INTRODUCTION
Biosimilars are becoming a game-changer in the rapidly changing landscape of the biopharmaceutical industry. Biosimilars are one of the fastest-growing areas within biopharmaceuticals due to expiring patents and more transparent regulatory processes. One of the key reasons behind the market growth over the next few years is the affordability requirement of treatments. The biosimilars are less costly as compared to the original cost of the products present in the market, making them cost-saving alternatives when compared with the over-priced branded drugs.
BIOSIMILAR VS GENERIC DRUGS-
A biosimilar is not considered a generic version of a biological medicine primarily due to the natural variability and complex manufacturing processes of biological medicines, which prevent the exact replication of their molecular microheterogeneity. Generic drugs are exact copies of brand-name drugs, containing the same active ingredients and matching in dosage form, safety, strength, route of administration, quality, performance characteristics, and intended use, making them bioequivalent to their brand-name counterparts. However, biosimilars are highly similar to their reference products but have permissible differences because they are derived from living organisms. Despite these differences, biosimilars have no clinically meaningful differences in safety, purity, or potency compared to the reference product.
BIOSIMILAR GUIDELINES:
a) In Indian jurisdiction: The Central Drugs Standard Control Organization, India’s national regulatory body, released new biosimilar guidelines effective from August 15, 2016. These guidelines are a slight modification of the previous “Draft Guidelines on Similar Biologics: Regulatory Requirements for Marketing Authorization in India” from 2012, which addressed pre-marketing and post-marketing regulatory requirements, manufacturing processes, and quality control. The 2016 guidelines place a greater emphasis on post-marketing requirements, with a significant change allowing the use of reference products licensed in any ICH country if they are not marketed in India.
India has a vast population, and a rising incidence of chronic diseases, and the original biologics cost more than biosimilars making it possible to earn significant potential in that country. India has a sound regulatory framework established by its Central Drugs Standard Control Organization (CDSCO) which ensures that market growth is facilitated through safety and efficacy. Indian pharmaceutical companies such as Biocon and Dr Reddy’s Laboratories have made huge investments in biosimilar development and global partnerships. On the other hand, they are facing challenges which include lack of awareness, increase in regulation, and competition among others even though they are affordable to many due to affordability as well as government support. However, the outlook for biosimilars in India seems bright given the increasing demand for low-cost therapy options coupled with ongoing industry R&D spending efforts.
RELATED CASE LAWS:
- Roche Products (India) Pvt. Ltd. vs. Drugs Controller General of India (DCGI) & Others (2016) case was Roche’s writ petition against DCGI and Biocon Ltd., on the ground that DCGI had wrongly allowed Biocon to market a biosimilar version of Trastuzumab, a breast cancer drug, Herceptin, originally marketed by Roche. Roche argued that Biosimilars were not in line with the required guidelines and standards for biosimilars in India by Biocon. The main issue raised from whether the approval satisfied biosimilar guidelines and whether Biocon did meet any prerequisite clinical trials or regulatory requirements. The Delhi High Court stressed the importance of strict regulation regarding complex processes and their potential harm caused by different ways of producing biological products. Therefore, it ordered DCGI to ensure that the process of approving such drugs follows guidelines put in place while paying particular attention to rigorous testing complying with biologic reference medicine likeness affirmation protocol. This case demonstrated government oversight is vital to ensuring the safety and efficacy of biosimilars in India through a proper regulatory framework/frameworks.
- In another case of Biocon Limited vs. Genentech Inc., & Others (2019), Biocon Limited and Mylan Pharmaceuticals sought to introduce a Trastuzumab biosimilar to India but were stopped by Genentech, the original developer of Trastuzumab, and Roche, who claimed that they infringed their patent and did not follow biosimilar guidelines. The proceedings revolved around whether or not the biosimilar made by Biocon and Mylan had infringed on Genentech’s patent as well as if it complied with Indian regulations. The Delhi High Court rejected the request for an interlocutory injunction filed by Genentech and Roche thus paving the way for Biocon and Mylan to sell their biosimilar. It said that after following due process, such a biosimilar had been approved by relevant regulatory authorities; however, issues relating to infringement of patents will be determined in full trial’. This case stressed how there was a need for affordable and accessible bio-similar drugs while at the same time maintaining a balance between patent rights thereby reinforcing the role of regulatory authorities in ensuring compliance with proper regulations before being marketed.
b) In US jurisdiction: The Biologics Price Competition and Innovation Act of 2009 (BPCI Act), amending the Public Health Service Act, establishes an abbreviated licensure pathway for biosimilars or interchangeable biological products. Manufacturers must submit a 351(k) Biologics License Application (BLA) demonstrating bio similarity through analytical, animal, and clinical studies. The Act grants 12 years of marketing exclusivity to reference biologics, with additional exclusivity for pediatric applications. The biosimilar Applicant and the reference product sponsor engage in a “patent dance” that could result in pre-launch litigation by exchanging patent information. The U.S. Supreme Court ruled that this patent dance is not mandatory. The BPCI Act also requires a second pre-launch notification for additional litigation opportunities.
