry, legal pathways remain. I've provided the new FDA Commissioner with a detailed legal framework leveraging HHS Secretary authorities under existing legislation. With John A. Squires recently appointed as USPTO Director, renewed dialogue may yield progress.

The Vision: A Transformed Biosimilar Market

These reforms will fundamentally reshape the biosimilar landscape:

 will mirror abbreviated new drug application filings—simpler than even 505(b)(2) applications

 for the over 100 remaining biological molecules currently without biosimilar competition

 will reflect actual competition, benefiting patients and health care systems

 will shift from significant large pharma dominance to diverse, innovative developers

 will dissolve as biosimilar adoption becomes routine, not exceptional

We're witnessing the transformation of biosimilar development from an exclusive, high-stakes game to an accessible, science-driven process. The elimination of clinical efficacy studies represents not just regulatory evolution but a triumph of scientific reasoning over institutional inertia.

For stakeholders navigating this new landscape, the message is clear: embrace the scientific paradigm, abandon outdated assumptions, and prepare for a market where biosimilar development is measured in months, not years, and millions, not hundreds of millions of dollars.

The final frontiers are within reach. The question isn't whether these changes will come—it's how quickly we can implement them.

For more insights on biosimilar regulation and development strategies, contact Dr. Sarfaraz K. Niazi at sniazi3@uic.edu


1. Fontanillo M, Körs B, Monnard A. Three imperatives for R&D in biosimilars. McKinsey & Company. August 19, 2022. Accessed October 29, 2025. 

https://www.mckinsey.com/industries/life-sciences/our-insights/three-imperatives-for-r-and-d-in-biosimilars

2. Niazi, SK. Advice to the US FDA to allow US Pharmacopeia to create biological product specifications (BPS) to remove side-by-side analytical comparisons of biosimilars with reference products. 

 2024;16:1013. doi:10.3390/pharmaceutics16081013

3. Pan FY, Chaemsupaphan T, Cartwright S, Leong R. Self-injection satisfaction and safety of CT-P17 (Yuflyma), a high-concentration adalimumab biosimilar, in patients with Crohn’s disease: a cross-sectional study. 

. 2025;9(4):e70230. doi:10.1007/s40259-024-00632-6

BioRationality: The FDA Sets Sights on Removing Clinical Efficacy Studies for Biosimilars

The limited entry of biosimilars and their still unaffordable cost

 due to the cost of development, which ranges from $100 to $300 million each.

 Most of this cost is attributed to clinical efficacy studies (CES)

 Europe took the lead, but the FDA continued to require CES, except for a few cytokines with pharmacodynamic properties, leaving the largest category of monoclonal antibodies requiring extensive clinical testing. The irony of these testing requirements is that these studies can never fail, but that was not fully appreciated, being the first of their kind of studies ever required by the regulatory agencies.

After decades of filing citizen petitions,

 and meeting with FDA decision makers, convincing US senators to introduce bills to amend the Biologics Price Competition and Innovation Act,

 things began to move. First came the removal of animal toxicology testing for biosimilars, which I had strongly objected

 to, followed by an administrative change to remove interchangeability as I had suggested to the FDA, effectively,

 but the major requirement of CES had remained intact for monoclonal antibodies. Finally, I received a letter on August 25, 2025, which indicated that the agency may finally officially waive CES for biosimilars.

 This position of the FDA will consolidate the regulatory framework for all regulated agencies, allowing for faster entry of biosimilars from smaller companies, which will lead to a significant reduction in their cost to patients.

Now, a lot will change about how the biosimilars are developed, marketed, and made available to patients. First, I see a fast retraction of big pharma staying in the biosimilar market—this is the same history that took place when generics came. Second, the market value of companies that are planning to invest heavily in CES will go down, and third, the associations that keep repeating the theme of using more biosimilars to save more will disappear.

This is the time for smaller companies to bring out their plans since the cost of a new biosimilar approval should not exceed $10 million if a US contract development and manufacturing organization is developing and supplying the biosimilar; many companies can shrink it to no more than a 505(b)(2) filing. No longer is there a need to discuss how to promote biosimilars; they will find their own way just like the generics have done. I began by writing the first book that identified them as biogenerics, then it went to biosimilars, and now it is returning to biogenerics.

