While Myozyme (alglucosidase alfa) made at another plant in Framingham is already registered on the US market as a treatment for Pompe disease, the FDA has ruled that the Allstron version must be considered a different product because of differences in the biological signature of the active molecule.
In essence, the agency is concerned about how the protein made at is glycosylated - the pattern of carbohydrate side chains that can have an impact on its behaviour in the body.
Genzyme will now be forced to file a new Biologics License Application (BLA) to sell Myozyme made at the plant, holding back the increase in production capacity by six months or more.
If Genzyme is hitting regulatory roadblocks trying to manufacture the same biologic - using the same production process - at an additional plant, then it suggests the barriers will be even higher for generic companies trying to prove that copycat versions made via a different process are truly bioequivalent.
Currently Myozyme is made in a 160 litre-scale bioprocessing facility but rising demand for the drug led Genzyme to ask for approval to make it in a much-larger, 2,000-litre bioreactor.
Seeing double Somewhat bizarrely, this will likely lead to a situation where there will be two versions of the same product on the market, differentiated by their production process, said Genzyme in a conference call, It pointed out that production at this larger scale has already been approved in more than 40 countries.
The company already has a completed clinical trial -called LOTS - that may form the basis of a new BLA for the 2,000-litre version of Myozyme which should avoid too much of a delay in bringing it to market.
It hopes to launch it in the first quarter of 2009, and will forgo an estimated $45m in lost revenues this financial year.
At present there is only one copycat version of a biologic drug on the US market - Sandoz' Omnitrope (somatropin) - despite years of wrangling about drawing up a regulatory route for approval of these so-called 'follow-on biologics'.
The FDA has made no secret of its concerns about the risk of immunogenic reactions when swapping from an innovator biological product to a follow-on biological product (or vice versa), saying that this should only occur with a physician's consent.
The two drugs must also not be considered interchangeable, said Department of Health and Human Services Secretary Michael Leavitt earlier this year when debate on the bipartisan US Biosimilars Act (H.R. 5629) introduced in March.
The agency's position is that there is a close relationship between the product's manufacturing process and its clinical attributes, so classical notions of bioequivalence - which underpin the small-molecule generic drug market - do not apply.
According to the FDA Omnitrope is not officially called a generic because it is not rated as therapeutically equivalent to any of the other approved human growth hormone (hGH) products.
It is however "sufficiently similar" to them for approval.
It was cleared under existing legislation - the 505(b)(2) pathway of the Hatch-Waxman Act - which is only really suitable for approving small, simple follow-on biologics.
For more complex applications a brand new regulatory route will have to be mapped out.
In this respect the US is lagging well behind the EU, which has already approved the first handful of biosimilars in order to provide lower-cost alternatives to brandname biologic drugs and alleviate some of the burden on cash-strapped healthcare systems of prescribing these drugs.