Introduction

Biosimilars, a category of biologic medications, are offering new hope for patients by providing cost-effective alternatives to original biologics, which are often expensive and complex. Biosimilars are a type of biologic medication that is safe and effective for treating many illnesses. A biosimilar and its original biologic have the same treatment risks and benefits. However, biosimilars may be available at a lower cost than the original biologics. Biosimilars are highly similar to their reference biologics but offer comparable safety, efficacy, and potency. They play a significant role in treating diseases like cancer, diabetes, and autoimmune disorders, making them essential in modern healthcare.

India, with its strong pharmaceutical sector, is at the forefront of biosimilar production. The country approved its first biosimilar in 2000, making it one of the early adopters globally. Since then, Indian companies have not only supplied the domestic market but have also become global leaders in biosimilars, contributing significantly to making biologic therapies more accessible.

This blog delves into the regulatory, legal, and industry landscape of biosimilars in India. It is designed for professionals in the pharmaceutical and healthcare sectors, legal experts dealing with intellectual property rights, and anyone interested in understanding the challenges and opportunities within the biosimilar industry. The authors hope to provide stakeholders with some insights into India’s evolving role as a leader in biosimilar development and the legal complexities that shape this fast-growing market.

Regulatory Framework in India

In India, biopharmaceuticals and generic medicines are considered to be drugs and regulated by the Central Drugs Standard Control Organization (CDSCO) under the Drugs and Cosmetics Act, 1940. The key regulatory documents governing biosimilars include the Drugs and Cosmetics Act (1940), New Drugs and Clinical Trial Rules (2019), Guidelines on Similar Biologics (2012, updated 2016), and more.

Due to their complexity, in general, rules regarding clinical trials are much more stringent for biosimilars than those applied to generics. Biosimilars are also regulated for various processes (e.g., clinical trials, import, and manufacture). These regulations ensure that biosimilars undergo rigorous testing through pre-clinical and clinical trials to guarantee their safety and efficacy.

However, the regulatory framework in India has been criticized for lacking clarity, particularly regarding enforcement. The Guidelines on Similar Biologics are comprehensive but remain guidelines rather than enforceable laws, leaving room for interpretation and legal disputes, and meaning that neither government nor industry can be held liable for violating these guidelines. Moreover, the existing biosimilar guidelines are poorly drafted, leaving the door open for innovators like Roche to raise a cloud of doubt over the launch of new biosimilars.

Comparison with the US

In the US, a legal framework for approving biosimilars was established in 2009, via the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The BPCI Act establishes an abbreviated approval pathway for biological products that are demonstrated to be ‘highly similar’ (biosimilar) to, or ‘interchangeable’ with, a US Food and Drug Administration (FDA)-licensed biological product. As of July 2024, the FDA has approved 58 biosimilars under this framework.

Unlike in India, where regulatory guidelines lack the legal force of law, the BPCI Act provides robust legislative backing, ensuring that both innovators and biosimilar manufacturers adhere to clear, enforceable rules.

Legal Challenges

Despite India’s advances in biosimilar development, legal challenges continue to arise due to the ambiguous regulatory environment. Several high-profile cases highlight the difficulties faced by biosimilar manufacturers in India.

A notable example is the Roche v. Zydus Lifesciences case, where Roche sued Zydus over its breast cancer biosimilar, Sigrima. Roche sought interim relief against the sale and distribution of Sigrima, claiming it infringed upon their patents IN 268632 and IN 464646. Zydus had entered a commercial licensing agreement with Dr. Reddy’s Laboratories to co-market Sigrima in India. Despite the ongoing legal proceedings, Zydus launched Sigrima after obtaining regulatory approval without informing the court on time. The Court recognized that allowing Zydus to continue selling Sigrima could unfairly disadvantage Roche if the product was later found to infringe on Roche’s patents. Therefore, in July 2024, the Delhi High Court issued a temporary injunction preventing Zydus from selling Sigrima due to patent infringement claims by Roche.

