The 'Revised Draft Guidelines on Similar Biologics' released recently by the Union Health Ministry will go a long way in bringing the much needed clarity on launch of the biosimilar drugs in the country as it will lay down the regulatory pathway for marketing authorization of similar biologics in India.

These guidelines, prepared by Central Drugs Standard Control Organization (CDSCO) and the Department of Biotechnology (DBT), address the regulatory pathway regarding manufacturing process and safety, efficacy and quality aspects for similar biologics. These guidelines also address the pre-market regulatory requirements including comparability exercise for quality, preclinical and clinical studies and post-market regulatory requirements for similar biologics.

These guidelines apply to similar biologics that contain well characterized proteins as their active substance, derived through modern biotechnological methods such as use of recombinant DNA technology. The demonstration of similarity depends upon detailed and comprehensive product characterization, preclinical and clinical studies carried out in comparison with a reference biologic. Similar biologic can only be developed against the reference biologics that has been approved using a complete data package in India. In case the reference biologic is not authorized in India, it should have been approved / licensed and marketed in an ICH (The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) country.

Any product can be considered as similar biologic, only if it is proven to be similar using extensive quality characterization against the reference biologic. Further product development should only be considered once the similarity of the similar biologic is demonstrated in quality to a reference biologic. These guidelines are applicable for similar biologics to be developed in India or imported into the country for marketing authorization.

The norms are for the guidance of all stakeholders and are not meant to substitute or rephrase the rules made under Drugs and Cosmetics Act, 1940 or any other relevant Acts and are subject to being in conformity with the Drugs and Cosmetics Act and Rules as may be amended from time to time.

Presently, several organizations are actively engaged in manufacturing and marketing of similar biologics in India. So far, these similar biologics were approved by RCGM and CDSCO using an abbreviated version of the pathway applicable to new drugs on a case-by-case basis. Since there are several such products under development in India, both regulatory agencies considered the need to publish a clear regulatory pathway outlining the requirements to ensure comparable safety, efficacy and quality of a similar biologic to the reference biologic. Based on demonstration of similarity in the comparative assessment, a similar biologic may require reduced preclinical and clinical data package as part of submission for market authorization.

The objective of this document is to provide guidelines to applicants to enable them to understand and comply with the regulatory requirements for the market authorization of similar biologics in India.

Experts opine that the new revised guidelines are almost aligned with global requirements. Released by India's Department of Biotechnology in 2012 for the first time, they have since been updated.

The new guidelines state that clinical studies done on similar biologics prior to market authorization are limited in nature, so post-marketing studies should be conducted and reports to be submitted to DCGI.

The plan for post-market studies needs to be captured in pharmacovigilance plan and an update on the studies should be submitted to the CDSCO.

As for regulatory requirements for marketing authorization in India, with regards to post-marketing safety and immunogenicity study, at least one non-comparative post-marketing clinical study with focus on safety and immunogenicity would need to be performed.

The study must be designed to confirm that the similar biologic does not have any concerns with regards to the therapeutic consequences of unwanted immunogenicity. If immunogenicity is evaluated in clinical studies, it is not mandatory to carry out additional non-comparative immunogenicity studies in post-marketing studies, said experts.

The guidelines also prescribe that Phase III trials for biosimilars must have at least 100 evaluable patients. The guidelines also permit a smaller trial population size for trials of biosimilars for treating rare or severe diseases or where therapeutic options are limited. The approval timelines have also been reduced by half for biosimilars.

“Currently, biologics constitute a significant portion of the therapeutics and they are expected to grow dramatically in the next decade. A clear guidelines regarding the requirements and regulatory pathway would facilitate the approval of novel and similar biologics. The new draft guidelines issued by CDSCO and the DBT, discusses the stringent criteria to be met by the similar biologicals in terms of demonstrating the structural and functional similarities between the per-existing and similar biologics. This would be very helpful to the companies aspiring to develop similar biologics,” said Professor Narasimha Murthy, University of Mississippi, USA and Founder Director, Institute for Drug Delivery and Biomedical Research, Bengaluru.

“Similar biologics is on huge demand as it is one of the potential ways of significantly reducing the cost of therapy of chronic ailments”, added Prof, Murthy.

 It is reported that the biosimilar market is attractive for Indian drug majors because it is set to reach $35 billion by 2020 from the estimated $1.3 billion in 2013. Deeper penetration with clearer regulatory pathways in developed markets and higher efficacy and safety in emerging markets will be the determining factors contributing to market growth.

At present over 10 blockbuster biologics with annual sales of $60 billion are facing patent expiries in Europe and the US during the next four years. Top Indian drug makers are repositioning their strategies from approvals to product launches to gain market capitalization. With the US biosimilar market undergoing several changes, countless growth opportunities exist for Indian companies.

According to industry sources, the LATAM adalimumab market which is an anti-inflammatory biologic medication alone is expected to reach $1.18 billion in 2023. The market was valued at $994.8 million in 2014, and projected to expand at a compounded annual growth rate of 0.4 per cent between 2015 and 2023.

However the high price of biologics is straining healthcare budgets in markets where they are reimbursed and in those where they are not reimbursed, they are unaffordable to most people.

According to experts, there is an urgent unmet need for more affordable versions of biologic products. The Big Pharma has realized this. Amgen, Merck, Boehringer Ingelheim, Novartis and Pfizer are reportedly working on 150 biosimilars to make up for imminent sales declines.

Though biosimilars have completed almost a decade in the European market, following the first biosimilar authorization in 2006, India is racing to catch up. Currently, 16 biosimilars exist in the European market. The US market has two biosimilars. Over 10 pharma players are competing in this arena in India, with around 15 Epoetin alfa which is a man-made, injectable drug for treating anemia., eight G-CSF(Granulocyte-colony stimulating facto) and four insulin biosimilars, among others.

The Indian biosimilar industry was worth $338 million in 2008, and is reportedly growing at 30 per cent .Currently, more than 50 biosimilar products are available in the Indian market, with sales over $900 million.