The
Indian pharmaceutical sector accounts for around 2.4 per cent of the
international pharmaceutical industry in terms of value and 10 per
cent in terms of volume and is likely to develop at a Compound Annual
Growth Rate (CAGR) of 15.92 per cent to US$ 55 billion by 2020 from
US$ 20 billion in 2015.

The
market of the Indian pharmaceuticals is the third largest in terms of
volume and 13th largest in terms of value and is the major provider
of generic drugs worldwide with the Indian generics accounting for 20
per cent of global exports. Recent market size of India is US$ 36
billion which is expected to US$ 55 billion by 2020 .With 71 per cent
market share, generic drugs form the largest segment of the Indian
pharmaceutical sector.

By
2016, India is expected to be the third biggest international generic
Active Pharmaceutical Ingredient (API) commercial market . This
necessitates working on differentiated products to bridge the gap
between the value and the volume. While the international biosimilar
market is expected to grow from US$1.7 billion in 2014 to US$30
billion by 2020, representing a CAGR of 62.1 percent, at a CAGR of
22.1%.

According
to a statement by IMS Health, from 2013-2018 generic drugs are
expected to account for 52 per cent of international pharmaceutical
growth, compared to 35 per cent for patented drugs. In general, sales
of generic drugs are forecast to increase from $267 billion in 2013
to $442 billion in 2017, at an yearly growth rate of 10.6 per cent.
Key factors include popular branded drugs losing their patent
protection (known as a “patent cliff”), support from governments
for generics, new differentiated generics/biosimilars coming into the
market, and merging of the industries.

India
holds the second largest number of Abbreviated New Drug Applications
(ANDAs) and is the world’s front-runner in Drug Master Files (DMFs)
submissions with the United States. The Indian government plans to
set up a US$ 640 million project fund to boost drug discovery and
strengthen pharmaceutical market. The ‘Pharma Vision 2020’ by the
government’s sector of pharmaceuticals proposes to make India a
major hub for drug discovery.

Conventionally,
pharmaceutical firms develop new patented drugs by investing huge
amounts of money (around or more than $ one billion) into R&D
department over 10-15 years. This is the amount of time and money
spent not only to develop some potential new drugs, but drive to
complete the long, expensive and arduous approval course needed by
the USFDA to prove that a drug is safe and effective, and then comes
to the market and reach the consumers. Since this prototype is too
expensive and time consuming, the FDA typically gives 20 years of
patent protection and a total monopoly on sales to innovators during
that period. This allows the innovators to retrieve their money, make
revenue, and start the new process of the next wave of innovative
drugs.

In
contrast, generic drug companies work in a different way. The amount
of money they need to spend to develop a generic is lesser than the
innovator branded drug firms, since the drug has already been
formulated and patented. In order to protect the innovator’s
patented drug and allow them to earn the money they have invested,
generic drugs can only be introduced after the 20 years of patent
protection has expired.

And
even then, FDA approved copies of patented drugs are only given a six
months’ exclusivity period if their generic is the first to market.
Once generic drugs are introduced in the market, generally they are
sold at discounts of 50 to 70 per cent compared to the branded
alternative and in the process branded drugs lose 90 per cent or more
than of their market stake to generics in a short period. The patent
for an anti-cholesterol drug (Lipitor) marketed by Pfizer with annual
sales of $10 billion expired in November 2011. Generic copies of the
drug quickly arrived in the market and, by 2014, about 97 per cent of
sales were from generic copies.

Now
a days, drugs going in to the off-patent are decreasing and also the
current generic growth is in a steady manner due to low margins,
price burden, competition and mature marketing strategies etc. These
factors should lead to some innovation in strategies to sustain the
generic market in future. It can be accomplished by exploring
nanoscience/nanotechnology for the generics and its commercial
development i.e. development of differentiated generics or
biosimilars.

The
patent cliff is a tendency that is likely to keep going. From
2011-2020, drugs with yearly sales of more than $200 billion will be
going off-patent. This may well lead not only to revenue losses for
the innovators of branded drug, but also the potential for
significant new revenues for generic drug firms. In fact, the patent
cliff has created adequate economic capitals and market clout for the
generic firms to help them changeover from fringe players into what
can be called the “New Big Pharma” industry, and move into
innovative and exciting zone and products.

