INDIA IS CAPABLE TO LEAD GLOBAL PHARMA INDUSTRY

Mohammad Shahbaz Alam

Objective of writing this article is to know more about factual information about fixed dose
combination available globally, create awareness to design guideline for FDC. India should
lead the world in formulation of FDC as there is no final guideline in place. India capable to
lead the world in terms of guideline designing of FDC because India is global hub of FDC till
to date. It is noteworthy fixed dose combination in herbal is available here since more than
5,000 years. Most importantly India has rationalised all FDC available coupled with
pharmacovigilance system to know the adverse events.
India, China, Malaysia, Indonesia, Korea, Russian countries and Middle East countries were
using fixed dose herbal combination since the early age of this world. Triphala and
Chaivanprash to name a few are globally established herbal FDC. Triphala is a combination
of
three
fruits
Amalaki (Emblica
officinalis), Bibhitaki (Terminalia
bellirica),
and Haritaki (Terminalia chebula). Triphala is used for constipation, indigestion, hyperacidity
and cleansing our system. In this modern hitech world no one dare to challenge old aged
herbal fixed dose formulation till to date. We should salute to super doctor and innovator of
herbal formulation such as Shen Nung (2696 BC), Hakeem Luqman (1100 BC), Acharya
Charak (300 BC), Ibne Sina and others. Herbal doctors at that early age of the world were
technically and spiritually very sound and it was need of the hour to treat patient effectively
by innovating fixed dose combination.
The development of fixed-dose combination drugs is becoming increasingly important from a
public health perspective and they are commonly used to manage some of the world's most
infectious diseases. Benefits such as cost-effectiveness, simple distribution logistics and
improved patient adherence all add to their importance.
CDSCO has given approval approximately more than 2000 FDC and it would cross to 3000,
whereas America has given only 200 FDC approval till to date. India is developing
pharmacovigilance data on more than 1400 million populations where America has only 325
million populations followed by UK just 65 million populations.
India has emerged as global economic super power and global leader. India has given world
global Yoga day and global student day and in days to come India is going to give lots of gift
to the world. Mangalayan is the most economical satellite in the world developed
indigenously. India has launched 20 countries satellite including USA and UK. America has
denied giving super computer to India and India taken it positively, developed Param 1000
super computer and now giving back to most of the countries. India has developed its own
economic version of hepatitis B vaccine in collaboration with Oman. Nalanda University is
witness that India had developed cure for HIV and AIDS at time but all research paper had
been destroyed by invaders. India has taken a paradigm shift and placing back on global
leadership chair.
FDC is a good alternative not only for patient compliance but also to augment profitability of
pharmaceutical sector. Global pharma majors are in foray of FDC launch because it is a
multibillion dollar business tool. They have already launched FDC globally and among the
leading companies are Merck with 10, Novartis with 9, and GlaxoSmithKline with 8, Abbott

6, Pfizer 6, Bayer 5, Boehringer 5, AstraZeneca 4, BMS 4, Gilead 4, Takeda 4 FDC products

and others 66.

We should feel proud that we have immense number of FDC approval from CDSCO. Now
we should take process patent on priority. Pharmaceutical companies should innovate more
and more FDC. CDSCO generally give priority in approval for FDC those approved
anywhere in US or Europe. CDSCO should remove block barrier that even any FDC if not
approved in US or Europe can be approved first time in the world by CDSCO. Tapentadol &
paracetamol combination has been rejected whereas Tramadol & paracetamol is approved
with CDSCO. It is noteworthy tramdol is 100% opiod where as tapendaol is 50% opiod and
50% non-opiod. Tapentadol is safer than tramadol. Hence tapentadol & paracetamol is better
alternative and it should be approved in India.

There was a myth that India is a global hub of irrational fixed dose combination and mostly
without cdsco approval fixed dose combination. In September, 2012 cdsco had stopped
further approval of FDC from state drug licensing authority and those FDC approved after
1988 after the introduction of Rule-22E were advised to apply for approval from cdsco.
Those applied for approval from cdsco are entitled to continue manufacturing and marketing
till the final decision. Those who had not applied for approval from cdsco are not allowed to
continue manufacturing and marketing. cdsco given directive to state drug licensing authority
to stop renewing manufacturing license to those who had not applied for approval from
cdsco. cdsco also given directive to state drug licensing authority not to issue any new license
to manufacture FDC.
In the mid of July, 2015 cdsco started giving approval/ rejection/show cause notice/phase-4
clinical trial to those who applied FDC. cdsco has taken a remarkable decision to provide safe
and quality medicine. PSUR (Periodic Safety Update Report) has to be submitted six monthly
in first year and then annually till forth year from the date of approval. cdsco made
mandatory for phase-4 clinical trial or PMS (Post Marketing Surveillance) for few FDC
application to safeguard the quality of medicine.

An analysis of fixed-dose combination (FDC) products can provide insight into evolving
therapeutic needs and point the way to new product opportunities. Now India has only
rational combination and cdsco is controlling quality of medicine by strong
pharmacovigilance system in place.

Of the 131 FDC products approved by the US FDA since 1990, it was previously noted that
the majority of these products comprise pharmaceutical actives that had been previously
approved. This is not surprising as the approval process for a new chemical entity (NCE) is
sufficiently challenging that combining two or more unapproved actives substantially
increases the associated risks and the costs. It is perhaps better to gain approval as a single
entity NCE, properly understand its characteristics in a large population, and then pursue
additional combination opportunities.
Of the 131 approved FDC products, a total of 87 (66%) were developed by, or in active
partnership with, Big Pharma companies. Among the leading companies were Merck with 10,
Novartis with 9, and GlaxoSmithKline with 8 FDC products. A list of companies is provided
in Table 1. Specialty Pharma companies accounted for an additional 42 FDC products. The
leading companies in this regard were Gilead with 4 and Valeant with 3. The remaining
Specialty Pharma companies for the most part developed 1 or at most 2 combination
products. Emerging biopharmaceutical companies, those without any product revenues,
accounted for the remaining 2 approved FDC products.

GlaxoSmithKlines Advair, a combination of fluticasone and salbutamol, has racked up more

than $75 billion in worldwide sales since its first approval in 1999. The success of Advair has
led other companies to introduce competing FDC products for the treatment of asthma and
other respiratory indications, some of which have achieved sales in excess of $1 billion
annually. A list of product approvals by therapeutic area is presented in Table 2.

Its not surprising that the majority of the 131 FDA-approved FDC products have been approved in
multiple markets around the world. What is surprising is that fully 41 of the total number of 131
products have only been approved in the US, or Canada. Of the 131 FDA-approved FDC products, a
total of 19 (15%) have managed to capture more than a billion dollars in annual sales.