1. Rathore AS, Gardner PJ, Chhabra H, Raman R. Global outlook on affordability of biotherapeutic drugs. 

 2024;1537(1):168-178. doi:10.1111/nyas.15171

2. Fontanillo M, Körs B, Monnard A. Three imperatives for R&D in biosimilars. McKinsey & Company. Published August 19, 2022. Accessed September 16, 2025. 

3. Niazi SK. Scientific justification and policy recommendations to the US Food and Drug Administration for waiving comparative efficacy studies. 

4. Brennan Z. Amgen's Leah Christl makes the case to keep the interchangeability designation for biosimilars. Endpoints News. Published September 12, 2023. Accessed September 16, 2025. 

https://endpoints.news/amgens-leah-christl-makes-the-case-to-keep-the-interchangeability-designation-for-biosimilars

5. Niazi SK. Biosimilars adoption: recognizing and removing the roadblocks. 

 2023;15:281-294. doi:10.2147/CEOR.S404175

6. Regulations.gov. Niazi and FDA. Published 2025. Accessed September 16, 2025. 

https://www.regulations.gov/search?filter=niazi%20fda

7. Niazi SK. A timely recommendation to the European Medicines Agency and the FDA on rationalizing comparative clinical efficacy testing of biosimilars. 

 2024;1:87. doi:10.1007/s44337-024-00107-6

8. Sen. Lee introduces biosimilar red tape elimination act. Senator Mike Lee’s 8. website. Published November 17, 2022. Accessed September 16, 2025. 

https://www.lee.senate.gov/2022/11/sen-lee-introduces-biosimilar-red-tape-elimination-act

9. Niazi SK. End animal testing for biosimilar approval. 

 2022;377(6602):162-163. doi:10.1126/science.add4664

10. Niazi SK. No two classes of biosimilars: urgent advice to the US Congress and the FDA. 

 2022;47(9):1352-1361. doi:10.1111/jcpt.13743

11. Professor Sarfaraz K. Niazi secures first-ever FDA acceptance to waive clinical efficacy studies for monoclonal antibody biosimilars. News release. Yahoo Finance. Published September 1, 2022. Accessed September 16, 2025. 

https://finance.yahoo.com/news/professor-sarfaraz-k-niazi-secures-142300145.html

BioRationality: No More Clinical Efficacy Testing for Biosimilars, Going From Biosimilars to Biogenerics

In a position paper submitted to the FDA Commissioner at his request, I have detailed the changes that are needed in the Biologics Price Competition and Innovation Act (BPCIA) to enable faster entry of affordable biosimilars.

| Image Credit: ArtemisDiana - stock.adobe.com

I believe the most creative proposal, based on legal analysis is how the FDA need not entertain any legislative changes or modifications to BPCIA to change all policies related to biosimilars. The Secretary of HHS is granted this authority, but it has been legally challenged in the past by stakeholders who oppose the expansion of biosimilars. In my comparative global analysis, I am teaching the FDA Commissioner how to create guidelines that will not be subject to legal challenges. Here are the changes I am proposing:

Make clinical efficacy studies nonmandatory, leaving the onus of proving that they are not necessary on the filer. However, where it is obvious, prevent developers from conducting such studies to avoid human abuse.

Remove the need for clinical pharmacology studies, pharmacokinetic, and pharmacodynamic if intravenous (IV) administration of the product is not required or where non-IV administration with instant absorption is possible.

Analytical similarity testing is divided into 2 parts: the first is molecular similarity, which does not require multiple lots of reference products; the second is matching the release specification rather than conducting a side-by-side analytical similarity assessment. This will also allow the use of legacy limits that do not require comparison.

Allow the US Pharmacopeia to create product release specifications (PRS) instead of a monograph and provide validated test methods, thereby eliminating the need to secure multiple lots of the reference product.

Products with identical formulation, whether current or prior (due to intellectual property issues), should be required.

No unmatched degradation product is allowed; it must be removed by chromatography—no scientific justification allowed.

Post-translation attributes must match in identity and quantity within a 10% tolerance.

The prescribing information will be the same as the reference product information, modified as needed, without any changes to the formulation.

All biosimilars should be interchangeable unless the prescribers suggest otherwise.

Biosimilars will be allowed a Drug Master File to allow developers to secure drug substance just like it is done for the active pharmaceutical ingredient. However, the drug product qualification must be met with a complete dossier.

The FDA is expected to take an active role in addressing double-patenting, following the recent withdrawal by the US Patent and Trademark Office.

Injection of biosimilars will require point-of-use filtration to reduce the risk of aggregates causing immunogenicity.

