[Ip-health] Salon: "Biosimilar," but not identical

[Hember, Miles]

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Would the brand name manufacturers go to the stand to swear that their
manufacturing processes didn't change *at all* from the batch that got
approval to the end of the production lifetime? I think it's highly unlikely
that no equipment got replaced (different stirrer = different reaction
progress, for example), wore out, went off calibration, or that
non-controlled factors hadn't interfered in some way not anticipated?
(temperature of plant varies with season, contaminants in
water/air/feedstocks change, mechanical stuff wears and electronic stuff
drifts)

If 'the process is the product' then we should be jolly strict with them
ensuring that the process doesn't change.... The qualification that was good
enough for FDA for a small molecule clearly isn't good enough for these....

There are points on both sides but when a group is so consistently underhand
it is just impossible to be charitable even if they deserve it sometimes!

Miles

-----Original Message-----
From: Thiru Balasubramaniam [mailto:thiru@cptech.org]
Sent: 27 July 2006 10:39
To: ip-health@lists.essential.org
Subject: [Ip-health] Salon: "Biosimilar," but not identical


http://www.salon.com/tech/htww/2006/07/26/biosimilars/print.html


    "Biosimilar," but not identical

*The new world of biogenerics: Cheap copies aren't what they used to be.*

*Andrew Leonard*

Jul. 26, 2006 | /The process is the product./ It's a slogan, currently
popular in the biopharmaceutical industry, that sounds like it could have
been coined by Marshall McLuhan on one of his off days. But there's a lot
going on beneath the bland surface: For starters, the sentence is a rallying
cry for brand-name-drug makers in their latest battle against generic
manufacturers;
<http://www.pharmaceutical-business-review.com/article_feature.asp?guid=7ACB
651F-7842-4E10-861C-CD864E00E9BC>
an oblique reference to the nearly infinite complexity inherent in current
biotechnology; and a snapshot of the confused state of pharmaceutical
regulation across the globe. That's good stuff, so let's try to unpack it.
(Thanks to the IP-Health mailing list
<http://lists.essential.org/pipermail/ip-health/2006-July/009886.html>
for tipping us off to the controversy.)

One reason why generics are cheaper than the drugs they copy is that
generics makers do not need to go through all the time and expense of
proving that their drugs are safe and effective. Once they've demonstrated
physiochemical "equivalence" to the original drug they're home-free. But in
the new age of biopharmaceuticals -- complex proteins derived from living
organisms, cultured from cells in a laboratory -- proving equivalence is
much tougher. These new biopharmaceuticals, which include drugs such as
interferon, human growth factor and erythropoietin
<http://www.smartmoney.com/barrons/index.cfm?story=20060725> (better known
to fans of the Tour de France as EPO), are constructed from molecules
containing thousands of atoms, manufactured in processes that involve
hundreds of steps. They are hard to copy, exactly.

In the last couple of years, some of the big names in biopharmaceuticals
have begun to go off-patent,
<http://www.iptonline.com/articles/public/IPTNINE63NoPrint.pdf> and many
more will follow in the next decade. This is opening the door for
biogenerics, or "biosimilars," as they sometimes are called, and you can
already find such drugs in China and India.
<http://www.biospectrumindia.com/content/BioBusiness/10511112.asp>
Consumers in the United States and European Union could potentially save
vast amounts on medical care if biogenerics were widely available. But
neither the U.S. nor the E.U. yet has a comprehensive regulatory structure
for biogenerics in place.

Reason No. 1 for this is that the brand-name manufacturers are fighting
tooth and nail to slow the entry of biogenerics. And this time around,
they've got some potent ammunition on their side. When it comes to proving
equivalence, biogenerics have a tougher row to hoe
<http://www.nature.com/nrd/journal/v5/n7/full/nrd2093.html> than your
old-school "small molecule" generic drug. Postmodern fans of complexity
theory will love this: According to current scientific thinking, using
"current analytical methods" it is impossible to fully "characterize"
<http://www.nature.com/nbt/journal/v22/n11/full/nbt1104-1357.html> the
physiochemical properties of the new proteins being cooked up by Big Pharma.
Not only are these proteins constructed out of thousands of atoms, but
specifying the exact dimensions of their warped and intricately
folded-in-upon-itself structures defies description. In other words, while
it might be feasible to say what a new drug /does,/ after extensively
testing it in clinical trials, it's not possible to say exactly what it
/is./ And if you can't describe the exact structure and essential nature of
the original, then, naturally, you can't say that something else is an exact
copy of it.

So when brand-name-drug makers say "the process is the product," they are
arguing that only those chemical entities that are made in exactly the same
way as the original can claim to be equivalent to the original.
Anything made differently is a different critter ... and, down the line,
might cause different results when used to treat patients.

In a perfect world, the brand-name manufacturers would prefer for the
European Union and the United States to simply forbid biogenerics from being
substituted for brand-name drugs. But they seem to be aware that they will
lose that battle, especially in the European Union, where many of the E.U.
member states are strongly interested in achieving public health cost
savings via biogenerics. So instead, the brand-name manufacturers are
fighting a defensive battle over labeling. They'd like generic manufacturers
to be required to use individual brand names,
<http://www.ebe-efpia.org/docs/pdf/Biosims_EBEEFPIAPosition_Naming%20_7July2
006.pdf>
or barring that, want all biogenerics to be explicitly tied, via their
names, to their original manufacturer.

Their reasons are ostensibly based on safety grounds. As it stands now, when
a doctor prescribes a drug, he or she can simply use the generic chemical
name of the preferred medicine and leave it up to the patient or health plan
administrator to decide whether to go brand name or generic. But say
something goes wrong. The patient experiences some unexpected side effect,
or, worst of all, dies. In the doctor's subsequent report to health
authorities, only the generic name of the treatment is prescribed, and no
one will know what drug was actually used, claim the brand-name
manufacturers. This will make it impossible to trace the true causes of the
adverse health event.

Generic makers and health activists say that the safety claims are a smoke
screen, that the real aim of the labeling plan is to protect market share.
And it is true, safety is a common excuse used by the drug industry in its
war against generics. But it's also true that the inherent complexity of the
new drugs on the market raises new questions of public safety.

Which brings us back to the troubling fundamental observation that the
complete physiochemical characteristics of the new proteins being cooked up
in laboratories across the globe defy definitive "characterization."
That implies a disturbing fuzziness about the state of our knowledge
concerning the leading edge of biotechnological innovation. It suggests that
we are now swimming in seas of complexity that are deeper than we can
fathom. And we've actually barely even dipped our toes in the water.

* -- Andrew Leonard*


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