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12:00 AM
Dec 20, 2010
 |  BioCentury  |  Regulation

Describing the Inevitable

EMA lays ground for bringing biosimilar mAbs to Europe in near term

About a decade ago, conventional wisdom held that mAbs are so complex that it would be extremely difficult, if not impossible, to develop biosimilar versions of them. While some mAb innovators may cling to this line of thinking, the writing on the wall says biosimilar mAbs are coming to the major markets, possibly as soon as 2013.

This is the conclusion stakeholders are drawing from EMA's draft guidelines laying out the non-clinical and clinical requirements for showing that a mAb-containing product is similar to another one already marketed.

The guidelines, issued last month, would give a biosimilar manufacturer the ability to do abbreviated clinical development using smaller trials with equivalence design and surrogate endpoints. Moreover, EMA would allow the follow-on developer to extrapolate its clinical efficacy and safety data to other indications.

Biosimilar developers contacted by BioCentury - and some of the innovators - generally concluded that EMA's approach is scientific. While there are differences of opinion on some details -- like the use of surrogate endpoints and the extrapolation of indications -- most stakeholders agreed the scientific and regulatory landscapes have evolved to the point where biosimilar mAbs are now possible.

Specifically, advances in biomanufacturing and in assays used to characterize mAbs, as well as the experience gained by regulatory agencies in evaluating the effect of manufacturing changes on innovator products, have made biosimilar mAbs a near-term reality.

The scope

EMA first put out guidelines on biosimilars in 2005, with six product-specific guidelines following in 2009 and 2010 (see BioCentury, July 18, 2005).

Last month's biosimilar mAb draft guidance is considered a product-specific guidance, just like those for recombinant human insulin and somatropin. In this case, the draft also covers fusion-based proteins based on IgG Fc. There are at least 11 such products with expiring patents and/or exclusivity in the next six years (see "Potential Biosimilar mAbs in Europe," A20).

The draft states that each biosimilar will be looked at on a case-by-case basis, which led some stakeholders to suggest there will be no further product-specific guidances for individual mAbs.

"It's clear that EMA wants the flexibility to address these issues on a case-by-case basis. That makes sense because we're talking about antibodies, which are a whole range of products," said Phoebe Mounts, a partner at the law firm Morgan, Lewis & Bockius, who represents innovator companies.

"It matters what the target is; it matters what the indication is. There are so many potential issues that you really do have to focus on a product-by-product basis," she said. "The reason this guidance is so detailed is to make sure it could apply to them all."

Mark McCamish, head of global biopharmaceutical development for Sandoz, a division of Novartis AG, told BioCentury he wasn't sure whether additional product-specific guidances would be needed. "This is enough to give reasonable guidance on a scientific basis," he said.

Sandoz has 8-10 biosimilars in development, including mAbs, but McCamish would not identify them or disclose their stages of development.

Other stakeholders, like Geoff Eich, director of regulatory affairs at Amgen Inc., voiced concern the draft might be too broad for a product-specific guidance. Amgen is not currently developing any biosimilar mAbs but is open to that possibility in the future, Eich told BioCentury.

Nikhil Mehta, VP and head of biologics regulatory affairs at Merck & Co. Inc., said the draft provides a good, broad framework to work with all mAbs, and suspects EMA eventually will put out mAb-specific guidelines, such as for tumor necrosis factor (TNF) alpha antagonists. At least five such innovator products are marketed in the EU for various autoimmune diseases.

Mehta would not disclose whether Merck is developing any biosimilar mAbs....

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