RELATED CASE LAWS:
1. Amgen Inc. v. Sandoz Inc. (2015): In the present case, the U.S. Court of Appeals for the Federal Circuit addressed the Biologics Price Competition and Innovation Act (BPCIA)’s “patent dance” provisions, ruling that these steps for resolving patent disputes are optional. Biosimilar applicants can choose not to engage in the “patent dance,” allowing the reference product sponsor to immediately bring a declaratory judgment action for patent infringement. This decision clarified that bypassing the “patent dance” does not violate federal law and may lead to earlier litigation and potentially quicker resolution of patent issues.
2. Sandoz Inc. v. Amgen Inc. (2017): In the present case the U.S. Supreme Court addressed ambiguities in the Biologics Price Competition and Innovation Act (BPCIA), ruling that biosimilar applicants do not need to wait for FDA approval to give notice of commercial marketing, allowing earlier market entry. The Court also ruled that while biosimilar applicants must provide their application and manufacturing information to the reference product sponsor, federal law does not enforce this requirement, although state law claims might still apply. This decision clarified procedural aspects of the BPCIA, potentially accelerating the availability of biosimilars and detailing information exchange obligations.
c) In the EU jurisdiction: The European Union’s biosimilar guidelines, established by the European Medicines Agency (EMA), provide a comprehensive framework for the approval and regulation of biosimilar products. These guidelines emphasize the importance of demonstrating bio similarity to a reference biologic through rigorous comparative studies, including analytical, preclinical, and clinical data. The goal is to ensure that biosimilars match the reference product in terms of quality, safety, and efficacy. The EU’s guidelines also cover pharmacovigilance requirements, interchangeability policies, and specific considerations for immunogenicity. By fostering a robust regulatory environment, the EU aims to enhance market competition, reduce healthcare costs, and increase patient access to biologic therapies.
Related case laws:
- Hospira UK Limited v. Genentech Inc. (2016): In this case, the High Court of England and Wales ruled in favor of Hospira, invalidating certain patents held by Genentech related to the manufacturing process of trastuzumab, marketed as Herceptin. The court found these patents lacked inventive steps, paving the way for Hospira and other biosimilar manufacturers to enter the market without the threat of patent infringement litigation. This decision underscored the critical role of patent validity challenges in facilitating competition and enhancing patient access to biosimilar treatments within the European Patent jurisdiction.
- Merck Sharp & Dohme Corp. v. Shionogi & Co., Ltd. (2019): In the present case the Regional Court of Dusseldorf ruled in favor of Shionogi, finding that Merck Sharp & Dohme Corp.’s (MSD) biosimilar product infringed upon patents covering ustekinumab, marketed as Stelara. The case centered on allegations of patent infringement related to ustekinumab’s formulation and manufacturing processes, highlighting the complexities biosimilar manufacturers face in navigating patent rights within the European Patent (EP) jurisdiction. This ruling underscores the importance of rigorous patent assessments and potential litigation or settlement negotiations for biosimilar market entry, impacting competition and patient access to affordable biologic treatments in Europe.
RECENT DEVELOPMENTS AND CHALLENGES IN BIOSIMILARS
The intricate structure and function of biological molecules, along with the several keywords (brand names, generic names, acronyms, and other descriptors) associated with a single molecule, make patent research and biosimilar analytics difficult and time-consuming. Adalimumab, for instance, is known by several names, including Humira, Trudexa, and Amjevita. Sequence searches for nucleotides and proteins are important but challenging, unlike chemical structure searches, because even incomplete sequences may be relevant. Furthermore, it is common for several assignees to collaborate on a single biosimilar, which calls for the meticulous gathering of all relevant patent documentation while taking the entire company structure into account. Businesses submit large families of patents, which makes it challenging to identify pertinent patents.
For example, the patent family for US6090382 related to Humira includes 129 publications. Beyond product patents, researchers must also consider patents covering composition, manufacturing processes, and methods of use, noting their varying expiration dates. For Adalimumab, while the product patent expired in 2016, over 70 related patents are still active, covering formulations, manufacturing methods, and treatment methods.
CONCLUSION
In the pharmaceutical industry, biosimilars and patent law landscapes present both opportunities and challenges for drug developers as well as providers. Globally, regulatory frameworks are changing thus for one to encourage innovation while maintaining patient access to cheap biologic therapies, they will need to know about and adjust to these intricacies. In conclusion, even though the coming of biosimilars could lead to increased accessibility to healthcare services bearing lowered costs, careful maneuvering through patent law, regulatory requirements, and court interpretations will be necessary for determining their future direction in the market.
