Q. 1For the SAE/AE reporting, normally the guidelines on CDSCO website talks about the AE/SAE occurring during the clinical trials only. What are the timelines for submission of SAE/AE after the product is marketed for more than 5 years?

Schedule Y recommends submission of PSUR till 4 years.

• Subsequent to approval of the product, new drugs should be closely monitored for their clinical safety once they are marketed. The applicants shall furnish Periodic Safety Update Reports (PSURs) in
• The PSURs shall be submitted every six months for the first two years after approval of the drug is granted to the applicant. For subsequent two years - the PSURs need to be submitted annually

However, there is no Indian guidance about timelines of AE/SAE submission beyond 5 yrs of marketing.

ICH E2D guidance recommends as follows:
Cases of adverse drug reactions that are both serious and unexpected are subject to expedited reporting.  When a Marketing Authorisation Holder (MAH) is uncertain whether an ADR is expected or unexpected, the ADR should be treated as unexpected.

In general, expedited reporting of serious and unexpected ADRs is required as soon as possible, but in no case later than 15 calendar days of initial receipt of the information by the MAH Holder.

Non-serious adverse reactions, whether expected or not, would normally not be subject to expedited reporting.  Non-serious ADRs should be included in the periodic safety update report according to the ICH E2C guideline.  

After the product is 5 years old on the market, it would be better to follow 1) safety reporting requirements in CDSCO marketing approval letter and 2) international practices.

Q 2. Is it allowed to conduct BA/BE/PK study in healthy paediatric volunteers in India? Can a Pharmacologist conduct BA/BE/PK study in healthy paediatric volunteers?

See the relevant info from regulations / guidelines.

• Schedule Y recommends:

(v) The paediatric studies should include-

(a) clinical trials,

(b) relative bioequivalence comparisons of the paediatric formulation with the adult formulation performed in adults, and

(c) definitive pharmacokinetic studies for dose selection across the age ranges of paediatric patients in whom the drug is likely to be used. These studies should be conducted in the paediatric patient population with the disease under study.

• ICMR 2006 recommends:

Before undertaking trial in children the investigator must ensure that -

a. children will not be involved in research that could be carried out equally well with adults;

b. the purpose of the research is to obtain knowledge relevant to health needs of children. For clinical evaluation of a new drug the study in children should always be carried out after the phase III clinical trials in adults.

It appears that in India BE studies cannot be conducted in children. Even the BE of paediatric formulation has to be conducted in adults.

In case any studies are planned in children, the investigator has to be a paediatrician.

Q 3 I had a small doubt regarding the medical devices. The device is a novel ventilator, manufactured in US, which is undergoing FDA premarket notification and CE approval. At this level, can the device be imported to India and marketed directly?

This device is not in the CDSCO list of notified devices. Hence it does not attract the provisions of Drugs and Cosmetics Act 1940 and rules there under. Hence, the port officers are advised by CDSCO through office memorandum of 8 Jan 2013, to release such non-notified devices with any no objection certificate from CDSCO.