In another case, Roche v. Cadila Healthcare and Hetero Drugs, Roche was the innovator of two cancer drugs ‘Trastuzumab INN’(brand name Herceptin) as well as ‘Bevacizumab INN’ (brand name Avastin). The patent for Trastuzumab lapsed in 2013, and Roche did not have a patent in India for the reference biologic Bevacizumab. In 2016, Roche filed separate suits against Cadila and Hetero Drugs, seeking a declaration that approvals granted by the DCGI for pre-clinical trials, and marketing its drug claimed to be a biosimilar version of Trastuzumab and Bevacizumab respectively, be declared invalid. Roche alleged that Cadila and Hetero are attempting to ride on the goodwill of their drugs to take unfair advantage of the same in selling their respective drugs by terming them as biosimilar, in the absence of conducting requisite tests and/or obtaining requisite approvals in consonance with the applicable laws.

The court, siding with Roche, held that the defendants claimed similarity with Roche’s innovator drug Trastuzumab/Bevacizumab without establishing bio-similarity through appropriate tests and conditions under the applicable laws. Given inherent differences in the compositions of alleged biosimilar drugs and innovators’ biological drugs and inadequate testing, defendants’ drugs should not have been approved, and they should be restrained from promoting and marketing their respective drugs.

The court further added that the impugned actions of the defendants are classic textbook cases of extended passing off and amount to dilution of the formidable and globally known reputation and goodwill of the plaintiffs’ innovator drugs, at the same time giving unfair and undue advantage to defendants. Without adequate testing and assessment pertaining to safety, efficacy, quality, and composition, using International Non-Proprietary Names (INNs) is legally impermissible and adds to public confusion.

Furthermore, the court added, “it is the pleaded case of the plaintiffs that they are not asserting rights under the patent, which has expired in 2013 as also that plaintiffs have no objection to the manufacture and sale of the impugned drugs by Cadila and Hetero as long as they are not claimed to be biosimilar and/or the parties do not use the INN, in the absence of the alleged non-compliance with the applicable laws.”

These cases demonstrate the legal complexities that arise from India’s underdeveloped biosimilar regulatory framework, creating a need for more robust laws to streamline the approval process.

Patenting Biosimilars in India

In addition to regulatory hurdles, patenting biosimilars poses another challenge. biosimilars are not exempt from fulfilling the patentability criteria of being novel, which involves inventive step and industrial application. However, patenting biosimilars becomes complicated, as the nature of biosimilars requires that they should be as close as possible to products that are already on the market and accordingly examined critically for patenting.

If novelty and inventiveness can be established, Indian patent law allows biosimilars to be patented, but manufacturers must carefully navigate this process to avoid infringing on existing patents while developing biosimilars that are similar enough to provide therapeutic equivalence. This complexity often results in patent disputes, as seen in the Roche cases, where the fine line between biosimilarity and patent infringement is often contested.

Industry Growth: Opportunities and Challenges

While legal challenges create uncertainty, India’s biosimilar industry continues to grow. The country’s pharmaceutical companies have become global leaders in biosimilar production, with Indian firms gaining USFDA approval for products like Herceptin (Trastuzumab), marking a significant milestone for the industry.

Despite the successful development and marketing of some biosimilars by Indian companies, research and development in this area will continue to face challenges regarding the development of biologics and biosimilars. In contrast to generics, which are similar rather than identical to the branded drug, biosimilars are much more complex and expensive to manufacture.

Further, contrary to the generics industry, biosimilars are also subject to more stringent clinical timelines, clearly defining regulatory procedures for large-scale, comprehensive clinical programmes establishing the safety and efficacy for the treatment of indicated disorders. The novelty of the biologic and biosimilar development process makes it difficult for new companies to enter this space.

Conclusion

India’s biosimilar industry has made impressive strides in the past two decades, becoming a global leader in this emerging sector. However, regulatory ambiguities, legal challenges, and the complex nature of biologic manufacturing continue to pose significant hurdles. The lack of clear, enforceable guidelines has led to costly legal battles and delayed market entry for many biosimilars.

For India to maintain its leadership position in the global biosimilar market, it must focus on refining its regulatory frameworks and patenting processes. With stronger laws and greater investment in R&D, India can continue to provide affordable biologic therapies to millions of patients worldwide, ensuring that biosimilars remain a key part of the future of healthcare.