The Central Drugs Standard Control Organization (“CDSCO”), has issued 6 noticed dated 21st February, 2020. The notices address the various concerns that were raised regarding Bioavailability (“BA”) and Bioequivalence (“BE”), Fixed Dose Combinations (“FDCs”), Investigational New Drugs (“IND”), grant of license/permission for import or manufacture of new drugs or conducting a clinical trial, sub-acute toxicity study report for injectable products for BA/BE study in human for export, and requirement of stability data for Certificate of Pharmaceutical Product (“COPP”), under the New Drugs and Clinical Trials Rules, 2019 (“NDCTR”), and clarify on the same.
The said clarifications provided by CDSCO have been listed below:
- Permission to conduct BA/BE study and clinical trial-
Under the provisions of the NDCTR, the CDSCO receives applications and can grant permission for conducting clinical trials/ BA-BE study as part of requirements for grant of permission to manufacture or import new drugs. Concerns were raised and changes were proposed for processing and approval of such applications for conducting clinical trials and providing BA-BE permissions simultaneously. It has been clarified that such applications (as processed under the NDCTR), if found satisfactory, the permission to conduct BA/BE study and clinical trial is granted simultaneously, provided that the clinical trial has to be conducted after the submission of the BA-BE study result.
- Approval of FDCs containing new drugs-
The CDSCO receives and processes applications for approval of FDCs as per provisions of the NDCTR. In this regard, stakeholders raised concerns that FDCs containing new drugs are approved only after approval of individual new drugs. It is clarified by CDSCO that there is no such requirement that approval process of new drug and FDC containing that particular new drug are sequential and that approval of the new drug needs to be obtained before approval of FDC containing that particular new drug.
- Fixing of limit of impurities in the specification of INDs-
The CDSCO receives and processes applications for clinical trial of INDs in accordance with provisions of the NDCTR. Concerns were raised regarding the fixing of limits of impurities in the specifications of such INDs. It is hereby clarified by CDSCO that the Investigational Product (“IP”) prescribes the general limits for impurities in specifications, but when the applicant submits scientific justifications in support of limits of impurities beyond the specified IP, the same is considered and accepted by CDSCO.
- Pre-submission meeting seeking guidance about the requirements of law and procedure for license/permission for import or manufacture of new drugs or conducting a clinical trial-
Any person who intends to make an application for grant of license or permission for import or manufacture of new drugs or to conduct a clinical trial, may request through a written application, for a pre-submission meeting with the Central Licensing Authority for seeking guidance regarding the requirements of law and procedure of such license/permission of manufacturing process, clinical trial or other requirements. The CDSCO has stated in this regard that as and when applications for pre-submission meeting is received, meetings are conducted and guidance is provided for the same in writing, to the applicant, as accordance with the NDCTR.
- Sub-acute toxicity study report for injectable products for BA/BE study in humans for export-
The CDSCO receives and processes applications for permission to conduct BA/BE study in humans for export. Addressing the concerns that sub-acute toxicity study report in at least two species for a minimum of 14 days is required to be submitted for innovator products, the CDSCO has clarified that sub-acute toxicity data for innovator products are neither required nor asked for conduct of BA/BE study in human for export.
- Requirement of Stability Data for COPP-
COPP is issued under the World Health Organization Good Manufacturing Practice (“WHO GMP”) Certification Scheme for the purpose of international commerce (for registration of products in foreign countries). Concerns have been raised to the CDSCO regarding requirement of stability data on the commercial batches before grant of the WHO GMP and COPP. In the notice, CDSCO has clarified that if the stability data is generated during development stage as per the WHO guidelines, no further stability data on the commercial batches are required before grant of WHO GMP and COPP.