Biosimilar Regulation in India

A biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product is known as Biosimilar.

This could be the single fastest-growing biologics sector in the next five years – albeit from a small base – spurred by the convergence of major dynamics that will see new biosimilars enter the US market, bring additional molecules to Europe, and open up oncology and autoimmune disease areas to biosimilars for the first time ever. Biosimilars also bring clear potential for payers in the emerging pharmaceutical or “pharmerging” markets, such as Brazil, China and India. India have developed new regulatory guidelines for Biosimilar.

In New guideline DCGI has made mandatory the preclinical evaluation of biosimilar. The non-clinical studies should be comparative in nature and design to detect differences if any, between the similar biologics and innovator recombinant product. These should be conducted with the final formulation of the similar biologics intended for clinical use, unless otherwise justified. The non-clinical study design may vary depending upon the clinical parameters such as therapeutic index, the type and number of indications applied for etc. Assays like receptor binding studies or cell based assays (e.g. cell proliferation assays) should be conducted, when appropriate to establish comparability of biological activity. In cases where invitro assays do not reflect the pharamacodynamics, in-vivo studies should be performed. Comparative repeat dose toxicity with immunogenicity testing is also made compulsory in given route of administration, local tolerance should be evaluated.

According to new guideline, comparative Pharmacokinetic (PK) study on healthy subjects, Pharmacodynamics (PD) studies in most patients or healthy volunteers. If PD marker is available in healthy volunteers, PD in healthy volunteers can be done. Followed by a Phase III, Comparative safety and efficacy in relevant patient population is also mandatory for all biosimilar. However, in certain cases it can be waived. DCGI has also mandated the submission of PSUR 6 monthly for first 2 years and then annually for next 2 years, along with a Post Market study.

Regulatory applications and approvals issued at different stages of biosimilars product development

No.	Stage	Agency involved	Application	Approval
1	Manufacturing permission for test, analysis & examination	DCGI	Not Spesific	Permission (Manufacturing NOC)
2	Manufacturing License for test, analysis & examination	Local FDA	Form 30	Form 29
3	R & D	Institutional Biosafety Committee (IBSC)	Not Spesific	Permission (IBSC minutes)
4	Non-Clinical studies permission	RCGM	Form C3	Form C4
5	Submission of Non-clinical study report	RCGM	Form C5	Form C6
6	Clinical Trials	DCGI	Form 44	Permission (CT NOC)
7	Manufacturing License for CT batches	Local FDA (subject to CT NOC)	Form 30	Form 29
8	Manufacturing & Marketing permission	DCGI	Form 44	1. Form 45/46 (Finished product) 2. Form 46A (Bulk product)
9	Commercial Manufacturing License	Local FDA	Form 27 D	Form 28 D

Kind Regards,