No consultation with stakeholders to avoid conflict of interest; only scientific opinions will be sought, and that too, not from organizations with an agenda.

No consultation with associations of biosimilar developers, as these are based on non-scientific views. In my opinion, drug distribution and other issues, such as pharmacy benefit managers, are not related to the FDA agenda.

351(k) applications will be treated as fast-track, with a token applied for faster approval; the maximum limit of approval from the filing date is no more than 6 months.

All these changes can be brought by introducing guidelines, regardless of the details or requirements listed in the BPCIA. The correct language of these guidelines is also provided in the detailed paper I have submitted to the US FDA Commissioner. I anticipate meeting him soon.

BioRationality: How the FDA Can Bypass Congress to Change Biosimilar Guidance

The peer-reviewed paper titled “Biosimilar Red Tape Elimination Act (S.2305): weakening FDA regulatory standards for biosimilars, undermining physician confidence and jeopardizing patient health” published in March 2025

was based on a webinar held by the Alliance for Safe Biologic Medicines (ASBM) in collaboration with the Generics and Biosimilars Initiative (GaBI). The journal publishing this paper summarized the presentations made in this webinar, concluding that the Biosimilar Red Tape Elimination Act (S.2305) weakens the FDA regulatory standards for biosimilars, undermining physician confidence and jeopardizing patient health. The authors of the paper reported they were clinicians presenting their analysis, which contradicted the FDA findings, commenting on the scientific rationale that is beyond the expertise of physicians. Of equal concern is the journal's partnership in arranging the webinar and publishing its results.

Image credit: Shutter2U - stock.adobe.com

The authors claimed that the ‘Biosimilar Red Tape Elimination Act (S.2305)

 would classify all biosimilars as interchangeable, highlighting its shortcomings, and the justification that similar acceptance in the European Union is common was questioned on the basis that the definition of ‘interchangeable’ differs between Europe and the US and that pharmacy-level substitution in Europe rarely occurs, an opinion that is incorrect and misleading. The presenters also suggested conducting animal toxicology or pharmacology studies, which have now been removed by the FDA, and clinical efficacy studies, which have also been removed by many agencies, including a prospective change at the US FDA. The views of presenters emphasized the need to conduct extensive additional studies to achieve interchangeable status, as perceived by 87% of webinar responders.

In April 2024, Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars, called on Congress to eliminate the regulatory distinction between interchangeable and non-interchangeable biosimilars. Yim stated that this change is now necessary because there are no longer any scientific or clinical reasons to differentiate between the two classes of products. She explained, “Instead of having 2 different levels of similarity, for example, we don’t feel like we can implement that.”

In October 2024, Inside Health Policy published an article stating, “Accumulated scientific evidence has led FDA to conclude clinical studies are mostly unnecessary to determine whether a biosimilar drug should be interchangeable with its reference product,” and “FDA’s accrued experience with switching between reference products and biosimilars, and global post-approval data, have not demonstrated clinical concerns with the practice; the officials say this provides support for the idea that a switching study is not necessary in most cases,” and “We were able to approve the majority [9/13] of interchangeable products without the need for a clinical switching study.”

However, the ASBM Whitepaper raises concerns about the FDA meta-analysis.

 Both authors noted that the FDA analysis is highly selective and limited, encompassing only 44 randomized controlled trials and their extension studies. Furthermore, efficacy impacts are not evaluated; only safety is evaluated. FDA regulatory approval for interchangeable biosimilar products is based on demonstrating that neither safety nor treatment efficacy is negatively affected.

Additionally, it extrapolates multi-switch safety data primarily from single-switch studies, with 64% of the studies being single-switch. Finally, it neglects real-world considerations, such as patient variability. Thus, according to the ASBM, the bill is supported by a weak study with flawed methodology. Physicians, when informed, overwhelmingly oppose the bill’s intent (deeming all biosimilars interchangeable). The bill’s primary supporters are payers, such as the Pharmacy Benefit Management Industry Trade Group and the Employee Retirement Income Security Act Industry Committee (representing large, self-insured employers).

I was involved in the drafting of the questioned bill, as mentioned in the press release when Senator Mike Lee (Republican, Utah) introduced it.

 I found that none of the objections from the ASBM hold any merit; however, promoting an opposition by a journal is not what I would consider ethical. This bill should be approved; there is no safety or efficacy risk, only the risk of supporting the views of big pharma companies, as presented by the ASBM and GaBI.

