30 June, 2016
Recently Indian Drug regulatory authority, the Central Drug Standard Control Organization (CDSCO) proposed revised guidelines for Similar Biologics 2016[1] (Proposed Guidelines) which might replace the previous Guidelines on Similar Biologics 2012[2] (Existing Guidelines). Some focal changes in the proposed guidelines are highlighted below:
- Reference to ICH approved Biologic available: In the proposed guidelines, a Biologic approved/licensed and marketed in a member country of The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human use (ICH) can be used as reference biologic in India. In the existing guidelines, a biologic had to be either licensed in India or licensed outside India for at least 4 years, before it could be selected as a Reference Biologic.
- Stricter Quality Comparison: In the proposed guidelines, a comparison of the molecular structure of the active drug substance in the Similar Biologic and the Reference Biologic would be mandatory. Additionally, the quality comparison would be governed by two quality attributes, i.e., Critical Quality Attributes (CQA – having direct impact on clinical safety and efficacy) and Key Quality Attributes (KQA – relevant for product and process consistency perspective).
- Approval for all indications on satisfying conditions of Waiver of Safety and Efficacy Study: As per the proposed guidelines, a Similar Biologic may be approved for all the indications of approved reference product, if the safety and efficacy study has been waived for such Similar Biologic based on comparable quality, non-clinical as well as convincing PK/PD data. If the phase III trial has to be waived for the Similar Biologic, it would be mandatory to gather immunogenicity in the PK/PD study, and immunogenicity would also be required to be generated during the post-approval Phase IV study.
- Waiver even in Non-Comparative Safety and Efficacy Study: For a Similar Biologic, if equivalence is demonstrated for both PK and PD, showing significant reduction in the residual risk in Phase I study, then Phase-III trials for such Similar Biologic product may be waived or if necessary, a single arm study in at least 100 evaluable subjects may be carried out in most sensitive indication to address any residual uncertainty.
- Number of patients defined in Safety and Immunogenicity Data: The number patients to be treated with the Similar Biologic in Phase IV study can be reduced, so that the total number of patients treated in both Phase III and Phase IV are at least 300, if pre-approval studies has been conducted for more than 100 patients.
- Revised Scope of Post-Marketing Studies (Phase IV Study): The proposed guidelines define that in post marketing stage, additional safety data may be collected by conducting a pre-defined single arm study of more than 200 evaluable patients and compared with historical data of the Reference Biologic product. The timeline to complete said study is also defined to be preferably within 2 years of marketing permission/manufacturing licence.
- Clarity on Fermentation/Upstream Process: The revised guidelines makes the requirements for Fermentation process (renamed as Upstream Process) clear where Manufacturer will now need to provide information on media components; reproducibility of at three fermentation batches; details of process kinetics, production formation, pH and temperature; data to verify protein yield and its consistency; and demonstration of overall reproducibility and scalability.
The proposed guidelines endeavour to clearly clarify the approval process of Similar Biologics in India thereby ensuring that new, essential and affordable Similar Biologic drugs reach the Indian population at large. However, it needs to be seen how best the Biosimilar Companies can capitalize with proposed guidelines.
[1] The proposed revised Guidelines on Similar Biologics 2016
[2] The guidelines on Similar Biologics 2012
For further information, please contact:
Vivek Kashyap, LexOrbis
mail@lexorbis.com
