door opens slightly for biosimilars in US
A simple US legislation, the Drug Price Competition and Patent Terms
Restoration Act of 1984, popularly called the Hatch-Waxman Act, allowed
the entry of generic pharmaceuticals and spawned the growth of the
global generics pharma industry now estimated at Rs 9.99 lakh crore.
The world has been waiting for an encore on biosimilars or
follow-on-biologics. Now there is a flood of legislative
proposal that seek to permit the sale of copy cat or generic versions
of many life-saving biotechnology drugs.
A flurry of legislative activity on this front to allow the entry of
biosimilar drugs had started after Democratic leader Barack Obama
assumed office as the President of the US in January 2009. He had
publicly supported the entry of biosimilar drugs to enhance reach,
increase affordability and reduce medicare costs.
A few bills to authorize the drug regulatory, the Food and Drugs
Administration (FDA), were introduced in March. But the most
significant proposal came from Senators, Charles E Schumer, a New York
Democrat, and Orrin G Hatch, a Utah Republican, through a proposal
called S. 726, have sought permission for biosimilars. Their
legislative proposal will be a companion piece for the Hatch-Waxman Act
and has suggested several far-reaching measures. The proposal is
supported by other influential senators like Susan Collins, Sherrod
Brown, Mel Martinez, Debbie Stabenow and David Vitter.
The Schumer-Hatch proposal seeks to reduce the exclusive marketing
period given to patented biotech drugs from the current 14
years to just five years. The legislation, introduced on March 26, has
caught global attention because of this drastic proposal on patent
exclusivity period. The US legislature has now adjourned for summer
vacation but the last minute proposal is a clear step to prepare the
ground for the introduction of biosimilars when the legislature
reassembles in a few months.
With both Democratic and Republican Senators proposing such a
legislation and the President who has to finally approve it, favoring
such a popular step, analysts are confident that biosimilars will be a
reality in the US market place sometime in the year 2010.
More significantly, the Schumer-Hatch proposal has overshadowed two
other competing legislative proposals introduced in the US Congress in
early March. On March 11, 2009, a bill, H. R 1427, titled,
“Promoting Innovation and Access to Life-Saving Medicine
Act,” was introduced in the US House of Representatives by
Henry Waxman with support from Frank Pallon, Nathan Deal and Jo Ann
Emerson. A week later, on March 11, another proposal, H.R.
1548, known as “Pathway to Biosimilars Act” was
introduced in the same legislature by Anna Eshoo, Jay Inslee and Joe
The US biotechnology industry is strongly opposed to the proposal to
allow the entry of biosimialr products. Nearly half-a-dozen blockbuster
biotech drugs are expected to reach their patent expiry stage in 2011
and these have annual sales exceeding Rs 55,092 crore ($11
billion). Top biotech companies like Amgen and Genentech will
be impacted severely by the entry of biosimilars.
“This legislation sets a path that jeopardizes our
ability to help meet President Obama’s call for a cure to
cancer ‘within our time’ and help realize the
promise of stem cell research. This bill seeks to cut prices but
instead cuts corners. This proposal leads us off the map as we seek an
effective, fair and safe pathway to the biosimilars market,”
said Jim Greenwood, the president of biotech industry lobby group,
Biotechnology Industry Organization (BIO), based in Washington DC.
However, consumer activists and generic drug companies are
ecstatic about the proposed entry of biosimilars. “The
crushing cost of biologic drugs is leaving far too many Americans
without access to life-saving treatments for devastating illness like
multiple sclerosis and cancer,” said Nancy LeaMond, vice
president of American Association of Retired Persons (AARP), in an
interview to the New York Times.
Added Dr Dhananjay Patankar, chief technical
officer, Intas Biopharmaceuticals Limited, India,
“The bill addresses lot of things which are good for
biosimilar manufacturers and provides three options to them that
include biosimilar without interchangeable, which is similar to the
European approach; biosimilar with total interchangeable (termed as
biogeneric), this is one step ahead of European Medicines Agency (EMEA)
as it has left the interchangeability to the member states, the bill
thus clearly introduces the idea of interchangeability; and lastly,
dissimilarity in safety, purity and potency. The provisions of the bill
could allow variants of existing biologics to be approved through an
abbreviated process. This is the first time
“biogeneric” as a term has been officially used.
For a long time the term itself was considered invalid.”
A regulatory pathway for biosimilars in the US and Europe could
completely change the dynamics of the biotech industry.