1. Schneider PJ, Spiegel A, McKibbin R, Reilly MS. Biosimilar Red Tape Elimination Act (S.2305): weakening FDA regulatory standards for biosimilars, undermining physician confidence and jeopardizing patient health. Generics and Biosimilars Initiative. October 31, 2024. Accessed June 23, 2025. 

https://www.youtube.com/watch?v=X6-dYZ7fjhM

2. Schneider PJ, Spiegel A, McKibbin R, Reilly MS. Biosimilar Red Tape Elimination Act (S.2305): weakening FDA regulatory standards for biosimilars, undermining physician confidence and jeopardizing patient health. Generics and Biosimilars Initiative. March 25, 2025. Accessed June 23, 2025. 

https://gabi-journal.net/biosimilar-red-tape-elimination-act-s-2305-weakening-fda-regulatory-standards-for-biosimilars-undermining-physician-confidence-and-jeopardizing-patient-health.html

3. S.2305 - Biosimilar Red Tape Elimination Act. Congress.gov. July 13, 2023. Accessed June 23, 2025. 

https://www.congress.gov/bill/118th-congress/senate-bill/2305

4. Review and approval. FDA. December 13, 2022. Accessed June 23, 2025. 

https://www.fda.gov/drugs/biosimilars/review-and-approval

5. Karins J. FDA drug center officials defend biosimilar switching policy change. Inside Health Policy. October 21, 2024. Accessed June 23, 2025. 

https://insidehealthpolicy.com/daily-news/fda-drug-center-officials-defend-biosimilar-switching-policy-change

6. Reilly MS, McKibbin RD. Misinformation about interchangeable biosimilars undermines US health policy, physician confidence, and patient health. 

. 2024;13(2):55-60. doi:10.5639/gabij.2024.1302.009

7. Considerations in demonstrating interchangeability with a reference product. FDA. May 20, 2019. Accessed June 23, 2025. 

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

8. Lee bill cuts drug prices and red tape. Senator Mike Lee. June 4, 2025. Accessed June 23, 2025. 

https://www.lee.senate.gov/2025/6/lee-bill-cuts-drug-prices-and-red-tape

The debate over the Biosimilar Red Tape Elimination Act raises critical concerns about FDA standards, physician trust, and patient safety in biosimilars.

BioRationality: Questioning Experts and Journals Reporting on Biosimilar Bill to Remove Interchangeability

Associations established to support biosimilars are currently represented by three entities: the 

), and the significant pharma representation by 

. The memberships of these 3 entities are highly diverse, with the Biosimilar Council being the smallest of the bunch.

Juliana Reed, executive director of the Biosimilar Forum, stated when she took over the role, “I am extremely excited to lead the most influential organization for the biosimilars industry at such a critical time. My top priority will be to work with our members, Congress, and the FDA as a voice for our industry and patients. I will advocate for commonsense policy solutions that give more patients access to life-saving, lower-cost biosimilars.”

I will analyze this perspective and offer advice on bringing this conviction to reality.

Unpacking the Core Issues: Beyond the Advertising Hype

The most common statements made by both biosimilar associations center on the roles of PBMs, prescriber and patient understanding, hurdles in distribution channels, and, to a lesser extent, development cost hurdles. They mainly advertise how much biosimilars are saving without adequately highlighting a crucial point: only a small number of biologicals are available as biosimilars because of the 

 This reality keeps smaller companies out of the market and large companies focused only on high-market products, as their development announcements can significantly affect their stock.

If we can bring down the development cost closer to the pathway for abbreviated new drug applications or 505(b)(2) filings, there will be little left to promote to make biosimilars accessible. I believe this is the fundamental challenge to biosimilar success.

Reconsidering Current Approaches: Where Advocacy Falls Short

The Biosimilar Council regularly references IQVIA reports, stating that only a few molecules have biosimilars available. However, I don’t think this view fully grasps that it is not in IQVIA's interest to reduce testing in patients; they are, after all, an excellent company to conduct these trials. My point here is that we should be questioning the 

 of all that testing, not just reporting on its current state.

The Biosimilar Council also remains engaged in the Inflation Reduction Act, where they argue that the reference product must not sell at a lower price; otherwise, biosimilars will have less incentive to enter the market. This is, in my opinion, a position that misunderstands the dynamics of market incentive for biosimilars.