The
term “Differentiated generics” has been given to the development
process for small molecule drugs which offer a therapeutic advantage
or vary from generic products. While generic products signify a
copycat form of the patented drug, differentiated generics represent
new therapeutic moieties that prove enhancements in delivery of
product, strategy or the manufacturing procedure. Differentiated
generics might be able to offer a low-risk, low-cost alternative to
the innovator pharmaceutical development of new medicines, due to
their shorter time for development. Conversely, the manufacturing of
a differentiated generic is more equivalent to that of a generic
moiety, as its mechanism of action is known and an established
profile of safety and efficacy.

Various
tactics used to manufacture the differentiated generics are Quality
by Design (QBD), inclusion of multifunctional excipient, modification
in design & dosage form and improving the pharmacokinetic
parameters & drug release by applying nanoscience/nanotechnology
such as enhancing solubility, increasing bioavailability and efficacy
and decreasing toxicity etc.

Such
an example of differentiated generic in which solubility enhancement
strategy was applied, a generic product of Amprenavir having aqueous
solubility 41 µg/ml and its differentiated generic, Fosamprenavir
has 300 µg/ml in which addition of the ionizable phosphate in the
amprenavir moiety results in decrease in dosing frequency i.e. eight
times a day to two times a day. Spornox capsule (Super Bioavailable
Itraconazole Capsule), a differentiated generic of itraconazole
capsule in which bioavailability enhancement through nanoparticulate
powder solid dispersion of itraconazole carried out results in
doubles the absorption rate and not need to be taken with food when
compared to generic itraconazole capsule. One of the examples of
differentiated generic is AmBisome, a liposomal product of
amphotericin B. In this case, Fungizome (colloidal dispersion) a
generic product having toxicity, LD50 value of 11 mg/kg while its
differentiated generic AmBisome has LD50 value of 175 mg/kg.

Biosimilars
can be defined as the biological product that is approved based on a
showing that it is highly similar to an FDA-approved biological
product, known as a reference product, and has no clinically
meaningful differences in terms of safety and effectiveness from the
reference product.The various strategies applied to develop the
biosimilars like overcoming conformational stability and
immunogenicity of biologics, advancement in delivery strategy of
protein and peptide products, etc. Such an example of biosimilars of
Trastuzumab are CanMab and Herzuma manufactured by Biocon/Mylan,
India and Celltrion, Korea respectively.

The
approval pathway for the differentiated generic also offers a less
complex clinical development process to products. NDA 505(b)(2)
application is the drug development pathway that manufacturers are
mandatory to file under in the United States for the development of
novel formulations and new combinations i.e. differentiated generics
or biosimilars. Significantly, this route allows manufacturers to
incorporate pre-existing data, including late-phase clinical
statistics, into its NDA by reference, which can lead to significant
savings in contrast to pursuing a NDA 505(b)(1). In addition,
provisional market exclusivity is guaranteed in the United States, as
the NDA 505(b)(2) pathway attracts a three-year period of exclusivity
for marketing, providing some degree of protection to product.

In
the coming years, generic market is almost going to capture the half
of the international pharmaceutical market share. The incredible
growth in generic market pulls stakeholders to capitalize more money
to develop the differentiated generics/biosimilars as the risk factor
is negligible and return is too high. The generic market can no
longer be indicted for being a mere copy version of patented drugs.
In fact, novelty leads to the manufacture of a new blockbuster
segment of differentiated generics/biosimilars with better
therapeutic effect when compared to the marketed products. These
differentiated generics are cost-effective, gives more patient’s
compliance which directly contributes in pleasing the unmet medical
needs of the masses. This new segment gives a modern view to the
generic market by following the QBD approach to develop the improved
therapeutic moieties and extends the exclusivity of generic medicines
for marketing. Similarly, the re-purposing of drug going off-patent
is also going to be a good option.

(The
author is Professor of Pharmacy, Faculty of Pharmacy, The
Maharaja Sayajirao University of Baroda, Vadodara)