VentureBeat

(UPDATED: See below.)

Yesterday, the WSJ Health Blog cited a WSJ story as evidence that “biogenerics” — that is, generic versions of biotech drugs, which currently don’t exist — need to be treated with caution. Unfortunately, that post missed a much more important point about biogenerics: The double standard that the biotech industry holds when it comes to determining whether different batches of biotech drugs are equivalent or not. The subject is still widely misunderstood, thanks in part to chaff kicked up by the biotechnology industry itself. (See our previous coverage here and here.)

The original WSJ story, written by David Armstrong and Geeta Anand, concerned production problems at a new Genzyme plant making Myozyme, the company’s new drug for a rare genetic condition called Pompe disease. Myozyme produced at the new plant, it turns out, differs measurably from that pumped out by the same genetically engineered cells at the company’s older manufacturing facility. In particular, the “new” Myozyme appears to contain less of a carbohydrate that helps muscle cells take in the drug. Because of this difference, the FDA has so far refused to approve the new manufacturing plant, which raises the prospect of Myozyme shortages and a financial hit for Genzyme.

The WSJ story itself didn’t delve into the issue of biogenerics. On the health blog, however, Armstrong wrote:

Making biologics is complicated work, and that’s one reason the biotech industry has voiced caution about legislation to allow generic versions of the medicines.

In the case of Myozyme, billions of cells from hamster ovaries growing in large stainless steel tanks produce the enzyme Pompe patients lack. The fact that Genzyme, which has loads of biotech experience, is having such difficulty ramping up production of its own drug heightens worries about the ability of generic manufacturers to accurately copy brand-name biotech drugs.

The first issue here is that there’s nothing new about biotechs finding that new production batches of a complicated protein differ in certain ways from older batches. I listed several examples in an online column I wrote for the WSJ more than three years ago, and there have undoubtedly been others since. Sometimes these differences are serious; more often, they’re not. When there is a major discrepancy, as there was for Genentech’s drug Raptiva (then called Xanelim) in 2001, the FDA requires the biotech to carry out clinical trials to ensure that the new production line is pumping out a drug that’s equivalent to the old stuff. So far, the FDA isn’t requiring Genzyme to conduct new clinical trials of Myozyme produced at the new facility, company spokesman Dan Quinn told me.

The second issue — and those of you who’ve followed these debates can probably see where I’m going — is that the biotech industry wants to have it both ways when it comes to the “complicated work” of making biologics. Where biogenerics are concerned, the industry insists that copycat versions of biotech drugs must undergo those expensive and lengthy clinical trials in the interests of “patient safety.” When it comes to their own drugs, however, biotech companies are perfectly willing to rely on a battery of simpler tests to ensure that a new production batch is equivalent to an old one, and only run clinical trials as a last resort (and when forced to by the FDA).

All of which suggests that it would probably suffice to subject any would-be copycat drug to the same set of tests that biotech manufacturers themselves must meet for a new production facility. If it passes, it’s approved. If not, then it’s time to consider clinical trials. In fact, this is pretty much the “case-by-case” strategy adopted by the House and Senate biogenerics bills — ones that I’m pretty sure the Biotechnology Industry Organization opposed. In any event, it doesn’t seem too much to ask that journalists covering these debates realize that the case against biogenerics is a lot weaker than the industry would like us to think.

UPDATE: This NPR story (via the LAT) makes some of the same mistakes. It’s not the complexity, folks — it’s whether there are reliable tests for ensuring that batches of these complex molecules are equivalent to one another short of clinical trials, which there most certainly are.

UPDATE REDUX: The In Vivo blog weighs in with a related story about the slow start to sales of Omnitrope, a generic human-growth hormone (which they refer to as a “biosimilar,” a word preferred by the biotech industry).

UPDATE, TAKE THREE: I revised the headline and first paragraph to better reflect the post’s main point. I also wanted to belatedly credit David Williams of the Health Business Blog for sparking this train of thought in the first place with this post. (I’d written about his thoughts on the subject earlier, but now that I’m thinking about it, there was no good reason not to mention it again.)

(Note: This item has been copied over to the Life Sciences page from its original location on the VentureBeat main page. To view it in its original context, with comments, click here.)

A second legislative fight for the biotech industry is shaping up in Washington over whether to give the Food and Drug Administration authority to approve “generic” versions of biotechnology drugs whose patents have expired.

Measures that would grant FDA that authority, introduced separately in the House and Senate, are billed as a natural cost-saving measure by supporters. They note the high cost of many biotech drugs and the fact that several best-sellers are expected to go off-patent over the next few years. To biotech’s biggest companies and their lobbyists, however, the effort could jeopardize public safety and the incentives that lead companies to spend vast sums in search of new drugs in the first place — at least unless the copycat products are required to go through the same arduous and expensive clinical trials as their brand-name counterparts.

