CDSCO approval essential to conduct clinical study of a new drug

We plan to conduct a study where a drug would be administered to paediatric subjects for the first time in India. Worldwide many studies have been reported. Is it necessary to take permission from regulatory authorities?

If the drug is administered first time in India, it would be considered a trial of new drug. As per 3rd July 2014 order of CDSCO, if a new drug is being evaluated, or a new use for an existing drug is being evaluated in academic study, CDSCO approval is essential.

For appropriate gender representation in EC, is there a guideline which mentions number of male/female members in the composition and in the forum?

There is no regulatory guideline. Appropriate gender representation means that the Ethics Committee should have a balanced representation of both genders. If an Ethics Committee has 9 members, it could have 5 male members and 4 female members or vice versa.

What are the different types of committees involved in clinical trial approval?

NDAC is involved in approval of all clinical trials and new drugs. NDAC is now Subject Expert Committee (SEC). There are 3 committees - SEC, Technical Committee and Apex Committee. All the committees evaluate the clinical trial of drugs/devices from the perspectives of 1) risk versus benefit to the patients, 2) innovation vis-a-vis existing therapeutic option and 3) unmet medical need in the country. All proposals are initially reviewed by SEC, then Technical Committee and finally by Apex Committee.

Do we need to notify the approved IMP manual from Ethics Committee?

As per Schedule Y Investigator Brochure has to be submitted to EC for review. The purpose of IMP is similar to IB. Hence, IMP manual has to be submitted to EC for review.

Is the restriction of 3 trials/investigator applicable to PMS study?

The restriction of number of trials to 3 would be applicable to all CDSCO approved trials. You need to check whether the PMS is a regulatory Phase IV - PMS, as CDSCO requires PMS to be conducted when they approve a new drug.

As per ICMR, there are different types of Phase IV studies. See below:

Phase IV - After approval of the drug for marketing, phase IV studies or post marketing surveillance is undertaken to obtain additional information about the risks and benefits resulting from long term usage of drug. These trials may not be necessary for approval of new drug for marketing but may be required by the Licensing Authority for optimizing its use.

In addition there are Phase IV studies that are designed to evaluate the marketed drug in specifically designed studies, which have inclusion/exclusion criteria, objectives and end points. The drug is used for the labeled indication in these studies. Therefore Licensing Authority permission is not needed. However, EC permission is needed.

A third type of post-marketing study involves evaluation of the drug for a new indication of a marketed drug, e.g. studies with letrazole. Here, DCGI permission and EC approval are needed which really makes the trial a Phase III study.

What are the guidelines for computer systems used in clinical trials?

US FDA’s guidelines for computerized systems used in clinical investigations applies to records in electronic form that are used to create, modify, maintain, archive, retrieve, or transmit clinical data required to be maintained, or submitted to the FDA.

The principles outlined in this guidance should be used for computerized systems that contain any data that are relied on by an applicant in support of a marketing application, including computerized laboratory information management systems that capture analytical results of tests conducted during a clinical trial. This guidance also applies to recorded source data transmitted from automated instruments directly to a computerized system (e.g., data from a chemistry autoanalyser or a holter monitor to a laboratory information system). This guidance also applies when source documentation is created in hard copy and later entered into a computerized system, recorded by direct entry into a computerized system, or automatically recorded by a computerized system.