Please clarify a) whether PMS and phase IV are the same, b) whether PMS required IEC approval and inform consent process and c) whether PMS required protocol or just needs to collect data from the centre without protocol and ICF.
Dr. Akshay Shah
Phase IV includes all activities conducted after the drug is approved. PMS is one of the phase IV studies. Please see ICMR 2006 guidance on phase IV.
Protocol is essential for all human studies. Pl see ICMR guideline recommendations on objectives of phase IV study and need for EC / DCGI approval.
Phase IV - The phase IV studies should have valid scientific objectives. 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. It is an important aspect of drug trial on the long term effects of the drugs and the adverse reactions induced by drugs, if any, should be brought to the notice of the Ethics Committee. There is a need to correlate the adverse events reported during phase IV trials with the toxicity data generated in animals, to draw markers for future warnings of potential adverse events likely to occur with other drugs. 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. These studies also include those on specific pharmacologic effect, drug-drug interaction(s), dose-response studies, trials designed to support use under approved indication(s) e.g. mortality/morbidity studies, clinical trials in a patient population not adequately studied in the pre-marketing phase, e.g., children; and epidemiological studies etc. Bioequivalence and bioavailability study also falls under this category.
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 labelled 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.
Is it appropriate to archive the e-copy (scanned pdf softcopy) of the records generated in bioequivalence studies as CDs, DVDs, floppies etc instead of archiving hardcopy of the data? If the CRO conducting BA/BE studies has several facilities throughout the country and has central archival at head office then is it appropriate to archive the data generated in the BA/BE study conducted at different facility (not the facility where central archival is situated) at central archival? Or archival of the data at the site where the study is conducted is obligatory?
Avadhut Sakhare
Most 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 see ICH GCP.
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 investigations 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. It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained.
The objective of archiving records/documents is to support audit / inspections.
These documents are also the ones which are usually audited by the sponsor's independent audit function and inspected by the regulatory authorities as part of the process to confirm the validity of the trial conduct and the integrity of data collected.
Hence, the crucial thing is that they should be available to the auditor / inspector when they visit the facility. It would be easier to locate them if they are kept near the facility to be inspected /audited.
Is it not mandatory in India to do BE studies before bringing a generic product to market?
Rendeep Rajendran
If a product falls into definition of new drug as per Drugs & Cosmetics Rules, BA/BE is required before marketing approval. According to 122 E a new drug considered as new drug for a period of four years from the date of its first approval. A generic can be marketed without BA/BE study if the product has crossed 4 years timeline.
I plan to conduct a small study in my clinic with a well known compound which is not currently in the market though for the indication I propose to test it for. There are oral formulation, but I have come to know of an ocular formulation which I want to test. This is an observational study with no invasive procedures. Do I need DCGI approval? Or is the IEC approval sufficient?
Dr. Parvathi
If the compound is new drug by regulatory definition as per Rule 122 E (see below), you need to obtain DCGI approval.
122 E (b) a drug already approved for certain claims, which is now proposed to be marketed with modified or new claims, namely, indications, dosage, dosage form (including sustained release dosage form) and route of administration.
As per this definition, if there is a change in formulation / route / indication, the drug is considered a new drug.
Dr Arun Bhatt is currently, president, ClinInvent, Research Pvt Ltd, Mumbai. Readers can send their queries at: arunbhatt@clininvent.com