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The European Union has reached an important stage in its efforts to make the region a biosimilars production center. The London-based
European Medicines Agency (EMA), which licenses EU pharmaceuticals, has finalized a guideline on biosimilar monoclonal antibodies
(mAbs) and is drafting another one on the key issue of quality of biosimilars (1, 2).
To supplement an eight-year-old basic regulation laying down the general principles behind the introduction of biosimilars,
EMA has issued a series of product-specific guidelines. These cover biosimilars for insulins, somatropins, granulocyte-colony
stimulating factor (G-CSF), epoetins, low-molecular weight heparin, and interferon-α (3). However, the guideline on mAbs is
seen as technically the most challenging because of the complexity of the drugs in terms of their biological structure, range
of clinical indications, and potential for unwelcome adverse effects, particularly immunogenicity.
The mAb guideline was published at the same time as a separate one specifically on immunogenicity in mAbs, which the EMA points
out are known to be associated with unwanted immunogenicity (4). Because the mAb guideline concentrates primarily on safety
and efficacy, quality matters are being covered by the general quality guideline for biosimilars, currently in the consultation
stage.
"The finalization of the EU mAbs guideline can be regarded as another major milestone in the scientific framework for biosimilars,"
says Suzanne Kox, senior director of scientific affairs, at the European Generic Medicines Association (EGA), which is in
Brussels.
The high cost of development
The EMA, unlike with nationally-approved generic drugs, is responsible for licensing biosimilars and has so far authorized
14—two somatropins, five epoetins, and seven G-CSF filgrastims. The publication of the mAb guideline is expected to trigger
a sizeable number of mAb biosimilars applications. As with previous guidelines, however, the one on mAbs confirms the expectation
that biosimilars production and development will be an expensive business because of the high cost of manufacturing facilities
and of conducting nonclinical and clinical trials.
"To get started in the biosimilars business, a lot of investment is required in biopharmaceutical production facilities—probably
around €300–400 million ($390–520 million)," said Andreas Barner, chairman of Boehringer Ingelheim, at an R&D conference at
Ludwigshafen, Germany, earlier this year. "Even more important will be the high cost of developing biosimilars because, for
the first time, nonoriginal medicines will have to be supported by large-scale clinical trials," he continued. "The sector
will suit companies which already have biopharmaceutical plants and have experience of bringing original compounds to the
market."
In the EU, the cost of regulatory compliance for biosimilars will be pushed up even further by the implementation of the
EU's new rules on pharmacovigilance, which stipulate additional postlaunch monitoring of biological drugs, particularly biosimilars,
and mAbs.
"[Pharmacovigilance] is particularly important with monoclonal antibodies as these are complex molecules with complex safety
profiles," says Alan Morrison, chairman of the regulatory affairs advisor committee of the UK Bioindustry Association (BIA).