A Clear Path Forward: Learning from International Success

Reed has spoken clearly that we must lower the cost of biosimilars, and that can only be achieved if we work together to convince the FDA to follow what the UK’s Medicines and Healthcare products Regulatory Agency 

. The European Medicines Agency is about to remove clinical efficacy testing. As a long-time advisor to the FDA, I have published another paper highlighting the urgency for the FDA to consider removing CESs.

This is another agenda that I believe the Biosimilar Council and Biosimilar Forum should take up. In this opinion column, I am asking them to promote this motivation to the FDA. I hope my paper will also help these associations understand my position that a lot of the issues facing the biosimilar space will be addressed once we address development costs.

1. Juliana M. Reed named executive director of the Biosimilars Forum. Press release. Biosimilars Forum; January 31, 2022. Accessed June 1, 2025. 

https://biosimilarsforum.org/2022/01/31/juliana-m-reed-named-executive-director-of-the-biosimilars-forum/

2. Munz K. Despite uptake barriers, real-world biosimilar data demonstrate safety, efficacy, cost-effectiveness. 

. April 17, 2024. Accessed June 2, 2025. 

https://www.ajmc.com/view/despite-uptake-barriers-real-world-biosimilar-data-demonstrate-safety-efficacy-cost-effectiveness

3. Niazi, S.K. Scientific justification and policy recommendations to the US Food and Drug Administration for waiving comparative efficacy studies. 

Biosimilar associations advocate for lower development costs and streamlined regulations to enhance patient access to affordable biosimilars.

BioRationality: The Urgency of Removing Clinical Efficacy Studies

The Indian Central Drugs Standard Control Organisation (CDSCO) has recently issued a draft guideline for biosimilars, which is a significant change in its perspective. The 2025 CDSCO Draft Guidelines on Similar Biologics

 represent a progressive shift toward harmonizing Indian regulatory requirements with global standards set by the European Medicines Agency (EMA)

, FDA, and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

A comparative analysis reveals significant alignment with the World Health Organization Technical Report Series 1043

 and recent practices of EMA and MHRA, particularly in minimizing animal testing, streamlining efficacy requirements, and emphasizing the totality of evidence from quality and in vitro assessments. However, some places still show room for refinement and clarification to match current global regulatory trends fully.

One of the most notable strengths of the CDSCO draft is its explicit de-emphasis on in vivo animal testing. The document strongly encourages using in vitro assays to establish comparability in nonclinical assessments. It introduces a tiered decision framework where in vivo studies may only be requested under specific conditions of residual uncertainty. This aligns closely with the EMA’s 2022 update, which allows for complete waiver of animal studies when in vitro and analytical data are sufficient to exclude safety or efficacy concerns, and with the MHRA guidance, which promotes the 3Rs principle (Replace, Reduce, Refine) to the point of near elimination of animal requirements.

Although slightly more conservative, the FDA has also begun to permit waivers for animal testing in specific biosimilar applications based on strong in vitro and analytical data. Thus, CDSCO’s updated stance reflects a marked philosophical convergence with these agencies, confirming India’s move toward a scientifically justified and ethically modern regulatory posture.

The CDSCO’s position on clinical efficacy testing also reflects a significant evolution. Like EMA and MHRA, the new CDSCO draft permits waivers of confirmatory phase 3 efficacy trials under defined conditions. These include high structural and functional comparability, PK/PD equivalence demonstrated using validated biomarkers, and robust immunogenicity and safety monitoring plans. This reflects a substantial shift from CDSCO’s earlier 2016 guidelines, which generally mandated confirmatory efficacy studies for most biologics. EMA had already moved in this direction with its 2014 update, and the MHRA removed the requirement for confirmatory efficacy studies in 2022 for products that meet high comparability standards. 

Although historically slower, the FDA issued a draft guidance in 2023, strongly suggesting that comparative efficacy trials may no longer be needed in most biosimilar applications if PK, PD, and immunogenicity data are convincing. In this respect, the CDSCO guidelines are both timely and scientifically justified. However, greater emphasis on biomarker validation, statistical justification of margins, and standardized PD endpoint use could bring further clarity and alignment with EMA’s robust sample size and statistical criteria guidelines.

Regarding immunogenicity testing, the CDSCO draft provides a detailed, multi-tiered framework that includes antidrug antibody incidence, neutralizing antibody titers, persistence, and clinical impact. The guidelines recommend risk-based immunogenicity testing, acknowledging that highly similar biologics like insulin or filgrastim with a long history of low immunogenicity may not require pre-approval immunogenicity studies. 

