Important Notice: Please note that the Union Health Ministry in India has recently amended the Drugs and Cosmetics Rules, 1945(DCR) and the appended Schedule Y implementing new regulatory requirements for research conducted in India effective as of January 30, 2013. These amendments and updates have been integrated into the information available on this site; however, further amendments and updates may follow. Please consult with independent Indian regulatory experts and/or legal counsel if contemplating research in India and/or to learn more about these regulatory changes.
Clinical Trial Data Requirements
Specific requirements to initiate clinical trials are based on Schedule Y and Appendices of The Drugs and Cosmetics Act and Rules, 2008. "Guidance for Industry on Submission of Clinical Trial Application for Evaluating Safety and Efficacy" is available here. Drugs that target life threatening/serious diseases or diseases of special relevance to India health status may qualify for abbreviated toxicological and clinical data requirements, as deemed by the Licensing Authority.
1. Clinical trial sponsors are required to submit to the Drugs Controller General of India Form 44 (Application for permission to import or manufacture a new drug or to undertake a clinical trial) and the following data:
-chemical and pharmaceutical data (Appendix I, item 2)
-animal pharmacology data (Appendix I, item 3 and Appendix IV)
-animal toxicology data (Appendix I, item 4 and Appendix III)
-human clinical pharmacology data (Appendix I, items 5,6,7). When Phase I data generated in another countries is submitted, the RA will grant permission to repeat Phase I trials and/or conduct Phase II trials and Phase II trials concurrently with other global trials for the drug.
-regulatory status in other countries (Appendix I, item 9.2). Sponsors should also include information if a drug has been withdrawn in any country by the manufacturer or by regulatory authorities.
-full prescribing information (Appendix I, item 10)
-complete testing protocol/s for quality control and an impurity profile (Appendix I, item 11)
2. Clinical trials can only be initiated after the Licensing Authority grants permission. The Licensing Authority should be informed of approval of each site by the IEC. If there are amendments to be made to the protocol, all amendments must be approved by the IEC that originally approved the study, and the Licensing Authority should be informed in writing. Clinical trials must be registered in the Clinical Trials Registry India (CTRI) before enrolling any patients. Any adverse events must be reported to CDSCO within 14 days of their occurrence. Annual status reports must be submitted on ongoing, completed, or terminated trials.
In a multi-center study a single application (as per Schedule Y) is made to RA for all sites. Investigator’s Undertaking for the site is submitted in the application in a template prescribed by RA (Investigator’s Undertaking Template). The proposed sites must be listed in the application; any additional sites included at a later date must be submitted separately.
Application to the RA is made in parallel with the EC submission; RA approval is not contingent on EC opinion however EC approvals should be submitted to the RA, if available, at the time of application. If not available at this time the RA expects to receive the EC approvals when they become available. The study should be initiated at the site only after both the RA and EC approvals are obtained. The applications are taken for review sequentially from the date of submission. The file is reviewed by a number of reviewers, each commenting on the application and passing it on to the subsequent reviewer. On occasion, the application is sent to external subject experts or to the Indian Council for Medical Research (ICMR) for expert review and opinion. All comments from the internal and, if applicable, the external reviewers are compiled and, on this basis, an opinion is conveyed or approval is granted.
A checklist of CDSCO's requirements to conduct a global clinical trial is available here.
Pursuant to a July 2014 MoH&FW order, an investigator may not be involved in the conduct of more than three clinical trials at one time. The order may be found here.
Clinical Trial Import Authorization
Drugs shipped from another country require a T-License (Trial License). T-Licenses can be applied for simultaneously with a clinical trial application. T-Licenses permit multiple shipments of the product for a period of one year. If the clinical trial will require exporting biological samples out of India, a separate application is necessary that can also be submitted simultaneously with other forms. More information on T-Licenses are available here.
Clinical Trial Estimated Timeline
If the clinical trials protocol has been approved in a Category A country (USA, UK, EMEA, Australia, South Africa, Canada, Germany, Switzerland, Japan), the studies are eligible for fast track review. Fast track review should take two to four weeks. Trials that have been not approved in one of the aforementioned countries ("Category B") should be approved in eight to twelve weeks. According to ICMR Guidelines and Standard Operations Procedures, a pending approval should last between 3 to 6 months.
In January 2014, the DCGI announced that CDSCO planned to introduce several new timelines for its review processes, including a 180 day timeline for clinical trial approval and 60 day timeline for clinical trial protocol amendements. More information is available here.
In May 2014, the DCGI published the following timelines for CDSCO approval. The timelines are available here.
Clinical Trial Costs
Phase I: 50,000 rupees.
Phase II: 25,000 rupees.
Phase III: 25,000 rupees.
In-Country Manufacturing Requirements
Guidance on the manufacturing of drugs is available in Chapter IV of The Drugs and Cosmetics Act and Rules, 2005.
State FDAs license most manufacturing, but DCGI approval is required for new drugs, blood products, sera, and vaccines. Licensing to manufacture requires basic information on the site, that the drug is produced to therapeutically justified specifications, and has new drug approval if appropriate. "Schedule M" also implements mandatory Good Manufacturing Practices (GMP) to comply with.
