FIRST TIME IN THE HISTORY OF CDSCO

Mohammad Shahbaz Alam

medicarechief@gmail.com
Aug 15, 2015
Dr.G.N.Singh, drug controller general of India made history by giving CDSCO a global
brand image. He stopped irrational approval of fixed dose combination which was generally
issuing by state licensing authority. Now on wards only rational combination will be
approved in India and clinical trial is mandatory to get approval. Apart from this clinical trial
phase-4 (Post marketing surveillance) and PSUR (periodic safety update report) have become
mandatory. He has made pharmacovigilance mandatory for new drugs specially fixed dose
combination to confirm whether adverse effects of drugs is there or not. Every six months
manufacturer has to submit PSUR to know the safety of drugs.
Drugs approved in phase III trials are often watched over a long period of time in phase IV
studies. Even after testing a new medicine on thousands of people, the full effects of the
treatment may not be known. Some questions may still need to be answered. For example, a
drug may get FDA approval because it was shown to reduce the risk of cancer recurrence.
But does this mean that those who get it are more likely to live longer? Are there rare side
effects that havent been seen yet, or side effects that only show up after a person has taken
the drug for a long time? These types of questions may take many years to answer, and are
often addressed in phase IV clinical trials.
The periodic safety update report for marketed drugs (PSUR) was designed to be a standalone document that allows a periodic but comprehensive assessment of the worldwide safety
data of a marketed drug or biological product. The PSUR can be an important source for the
identification of new safety signals, a means of determining changes in the benefit-risk
profile, an effective means of risk communication to regulatory authorities and an indicator
for the need for risk management initiatives, as well as a tracking mechanism monitoring the
effectiveness of such initiatives. For these reasons, the PSUR can be an important
pharmacovigilance tool
Fixed dose combination approval already approved by state licensing authority is very hot
topic for Indian pharmaceutical industry. CDSCO started giving FDC approval since 1961
and given approval approximately more than 1500 till to date. State licensing authority given
huge number of FDC approval which is not possible to count. CDSCO took it seriously
because globally there is hue and cry that India is flooded with irrational FDC. The strongest
DCGI in the history of CDSCO is non another but Dr.G.N.Singh who issued notification to
all state licensing authority and to the industry in OCT 2012 to stop giving fresh FDC
approval. CDSCO directed manufacture to submit application for approval from its office so
that they can justify rational combination.
In the month of July, 2015, CDSCO started giving approval, rejection, show cause notice and
recommended to conduct phase-4 clinical trials. Industry is happy with the decision taken by

CDSCO for approval and rejection of FDC. But there are so many things need to be
improved and CDSCO should join hands with all stake holders including manufacturers and
regulatory consultant.
BOX ITEM
This time CDSCO should invite all stake holders as how to reply back periodic safety update
report and clinical trial phase-4 protocol and executive summary. It would be nice enough for
stake holders if CDSCO organise workshop and call them to know in brief about as how to
write protocol for phase-4 clinical trials and executive summary so that they can respond the
query fearlessly. Most of the manufactures are not aware about periodic safety update report
(PSUR) then how come they will submit reply. In India, Pharmacovigilance is in a very
nascent stage but it is need of hour to implement in a very strong way.
The development of fixed-dose combinations (FDCs) is becoming increasingly important
from a public health perspective. Such combinations of drugs are being used in the treatment
of a wide range of conditions and are particularly useful in the management of HIV/AIDS,
malaria and tuberculosis, which are considered to be the foremost infectious disease threats in
the world today. According to USFDA, The rationality of FDCs should be based on certain
aspects such as, the drugs in the combination should act by different mechanisms, the
pharmacokinetics must not be widely different, the combination should not have supraadditive toxicity of the ingredients and there should not be drug-drug interaction.
Noteworthy without clinical trial it is not possible to confirm whether any combination drug
is rational or irrational. It is only possible after clinical to confirm pharmakodynamic (Mode
of action), pharmacokinetic (absorption, distribution, metabolism & excretion), drug-drug
interaction and additive supra adverse effects.