Here, the industry relies on an argument that is one part science and one part misdirection. Biotech drugs generally consist of large, complex proteins that are much more difficult to understand than the relatively straightforward active chemical ingredients in traditional pills. The industry argues that it’s impossible to analyze copycat biotech drugs thoroughly enough to know whether or not they’re identical — or at least close enough — to a name-brand version. Which, of course, leads to the demand that copycat biologics run the same human-trial gauntlet as name-brand drugs, a requirement that might run up development costs so high that a “generic” biotech drug wouldn’t necessarily be any cheaper than its rival.

The problem here is that some biotech-drug proteins aren’t so complex as to defy analysis. The FDA, for instance, already approved a copycat version of human growth hormone called Omnitrope a year ago, after a variety of laboratory and limited human tests allowed FDA scientists to determine that it was “highly similar” to its name-brand cousin. That sort of testing isn’t possible for all biologic proteins, but as analytical laboratory technology gets better, so will the FDA’s ability to correctly assess the similarity of even complex protein drugs. Last month, in fact, FDA Deputy Commissioner Janet Woodcock testified before Congress that the agency already has the skills to make those assessments in some cases. Since the bills in question simply give the FDA the authority to authorize copycat versions of biotech drugs when the evidence warrants it, it’s hard to see what all the shouting is about.

Except, of course, that this fight — like most such Beltway brawls — is at heart about money. Unlike Big Pharma, which has to brace itself for generic competition every time a billion-dollar drug approaches the end of its patent lifetime, biotech companies face little threat of pricing pressure even when patent protection lapses on their cash cows (such as Amgen’s Epogen, a version of the erythropoietin molecule pictured above). Given that annual costs for many best-selling biotech drugs run into the tens of thousands of dollars — even hundreds of thousands in some cases — the green at stake is truly astonishing.

As for the innovation argument, it helps to remember that patents are limited, artificial monopolies created for public-policy reasons that are written into the Constitution itself. If innovation in the biotech industry really depends upon perpetual monopolies over incredibly expensive drugs — well, let’s just say that this is not an argument you’re likely to hear explicitly from a biotech representative any time soon.

A second legislative fight for the biotech industry is shaping up in Washington over whether to give the Food and Drug Administration authority to approve “generic” versions of biotechnology drugs whose patents have expired.

Measures that would grant FDA that authority, introduced separately in the House and Senate, are billed as a natural cost-saving measure by supporters. They note the high cost of many biotech drugs and the fact that several best-sellers are expected to go off-patent over the next few years. To biotech’s biggest companies and their lobbyists, however, the effort could jeopardize public safety and the incentives that lead companies to spend vast sums in search of new drugs in the first place — at least unless the copycat products are required to go through the same arduous and expensive clinical trials as their brand-name counterparts.

Here, the industry relies on an argument that is one part science and one part misdirection. Biotech drugs generally consist of large, complex proteins that are much more difficult to understand than the relatively straightforward active chemical ingredients in traditional pills. The industry argues that it’s impossible to analyze copycat biotech drugs thoroughly enough to know whether or not they’re identical — or at least close enough — to a name-brand version. Which, of course, leads to the demand that copycat biologics run the same human-trial gauntlet as name-brand drugs, a requirement that might run up development costs so high that a “generic” biotech drug wouldn’t necessarily be any cheaper than its rival.

The problem here is that some biotech-drug proteins aren’t so complex as to defy analysis. The FDA, for instance, already approved a copycat version of human growth hormone called Omnitrope a year ago, after a variety of laboratory and limited human tests allowed FDA scientists to determine that it was “highly similar” to its name-brand cousin. That sort of testing isn’t possible for all biologic proteins, but as analytical laboratory technology gets better, so will the FDA’s ability to correctly assess the similarity of even complex protein drugs. Last month, in fact, FDA Deputy Commissioner Janet Woodcock testified before Congress that the agency already has the skills to make those assessments in some cases. Since the bills in question simply give the FDA the authority to authorize copycat versions of biotech drugs when the evidence warrants it, it’s hard to see what all the shouting is about.

Except, of course, that this fight — like most such Beltway brawls — is at heart about money. Unlike Big Pharma, which has to brace itself for generic competition every time a billion-dollar drug approaches the end of its patent lifetime, biotech companies face little threat of pricing pressure even when patent protection lapses on their cash cows (such as Amgen’s Epogen, a version of the erythropoietin molecule pictured above). Given that annual costs for many best-selling biotech drugs run into the tens of thousands of dollars — even hundreds of thousands in some cases — the green at stake is truly astonishing.

As for the innovation argument, it helps to remember that patents are limited, artificial monopolies created for public-policy reasons that are written into the Constitution itself. If innovation in the biotech industry really depends upon perpetual monopolies over incredibly expensive drugs — well, let’s just say that this is not an argument you’re likely to hear explicitly from a biotech representative any time soon.