In India, access to health care facilities is still limited to a very small percentage of population owing mostly to unavailability of affordable drugs and treatment. Surprisingly, this predicament has persisted despite the presence of strong and competent generic pharmaceutical industry which hitherto has been fully supported by both government policies and statutory framework in its endeavour to provide drugs as cheaply as possible. As India looks for newer avenues to meet the healthcare needs of its huge 1.2 billion population "Biosimilars" or "Similar Biologics" represent significant potential.
What exactly are Biosimilars?
"Biosimilars" are similar versions of innovator pharmaceutical product, though not their generic equivalents, which are marketed after the expiration of the patent. As an enormous no. of pharmaceutical patents are expiring in the coming years, biosimilar industry is sure to grow and its capability to produce affordable biotech medicines would further expand. And to ensure optimum development and growth of the market for biosimilars in India, Indian government has already issued "Guidelines on Similar Biologics: Regulatory requirements for market authorization in India" in the year 2012 which lays down specific standards for development and evaluation of similar biologics in India. These guidelines seek to ensure comparability of safety, efficacy and quality between the innovator biologic product and the biosimilar. Since biosimilar products are not identically similar to the reference innovator product, any variation needs to be assessed in detail to ensure that there is no therapeutic consequence for the patient. This essentially means that biosimilar developers do not only have to perform clinical trials on the newly developed biosimilar drug but also on the original product and compare the data to ensure efficacy and safety. The determination that the biosimilar product is similar to the original biologic in terms of structural characteristics, safety, efficacy and quality can only be made after careful scrutiny of analytical, clinical and non-clinical data. Accordingly, biosimilars require a comprehensive evaluation before they can be safely marketed and that is sought to be achieved by the above mentioned guidelines which establish appropriate regulatory pathways to ensure cost effective and safe production of biosimilars in India.
Before Biosimilars can be marketed- Crossing the regulatory threshold
All the biosimilars whether manufactured in India or imported into the country have to follow a multi-step procedure to get marketing authorization in India. The regulatory bodies responsible for approval of 'similar biologics' in India are the: Department of Biotechnology (DBT) under the Ministry of Science and Technology through its Review Committee on Genetic Manipulation (RCGM) and the Central Drugs Standard Control Organization (CDSCO) under the Ministry of Health and Family Welfare.
The starting point of the regulatory framework enunciates that a similar biologic can be developed in India only if the reference biologic chosen is a licensed innovator product in India. If the reference biologic is not a licensed or marketed innovator product in India then it should have been licensed and marketed for minimum of 4 years post approval in innovator's jurisdiction having well established regulatory framework. Only when this fundamental criterion is fulfilled the multi-step approval process can be initiated.
In the first step of approval, applicant is permitted to conduct studies with the reference biologic so as to generate information regarding manufacturing processes and product characterization. Once the applicant generates the above information, it is submitted along with basic clinical information and preclinical study protocols to the RCGM. In the second step applicant receives the approval to conduct pre- clinical trials which again requires a no. of studies to be made. After the successful evaluation of preclinical study reports, in the third step approval for clinical trials is given. Once all the clinical studies have been successfully completed, in the fourth step applicant can submit an application for market authorization to DGCI (Drug Controller General of India). Once the applicant receives marketing authorization, the similar biologic can be sold in India. Once such marketing authorization is received, the Applicant is required to submit a post-marketing risk management plan.
Important lessons from Roche-Biocon Lawsuit
As is clearly evident the approval process required to develop similar biologics in India stipulates compliance with a long prescribed procedure and would essentially require a significant period of time. Interestingly in one of the recent pharmaceutical lawsuits before Delhi High Court wherein Roche sued Indian pharmaceutical company Biocon and US based global generic Mylan for launching first biosimilar version of its original cancer drug "Herceptin" in India, one of the major contentions of Roche was that launch of "CANMAB" which was said to be biosimilar version of Roche's Herceptin was not in accordance with the guidelines prescribed for similar biologics. After all, what the guidelines prescribe is a long process. However drug was approved by DGCI in considerably short period of time. Moreover there was no public record to show that clinical trials were actually conducted before the drug was approved. Considering that the procedure for approval is multi –step requiring a lot of time, approval for the drug could not have been granted legally in such short span of time by the Drug Controller, Roche claimed. And in absence of compliance with due procedure for approval and non-conduct of appropriate tests the drug cannot be regarded as a biosimilar version and was being misrepresented as such in order to pass off the drug as being of same quality and reputation as Roche's Herceptin . Delhi High Court, accordingly restrained Biocon and Mylan from launching CANMAB without requisite approvals emphasizing the importance of following the prescribed procedure before a biosimilar drug can be sold in the market.
Concerns of Generic manufacturers
At this juncture, India certainly needs cost effective production of biosimilars in order to effectively address its health concerns and detailed and structured guidelines by the Government in this direction are indeed welcome. However, the high threshold of regulatory guidelines coupled with technical requirements and the risk of patent infringement litigation acts as a major deterrent for the generic manufacturers who want express commitment from the government that once they invest in something as complex as biosimilars, they would be allowed to launch it. Many of them have even suggested that a compulsory license be granted prior to development of biosimilars. In view of international obligations this may not always be possible and it's important for the government to alleviate the concerns of the biosimilar developers without comprising on the regulatory compliance.
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