GCP QA - With Arun Bhatt

Q 1. Please clarify regulatory reporting requirements for on serious adverse events (SAE) from:

• Clinical Trial cases
• Spontaneous Cases
• Non Trial Case Reports

Dr. Vikram Narasimha

In recent years, the Indian regulatory authorities have been increasing their focusing on drug safety and pharmacovigilance and we are moving towards global processes.

Please note the Indian GCP and Schedule Y use adverse event and adverse drug reaction at many places together or separately. In this situation, I feel we should follow the global practices and report all SAE / serious ADRs to DCGI irrespective of the causality and lack of clear regulatory guidelines.

The specific responses are as follows:

Clinical Trial cases

A] Are only serious and unexpected events [regardless of causality with the study drug] required to be reported to DCGI?

Yes. SAE definition does not require causality. Any unexpected serious adverse event (SAE) (as defined in GCP Guidelines) occurring during a clinical trial should be communicated promptly (within 14 calendar days) by the Sponsor to the Licensing Authority and to the other Investigator(s) participating in the study.

B] Are only Local Cases [Originating in India] required to be reported to DCGI?

Sch Y refers to SAE from an approved clinical trial, which is nowadays part of global multi- country trial. It does not differentiate between local and foreign cases.

C] What types of foreign cases [originating outside India] are required to be reported to DCGI?

There is no Indian guideline. However, most multinational companies report all foreign cases of a global clinical trial concurrently ongoing in India to DCGI.

D] What types of foreign cases are required to be reported to Ethics Committees (EC) in India?

As per GCP guidelines, it is the sponsor's and investigator's responsibility to report all SAEs to EC.

The sponsor should provide ADR / AE reporting forms to the Investigator(s) / Institution(s). The sponsor should expedite the reporting to all concerned (including the Ethics Committee and the regulatory authorities) of all serious and/or unexpected adverse drug reactions

Investigator should report all adverse drug reactions and adverse events that are serious and / or unexpected to EC.

All SAEs received by the investigators as a notification from sponsor should be reported to ECs.

Spontaneous Cases

A] Are only Serious unexpected and related cases required to be reported to DCGI?

All cases involving serious unexpected adverse reactions must be reported to the licensing authority within 15 days of initial receipt of the information by the applicant.

B] Are only Local cases required to be submitted to DCGI? Yes

C] What types of foreign cases [originating outside India] are required to be reported to DCGI? There is no specific guideline.

Non Trial Case Reports

A] If any overseas safety report is available from a clinical trial [ related to study medication] for which there are no concurrent trials being conducted in India but the product is marketed in India, is this required to be submitted to DCGI?

As far as I know, Indian company is unlikely receive an SAE, if India is not part of the trial. However, if the product is marketed in India, you have to report the same to DCGI as part of PSUR.

Q2: If in a clinical trial, we are taking blood sample for HIV testing, do we need to counsel the subject for the same as result may be positive or negative. Do we have any guidelines for this?

Dr. Vikram Narasimha

Many ECs insist on a separate consent for HIV testing, if this is part of a trial. The guidelines for counseling are as per the current accepted medical norms. There are no separate guidelines for routine HIV testing for clinical trials

Q 3 What is the regulatory strategy in getting approval for the medical devices from Regulatory authority of India? What are the documents necessary for the same?

S Lakshmanan

The procedure is similar to Drugs. The documents will depend on the device. Pl see Indian GCP guidelines section 7.3.

All the general principles of clinical trials described for clinical trials should also be considered for trials of medical devices. As for the drugs, safety evaluation and pre-market efficacy of devices for 1-3 years with data on adverse reactions should be obtained before pre-market certification. The duration of the trial and extent of use may be decided in case to case basis by the appropriate authorities. However, the following important factors that are unique to medical devices should be taken into consideration while evaluating the related research projects.


7.3.2. Guidelines

• Safety data of the medical device in animals should be obtained and likely risks posed by the device should be considered.
• A clinical trial of medical devices is different from drug trials, as former can not be done in healthy volunteers. Hence phase I of drug trial is not necessary for trial on devices.
• Medical devices used within the body may have greater risk potential than those used on or outside the body, for example, orthopaedic pins Vs crutches.
• Medical device not used regularly have less risk potential than those used regularly, for example, contact lens Vs intraocular lenses.
• Safety procedures to introduce a medical device in the patient should also be followed as the procedure itself may cause harm to the patient.
• Informed consent procedures should be followed as in drug trials. The patient information sheet should contain information on following procedures to be adopted if the patient decides to withdraw from the trial.