India’s latest biosimilar guidelines of August 2016 are considerably on par with global requirements. There is now enhanced scope for product registrations, said Dr. Bobby George, vice president & head, regulatory affairs, Reliance Life Sciences.
The applicable guidelines in India are Drugs and Cosmetics Act & Rules; r-DNA safety guidelines, 1990; Guidelines for generating preclinical data for r-DNA products & other biologicals, 1999; IBSC guidelines, 2011; CDSCO guidance for industry, 2008; and CDSCO-DBT guidelines on similar biologics, 2016.
There is now more clarity on data requirements at different stages of development of similar biologic (SB). Safety surveillance needs to be given more priority now. Companies who are mid-way through their drug development processes need to adapt to the new requirements quickly. The abbreviated data requirements are applicable only for preclinical and clinical development program but not for the quality data through demonstration of comparability to the reference biologic (RB), he added.
While highlighting on the opportunities, threats and differences from the 2012 guideline, he focused on the regulatory requirements for market authorisation in India. If the RB is not marketed in India, then it should be licensed in any ICH country. This is in contrast to the 2012 guideline, which mentioned that the RB should have been licensed and widely marketed for four years post approval in the country where the innovator product was approved with a well-established regulatory framework, said Dr. George who was speaking at the Bio Pharma Asia Convention at Singapore recently.
In manufacturing, ‘upstream process’ data should now be described in detail including media components used for cell growth. Further, details of upstream process kinetics data from consistency batches need to be submitted. The 2012 guideline just mentions that ‘fermentation process’ data should be from a representative batch.
In the case of ‘downstream process’, additional requirements have now been included. The regulatory submission should incorporate detailed description of the methods followed for cell harvesting and extraction of the protein; description of post translational variation, if any; virus clearance validation studies as well. Besides, one needs to provide details on the removal of impurities like product related variants, he said.
The process related impurities pose a risk of immunogenicity he said. The critical quality attributes (CQAs) have direct impact on the clinical safety or efficacy but must be controlled within limits that need to be established based on the RB. The product shelf life would now be assigned based on the extent of available real time stability data only as per current guideline. The safety data collectively from phase 3 and 4 trials should now be derived from a minimum of 300 patients treated with SB pointed out Dr. George.