According to Schedule Y of The Drugs and Cosmetics Act and Rules, 2005 and Indian Council of Medical Research, sponsors are required to have an insurance policy that covers serious adverse events experienced by trial participants during a trial.
The Central Drugs Standard Control Organization (CDSCO) published its final rule on compensation for clinical trial deaths, which took effect on May 30, 2014. The rule requires that, within 30 days of the death of a clinical trial participant, an Independent Expert Committee will examine the death report, determine causation of death, and recommend to the CDSCO the amount of compensation the sponsor should pay. The CDSCO will make a final decision on the amount of compensation, and the sponsor will have 30 days to pay the amount. The final rule is available here.
In January 2013, India added an injury compensation clause (122-DAB) which states that if a clinical trial subject sustains an injury, he or she is entitled to free medical management as long as required and financial compensation. The Licensing Authority can suspend or cancel the clinical trial, and/or restrict the Sponsor from conducting future clinical trials in the country. In April 2014, India’s Ministry of Health and Family Welfare amended 122-DAB. Most notably, the draft amendment states that if a clinical trial subject is injured during a trial, the sponsor is responsible for providing free medical management as long as needed, or until it is proven that the injury is unrelated to the trial (whichever is earlier). The proposed rule places the burden of proof on the sponsor to demonstrate that an injury is unrelated to a trial.
Pursuant to a July 2014 MoH&FW order, compensation must be provided to trial participant or their nominee if an injury or death is found at a later stage to be caused by a drug-related anomaly. The order may be found here.
Pursuant to a July 2014 MoH&FW order, ancillary care must be provided for a patient suffering from any other illnesses who is participating in a clinical trial. The order may be found here.
Phase 3 Requirements (if different)
Pursuant to a July 2014 MoH&FW order, if Indians participated in a global Phase 3 trials, the number must be adequate in order to be considered for approval in India. The order may be found here.
Precedent (Clinical Trials Approved/Denied in Last 2 Years)
212 clinical trials approved from May 2011 to May 2013.
Product Registration Data Requirements
Requirements for new drug approval are outlined in CDSCO's Guidance for Industry.
Pursuant to a July 2014 MoH&FW order, a clinical trial waiver in Indian population for a drug that has already been approved outside of India will be considered in national emergencies, urgent situations, epidemics, and for orphan drugs for rare diseases and conditions that have no therapy currently. The order can be found here.
Pursuant to a July 2014 MoH&FW order, when evaluating a new drug there are 10 drug properties and 8 study factors that should be considered due to their likely sensitivity to ethnicity. The order and full list of factors can be found here.
Pursuant to a July 2014 MoH&FW order, if Indian participants are involved in a global clinical trial of a new chemical entity for a disease that is prevelant in India, after it is approved in the innovator well regulated market approval should be sought in India . The order can be found here
Product Registration Timelines
In January 2014, the DCGI announced that CDSCO planned to introduce several new timelines for its review processes, including a 270 day timeline for product registration approval. More information is available here.
In May 2014, the DCGI published the following timelines for CDSCO approval. The timelines are available here.
Product Registration Costs
It is unspecified if there are additional fees for product registration. US$1500 fee is assessed to register an overseas manufacturer's premises and US$1000 for each individual drug. A US$5000 fee is assessed by Indian Drug Authorities when premises of a foreign manufacturer must be inspected. The import license fee is 1000 rupees for a single drug and 100 rupees for an additional drug.
Product Registration Follow-Up Requirements
Once approved, the drug must be launched within six months or the CDSCO will revoke the license to market the product. Periodic Safety Update Reports (PSURs) must also be submitted every six months for the first two years following approval, and annually thereafter. PSURs must be submitted within 30 calendar days of the last day of the reporting period. The RA may extend the total duration PSURs must be submitted. More information on PSUR submission is available here.
Post Registration Labeling Requirements
Labelling requirements are outlined in Part 9 "Labelling and Packing of Drugs Other Than Homeopathic Medicines" in the Drugs & Cosmetics Act available here.
Post Registration Pharmacovigilance Requirements
The Steering Committee oversees the Pharmacovigilance Program in India (PvPI). The Steering Committee is chaired by the DCGI, and is responsible for managing reports of Adverse Drug Reactions (ADRs), increase awareness about the importance of ADR reporting, monitoring risk profiles of drugs, and generate evidence and provide guidance to CDSCO on safety related regulatory decisions.
PvPI collaborates with the World Health Organization (WHO) Uppsala Monitoring Centre (UMC), which provides training and technical assistance to PvPI. UMC developed the software that sites use to report ADRs (Vigiflow for drugs and Paniflow for vaccines). Data submitted to document ADRs is outlined in Appendix XI of Schedule Y.
Pursuant to a July 2014 MoH&FW order, If two or more countries remove a drug from market then it will be considered for re-examination. The order may be found here.
Pursuant to a July 2014 MoH&FW order, a unit will be created within CDSCO to work with agencies such as the Indian Council of Medical Research to conduct post-market surveillance studies. The order may be found here.
March 5, 2015.