San Francisco/New Delhi: The Indian government has announced a revised set of guidelines for manufacturing and marketing of similar biologics in the country to help Indian companies tap a large size of a potential $290 billion global market for biosimilars.
“These guidelines will help increase access to some of the key medicines for Indian patients and also create a dynamic manufacturing industry of similar biologics in India,” said India’s Minister for Health and Family Welfare, Dr J P Nadda in a video message to the ongoing BIO International Convention in San Francisco on June 8, 2016.
The Association of Biotechnology-Led Enterprises (ABLE) team led by Chairperson Dr Kiran Mazumdar-Shaw has been working closely with the regulators over the past year to formulate the new biosimilars guidelines. Two final meetings in May 2016 drafted most of the new guidelines.
While Dr Shaw referred to some of the salient features of the new guidelines that revised the original 2012 policy statement of the subject, ABLE’s senior advisor, Ms Guljit Chaudhri gave more details of the biosimilar guidelines at a special session on the subject at the India Pavilion at the BIO conference.
- If the reference biologic (for which the biosimilar is being developed) is not marketed in India, (i.e. EU, Japan, US, Canada and Switzerland)
- CDSCO (Central Drug Standard Control Organization) is calling for specific post marketing safety data “through a predefined single arm study of generally, more than 200 evaluable patients and compared to historical data of the Reference product. The unless otherwise justified.”
- CDSCO added primary endpoint should be safety (Phase IV), while secondary endpoint should be safety and immunogenicity.
- “If immunogenicity is evaluated in clinical studies, it in post marketing studies
- “If the firm conducts preapproval studies that included more than 100 patients on the proposed Similar Biologic drug, so that the safety data (from both Phase III and IV) is derived from a minimum of 300 patients treated with the Similar Biologics.”
- If a product is found to be similar “in preclinical, in vitro characterization having established PK [pharmacokinetic] methods and a PD [pharmacodynamic] marker that is surrogate of efficacy, the residual risk is significantly reduced in the Phase I study if equivalence is demonstrated for both PK and PD. an appropriate single arm study in at least 100 evaluable subjects may be carried out in the most sensitive indication to address any residual uncertainty.”
- “In case the safety and efficacy study is waived all the indications approved for reference product may be granted based on comparable quality, non‐clinical as well as convincing PK/PD data. Wherever the phase III trial is waived, the immunogenicity should have been gathered in the PK/PD study and will also need to be generated during post approval Phase IV study.
These guidelines will make it easy for India’s biotech companies to plan the manufacturing process very well.
So far India has approved the manufacturing of 48 biosimilar products in the country. Experts explained this is how the new guidelines will help biosimilar manufacturers.
- CDSCO “Fermentation Process Development,” which it now calls “Upstream Process Development,” though the requirements under the Development, which it now calls “Upstream Process Development”
- Upstream process should be described in detail including media components used for cell growth.
- At least three batches of reproducible fermentation data at pilot scale (batch size adequate to give enough purified product to generate preclinical data)
- Upstream process should be well controlled and monitored.
- Manufacturers should include details of upstream process kinetics data from consistency batches indicating cell growth, product formation,pH, temperature, dissolved oxygen, major nutrient consumption pattern and agitation rate.