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Indian Biosimilar Standards: A Work in Progress


India has tightened up guidelines for biosimilar development in a quest to achieve standards equivalent to those in Europe and the United States.

The story of biologics and biologic copy products in India is very much a story about a work in progress. Although some companies are producing genuine biosimilars on par with international standards, many products fall into categories that are not comparable to biosimilar quality in the West. Recently, Indian regulators have endeavored to provide a pathway toward biosimilar development that meets international standards.

Newer, more comprehensive guidelines issued by Indian authorities in 2016 were intended as an upgrade to standards from 2012 that governed similar biologics, India’s term for biosimilars. “A similar biologic product [in India] is that which is similar in terms of quality, safety, and efficacy to an approved reference biological product based on comparability,” the authors of a recent paper explained.

The authors noted India’s success in providing access to biologics, stating that approximately 60 biologics have been approved in India, almost half of which are similar biologics. In India, the cost of similar biologics “is approximately half the cost of innovator products,” and patient assistance programs address affordability and improve access.

However, there is also the potential for compromise: almost 20 similar biologics to infliximab, etanercept, adalimumab and rituximab were approved based on the less-stringent 2012 guidelines and were supported by limited clinical data.

The authors discuss the difficulty of producing biologics and true copies of originator products in a country that does not have the resources that the West does. “It remains a big challenge for a biosimilar manufacturing company to develop a similar product, as detailed information on the process of manufacturing of the original drug is patent protected and also because the same cell line is not available to the biosimilar manufacturer. Any changes in the manufacturing process such as use of different cell lines, growth medium, and protein purification processes can also result in variations in the final product,” the authors wrote.

Further, doubts about the quality of biologics persist and small patient population sizes during trials conducted to demonstrate bioequivalence to reference products may not produce the volume of data necessary to satisfy the need for statistical clarity, the authors wrote.

“In controlled clinical studies of biologics, particularly biosimilars, safety concerns may occur beyond the study completion. Long-term evaluations, such as postmarketing studies of biological agents, are required as there are only limited patient experiences available during approval in terms of safety and immunogenicity. Side effects related to the long-term use, off-label use, drug-drug interactions, or use in comorbid conditions can only be identified on exposure to the drug after its approval,” they said.

Not Quite Biosimilars

The authors contend that intended copies, also called biomimics or noncomparable biologics, need to be distinguished from similar biologics to prevent physician and patient confusion. They cite significant differences in the approval process for these products. Unlike similar biologics, intended copies do not undergo comparative clinical studies or analytical studies to demonstrate similarity to the reference product and have not been equated with similar biologics under the 2016 regulatory guidelines. With so little data, patients “face a greater risk of therapeutic failure and side effects” from these products, the authors reasoned.

Similar biologic products were evaluated on a case-by-case basis prior to the first approval guidelines for similar biologics released by India’s Central Drugs Standard Control Organization (CDSCO) in 2012. The 2016 guidelines were developed with some input from the World Health Organization (WHO) and “expert consensus opinion.” The goal of the 2016 rules was “to provide a well-defined pathway at par with international regulations,” although there is lingering controversy over whether India’s current guidelines achieve international standards.

The authors compared CDSCO’s 2016 guidelines with those of the FDA, the European Medicines Agency (EMA), and the WHO. Like the guidelines from the FDA, the EMA, and the WHO, India’s require demonstration of similarity to the originator product in nonclinical studies, a comparative pharmacokinetic and pharmacodynamic study in humans, a comparative clinical efficacy and safety trial in a relevant medical condition (India’s guidelines specify the trial should include more than 100 patients), and postmarketing safety monitoring.

The authors also highlighted “key considerations” regarding the current guidelines, which they say should be addressed in future iterations.

Interchangeability is not addressed in India’s biosimilar guidelines, and the authors noted that reference products are often switched for similar products “randomly by the prescriber or pharmacist based on the product cost and assumed patient affordability.” In Europe, interchangeability is determined by individual member states. The United States has a process for biosimilar products to demonstrate interchangeability, but no biosimilar has yet met this standard.

Nomenclature is also not addressed in CDSCO’s 2016 guidelines. The authors commented that accurate safety monitoring of biologics and biosimilars depends on identifiability “with easily distinguishable product names.” The WHO recommends a 4-letter suffix with the international nonproprietary name to distinguish a biosimilar from its reference product and other biosimilars to that reference product. However, biosimilar suffixes have been controversial, as they are thought to cause patient hesitance or confusion.

The authors also expressed concern about transparency in labeling, saying the package insert for a similar biologic should clearly disclose the extent of similarity to the reference product with respect to safety, immunogenicity, and efficacy.

Overall, the researchers view the 2016 regulations as successful in improving “stringency” in the approval process and more closely matching the safety requirements of international guidelines. However, some experts consider the 2016 requirements less stringent than EU and US standards.


Jois R, Mukherjee S, Rajeswari S, Rath PD, Goyal V, Gupta D. Similar biologics in India: a story of access or potential for compromise? Indian J Med Res. 2020;152(5):456-467. doi:10.4103/ijmr.IJMR_43_18

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