If a drug is approved in 2000 (and therefore an old drug) and is available in cream form for topical use, now if a foam formulation of the same drug is to be registered, then do we need to conduct clinical trials? If yes, then, a phase III trial or a therapeutic equivalence trial? Will this formulation be considered as new drug?
Ashish Chavda
A change in the formulation makes it a new drug. You will have to conduct trials to get manufacturing permission to market the product. The nature of trial depends on what you want to establish. Therapeutic equivalence trial is a good option if you wish to compare the approved formulation to a new formulation. You will have to have all other data (See Appendix I and Ia of Schedule Y) to support your application for manufacture and marketing. You need to consult DCGI office on, 1) what type of trial they require, 2) what data they require.
This is regarding archival of source data documented on paper in clinical trials. We generally archive the source (paper) data for around 10 years. Can the source paper data be scanned and subsequently destroyed?
Ruchira Jackson
See ICH GCP recommendation: 4.9.5 Essential documents should be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period however if required by the applicable regulatory requirements or by an agreement with the sponsor.
Most of the companies archive data for 15 yrs or longer (some regulatory agencies e.g. Canada require longer archival of 25 yrs).
If you wish to scan the data, you need to follow current guidelines of keeping data in electronic format. Please check FDA's 2007 guidance on computerized systems and CFR 312.57 and 62.
Please clarify for the observation/non-interventional study, where there is no regulatory approval required and the study is initiated based on Ethics Committee approval. Does the sponsor holds the responsibility of reporting the AE to regulatory authority irrespective of reporting to EC?
Divya
Yes. The non-intervention studies are usually done as part of assessment of post-marketing safety of drugs. Hence, the sponsor is responsible for reporting AE to regulatory agency.
Please see the description below. As these studies are part of Pharmacovigilance plan, all regulatory / ethical requirements for pharmacovigilance/safety reporting have to be met.
ICH E2E Pharmacovigilance Planning (PVP).
3.2.1 Design and conduct of observational studies.
Carefully designed and conducted pharmacoepidemiological studies, specifically observational (non-interventional, non-experimental) studies, are important tools in pharmacovigilance. In observational studies, the investigator "observes and evaluates results of ongoing medical care without 'controlling' the therapy beyond normal medical practice." Before the observational study that is part of a Pharmacovigilance plan commences, a protocol should be finalised. Experts from relevant disciplines (e.g., pharmacovigilance experts, pharmacoepidemiologists and biostatisticians) should be consulted. It is recommended that the protocol be discussed with the regulatory authorities before the study starts. It is also suggested that the circumstances in which a study should be terminated early be discussed with regulatory authorities and documented in advance. A study report after completion, and interim reports if appropriate, should be submitted to the authorities according to the milestones within the Pharmacovigilance plan.
What can be done to check cross-participation of subjects in various CROs?
Dr Muneesh Garg
Please see below the ABPI 2007 phase I recommendation.
Trial subjects must provide proof of identity before they take part in a trial and should be monitored and prevented from taking part in too many trials. The ways are:
● by counselling the subject;
● by including warnings in the information leaflet and consent form;
● for units to keep a register of their clinical trials and subjects who have taken part in them;
● by contacting the general practitioner;
● by being vigilant when screening trial subjects, e.g. look for evidence, such as needle marks on the forearm and low blood counts, that the subject may have taken part in a trial recently; and
● by using an internet-
based central register e.g. TOPS used by most UK phase 1 units.
Dr Arun Bhatt is currently, president, ClinInvent, Research Pvt Ltd, Mumbai.
Readers can send their queries at: arunbhatt@clininvent.com