According to a report by PricewaterhouseCoopers (PWC) titled,
‘Opportunities and barriers in the biosimilar market:
Evolution or revolution for generics companies?’,
biopharmaceutical drugs or biologics have outperformed the
pharmaceutical market largely due to two factors: they address areas of
clinical need that are unmanageable with conventional therapeutics
including many cancers and genetic diseases, and biosimilars are able
to command a premium price. At some point the patents protecting the
successful biologic will expire and the potential of a sizable market
will attract generic companies. Some of the leading biosimilar products
or targets include erythropoietin, granulocyte-colony stimulating
factor (G-CSF), interferon alpha, interferon beta, human growth
hormone, and recombinant human insulin.
The provision for exclusivity period of first biogeneric (with
interchangeability) will help the biosimilar companies to develop high
quality drugs and it also recognizes the fact that analytical and
clinical studies can be designed to prove complete equivalence.
While predicting the outcome of the final bill Dr Patankar stated,
“Similar to EMEA, product-specific guideline with respect to
the non-clinical and clinical requirements should be specified. Also a
clear guideline with respect to requirements for the biosimilar and
biosimilar with complete interchangeability has to be specified for
each product. Similar to EMEA all the comparabilities of quality,
safety and efficacy are required with reference product. However it is
not specified that the reference product has to be from the US, the
industry needs one reference medicinal product for the US and the
“Data exclusivity is an important element of the bill, the
key would be to get clear guidelines for the introduction of
biosimilars in the US, with definite time lines. If the final bill is
passed in its current form, it will dramatically alter the face of the
biotech industry and existing biotech giants will have to face
competition for the first time in their market. The introduction of
biosimilars would bring down the cost of medicines for critical
diseases in the US and make them available to a wider
population,” said KV Subramaniam, president and CEO, Reliance
Life Sciences, India.
Favorable for India
Indian Biotech Inc. has lauded the bill with the contention that this
can open up new avenues and markets for Indian companies that have
already ventured into biosimilars. Dr MK Sahib, director, Genomics and
Biotechnology, Wockhardt, India, said, “The biosimilar bill
definitely brings good news for those Indian companies that have
already ventured into the space and have filed Abbreviated New Drug
Applications (ANDAs) in the US, the bill will give them an
upper hand over those who are not focusing on biosimilars
“The US is the largest market for biopharmaceutical products,
accounting for about 50 percent of global sales. The biosimilar bill
will allow Indian companies operating in the biosimilars space to gain
access to the largest market in the world for their products. This is a
positive sign for domestic biopharmaceutical companies,”
commented Subramaniam. Reliance Life Sciences has launched three
biosimilars-ReliPoietin [Erythropoietin (EPO)], ReliGrast [Granulocyte
colony stimulating factor (GCSF)], and ReliFeron (Interferon Alpha 2b)
in the domestic market in 2008. Reliance Life Sciences is currently
working on a range of biosimilars, which are at different stages of
development viz. clinical trials, pre-clinical studies, process
development and molecular biology.
“We are concurrently conducting clinical trials for two
biosimilars - EPO and GCSF - in Europe. Further, Reliance Life Sciences
has built significant manufacturing capacity for biopharmaceuticals and
all these facilities are compliant with USFDA and EMEA standards. Also,
Reliance Clinical Research Services (RCRS), the contract research
organization (CRO) arm of Reliance Life Sciences, is capable of
conducting clinical studies for these products in multi-country setting
and as per ICH-GCP protocols,” added KV Subramaniam.
Moreover, despite Obama vouching in for cheap healthcare, several
experts opine that the age of generics is over. “The biotech
companies in the US have mastered themselves in small molecules, which
have provided a good opportunity for them all this while. Biosimilars
on the other hand is limited to a small number of players in the
market, so the competition is comparatively low, this will be a great
boost for biosimilar players in the market,” added Dr Sahib.
Generics did have a revolutionary impact but experts opine that
biosimilars will have much more impact if a regulatory pathway is
It will definitely not be a cakewalk for Asian companies despite the
attractive prospects that the biosimilar markets offer. A PWC report
points at two important challenge areas. Firstly sales of most
biopharmaceuticals are higher in the US than the rest of the world.
However, there is unlikely to be a regulatory pathway for most
biosimilars in the US until after 2010. The commercial decision on the
new products will be taken on the basis of the sales a biosimilar can
generate in Europe. The biosimilar market will be characterized by
price competition, even when there is only one or a very limited number
of players for a given product, this will constrain the size of the
commercial opportunity. Manufacturers of branded products are likely to
use sophisticated defensive tactics, including the development of
complex biopharmaceuticals, to make their presence felt in the market.
Indian companies including those companies that have ventured into
biosimilar space should have to find a solution to overcome these
obstacles before setting out to exploit the US market.
Narayanan Suresh and
Nayantara Som with inputs from Jahanara Parveen and Shalini Gupta