This is consistent with the EMA’s 2017 guideline on immunogenicity assessment, which classifies products based on immunogenicity risk and allows waivers for low-risk categories when paired with rigorous analytical comparability. The FDA and MHRA also take a risk-based view but often still expect immunogenicity data for higher-risk categories, such as monoclonal antibodies. CDSCO’s adoption of the same principles and its provision for post-marketing immunogenicity surveillance when pre-market data are waived reflect regulatory maturity and ethical responsibility.

However, some ambiguities remain in the CDSCO document. For example, the statistical methodology recommended for analytical similarity assessments includes a preference for min–max intervals due to the practical constraint of batch availability. Still, the statistical justification and interpretation of outliers require more precise articulation. 

EMA generally prefers tolerance or equivalence interval testing based on sample size and criticality, and the FDA often requests equivalence testing using 90% confidence intervals with predefined acceptance margins for all key quality attributes. CDSCO allows these methods but does not mandate them or provide firm criteria for sample size justification, leaving room for potentially inconsistent applications across applicants. Greater specification would enhance regulatory predictability and alignment.

Another area that would benefit from enhancement is the explanation of the rationale behind the extrapolation of indications. While the CDSCO guideline broadly permits extrapolation if analytical similarity, mechanism of action, receptor engagement, and immunogenicity profile are sufficiently established, there is minimal discussion on how divergent clinical populations or routes of administration should be factored into this decision. EMA’s guidance is more explicit, often requiring justification based on receptor expression, disease pathology, and clinical similarity across indications. MHRA and FDA follow similar principles. More prescriptive language from CDSCO would ensure consistent decisions across therapeutic areas and reduce sponsor uncertainty.

In conclusion, the 2025 CDSCO draft guidelines represent a meaningful and commendable step toward global regulatory alignment in the oversight of biosimilars. The agency has embraced major global trends—especially the reduction of animal and human efficacy testing—in favor of a scientifically robust, risk-based, and ethically sound framework.

While the guidance is harmonized mainly with EMA, MHRA, and emerging FDA positions, further refinement is needed in statistical testing, PD biomarker validation, immunogenicity risk stratification, and extrapolation justification to ensure clarity, consistency, and global acceptability. With these improvements, CDSCO’s framework could serve as a model for emerging markets seeking to modernize their biosimilar regulatory pathways.

1. Draft guidelines on similar biologics 2025. Directorate General of Health Services CDSCO. Accessed May 19, 2024. 

https://cdsco.gov.in/opencms/resources/UploadCDSCOWeb/2018/UploadPublic_NoticesFiles/Draft%20Guidelines%20on%20Similar%20Biologics%202025.pdf

2. Reflection paper on a tailored clinical approach in biosimilar development. EMA. January 2, 2025. Accessed May 19, 2025. 

https://www.ema.europa.eu/en/reflection-paper-tailored-clinical-approach-biosimilar-development

3. Guidance on the licensing of biosimilar products. MHRA. Updated February 27, 2025. Accessed May 19, 2025. 

https://www.gov.uk/government/publications/guidance-on-the-licensing-of-biosimilar-products/guidance-on-the-licensing-of-biosimilar-products

4. Guideline for the production and quality control of monoclonal antibodies and related products intended for medicinal use. WHO. April 22, 2022. Accessed May 19, 2025. 

https://www.who.int/publications/m/item/trs1043-annex4

BioRationality: The Revised Indian Biosimilar Guidelines Finally Bring Rationality

The office of Senator Paul (R-KY) contacted me a few weeks ago, asking how we can amend the Biologics Price Competition and Innovation Act (BPCIA) to reduce the regulatory hurdles, and requested specific language to be made as part of an amendment. I provided complete details with extensive documentary support. 

I am pleased that on April 8, 2025, US Senator Rand Paul (R-Kentucky) introduced legislation to streamline the approval process for biosimilars by eliminating costly and redundant clinical study requirements.

 I believe that Paul’s Expedited Access to Biosimilars Act will increase market competition, lower drug prices, and improve access to more life-saving treatments.

The bill retains the FDA’s requirement for pharmacokinetic (PK) studies, but it will eliminate the FDA’s blanket requirement of immunogenicity, pharmacodynamics (PD), and clinical efficacy requirements (CES) unless scientifically warranted. Notably, the regulatory agencies in the UK and European Union (EU) have dropped the blanket requirement for these redundant studies after years of research, which determined that early-stage PK studies were sufficient for biosimilar approval.